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Clinical Parasitology









Dr- Mohamed Ben Rashed

MBBCh, DCH, DTCH, Msc, PhD

Clinical Parasitology and Medical Entomology Department
Medical Faculty / Alfatah University
Tripoli/Libya








First Edition





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Preface

I am presenting this book , to convey the correct , and modern information
to become as a reference in the field of parasites when desired by any of
the medicals and their assistants, especially for medical students of third
class, and the teaching members of this field. I exert my best efforts to
collect and to add of the best benefit from various modern books and
references, most of it from the internet. I tried to do my best to write the
most important on diagnostic and remedy due to my profession as a
physician, I know the need of medicine student in this subject, away from
the applied parasitology. I did my best to present this book in a complete
image, which is considered the first edition. If there is any incompletion or
non clear of any part, I will correct that in the coming edition.
In intended more explaining in some of the diseases such as Malaria,
Leishmaniasis,Hydatid disease, Bilharziasis and others, because these are
the most important and dangerous of parasitic diseases which can leads to
fatal illnesses in the hospitals according to my experience.
At last I wrote this to be an easy scientific reference to the student, that
because I found many of them suffering and asking of non availability of
any specific comprehensive reference covering their needs, also due to the
expensive price of the references. And the contradictions of the teaching
members on the priority of teaching, this happened in the different medical
faculties in the Jamahirya. Whereas most of them concentrating in the
applied phase , and not the clinical one.



Mohamed Ben Rashed












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Acknowledgments

Acknowledgement to Centers for Disease Control and Prevention,
Division of Parasitic Diseases, for permission to copy Life cycle figures
and photographs.

I also acknowledge with gratitude the assistance received from:

Dr-Badereddin Annajar , for his effort to design the picture of the book
cover.
Dr-Wafa Kara, for commenting on the Cestodes and Nematodes chapters.


The Author


















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Contents

CHAPTER
1
Introduction6

CHAPTER
2
Parasitism,and parasitic association8

CHAPTER
3
Protozoa:Immune defence,and Pathology12

CHAPTER
4
Protozoa of human body.20

CHAPTER
5
Blood Protozoa(Haemoflagellates)67

CHAPTER
6
Other Blood and Tissue Protozoa..84

CHAPTER
7
Blood sporozoa (Malaria,and Babesia)..100

CHAPTER
8
Tissue sporozoa (Coccidia)..137

CHAPTER
9
Microsporidia163

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CHAPTER
10
Helminthes-Flukes(Trematodes)..168

CHAPTER
11
Helminths-Cestodes (Tapeworms)...205

CHAPTER
12
Nematodes (Round worms)/Blood and Tissue Nematodes243

CHAPTER
13
Intestinal Nematodes302

CHAPTER
14
Other Worms (Pentastomida, Leeches)..340

CHAPTER
15
Opportunistic Parasite and Pseudoparasites.343

CHAPTER
16
Antiparasites (Drugs).....346

CHAPTER
17
Common symptoms and signs of human parasitic disease365

References...387

Index395



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CHAPTER ONE (1)

Introduction

Many people in the tropic and subtropic countries suffer from poor
nutrition, poor living conditions and a poor environment and from the poor
health that such conditions bring. They therefore suffer most of the
diseases that affect man kind throughout the world. But on top of this
burden, they must endure the heavy consequences of diseases specific to
their situation: the so-called tropical diseases. These diseases such as
malaria, schistosomiasis, lymphatic filariasis, Chagas disease,
onchocerciasis, leishmaniasis, and African sleeping sickness cause
tremendous pain and suffering, from deformities to blindness, brain
damage and death. these tropical parasitic diseases impede national and
individual development, make fertile land inhospitable, impair intellectual
and physical growth, and exact a huge cost in treatment and control
programmes". Tropical parasitic diseases were once considered diseases of
the rural poor. They still are; but today they are also becoming diseases of
development, closely associated with people's need to earn income for
example, with the recent massive migration from rural to urban areas, and
with new irrigation and mining projects. The diseases have become "the
diseases of the new frontier" the diseases which rob people of their hope.
Nor are these diseases confined to the tropics. Tourism, trade, business
travel and immigration are bringing cases of the diseases into the
industrialized world, where health systems are unused to diagnosing them.
Diagnoses often come too late, and case fatalities are unacceptably high.
Tropical diseases should therefore be matters of global concern. They
have been of the highest priority to the World Health Organization from
its very first days of existence. Infections of humans caused by parasites
number in the billions and range from relatively innocuous to fatal. The
diseases caused by these parasites constitute major human health problems
throughout the world. (For example, approximately 30 percent of the
world's population is infected with the nematode Ascaris lumbricoides.)
The incidence of many parasitic diseases (e.g., schistosomiasis, malaria)
have increased rather than decreased in recent years. Other parasitic
illnesses have increased in importance as a result of the AIDS epidemic
(e.g., cryptosporidiosis, Pneumocystis carinii pneumonia, and
strongyloidiasis). The migration of parasite-infected people, including
refugees, from areas with high prevalence rates of parasitic infection also
has added to the health problems of certain countries. The unicellular
parasites (protozoa) and multicellular parasites (helminths, arthropods) are
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antigenically and biochemically complex, as are their life histories and the
pathogenesis of the diseases they cause. During their life, parasitic
organisms typically go through several developmental stages that involve
changes not only in structure but also in biochemical and antigenic
composition. Some helminth larval stages have little resemblance to the
adult stages (for example, those of tapeworms and flukes). Some parasitic
protozoa also change greatly during their life history; for example,
Toxoplasma gondii is an intestinal coccidian in cats but in humans takes
on a different form and localizes in deep tissues. Some of these infections
can convert from a well-tolerated or asymptomatic condition to life-
threatening disease. Many parasitic infections are transmitted from
animals to humans (zoonotic infections); the human disease may or may
not resemble the disease caused in the lower animal host.




























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CHAPTER TWO (2)
Parasitism and Parasitic Associations
A parasite is an organism that obtains food and shelter from another
organism and derives all benefits from this association. Parasites can be
divided into different classes of parasite :Obligatory parasites.These
parasites can only survive in a host and therefore go directly from one host
to another. This may involve complex life cycles.Examples are:
Trichomonas, Taenia andTrichinella Temporary parasites. These
parasites spend only part of their lives as a parasite and another part as
free-living organism. Examples are: Fasciola hepatica (Liver fluke ) ,
Schistosoma ,Ascaris and Haemonchus .Facultative parasites. These
organisms are normally free living and infect a host only by
accident.Examples: some free-living amoeba such as: Naegleria,
Aacanthameba.Parasites that live inside the body are termed
endoparasites whereas those that exist on the body surface are called
ecto-parasites. Parasites that cause harm to the host are pathogenic
parasites while those that benefit from the host without causing it any
harm are known as non-pathogenic (commensals).
Parasitism :Here one of the associates live either partly or wholly at the
expense of the other associate, the other partner (the host organism) not
gaining anything from the association. This association may give rise to
extreme pathology in the host, or the parasitism may be generally not very
pathogenic. Parasitism is carried out by many organisms, the main groups
including viruses, bacteria, protozoa (these usually being endoparasitic),
and various metazoan groups (multicellular eukaryotic animals), these
being mostly groups of helminths (often endoparasitic), and arthropods
(usually ectoparasitic).
Symbiosis: Here both associates are dependent on each other. Examples
being the association of flagellate protozoa in the gut of termites, where
termites are dependent on the protozoa breaking down their foodstuffs,
and the protozoa are dependent on the termites as host organisms. Another
good example here which is often cited is the association between clown
fish and anemones in tropical reefs, where the fish derives food and
protection from the anemones and is dependent on anemone for protection
whilst the anemone does not appear gain anything by the association,
except possibly cleaning. However it has been observed that in some
cases, in the absence of the fish partner the anemones tend to disappear
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from their reef home, indicating a true symbiotic rather than a mutualistic
or commensal relationship. Other more well known example are found
with the lichens, symbiotic organisms composed of fungi and algae, and
the flagellate protozoans found in the gut of termites.
Mutualism :Here the associates may or may not be dependent on each
other for their existence, but both benefit when they are associated. A
good example of this occurs with the association of sea anemones on the
backs of crabs. Both gain something from the association (the anemone
providing some food for the crab, which in turn gives extra motility to the
anemone), but both can survive on their own.
Commensalism :Again neither associate is dependent on the other for its
existence, but in this case only one of the partners benefits when they are
associated, the other being unaffected. An example of this, found in
humans, are the non-pathogenic obligate commensal protozoa such as the
amoebae Entamoeba gingivalis, commonly found in the mouth, feeding of
bacteria, dead epithelial cells and food particles. Purely commensal
relationships tend to be rather rare, as on closer inspection elements of
mutualism or parasitism may become apparent.
The organism that harbors the parasite and suffers a loss caused by the
parasite is a host.
Hosts: Parasitic helminths may have either simple or complicated
lifecycles. The terms used to describe the hosts harboring different stages
in these lifecycles are however the same. Firstly the adult parasites are
found in the Definitive Host; Depending on parasitic species , the
definitive host is either: the host in which sexual reproduction takes place,
e.g. a human is a definitive host for S. haematobium whereas an
Anopheles mosquito is the definitive host for malaria . Or the host in
which the mature or most highly developed form of the parasite occurs e.g
a human is the definitive host for the trypanomes that cause African
trypanosomiasis. Intermediate Hosts; This term is used to describe the
species of host or hosts, other than the definitive host, that are essential to
complete the indirect life cycle of a parasite e.g the tsetse fly is the
intermediate host for the Trypanosoma species that cause African
trypanosomiasis. In the life cycles of parasitic worms, intermediate hosts
harbour the larval forms. Snails serve as the intermediate hosts for all the
flukes that parasitize humans. Reservoir Host; The host of an infection in
which the infectious agent multiplies and/ordevelops , and upon which the
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agent is dependent for survival innature ; the host essential for the
maintainance of the infection during times when active transmission is not
occurring.
Note; that when describing hosts of parasitic protozoa these terms are
slightly different owing to the asexual characteristics of many of these
organisms. With parasitic protozoa the vertebrate host is generally referred
to as the definitive host, whilst the invertebrate is the intermediate host.
Some parasitic nematodes (e.g. Strongyloides stercoralis) are Facultative
parasites, having completely free living lifecycles in addition to parasitic
ones. The two terms definitive and intermediate host are the most
important in parasitology when referring to the type of host.

Other types of host.

Accidental Hosts are those in which the parasite do not normally develop
(due, for example to lack of exposure to infective forms of the parasite),
but when occasionally chance infections do occur, the parasite is able to
complete its lifecycle. Hosts where the parasite can complete its lifecycle
are called Permissive Hosts, and include true definitive and intermediate
hosts as well as many accidental hosts. Examples here include such
parasites as Fasciola hepatica, where the normal definitive hosts are
ruminants, but humans and other animals may also be infected and viable
adult parasites develop. Another example is human infection with the
nematode Angiostrongylus cantonensis in the far east. In comparison
another form of the accidental host is the Non-Permissive Host where the
parasite, although it may develop to some extent, reaches effectively a
dead end, the parasite not being able to complete its lifecycle and
eventually dying within the host. These forms of infection often occur
where the parasite has intermediate hosts which may be accidentally
ingested by animals other than the true definitive host. For example, with
various marine ascarids of the family Anisakidae such as Anisakissp.,
which give rise to the condition of 'Anisakiasis' on ingestion of raw
infected fish. Paratenic host; transmission of a parasite from one host to
another without the occurrence of maturation or development of the
parasite . In such a host a parasite remains viable but does not develop.
Paratenic Hosts may also be included in parasitic helminth lifecycles. In
these forms of infection the parasites undergo an arrested development on
infection, larval forms accumulating in these hosts until they have a
chance of infecting the definitive host . These hosts are therefore not
essential to completion of the parasites lifecycle. This is in contrast to the
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case with true intermediate hosts whose ingestion is essential to the
lifecycle, for example Ecchinococcus sp.
Vectors
Biological vectors
Examples:
o haematophagous athropodes such as mosquitoes and other
biting insects
Mechanical vectors
Examples:
o flies for transport of amoebal cysts
Zoonosis; A parasitic infection in which the normal host is an animal , but
can produce disease in humans if they become infected accidentally. Some
of the most important parasitic diseases are zoonoses e.g leishmaniasis,
trypanosomiasis trichinellosis etc.
Autoinfection; means...that you become not only definitive host, but also
transient. Yo forget to wash hands after bathroom, and injest what you
have been putting out. Can also mean that one will regurgitate the parasite,
and inhale it to its predeliction site, or vise versa, cough up the stuff and
swallow it to grow in the GI tract, from where it will burrow through
intestine to blood and back to lungs.


















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CHAPTER THREE (3)
Protozoa
Immune defences and Pathology
Introduction
form part of the Kingdom Protista. This kingdom is made up of all the
single celled organisms and are commonly motile. Some protozoans are so
small that they parasitise the cells of the host they inhabit. Protozoans may
live in all parts of the body, including the gut, the mouth, the skin, the
blood, the liver, the spleen, the genital tract, the lungs and the heart.
Body defenses (immunity)
Resistance is the ability of a host to defend itself against a pathogen.
Resistance to parasitic protozoa appears to be similar to resistance against
other infectious agents, although the mechanisms of resistance in
protozoan infections are not yet as well understood.Resistance can be
divided into two main groups of mechanisms: (1) nonspecific
mechanism(s) or factor(s) such as the presence of a nonspecific serum
component that is lethal to the parasite; and (2) specific mechanism(s)
involving the immune system. Probably the best studied nonspecific
mechanisms involved in parasite resistance are the ones that control the
susceptibility of red blood cells to invasion or growth of plasmodia, the
agents of malaria. Individuals who are heterozygous or homozygous for
the sickle cell hemoglobin trait are considerably more resistant to
Plasmodium falciparum than are individuals with normal hemoglobin.
Similarly, individuals who lack the Duffy factor on their red blood cells
are not susceptible to P vivax. Possibly both the sickle cell trait and
absence of the Duffy factor have become established in malaria-endemic
populations as a result of selective pressure exerted by malaria.
Eepidemiologic evidence suggests that other inherited red blood cell
abnormalities, such as thalassanemia and glucose-6-phosphate
dehydrogenase deficiency, may contribute to survival of individuals in
various malaria-endemic geographical regions . A second well-
documented example of a nonspecific factor involved in resistance is the
presence in the serum of humans of a trypanolytic factor that confers
resistance against Trypanosoma brucei brucei, an agent of
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trypanosomiasis (sleeping sickness) in animals. Although nonspecific
factors can play a key role in resistance, usually they work in conjunction
with the host's immune system. Different parasites elicit different humoral
and/or cellular immune responses. In malaria and trypanosome infections,
antibody appears to play a major role in immunity. In both T cruzi and T
brucei gambiense infections, antibody-dependent cytotoxic reactions
against the parasite have been reported. Although antibody has been
shown to be responsible for clearing the African trypanosomes from the
blood of infected animals, recent evidence suggests that the survival time
of infected mice does not necessarily correlate with the ability of the
animal to produce trypanosome-specific antibody. In other words,
resistance as measured by survival time may not solely involve the
specific humoral immune system. Cellular immunity is believed to be the
single most important defense mechanism in leishmaniasis and
toxoplasmosis. In animals infected with Toxoplasma, the activated
macrophage has been shown to play an important role in resistance.
Accordingly, resistance to the protozoan parasites most likely involves
nonspecific factors as well as specific humoral and/or cellular
mechanisms. Cytokines are involved in the control of both the immune
response and pathology. It has become apparent that there are subsets of
both helper (h) and cytotoxic (c) T-cells that produce different profiles of
cytokines. For example, produces gamma interferon (IFN-gamma), and
interleukin-2 (IL-2) . IFN-gamma are important in resistance to
Leishmania, T cruzi and Toxoplasma infections. The cytokines produced
by T and other cell types do not act directly on the parasites but influence
other host cell types. The response of cells to cytokines includes a variety
of physiological changes, such as changes in glucose, fatty acid and
protein metabolism. For example, IL-1 and tumor necrosis factor will
increase gluconeogenesis, and glucose oxidation. It should be noted that
cytokines influence the metabolism not only of T-cells, but also a variety
of other cell types and organ systems. Cytokines can also stimulate cell
division and, therefore, clonal expansion of T and B-cell subsets. This can
lead to increased antibody production and/or cytotoxic T-cell numbers.
The list of cytokines and their functions is growing rapidly, and it would
appear that these chemical messages influence all phases of the immune
response. they are also clearly involved in the multitude of physiological
responses (fever, decreased food intake, etc.) observed in an animal's
response to a pathogen, and in the pathology that results. Unlike most viral
and bacterial infections, protozoan diseases are often chronic, lasting
months or years. When associated with a strong host immune response,
this type of chronic infection is apt to result in a high incidence of
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immunopathology. The question also arises of how these parasites survive
in an immunocompetent animal. Protozoal infection results in tissue
damage leading to disease. In chronic infections the tissue damage is often
due to an immune response to the parasite and/or to host antigens as well
as to changes in cytokine profiles. Alternatively, it may be due to toxic
protozoal products and/or to mechanical damage.
Immune escape Mechanisms
The protozoa parasites have the ability to protect and avoid itself from
immune system traps and mechanisms in various ways. Parasite escape
mechanisms may include a number of different phenomena. In antigenic
masking, the parasite becomes coated with host components and so fails to
be recognized as foreign. The parasite may pass part of its life cycle in an
intracellular location, for example, in erythrocytes or macrophages, in
which it is sheltered from intracellular digestion and from the cytotoxic
action of antibody and/ or lymphocytes. Some parasites practice antigenic
variation, altering their surface antigens during the course of an infection
and thus evading the host's immune responses. Finally, the parasite may
cause immunosuppression, reducing the host's immune response either to
the parasite specifically or to foreign antigens in general. These strategies
are discussed in more detail below. Strategies are mechanisms by which
parasites avoid the killing effect of the immune system in an
immunocompetent host.

Escape mechanisms used by protozoal parasites include the following.

A-Antigen masking
It has been hypothesized that in some cases antigen-antibody complexes in
serum of infected animals bind to the parasite's surface, mechanically
blocking the actions of cytotoxic antibodies or lymphocytes and directly
inhibiting the actions of lymphocytes. This type of immune escape
mechanism has been proposed for tumor cells and for the parasitic
helminths. Because the trypanosomes carry immunoglobulins on their cell
surfaces, they may use a similar mechanism; however, no direct evidence
has yet been reported.



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B-Intracellular location
Many protozoan parasites grow and divide within host cells. For example,
Plasmodium parasites grow first in hepatocytes and then in red blood cells.
Leishmania and Toxoplasma organisms are capable of growing in
macrophages. Although some parasites, such as Plasmodium, are
restricted to a limited number of host cell types, others, such as T cruzi and
Toxoplasma, appear to be able to grow and divide in a variety of different
host cells. An intracellular refuge may protect a parasite from the harmful
or lethal effects of antibody or cellular defense mechanisms. For example,
Plasmodium may be susceptible to the actions of antibody only during the
brief extracellular phases of its life cycle (the sporozoite and merozoite
stages). It should be remembered that Plasmodium actually resides in a
membrane-bound vacuole in the host cell. Thus, plasmodia are shielded
from the external environment by at least two host membranes (the outer
cell membrane and an inner vacuole membrane). Although intracellular
plasmodia are very well protected from the host's immune response early
in their growth, this strategy does create physiologic problems for the
parasite. For example, the parasite must obtain its nutrients for growth
through three membranes (two host and one parasite), and must eliminate
its waste products through the same three membranes. Plasmodia solve
this problem by appropriately modifying the host cell membranes.
Parasitic proteins are incorporated into the red blood cell outer membrane.
The host eventually responds to these antigens, and this response
ultimately leads to the increased removal of infected host cells. The
sporozoite stage is exposed to protective antibody for only a brief period,
and even a single sporozoite that escapes immune elimination will lead to
an infection. A number of parasitic protozoa reside in macrophages.
Although these organisms are protected from external immune threats,
they must still evade digestion by the macrophage. One of the best-studied
examples of a protozoan parasite able to survive in the phagolysosome is
Leishmania. It has been suggested that the resistance of this parasite to the
host's hydrolytic enzymes is due to surface components that inhibit the
host's enzymes and/or to the presence of parasitic enzymes that hydrolyze
the host's enzymes.
C-Antigenic Variation
Three major groups of parasitic protozoa are known to be able to change
the antigenic properties of their surface coat. The African trypanosomes
can completely replace the antigens and exhibits a new humoral response.
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These alterations in serotype are one important way in which the African
trypanosomes escape their host's defense mechanism. Although less well-
characterized, similar changes are reported to occur in Plasmodium,
Babesia.It has been estimated that African trypanosomes have
approximately 1,000 different genes coding for surface antigens. The
antibody response does not induce the genetic switch, but merely selects
variants with new surface antigens out of the original population.
Considerably less information is available on the phenomenon of antigenic
variation in malaria or babesiosis.
D-Immunosuppression
Immunosuppression of the host has been observed with almost every
parasitic organism carefully examined to date. In some cases the
suppression is specific, involving only the host's response to the parasite.
In other cases the suppression is much more general, involving the
response to various nonparasite antigens. It has not yet been proven that
this immunosuppression allows the parasites to survive in a normally
immunocompetent host. However, one can postulate that
immunosuppression could permit a small number of parasites to escape
immune surveillance, thus favoring establishment of a chronic infection.
This mechanism might be particularly effective in parasites undergo
antigenic variation, since it could allow the small number of parasites with
new surface antigens to go undetected initially. Immunosuppression
experimentally induced by various extraneous agents has certainly been
shown to produce higher parasitemias, higher infection rates, or both.
Therefore, the hypothesis that parasite-induced immmosuppression
increases the chance for a parasite to complete its life cycle makes sense.
It should be noted that immunosuppression can be pathogenic itself. A
reduced response to nonparasite antigens could favor secondary infections.
Patients of malaria or trypanosomiasis have been shown to be
immunosuppressed and suffering from secondary infections, may often be
involved in death from African trypanosomiasis. A variety of mechanisms
have been suggested to explain the immunosuppression observed in
protozoan infections. The most common mechanisms proposed are (1) the
presence in the infected host of parasite or host substances that
nonspecifically stimulate the growth of antibody-producing B cells, rather
than stimulating the proliferation of specific antiparasite B-cells; (2)
proliferation of suppressor T-cells and/or macrophages that inhibit the
immune system by excretion of regulatory cytokines; and (3) production
by the parasite of specific immune suppressor substances.
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Summary of immune escape
a-Antigenic Masking: Antigenic masking is the ability of a parasite to
escape immune detection by covering itself with host antigens.
b-Intracellular Location: The intracellular habitat of some protozoan
parasites protects them from the direct effects of the host's immune
response. By concealing the parasite antigens, this strategy also delays
detection by the immune system.
c-Antigenic Variation: Some protozoan parasites change their surface
antigens during the course of an infection. Parasites carrying the new
antigens escape the immune response to the original antigens.
d-Immunosuppression: Parasitic protozoan infections generally produce
some degree of host immunosuppression. This reduced immune response
may delay detection of antigenic variants. It may also reduce the ability of
the immune system to inhibit the growth of and/or to kill the parasites.
Pathology
The protozoa can elicit humoral responses in which antigen-antibody
complexes in the region of antibody excess activate Hageman blood
coagulation factor (Factor XII), which in turn activates the coagulation,
fibrinolytic, kinin and complement systems. It has been suggested that this
type of immediate hypersensitivity is responsible for various clinical
syndromes in African trypanosomiasis, including blood hyperviscosity,
edema, and hypotension. Similar disease mechanisms would be expected
in other infections by protozoa involving a strong humoral immune
response. Immune complexes have been found circulating in serum and
deposited in the kidneys and other tissues of humans and animals infected
with protozoans. Antigen and antibody have been directly visualized in the
glomeruli of infected animals by light and electron microscopy.
Inflammatory cell infiltrates accompany these deposits, and signs of
glomerulonephritis are usually seen. African trypanosomes and
presumably their antigens are also found in a variety of extravascular
locations. Immune complexes, cellular infiltrates, and tissue damage have
been detected in these tissues. Another important form of antibody-
mediated pathology is autoimmunity. Autoantibodies to a number of
different host antigens (for example, red blood cells, laminin, collagen,
and DNA) have been demonstrated. These autoantibodies may play a role
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in the pathology of parasitic diseases in two ways. First the antibodies may
exert a direct cytotoxic effect on the host cells; for example,
autoantibodies that coat red blood cells produce hemolytic anemia.
Alternatively, autoantibodies may be pathogenic through a buildup of
antigen-antibody complexes in the kidneys or other tissues, leading to
glomerulonephritis or other forms of immediate hypersensitivity. A
particularly good example of a protozoan infection in which autoimmunity
appears to be an important contributor to pathogenesis is T cruzi infection.
In this case, there is substantial evidence that host and parasite share cross-
reacting antigens. Antibodies and cytotoxic lymphocytes to these antigens
appear to be harmful to host tissue. This type of experimental data,
combined with the fact that the parasite itself seems not to cause the tissue
pathology, lead one to conclude that autoimmunity may play a key role in
pathogenesis. Cellular hypersensitivity is also observed in protozoan
diseases. For example, in leishmaniasis (caused by Leishmania tropica),
the lesions appear to be caused by a cell-mediated immune response and
have many, if not all, of the characteristics of granulomas observed in
tuberculosis or schistosomiasis. In these lesions, a continuing immune
response to pathogens that are able to escape the host's defense
mechanisms causes further influx of inflammatory cells, which leads to
sustained reactions and continued pathology at the sites of antigen
deposition. During a parasitic infection, various host cell products
(cytokines, lymphokines, etc.) are released from activated cells of the
immune system. These mediators influence the action of other cells and
may be directly involved in pathogenesis. An example is tumor necrosis
factor (TNF), which is released by lymphocytes. TNF may be involved in
the muscle wasting observed in the chronic stages of African
trypanosomiasis. TNF has also been implicated in the cachexia and
wasting in Leishmania donovani infection, cerebral malaria in P
falciparum in children and decreased survival in T cruzi-infected mice. It
is apparent that mediators involved in resistance to protozoan parasites
may also lead to pathology during a chronic infection. There appears to be
a delicate balance between the factors involved in resistance to infectious
agents and those which ultimately produce pathology and clinical disease.
Numerous authors have suggested that toxic products produced by
parasitic protozoa are responsible for at least some aspects of pathology.
For example, the glycoproteins on the surface of trypanosomes have been
found to fix complement. This activation of complement presumably
results in the production of biologically active and toxic complement
fragments. In addition, trypanosomes are known to release proteases and
phospholipases when they lyse. These enzymes can produce host cell
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destruction, inflammatory responses, and gross tissue pathology.
Furthermore, it has been hypothesized that the trypanosomes contain a B-
cell mitogen that may alter the immune response of the host by eliciting a
polyclonal B-cell response that leads to immunosuppression. Finally it has
recently been shown that the African trypanosomes also contain an
endotoxin which is presumably released during antibody- mediated lysis.
Parasitic protozoa have also been reported to synthesize (or contain) low-
molecular-weight toxins. However, parasitic protozoa are generally not
known to produce toxins with potencies comparable to those of the classic
bacterial toxins (such as the toxins responsible for anthrax and botulism).
One possible exception is the African trypanosomes which are suggested
to contain an endotoxin.














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CHAPTER FOUR (4)
Protozoa of human body
Protozoa Taxonomy
Kingdom: Protista

Phylum: Subphylum: Genera:
Sarcomastigophora
Mastigophora (mastigo =
whip = flagellates)
Trypanosoma, Leishmania, Giardia,
Trichomonas
Sarcodina (amoebae)
Entamoeba, Naegleria,
Acanthamoeba
Apicomplexa
Plasmodium, Toxoplasma,
Cryptosporidium, Isospora
Ciliophora

Balantidium

Niches of protozoa in the Human Body:
1. Skin: Leishmania
2. Eye: Acanthamoeba
3. Mouth: Amoebae and flagellates (usually non-pathogenic)
4. Gut: Giardia, Entamoeba (and invasion to liver), Cryptosporidium,
Isospora, Balantidium
5. G.U. tract: Trichomonas
6. Bloodstream: Plasmodium, Trypanosoma
7. Spleen: Leishmania
8. Liver: Leishmania, Entamoeba
9. Muscle: Trypanosoma cruzi
10. CNS: Trypanosoma, Naegleria, Toxoplasma, Plasmodium

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The protozoa which parasitise humans may be divided into a
number of different groups :
The Amoebae
The Flagellates
The Ciliates
The Sporozoa
The Microsporidia
The Amoebae
Amoebae can live in a number of places around the human body, but most
are found in the intestine. Amoebae creep about by extending parts of their
bodies to form pseudopods . They also use these pseudopods to capture
food, surrounding what they are about to eat and eventually engulfing it.
Pathogenic Amoebae
Amoebiasis (E.histolytica infection)
Amebiasis - is an infection caused by the protozoal organism Entamoeba
histolytica and includes amebic colitis and liver abscess. It is found in all
parts of the world where environmental sanitation is poor. The organism
may behave as a parasite (by harming the host) or as acommensal (when it
does no harm to the host). It is a disease of man-although some monkeys
may have it and the monkeys infection is transmissible to man. People
contract the condition if they eat or drink faecally contaminated food or
water. In extreme conditions this amoeba may create abscesses in the
liver. This amoeba forms cysts to protect it from harsh conditions.
Etiology
E. histolytica is the major cause of amebic dysentery.


- 22 -

Morphology
Trophozoite: This form has an ameboid appearance (Fig -1- A&B). The
organism has a single nucleus with a distinctive small central karyosome .
The fine granular endoplasm may contain ingested erythrocytes . The
nuclear chromatin is evenly distributed along the periphery of the nucleus.
A . B
Fig:-1-E.histolytica trophozoite (A-drawing line)
Trophozoites of Entamoeba histolytica/E.dispar (Reminder: in the absence
of erythrophagocytosis, the pathogenic E. histolytica is morphologically
indistinguishable from the nonpathogenic E. dispar) Each trophozoite has
a single nucleus, which has a centrally placed karyosome and uniformly
distributed peripheral chromatin. This typical appearance of the nucleus is
not always observed: some trophozoites can have nuclei with an eccentric
karyosome. The cytoplasm has a granular appearance. Entamoeba
histolytica trophozoites measure usually 15 to 20 m (range 10 to 60 m),
tending to be more elongated in diarrheal stool. The ingested erythrocytes
appear as dark inclusions( Fig-1-B). Erythrophagocytosis is the only
characteristic that can be used to differentiate morphologically E.
histolytica from the nonpathogenic E. dispar. Note: The trophozoite of
Entamoeba histolytica is the active, motile feeding stage that causes
pathology in colon. The trophozoite of Entamoeba histolytica is
anaerobic. It has no mitochondria. Cannot survive in the environment.
E.dispar trophozoites similar to E.histolytica trophozoite ,usually 15-
m,extend pseudopodia,progressive movement (non-invasive and it is no t
erythrophagocytosis).
Cyst: Cysts of Entamoeba histolytica, are usually spherical and often
(Fig-2-). Mature cysts have 4 nuclei. The nuclei have characteristically
centrally located karyosomes. The cysts in contain chromatoid bodies .
Entamoeba histolytica cysts usually measure 12 to 15 m.Note: The cyst
of Entamoeba histolytica is the form of the organism that survives in the
- 23 -

environment. The cyst of Entamoeba histolytica is resistant to chlorine
and cold water. It is killed by heat and desiccation and removed by
filtration. E.dispar cysts indistinguishable from E.histolytica . Cysts size
12-15 m , have 4 nuclei and blunt chromatoid bodies.

Fig:-2- E.histolytica Cyst (drawing line)
Epidemiology
In developed countries, infection occurs primarily among travelers to
endemic regions, recent immigrants from endemic regions, homosexual
males, immunosuppressed persons, and institutionalized individuals.
Transmission usually occurs by food-borne exposure, particularly when
food handlers are shedding cysts or food is cultivated in feces-
contaminated soil, fertilizer, or water. Less common means of
transmission include contaminated water, oral and anal sexual practices. It
is the third leading parasitic cause of death worldwide, surpassed only by
malaria and schistosomiasis. On a global basis, amebiasis affects
approximately 50 million persons each year, resulting in nearly 100,000
deaths. 0.5 to 50% of the population world wide harbors E. histolytica
parasites with the higher rates of infection being in underdeveloped
countries. Infection is associated with poor hygiene. Humans are the
principal host, although dogs, cats and rodents may be infected.
Mortality/Morbidity
Amebic infections lead to significant morbidity while causing variable
mortality as described below.
Mortality rate in patients with uncomplicated amebic liver abscess
is less than 1%.
Fulminant amebic colitis has a mortality rate of more than 50%.
Pleuropulmonary amebiasis has a mortality rate of 15-20%.
- 24 -

Amebic pericarditis has a case fatality rate of 40%.
Cerebral amebiasis is highly fatal, with a 90% death rate.
Increased severity of amebiasis is noted in children (especially
neonates), women who are pregnant or postpartum, individuals
who use corticosteroids, individuals with malignancy, and
malnourished individuals.
Sex: Invasive amebiasis, including amebic liver abscess, is much more
common in adult males than in females. However, amebic liver abscess is
equally common in both sexes among prepubertal children. E histolytica
infection is distributed equally between sexes. Therefore, the higher
proportion of men with invasive amebiasis may be due to a male
susceptibility to invasive disease.
Age: Symptomatic intestinal amebiasis occurs in all age groups. Liver
abscesses due to amebiasis are 10 times more frequent in adults than in
children.

Transmission and Life cycle
Cysts and trophozoites are passed in feces (1). Cysts are typically found
in formed stool, whereas trophozoites are typically found in diarrheal
stool. Infection by Entamoeba histolytica occurs by ingestion of mature
cysts (2)in fecally contaminated food, water, or hands. Excystation
(3)occurs in the small intestine and trophozoites (4)are released, which
migrate to the large intestine. The trophozoites multiply by binary fission
and produce cysts (5), and both stages are passed in the feces (1). Because
of the protection conferred by their walls, the cysts can survive days to
weeks in the external environment and are responsible for transmission.
Trophozoites passed in the stool are rapidly destroyed once outside the
body, and if ingested would not survive exposure to the gastric
environment. In many cases, the trophozoites remain confined to the
intestinal lumen (A): noninvasive infection, of individuals who are
asymptomatic carriers, passing cysts in their stool. In some patients the
trophozoites invade the intestinal mucosa (B): intestinal disease), or,
through the bloodstream, extraintestinal sites such as the liver, brain, and
lungs (C): extraintestinal disease), with resultant pathologic
manifestations. It has been established that the invasive and noninvasive
- 25 -

forms represent two separate species, respectively E. histolytica and E.
dispar. These two species are morphologically indistinguishable unless E.
histolytica is observed with ingested red blood cells
(erythrophagocystosis). Transmission can also occur through exposure to
fecal matter during sexual contact (in which case not only cysts, but also
trophozoites could prove infective).



- 26 -

Clinical features
Symptoms
Asymptomatic infections are common following ingestion of the
parasite. E dispar does not cause invasive disease or antibody
production. As many as 90% of E histolytica infections are also
asymptomatic. The infection is self-limited but may be recurrent.
Only antigen detection tests can distinguish between E histolytica
and E dispar.
Acute amebic colitis has a gradual onset presenting with a 1- to 2-
week history of abdominal pain, diarrhea, and tenesmus. Stool
samples, which are watery and contain blood and mucus, have
little fecal material. Fever is noted in only a minority of patients.
Lower quadrant abdominal tenderness may be noted.
Fulminant amebic colitis is a rare complication of amebic
dysentery. It presents with a rapid onset of severe bloody diarrhea,
severe abdominal pain, and high fever. Children younger than 2
years are at increased risk. Intestinal perforation is common.
Chronic amebic colitis is clinically similar to inflammatory bowel
disease. Recurrent episodes of bloody diarrhea and vague
abdominal discomfort develop in 90% of patients with chronic
amebic colitis who have antibodies to E histolytica. Consider
amebiasis in all patients in whom inflammatory bowel disease is
suspected before administering steroids. A biopsy of colonic ulcers
reveals trophozoites in patients with amebiasis.
Ameboma is a localized chronic infection of the cecum or
ascending colon. It presents as a right lower quadrant abdominal
mass, which may be mistaken for carcinoma, tuberculosis, Crohns
disease, actinomycosis, or lymphoma. Biopsy findings assist in
establishing the correct diagnosis.
Amebic liver abscess (Fig-3-)is the most common form of
extraintestinal amebiasis. The male-to-female ratio is 10:1. It is
rare in children. An estimated 95% of amebic liver abscesses
related to travel develop within 5 months.
- 27 -


Fig:-3- Amebic liver abscess
1-Amebic liver abscess appears with an abrupt onset of high fever; a
cough; and dull, aching, constant abdominal pain in the right upper
quadrant or epigastrium, usually lasting fewer than 10 days. The pain is
constant and may radiate to the right scapula and shoulder. It may become
pleuritic and may increase when the patient lies on the right side. In left
lobe liver abscess, the pain may be predominantly epigastric and may
radiate to the left shoulder. Anorexia, nausea, and vomiting may occur.
2-A small subset of patients with amebic liver abscess has a subacute
presentation with vague abdominal discomfort, weight loss, and anemia.
Jaundice is unusual.
3-Pleuropulmonary amebiasis is usually caused by a ruptured right lobe
liver abscess. The typical age group is 20-40 years. The male-to-female
ratio is 10:1. Approximately 10% of patients with amebic liver abscess
develop pleuropulmonary amebiasis, which presents with cough, pleuritic
pain, and dyspnea. A hepatobronchial fistula is an unusual problem
characterized by the expectoration of sputum resembling anchovy paste.
The trophozoites of E histolytica may be found in the sputum sample.
Note:In general the commonest symptoms are: Right upper abdominal
pain ,Right sided chest pain worse on a deep breath, Diarrhea precedes
infection in 20% of patients ,Weight loss, malaise, and jaundice may
occur.
Amebic peritonitis is generally secondary to a ruptured liver
abscess. Left lobe liver abscesses are more likely to rupture.
Patients present with fever and rigid distended abdomen. Roughly
2-7% of liver abscesses rupture into the peritoneum.
- 28 -

Amebic pericarditis is rare but is the most serious complication. It
usually is caused by a rupture of the left liver lobe abscess and
occurs in 3% of patients with hepatic amebiasis. It presents with
chest pain and the features of congestive heart failure.
Cerebral amebiasis has an abrupt onset and rapid progression to
death in 12-72 hours. The patient presents with altered
consciousness and focal neurologic signs. CT scan shows irregular
lesions without a surrounding capsule or enhancement. A tissue
biopsy sample reveals the trophozoites.
Genitourinary involvement may cause painful genital ulcers or
fallopian tube amebiasis.
Signs
Patients with acute amebic colitis may have lower quadrant
abdominal tenderness. Fever is noted in only a minority of patients.
Dehydration is uncommon. Occult blood is nearly always present
in stools.
Amebic liver abscess may present with fever and tender
hepatomegaly. Right lower intercostal tenderness may be elicited,
particularly posteriorly. Breath sounds may be diminished at the
right lung base, and rales may be heard. A small subset of patients
has a subacute presentation with hepatomegaly, weight loss, and
anemia. Jaundice is unusual.Note:The commonest signs are : Ill-
appearance ,Fever ,Tender right upper abdomen, Palpable liver
(liver can be felt) whereas the liver is not easily felt,Tenderness in
chest wall of right chest
Pleuropulmonary amebiasis may produce findings of right-sided
pleural effusions, empyema, basilar atelectasis, pneumonia, and
lung abscess.
Patients with amebic peritonitis present with fever and a tender,
rigid, and distended abdomen.
Amebic pericarditis presents with features of congestive heart
failure. A pericardial friction rub may be audible.
- 29 -

Cerebral amebiasis presents with altered consciousness and focal
neurologic signs. CT scan shows irregular lesions without a
surrounding capsule or enhancement.
Genital ulcers due to amebiasis have a punched-out appearance
and profuse discharge.
Note; Reported cases of destructive amoebic infections of the penis result
from anal intercourse with a partner with amoebiasis, and comparable
lesions may affect the vulva.
Note; Amebic ulceration involving the caecal area or appendix may
simulate acute appendicitis, when there is extensive cecal ulceration
surgical intervention may be disastrous.
Note; Other Problems to be Considered for differential diagnosis
Infectious
Campylobacter
Shigella
Salmonella
Yersinia
Enteroinvasive Escherichia coli
Enterohemorrhagic Escherichia coli
The main differences between amoebic and bacillary dysentery are
outlined in the Table-1-
Amoebic dysentry Bacillary dysentry
Gradual onset Acute onset
No significant fever or vomiting Fever and usually vomiting
Faeces (fresh) Faeces (fresh)
Offensive odour Odourless
Blood and mucus Often watery and bloody
Acid pH Alkaline pH
Motile amoebae containing red
cells
Nomotile amoebae containing red
cells


- 30 -

Noninfectious
Inflammatory bowel disease
Ischemic colitis
Diverticulitis
Arteriovenous malformation
Pathology
E. histolytica frequently lives as a commensal within the large intestine
with no overt clinical manifestations. However, trophozoites can invade
the colonic epithelium and produce ulcers and dysentery. This invasive
disease can become progressively worse and lead to extraintestinal
amebiasis . In other words, E. histolytica is a facultative pathogen that
exhibits a wide range of virulence. The non-invasive disease is most often
asymptomatic, but can cause diarrhea or other gastro-intestinal symptoms
such as abdominal pain or cramps. This non-invasive infection can persist
or progress to an invasive disease in which trophozoites penetrate the
intestinal mucosa and kill the epithelial cells. The early lesion is a small
area of necrosis, or ulcer, characterized by raised edges and virtually no
inflammation between lesions (Fig-4-). The ameba will spread laterally in
the submucosa (beneath the epithelium) and and kill host cells as they
progress. This results in the classic 'flask-shaped' ulcer with a small
opening and a wide base (Fig-5-). Trophozoites are most numerous at the
boundary between the healthy tissue and the necrotic tissue. These
invasive ameba are ingesting host cells and trophozoites with ingested
erythrocytes are often evident. These hematophagous trophozoites are
sometimes found in the dysenteric feces. Cyst production decreases during
the invasive stage of the infection and cysts are never found in the tissue
lesions.

Fig:-4- Amebic ulcers in Colon. Fig:-5- Flask shape Amebic ulcers in
Colon C/S.
- 31 -

The ulcerative process may continue to expand laterally or downward. If
large numbers of ulcers are present, they may coalesce which could lead to
a localized sloughing off of the intestinal wall. Ulcer expansion can also
penetrate the serous layer and lead to perforation of the intestinal wall.
This perforation can lead to local abscesses or a generalized peritonitis.
Amebic ulcers can also become secondarily infected with bacteria which
may confuse the clinical picture. In addition, E. histolytica infection can
occassionally lead to the formation of an amebic granuloma, also called an
ameboma (see above). The ameboma is an inflammatory thickening of
the intestinal wall around the ulcer which can be confused with a tumor.
Amebiasis can also progress to a systemic, or extraintestinal infection.
Dissemination from the primary intestinal lesion is predominantly via the
blood stream, but can also occur by direct extension of the lesion. The
liver is the most commonly affected organ and this is probably due to the
direct transport of trophozoites from the large intestine to the liver via the
hepatic portal vein . Initially the lesions are small foci of necrosis which
tend to coalesce into a single abscess as they expand. This hepatic abscess
will continue to enlarge as the trophozoites progessively destroy and
ingest host cells. The center of the abscess, consisting of lysed
hepatocytes, erythrocytes, bile and fat, may liquify and this necrotic
material (sometimes incorrectely called pus filled by trophozoites) will
range in color from yellowish to reddish brown. Secondary bacterial
infections in the liver abscess are not common (~2%). E. histolytica is
found primarily in the colon where it can live as a non-pathogenic
commensal or invade the intestinal mucosa . The ameba can metastasize to
other organs via a hematogenous route . Hematogenous spread of
trophozoites to other sites of the body and cause a spectrum of illness (see
Table-1-), such as the lungs or brain, is rare, but does occur. Pulmonary
infections generally result from a direct extension of the hepatic lesion
across the diaphram and into the pleura and lungs. Cutaneous lesions
formed as a result of hepatic or intestinal fistula can also occur, although
extremely rare. Other cutaneous lesions include perianal ulcers and
involvement of the genitalia, including the penis of homosexuals. These
later manifestations are likely due to the skin or mucuous membranes
coming in contact with invasive trophozoites.


- 32 -

Possible mechanisms of pathogenesis:
Infection with E. histolytica does not always lead to invasive disease,
though, in that only about 10% of the infected individuals will develop
symptomatic invasive amebiasis. The factors responsible for the
pathogenesis of E. histolytica are not well understood. Pathology results
from host-parasite interactions, and therefore, host factors, parasite factors
or a combination of both may contribute to the disease state. For example,
the development of invasive disease could be due to quantitative or
qualitative aspects of the host immune response. Recruitment of
neutrophils and intense inflammation are noted in the early phases of
amebic invasion. However, inflammation surrounding established ulcers
and abscesses if often minimal given the degree of tissue damage.The
nature of protective immune reponses is not clear. Mucosal IgA responses
do occur as a result of infection, but it is unclear whether this response
plays a role in eliminating the parasite. Similarly, high titers of serum
antibodies develop in patients with liver abscesses. However, since the
invasive disease is often progressive and unremitting, the role of these
anti-ameba antibodies is in question. Cell-mediated responses appear to
play a role in limiting the extent of invasive amebiasis and protecting the
host from recurrence following successful treatment. Resistance to the
host immune response is another possible virulence factor which could
contribute to the development and exacerbation of invasive disease. E.
histolytica rapidly degrades secretory IgA and possibly suppresses T-cell
responses to E. histolytica antigens. E. histolytica is also able to kill cells,
including neutrophils and other immune effector cells, in a contact
dependent manner. Lysis of neutrophils could also release toxic products
which contribute to the destruction of host tissue. However, the role of
these various phenomenon play in pathogenesis is not known.
Invasion of intestinal mucosa by E. histolytica is an active process
mediated by the parasite and distinct steps can be recognized (Fig-6-).
Trophozoites adhere to the mucus layer (step 1). This adherence per se
probably does not contribute to pathogenesis and is simply a mechanism
for the ameba to crawl along the substratum. Depletion of the mucus
barrier allows for the trophozoite to come in contact with epithelial cells.
Epithelial cells are killed in a contact dependent manner leading to a
disruption of the intestinal mucosa (step 2). The trophozoites will continue
to kill host cells in the submucosa and further disrupt the tissue as they
advance (step 3). Disruption of the intestinal wall (step 4) or metastasis
via the circulatory system (step 5) is also possible. Adherence,
- 33 -

cytotoxicity, and disruption of the tissues are important factors in the
pathogenesis of E. histolytica. Parasite proteins which could play a role in
these processes include proteolytic enzymes such as: the Eh-lectin,
amebapore, and protease.

Fig:-6- Possible mechanism of intestinal mucosa invasion by E.histolytica.

Amebic infection complications
Intestinal disease
o Asymptomatic infection
o Symptomatic noninvasive infection
o Acute proctocolitis (dysentery)
o Fulminant colitis with perforation
o Toxic megacolon
o Chronic nondysenteric colitis
o Ameboma
o Perianal ulceration
o Bowel perforation
o Gastrointestinal bleeding
o Stricture formation
o Fistula formation
o Intussusception
Extraintestinal disease
o Liver abscess
o Secondary bacterial infection of amebic liver abscess
(uncommon)
- 34 -

o Pleuropulmonary disease
o Peritonitis
o Pericarditis
o Brain abscess
o Genitourinary disease
o Empyema
o Brain abscess
Laboratory diagnosis
Clinical diagnosis is based on a history of residence in an endemic area.
Symptoms are the keys to diagnosis. In the laboratory, the infection is
confirmed by finding cysts in the stool .
Stool
Light microscopy: Perform stool examination in patients in whom
intestinal amebiasis is suspected. This may aid in the workup, but does not
make a specific diagnosis because one cannot distinguish between E
histolytica and E dispar using a microscope.
Other stool tests
1-Occult blood is almost always present in invasive disease.
2-Fecal leukocytes may be absent.
Serum tests
Antibody tests
-Antibody detection is most useful in patients with extraintestinal disease,
ie, amebic liver abscess, when organisms are generally not found on stool
examination. Several methods are commercially available for antibody
detection.
1-Indirect hemagglutination antibody (IHA) test detects antibody specific
for E histolytica. Antibody titers of more than 1:256 95% of patients with
extraintestinal amebiasis, 70% of patients with active intestinal infection,
and 10% of asymptomatic individuals. IHA is not useful in differentiating
acute from previous infection because high titers may persist for years
- 35 -

after successful treatment. False-positive reactions at titers higher than
1:256 are rare.
2-Immunodiffusion (ID) is simple to perform, making it ideal for the
laboratory that has only an occasional request for amebic serology.
However, it requires a minimum of 24 hours to complete, as compared to
2 hours for the IHA . ID is slightly less sensitive than IHA , but is equally
specific.
3-Although detection of immunoglobulin M (IgM) antibodies specific for
E histolytica has been reported, sensitivity in patients with current
invasive disease is only about 64%.
Imaging studies
1-Chest radiography may reveal elevated right hemidiaphragm and a right-
sided pleural effusion in patients with amebic liver abscess.
2-Ultrasonography is preferred for the evaluation of amebic liver abscess
because of its low cost, rapidity, and lack of adverse effects. A single
lesion is usually seen in the posterosuperior aspect of the right lobe of the
liver. Multiple abscesses may occur in some patients.
3-CT may be slightly more sensitive than ultrasonography. In cerebral
amebiasis, CT shows irregular lesions without a surrounding capsule or
enhancement.
4-MRI reveals high signal intensity. Perilesional edema and enhancement
of rim are noted after injection of gadolinium (86%).
Note:Complete resolution of liver abscess may take up to 2 years. Repeat
imaging is not indicated if the patient is otherwise doing well.
Other Tests:
Leukocytosis may be noted, but eosinophilia is not a feature of
amebiasis.
Mild anemia may be noted.
The erythrocyte sedimentation rate is generally elevated.
- 36 -

Cholesterol may be elevated.
Liver function tests reveal elevated alkaline phosphatase in 80% of
patients, elevated transaminases, and reduced albumin.
Urinalysis may reveal proteinuria.
Procedures
Rectosigmoidoscopy and colonoscopy may provide useful
diagnostic information in intestinal amebiasis. Consider
rectosigmoidoscopy and colonoscopy before using steroids in
patients in whom inflammatory bowel disease is suspected. Small
mucosal ulcers covered with yellowish exudates are observed. The
intervening mucosa appears normal . Biopsy results and a scraping
of ulcer edge may show trophozoites. Indications for endoscopy in
suspected intestinal amebiasis include the following:
o Stool examination is negative, but the serum antibody test
is positive.
o Stool examination is negative, but immediate diagnosis is
required.
o Stool examination and the antibody test are negative, but a
high suspicion exists.
o Evaluation of chronic intestinal syndromes or mass lesions
is desired.
Aspiration of liver is indicated only for large abscesses (>12 cm),
imminent abscess rupture, failure of medical therapy, or presence
of left lobe abscesses. Localized swelling or bulging of the rib-
cage or abdominal wall. Marked local tenderness or oedema. A
very raised diaphragm.
Histologic Findings: Infection of the human colon by E histolytica
produces focal ulceration of the intestinal mucosa. Histopathological
examination reveals numerous E histolytica trophozoites. Due to the lysis
of cells by E histolytica, acute inflammatory cells seldom are found in the
biopsy material .
- 37 -

Treatment
Activity against anaerobic bacteria and protozoa is exhibited by several
agents. Metronidazole is considered the drug of choice for symptomatic,
invasive disease. Paromomycin is the drug of choice for noninvasive
disease. Because parasites persist in the intestine of 40-60% of patients
treated with metronidazole, follow it with Paromomycin to cure luminal
infection. Do not give the 2 medications at the same time because the
diarrhea that often results from paromomycin might be confused with
continuing active intestinal disease from the parasite.
Several other drugs are available for the treatment of amebiasis and the
choice of drugs depends on the clinical stage of the infection (Table-2-).
Table-2-Amebiasis Treatment
Disease Drug
Asymptomatic Iodoquinol, or Diloxanide
furoate
Nondysenteric, Dysenteric, or
Extraintestinal
Tinidazole + lumenal
agent
Prevention and Control measures are similar to other diseases
transmitted by the fecal-oral route. The major difference is that
humans are the only host for E. histolytica and there is no
possibility of zoonotic transmission. Health education in regards to
improving personal hygiene, sanitary disposal of feces, and hand
washing are particularly effective. Protecting water supplies will
lower endemicity and epidemics. Like Giardia, Entamoeba cysts
are resistant to standard chlorine treatment. The amount of chlorine
normally used to purify water is inadequate in killing the cysts.
Drinking water can be rendered safe by boiling, 0.22 m filtration,
or iodination with tetraglycine hydroperiodide. Bottled water may
be used for drinking when traveling to endemic areas. Eating only
cooked food or self-peeled fruits in endemic areas minimizes risk.
Avoid eating raw fruits and salads, which are difficult to sterilize.
Disease transmission can be reduced by early treatment of carriers
in nonendemic areas. Vaccination for amebiasis currently is being
investigated. One potential vaccine candidate is the galactose-
inhibitable adherence lectin of E histolytica.

- 38 -

Prognosis
Intestinal infections due to amebiasis generally respond well to
appropriate therapy. The severity of amebiasis is increased in the
following individuals:
o Children, especially neonates
o Pregnant and postpartum women
o Those using corticosteroids
o Those with malignancies
o Malnourished individuals
Mortality rate in patients with uncomplicated amebic liver abscess
is less than 1%.
Fulminant amebic colitis has a mortality rate of more than 50%.
Pleuropulmonary amebiasis has a 15-20% mortality rate.
Amebic pericarditis has a case fatality rate of 40%.
Cerebral amebiasis is highly fatal with a 90% death rate.
Commensals; Nonpathogenic Intestinal Amoebae
Several Entamoeba species infect humans commonly found in peoples'
intestines and stool specimens never make them sick. Germs that don't
cause illness are called "nonpathogenic." These parasites do not harm the
body. They are found only in the intestines, never in other parts of the
body.You might have become infected by swallowing something, such as
food or water, or touching something (and then putting your fingers in
your mouth) that was contaminated with stool from an infected person. No
symptoms caused by these amebae. The parasites stay For weeks, months,
or years. But they never spread from the intestines to other parts of the
body. No need for treatment. These parasites are harmless.

- 39 -

Endolimax nana-cysts (Fig:-1-)are smaller than E.histolytica cysts,
round tooval in shape , and possess four nuclei which looks like punched
out holes. The cysts of E. nana do not have chromatoid bodies. The cysts
measure 6 to 8 m (range 5 to 10 m).

Fig:-1- Endolimax nana-cysts ( In-drawing line)
Endolimax nana trophozoites. (Fig:-2-) The trophozoites each have one
nucleus with a characteristically large, irregularly shaped, blot-like
karyosome (line drawing). Their nucleus has no peripheral chromatin.
Their cytoplasm is granular and vacuolated. The trophozoites measure
usually 8 to 10 m (range 6 to 12 m).

Fig:-2- Endolimax nana trophozoites. ( drawing line).
Entamoeba coli-cysts. (Fig:-3-A&B-)are larger than E.histolytica,
measuring 15-30m. They containing > 4 up to 8 nuclei, occasionally
needle-like chromatid bodies are seen. The cysts show a greater variation
in shape andsize than those of E. histolytica.
- 40 -


Fig:-3- Entamoeba coli-Cysts (drawing line)
Trophozoites of Entamoeba coli. (Fig-4-)The trophozoites each have one
nucleus with characteristically a large, eccentric karyosome and coarse,
irregular peripheral chromatin. The cytoplasm is coarse and vacuolated .
Occasionally the cytoplasm contains ingested bacteria , yeasts or other
materials. The trophozoites of E. coli measure usually 20 to 25 m, but
they can be elongated and reach up to 50 m.





Fig:-4- Entamoeba coli-Trphozoite (drawing line)
Iodamoeba buetschlii cysts. (Fig-5-) The cyst , have only one nucleus
with a large, usually eccentric karyosome. They do not have chromatoid
bodies but have a compact, well defined glycogen mass. The cysts
measure usually 10 to 12 m (range 5 to 20 m) and their shape varies
from ovoidal to rounded. resemble morphologically those of E. histolytica
but they can be differenctiated by their smaller siize.
- 41 -


Fig:-5- Iodamoeba buetschlii Cysts (A- drawing line).
Iodamoeba buetschlii trophozoites (Fig -6-). The trophozoites ,each
have one nucleus with a large, usually central karyosome surrounded by
refractile, achromatic granules. Their cytoplasm is coarsely granular,
vacuolated and can contain bacteria, yeasts or other materials. The
trophozoites measure usually 12 to 15 m (range 8 to 20 m).

Fig:-6- Iodamoeba buetschlii Trophozoite(A- drawing line).
Entamoeba hartmanni cysts, (Fig-7-) Cysts of E. hartmanni when
mature have 4 nuclei and elongated chromatoid bodies with rounded ends.
Resemble morphologically those of E. histolytica but they can b
differentiated by their smaller size. Cysts of E. hartmanni measure usually
6 to 8 m (range 5 to 10 m) .
- 42 -


Fig:-7- Entamoeba hartmanni cysts ( in drawing line).
Entamoeba hartmanni trophozoites, (Fig-8--) Entamoeba hartmanni is
often called a "small histolytica" because these two species share many
morphological characteristics, except their size. The trophozoites of E.
hartmanni have one nucleus with fine peripheral chromatin and a small,
often centrally located karyosome. The cytoplasm is finely granular.
Trophozoites of E. hartmanni measure usually 8 to 10 m (range 5 to 12
m ) and are smaller than those of E. histolytica (10 to 60 m).

Fig:-8- Entamoeba hartmanni Trophozoite (A-in drawing line).
Entamoeba polecki cysts. (Fig-9-)The cysts have one nucleus (rarely
two) with a small, usually eccentric karyosome (which can also be rather
pleomorphic). Their cytoplasm contains small inclusions and an
"inclusion mass", which stains only weakly in iodine. The cysts measure
usually 11 to 15 m (range 9 to 18 m) and their shape varies from
spherical to oval. The cysts are similar to E. histolytica except that the
mature cyst has a single nucleus.
- 43 -


Fig:-9-Entamoeba polecki Cysts.(in drawing line).
Entamoeba polecki trophozoites. (Fig-10-) The trophozoites each have
one nucleus that usually has small, discrete karyosomal chromatin and
evenly distributed peripheral chromatin. Their cytoplasm is coarsely
granular, vacuolated and can contain bacteria and yeasts (C). The
trophozoites measure usually 15 to 20 m (range 10 to 25 m). E. polecki
is usually associated with pigs and monkeys, but human cases have been
occasionally documented. It appears to be geographically restricted to
particular areas such a Papua, New Guinea. The trophozoites are similar to
E. coli, except a little smaller.

Fig:-10- Entamoeba polecki Trophozoite.(in drawing line).
Entamoeba gingivalis- it is a non-pathogenic inhabitant of the mouth,
present chiefly in the tartar of teeth and gingival pocked. Characterised by
large number of food vacuoles and dark-staining bodies derived from the
nuclei of degenerated cells in the cytoplasm. E. gingivalis can be
recovered from the soft tartar between teeth and exhibits a similar
morphology to E. histolytica except that it has no cyst stage. E. gingivalis
can also multiply in bronchial mucus, and thus can appear in the sputum.
In this case it could be confused with E. histolytica from a pulmonary
abscess. E. gingivalis trophozoites will often contain ingested leukocytes
- 44 -

which can be used to differentiate it from E. histolytica. The trophozoites
are most often recovered from patients with periodontal disease, but an
etiology between the organism and disease has not been established and E.
gingivalis is considered to be non-pathogenic.
Aspseudoparasite and pitfalls
It is an object that resembles a parasite or the egg of a parasite but is either
not a parasite at all or not parasitic in the host. Pseudoparasite has been
used by some to designate commensal organisms, such as B.hominis.
Many kinds of yeasts normally present in the stool may be confused with
cyst of some of the intestinal protozoa, blastocystis may occur in the feces.
However the organism, likethe pathogenic intestinal bacteria, cannot be
recognized morphologically and must be isolated and identified by
specialized technique when indicated
Blastocystis hominis
Etiology
The causal agent has a spherical form and ranges from 5-30 m in
diameter. It thus resembles amebic cysts in both size and shape, it differs
sharply from them in internal organization.
The taxonomic classification of Blastocystis hominis is mired in
controversy. It has been previously considered as yeasts, fungi, or
ameboid, flagellated, or sporozoan protozoa. Recently, however, based on
molecular studies, especially dealing with the sequence information on the
complete SSUrRNA gene, B. hominis has been placed within an informal
group under the kingdom Chromista.
Morphology
Blastocystis hominis cyst-like forms. The sizes vary from 4 m to 10 m.
The nuclei in the peripheral cytoplasmic rim are clearly visible (Fig-1-).


- 45 -


Fig:-1- Blastocystis hominis cyst.
Epidemiology
Worldwide.
Transmission and Life Cycle:
Knowledge of the life cycle and transmission is still under investigation,
therefore this is a proposed life cycle for B. hominis. The classic form
found in human stools is the cyst, which varies tremendously in size from
6 to 40 m (1). The thick-walled cyst present in the stools (1)is believed
to be responsible for external transmission, possibly by the fecal-oral route
through ingestion of contaminated water or food (2). The cysts infect
epithelial cells of the digestive tract and multiply asexually (3), (4).
Vacuolar forms of the parasite give origin to multi vacuolar (5a)and
ameboid (5b)forms. The multi-vacuolar develops into a pre-cyst (6a)that
gives origin to a thin-walled cyst (7a), thought to be responsible for
autoinfection. The ameboid form gives origin to a pre-cyst (6a), which
develops into thick-walled cyst by schizogony (7b). The thick-walled cyst
is excreted in feces (1).

- 46 -



Clinical features
Whether Blastocystis hominis can cause symptomatic infection in humans
is a point of active debate. This is because of the common occurrence of
the organism in both asymptomatic and symptomatic persons. Those who
believe symptoms could be related to infection with this parasite have
described a spectrum of illness including watery diarrhea, abdominal pain,
perianal pruritus, and excessive flatulence.
Laboratory diagnosis
Diagnosis is based on finding the cyst-like stage in feces. Permanently
stained smears are preferred over wet mount preparations because fecal
- 47 -

debris may be mistaken for the organisms in the latter. Do not wash
specimens in water (e.g., during concentration procedures) as this will lyse
the organisms, resulting in false negatives.
Treatment
Despite the controversial clinical significance of this organism,
metronidazole or iodoquinol has been reported to be effective.
Free-living amoebae
Two rare types of amoebae may cause significant problems.
Acanthamoeba and Naegleria are amoebae which normally in still bodies
of freshwater. If they get into our bodies, they can cause a severe and often
fatal infection of the brain membranes (eosinophilic meningitis). These
infections are so nasty, that sufferers may die before the infection can be
diagnosed. These are free-living amebae are of particular significance in
immunocompromised hosts.
Naegleriasis (Naegleria fowleri infection)
Naegleriasis (primary amebic meningoencephalitis) in children and young
adults.
Etiology
Naegleria fowleri , Free living organism commonly found in lakes,
swimming pools, tap water, heating and air conditioning units and in the
soil .
Morphology
N. fowleri has three stages, Uninucleated cysts (7-10m). Ameboid
(trophozoite) form , diameter 7 to 20 m, some transform to flagellate
forms with 2 flagella, 20 to 30 m in length. The amebae are very active
and extend and retract pseudopods.
(1)Naegleria fowleri trophozoite in spinal fluid. Note; the typically large
karyosome and the monopodial locomotion. (2)These cells have
characteristically large nuclei, with a large, dark staining karyosome.
- 48 -

Epidemiology
Worldwide distribution.
Transmission and Life Cycle
This organism is a flagellate that may inhabit warm waters (in soil, dust,
spas, warm springs, heated swimming pools, etc.) and gain access via the
nasal passage Invasion through the olfactory neuroepithelium.to the brain
and cause encephalitis ).Free-living amebae belonging to the genera
Naegleria are important causes of disease in humans and animals.
Naegleria fowleri produces an acute, and usually lethal, central nervous
system (CNS) disease called primary amebic meingoencephalitis (PAM).
N. fowleri has three stages, cysts (1), trophozoites (2), and flagellated
forms (3), in its life cycle. The trophozoites replicate by promitosis
(nuclear membrane remains intact) (4). Naegleria fowleri is found in fresh
water, soil, thermal discharges of power plants, heated swimming pools,
hydrotherapy and medicinal pools, aquariums, and sewage. Trophozoites
can turn into temporary flagellated forms which usually revert back to the
trophozoite stage. Trophozoites infect humans or animals by entering the
olfactory neuroepithelium (5)and reaching the brain. N. fowleri
trophozoites are found in cerebrospinal fluid (CSF) and tissue, while
flagellated forms are found in CSF.

- 49 -



Clinical features and Pathology
Incubation period varies from 2-3 days to as long as 7-15 days. Disease
usually fatal after 3-7 days. Acute primary amebic meningoencephalitis
(PAM) is caused by invasion of the central nervous system by Naegleria
fowleri, is an acute, rapidly progressive infection, acquired while
swimming or diving in fresh water. A day or so of prodromal symptoms of
headache and fever is followed by the rapid onset of nausea and vomiting
accompanied by signs and symptoms of meningitis with involvement of
the olfactory, frontal, temporal and cerebellar areas. Meningeal irritation
may be accompanied by stiff neck, generalized seizures, and Kernigs sign.
Disturbances in the sense of smelling or taste noted in early due to
olfactory lobe involvement. Focal neurologic deficits, other meningeal
signs, Patients often become irrational. Progresses rapidly (<10 days) and
frequently to coma and death.
- 50 -

Laboratory diagnosis
In Naegleria infections, the diagnosis can be made by recognition of the
organism in the CSF or brain tissue with the finding of trophozoites by
microscopic examination of cerebrospinal fluid (CSF). For confirmation
culture and / or special staining e.g. indirect antibody tests.
Treatment
Amphotericin B has been successfully used to treat PAM caused by
Naegleria fowleri.
Acanthamoebiasis (Acanthamoeba infection) and Balamuthiasis (Balamthia
madrillaris infection)
Acanthamoeba spp. And Balamuthia mandrillaris are opportunistic free-
living amebae capable of causing granulomatous amebic encephalitis
(GAE) in individuals with compromised immune systems. The first
known isolate of this amoeba was from a Mandrill Baboon (Papio sphinx)
at San Diego Wild Animal Park. Balamuthia mandrillaris (presently the
only described species in the genus) was soon recognised as causing
encephalitis in humans . Since then more than 80-90 incidents of
granulomatous amoebic encephalitis (GAE) caused by Balamuthia have
been reported, with only two cases that have survived to date. There is of
course a strong suspicion that infection and probably all amoebal
infections are grossly underestimated due to the general similarity of the
symptoms caused by other agents (bacterial, viral) and the general lack of
awareness of amoebal pathogenicity.
Etiology
While only one species of Naegleria is known to infect humans, several
species of Acanthamoeba are implicated, including A. culbertsoni, A.
polyphaga, A. castellanii, A. astronyxis, A. hatchetti, and A. rhysodes. An
additional agent of human disease, and Balamuthia mandrillaris.
Morphology
Several species of free-living Acanthemeba are pathogenic to man.
Trophozoite diameter 10-40 m, Ameboid form with spiral-like
pseudopodia. Double walled irregular cysts (15-30 m). Trophozoites of
- 51 -

Balamuthia are characterised by a peculiar ribbon-like endoplasmic
reticulum. The nucleolus is very dense and it seems split in two, a feature
that usefully distinguish this amoeba from Acanthamoeba especially when
encountered in histological section. The nucleus appears to posses peculiar
cytoplasmic vesicles . The amoeba produces a cyst, but no flagellate
stage has been described. The cyst bears a superficial resemblance to
Acanthamoeba being about 15 m (microns) in diameter but E.M. reveals
that it has a triple wall . this however often looks like a double wall by
light microscope, again like Acanthamoeba. The trophozoite is around 15-
60 m (microns) in diameter and may be bi-nucleate . The amoeba is
described as "walking" by crab-like movement by arm like trunk and
pseudopods and at ~0.15 m/sec , locomotion is slow compared to other
amoeba.
Epidemiology
World wide distribution, free living organism, Acanthamoeba spp. have
been found in soil; fresh, brackish, and sea water; sewage; swimming
pools; contact lens equipment; medicinal pools; dental treatment units;
dialysis machines; heating, ventilating, and air conditioning systems;
mammalian cell cultures; vegetables; human nostrils and throats; and
human and animal brain, skin, and lung tissues. B. mandrillaris however,
has not been isolated from the environment but has been isolated from
autopsy specimens of infected humans and animals.
Transmission and life cycle (see N.fowleri)
Infection by inhalation of dust, aspiration of water, penetration of skin.
Invasion through the olfactory neuro-epithelium. Direct infection of the
cornea, e.g. after contact lens wear, possible. they normally reside in soil
and can infect children who swallow dirt while playing on the ground.
Acanthamoeba spp. and Balamuthia mandrillaris are opportunistic free-
living amebae capable of causing granulomatous amebic encephalitis
(GAE) in individuals with compromised immune systems. Unlike N.
fowleri, Acanthamoeba and Balamuthia have only two stages, cysts (1)and
trophozoites (2), in their life cycle. No flagellated stage exists as part of
the life cycle. The trophozoites replicate by mitosis (nuclear membrane
does not remain intact) (3). The trophozoites are the infective forms and
are believed to gain entry into the body through the lower respiratory tract,
ulcerated or broken skin and invade the central nervous system by
- 52 -

hematogenous dissemination (4). Acanthamoeba spp. and Balamuthia
mandrillaris cysts and trophozoites are found in tissue.
Clinical features and Pathology
Acanthamoeba spp. causes mostly subacute or chronic granulomatous
amebic encephalitis (GAE), with a clinical picture of headaches, altered
mental status, and focal neurologic deficit, which progresses over several
weeks to death. In addition, Acanthamoeba spp. can cause granulomatous
skin lesions and, more seriously, keratitis and corneal ulcers following
corneal trauma or in association with contact lenses . Acanthamoeba are
able to penetrate the cornea and causes abscesses, which rapidly lead to
visual deterioration and blindness. It also cause conjunctivitis, iritis, and
uveitis.
In normal individuals the infection may cause mild disease (pharyngitis)
or remain asymptomatic, rarely cause of granulomatous amebic
encephalitis (GAE), uveitis, keratitis, chronic granuloma of the skin and
internal organs in immunocompetent persons. but in immunodeficient
individuals, the organism may penetrate the esophageal mucosa and reach
the brain where it causes granulomatous encephalitis . Incubation period :
several weeks or months are necessary to establish granulomatous amebic
encephalitis. There are in the region of 100 published cases of amoebic
encephalitis caused by Balamuthia. Balamuthia presents with a wide
range of symptoms, and too few cases have been studied to give any clear
picture. If the patient seeks medical attention early in the course, skin
lesions are frequently described especially it seems in young patients ,
although these have been reported in adults . Many patients present with
seizures or focal paralysis resulting from infection already present in the
brain. In other cases Balamuthia produced symptoms that mimicked a
brain stem glioma . Very low CSF glucose levels have been recorded in
one case at least .. Many animals have also been found to have become
infected with Balamuthia including, horse , gorilla and other primates .
.Laboratory diagnosis
The diagnosis can be made from microscopic examination of stained
smears of biopsy specimens (brain tissue, skin, cornea) or of corneal
scrapings, which may detect trophozoites and cysts. Cultivation of the
causal organism, and its identification by direct immunofluorescent . Anti-
sera have been used to test for the presence of Balamuthia and more
- 53 -

modern (and reliable) techniques such as specific PCR probes have also
been developed . Contrast enhanced computed tomography (CT) scans is
very useful in diagnosis of encephalitis .
Treatment
Although most cases of brain (CNS) infection with Acanthamoeba have
resulted in death, patients have recovered from the infection with proper
treatment. Acanthamoeba infection are highly resistant to
chemotherapeutic agents, especially in the encysted stage. For local
lesions of eye and skin , topical use of 0.1% propamidine isethionate
(Brolene) plus neomycin-polymyxin or oral itraconazole plus topical
miconazole. B-gramicidin ophthalmic solution has been a successful
approach; keratoplasty is often necessary in severe infections. Eye and
skin infections caused by Acanthamoeba spp. are generally treatable.
Balamuthia Treatment is uncertain as would be expected for such a
comparatively rarely encountered pathogen. To date only two patients are
known to have survived infection with confirmed Balamuthia .A patient is
reported to have been treated successfully a patient diagnosed with
Balamuthia encephalitis (at Santa Cruz Medical Clinic under the care of
Dr T. Deetz) with the drugs:- Clarithromycin 500 mg 3 times daily,
flucanozole 400 mg daily, sulphadiazine 1.58g every 6 hours and 5-
fluorocytosine 1.5g every 6 hours. It was noted however that the patient
was left with neurological deficits . Some of the antibiotics generally used
to treat this disease (5-fluorocytosine, flucanozole and sulphadiazine) were
found to have no effect on Balamuthia, in vitro .
Flagellates
Intestinal Flagellates
Although the Flagellates are closely related to the amoebae, their bodies
tend to keep the one shape (with some minor bends and twists). Flagellates
move about by moving one or more whip-shaped bodies known as flagella
. Beating these whips through the water moves them around, just like a
snake uses its body to swim. Like the amoebae, parasitic flagellates can
live in a number of different parts of the body. There are pathogenic and
commensal species. One species that lives in the gut is Giardia
intestinalis.

- 54 -

Giardiasis (Giardia lamblia infection)
Etiology
Giardia lamblia (a flagellate)
Morphology
Trophozoites of G. Lamblia; (Fig-1-) Each cell has two nuclei with a
large, central karyosome. Cell size: 9 to 21 m in length. The cytoplasm
contains four nuclei and many of the structures seen in the trophozoite.
Note: The trophozoite of Giardia lamblia is the active, motile feeding
stage that causes the pathology in small intestine. The trophozoite of
Giardia lamblia is anaerobic, It has no mitochondria. The trophozoite of
Giardia lamblia does not cause invasive disease or inflammation. The
trophozoite of Giardia lamblia attaches to enterocytes via the adhesive
disk.The trophozoite of Giardia lamblia cannot survive in the
environment.

Fig:-1-G. Lamblia Trophozoites .
Cysts of G. Lamblia; Size: 8-12 m in length. These cysts have two
nuclei each (more mature ones will have four). Note: The cyst of Giardia
lamblia is the form of the organism that survives in the environment. It is
acquired by ingestion of fecally contaminated food or water. The cyst of
Giardia lamblia is resistant to chlorine and cold water. It is killed by heat
and desiccation and removed by filtration.
Epidemiology
Giardia has worldwide distribution. It is the most frequent protozoan
intestinal disease and the most common identified cause of water-borne
- 55 -

disease associated with breakdown of water purification systems, drinking
from contaminated streams.
Transmission and Life cycle


Cysts are resistant forms and are responsible for transmission of
giardiasis. Both cysts and trophozoites can be found in the feces
(diagnostic stages) (1). The cysts are hardy and can survive several
months in cold water. Infection occurs by the ingestion of cysts in
contaminated water, food, or by the fecal-oral route (hands or fomites)
(2). In the small intestine, excystation releases trophozoites (each cyst
produces two trophozoites) (3). Trophozoites multiply by longitudinal
- 56 -

binary fission, remaining in the lumen of the proximal small bowel where
they can be free or attached to the mucosa by a ventral sucking disk (4).
Encystation occurs as the parasites transit toward the colon. The cyst is
the stage found most commonly in nondiarrheal feces (5). Because the
cysts are infectious when passed in the stool or shortly afterward, person-
to-person transmission is possible. While animals are infected with
Giardia, their importance as a reservoir is unclear.
Clinical features and Pathology
The clinical features associated with Giardia infection range from total
latency (ie, asymptomatic), to acute self-resolving diarrhea, to chronic
syndromes associated with nutritional disorders, weight loss and failure to
thrive. Children exhibit clinical symptoms more frequently than adults and
subsequent infections tend to be less severe than initial infections. The
incubation period is generally 1-2 weeks, but ranges of 1-75 days have
been reported. The first symptoms of acute giardiasis include nausea, loss
of appetite(anorexia) and an upper gastro-intestinal uneasiness. These
symptoms are often followed or accompanied by a sudden onset of
explosive, watery, foul-smelling diarrhea. Stools associated with Giardia
infection are generally described as loose, bulky, frothy and/or greasy with
the absence of blood or mucus, which may help distinguish giardiasis from
other acute diarrheas. Other gastro-intestinal disturbances associated with
giardiasis include: flatulence, bloating, cramps, and foul sulfuric belching .
The acute stage usually resolves spontaneously in 3-4 days and is often not
recognized as being giardiasis. Occasionally, though, an acute infection
will persist and lead to malabsorption, steatorrhea (excessive loss of fat in
the feces), debility (loss of strength) and weight loss. Some of the
individuals who resolve the acute symptoms do not clear the infection, but
become asymptomatic cyst passers without clinical manifestations,
whereas others may have a few brief recurrences of the acute symptoms.
Acute infections can also develop into long-standing subacute or chronic
infections which in rare cases last for years. The typical chronic stage
patient presents with recurrent brief episodes of loose foul stools which
may be yellowish, frothy and float, accompanied by intestinal gurgling,
abdominal distention and flatulence. Between episodes the stools are
usually mushy, but normal stools or constipation can also occur. Cramps
are uncommon during chronic infections, but sulfuric belching is frequent.
Anorexia, nausea, and epigastric uneasiness are additional frequent
complaints during chronic infections. In the majority of chronic cases the
parasites and symptoms spontaneously disappear.
- 57 -

The specific mechanisms of Giardia pathogenesis leading to diarrhea and
intestinal malabsorption are not completely understood and no specific
virulence factors have been identified. Attachment of trophozoites to the
brush border could produce a mechanical irritation or mucosal injury. In
addition, normal villus structure is affected in some patients. For example,
villus blunting (atrophy) and crypt cell hypertrophy and an increase in
crypt depth have been observed to varying degrees. The increase in crypt
cells will lead to a repopulation of the intestinal epithelium by relatively
immature enterocytes with reduced absorptive capacities. An increased
inflammatory cell infiltration in the lamina propria has also been observed
and this inflammation may be associated with the pathology. Giardia
infection can also lead to lactase deficiency (see lactose intolerance below)
as well as other enzyme deficiencies in the microvilli. This reduced
digestion and absorption of solutes may lead to an osmotic diarrhea and
could also explain the malabsorption syndromes. Thus far, no single
virulence factor or unifying mechanism explains the pathogenesis of
giardiasis.Note: Malabsorptive syndrome is a severe form of the disease
characterized by steatorrhea, disaccharide enzyme deficiency, and B
12

malabsorption. In severe disease, lactase deficiency is seen and may
persist.
Post-Giardia Lactose Intolerance; Some patients may present with a
lactose intolerence during active Giardia infections which can persist after
parasite clearance. This clinical manifestation is due to the parasite-
induced lactase deficiency and is most common in ethnic groups with a
predisposition for lactase deficiency. Lactase is an enzyme that breaks
down lactose, a sugar found in milk, to monosaccharides which can be
absorbed. This lactose intolerence syndrome should be considered in
persons who still present mushy stools and excessive gas following
treatment, but have no detectable parasites.
Steatorrhea; Malabsorption, characteriszed by the presence of fat in the
stools, is seen in certain parasitic infections .The most common of these is
giardiasis, which may make its presence known by flatulence and the
production of foul- smelling, fatty stools. Unfortunately, Giardia-induced
malabsorption does not necessarily disappear with eradication of the
infection but may persist some time thereafter.
Immunology
There is some role for IgA and IgM and there is increased incidence of
infection in immunodeficient patients (e.g. AIDS).
- 58 -

Laboratory diagnosis
Symptoms, history, epidemiology are used in diagnosis. Giardia caused
dysentery is distinct from other dysenteries due to lack of mucus and
blood in the stool, lack of increased PMN leukocytes in the stool and lack
of high fever is confirmed by finding cysts or trophozoites in feces or in
duodenojejunal aspirates or biopsies. Detection of the parasites can be
difficult since Giardia does not appear consistently in the stools of all
patients. Some patients will express high levels of cysts in nearly all the
stools, whereas others will only exhibit low parasite counts in some of the
stools. A mixed pattern, in which periods of high cyst excretion alternate
with periods of low excretion, has also been observed. In addition,
parasites are easier to find during acute infections than chronic infections.
Aspiration and biopsy may also fail to confirm the infection due to patchy
loci of infection, and some question the usefulness of these invasive
procedures. Stool examination is the preferred method for Giardia
diagnosis. Three stools taken at intervals of at least two days should be
examined. Watery or loose stools may contain motile trophozoites which
are detectable by the immediate examination of wet smears. Otherwise the
specimen should be preserved and stained due to trophozoite lability. The
cysts are relatively easy to recognize in either direct or stained smears. In
addition, diagnostic kits based on immunofluorescence or the detection of
antigens are also available. Diagnosis can also be made by examining
duodenal fluid for trophozoites. Duodenal fluid is obtained by either
intubation or the Enterotest (also called 'string test'). The Enterotest
consists of a gelatin capsule containing a nylon string of the appropriate
length. The free end of the string is taped to the patient's face and the
capusule is swallowed. After four hours to overnight the string is retrieved
and the bile-stained mucus on the distal portion of the string is scraped off
and examined by both wet mount and permanent staining.
Intestinal biopsy;A small intestinal biopsy, preferably from multiple
duodenal and jejunal sites, may also reveal trophozoites attached to the
intestinal epithelium.
Note;To distinguish giardiasis from other conditions causing diarrhea or
malabsorption, such as celiac disease and other causes of Tropical sprue
(in tropical countries, steatorrhea is associated with post-infective tropical
malabsorption due to giardiasis , strongyloidiasis, capilariasis etc) the
development of anaemia is uncommon. Note; If the diagnosis is strongly
suspected on clinical grounds , but no parasites can be found , a
- 59 -

therapeutic trial with metronidazole is justified. Because of its activity
against anaerobic bacteria, it may cause temporary improvement in
tropical sprue, and so yield inconclusive results.
Treatment and Control
Infected individuals should be treated since Giardia can persist and lead to
severe malabsorption and weight loss. Treatment is effective at reducing
morbidity and there are no sequelae. Metronidazole (Flagyl), effectively
clears the parasite (cure rates approximately 85%) and is the drug of
choice. Other effective drugs include: quinacrine (Atabrine), tinidazole
(Fasigyn), furazolidone (Furoxone), and paramomycin (Humatin).
Tinidazole is effective as a single two gram dose; paramomycin is not
absorbed and may be useful during pregnancy. The widespread
distribution of Giardia and the infectivity of the cysts make it unlikely that
human infection will be completely eliminated. Control measures to
prevent or reduce Giardia infection will depend on the specific
circumstances of transmission, but in general involve measures which
prevent the ingestion of substances contaminated with fecal material.
Health promotion and education aimed at improving personal hygiene, and
emphasizing hand washing, sanitation and food handling, are effective
control activities for the reduction of person-to-person transmission.
Special attention to personal hygiene in high-risk situations such as day-
care centers and other institutions is needed. Treatment of asymptomatic
household members prevents reinfection in non-endemic areas. However,
the value of treating asymptomatic carriers in hyperendemic communities
is questionalbe since reinfection rates are high. The socio-economic
situation in many developing countries makes it difficult to prevent
infection. Public health measures to protect water supplies from
contamination are required to prevent epidemics and to reduce endemicity.
Tourists should not drink tap water without additional treatment in places
where purity is questionable. Boiling or iodine treatment kills Giardia
cysts, but standard chlorination does not. There are no safe or effective
chemoprophylatic drugs for giardiasis. If treatment with one drug fails,
repeat the course, or change to another drug. If diarrhea persist after
treatment of giardiasis, it is not always due to failure to eliminate the
infection. Some patients may have secondary lactose intolerance following
giardiasis. And some may have other concomitant disease such as tropical
sprue.



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Non-pathogenic Intestinal flagelates

The human intestine also plays host to a range of commensal flagellates,
including Trichomonas hominis (7-15m, jerky movement, oval to round,
4 anterior flagella and its axostyle extends beyond body and one nucleus
its undulating membrane along length of body with free flagellum). ) and
Chilomastix mesnili (10-20 m, rotary movement, have pointed tail , 3
anterior flagella and the body have spiral groove and contain one nucleus)
both are asymptomatic (non-pathogenic) .Dientamoeba fragilis (see
below)

Dientamoebiasis (Dientamoeba fragilis infection)

Until recently Dientamoeba considered by most parasitologists to be an
ameba. Despite the lack of flagella, various protozoologist have
recognized its flagellate affinities. And classified among the trichomonads.
Dientamoeba is known to live in mucosal crypts of large intestine and has
been rarely to ingest red blood cells; apparently never invades the tissues

Etiology

Despite its name, Dientamoeba fragilis is not an ameba but a flagellate.
This protozoan parasite produces trophozoites; cysts have not been
identified. Infection may be either symptomatic or asymptomatic.

Morphology
The organism (trophozoite) round (Fig-1--). Pseudopodia are hyaline,
broad, and leaf-like in appearance, with characteristic serrated margins.
Dientamoeba fragilis trophozoites . Dientamoeba fragilis is a flagellate
that must be morphologically differentiated from the amebas, especially
Endolimax nana and Entamoeba hartmanni. Trophozoites usually
measure 9 to 12 m (range 5 to 15 m). While most trophozoites are
typically binucleate, some have only one nucleus. The cyst has not been
identified.

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Fig:-1- Dientamoeba fragilis trophozoite (in drawing line) .

Epidemiology

Worldwide distribution
Transmission and Life Cycle

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The complete life cycle of this parasite has not yet been determined, but
assumptions were made based on clinical data. To date, the cyst stage has
not been identified in D. fragilis life cycle, and the trophozoite is the only
stage found in stools of infected individuals(1). D. fragilis is probably
transmitted by fecal-oral route (2)and transmission via helminth eggs (e
Ascaris, Enterobius spp.) has been postulated(3). Trophozoites of D.
fragilis have characteristically one or two nuclei (1), (4), and it is found in
children complaining of intestinal (e.g., intermittent diarrhea, abdominal
pain) and other symptoms (e.g., nausea, anorexia, fatigue, malaise, poor
weight gain).
Clinical features
Symptoms that have been associated with infection include diarrhea,
abdominal pain, anorexia, nausea, vomiting, fatigue, and weight loss.
Laboratory diagnosis
Infection is diagnosed through detection of trophozoites in permanently
stained fecal smears (e.g., trichrome). This parasite is not detectable by
stool concentration methods. Dientamoeba fragilis trophozoites can be
easily overlooked because they are pale-staining and their nuclei may
resemble those of Endolimax nana or Entamoeba hartmanni.
Treatment
Safe and effective drugs are available. The drug of choice is iodoquinol.
or metronidazole can also be used.
Extraintestinal Flagellates
Trichomoniasis (Trichomonas vaginalis infection)
Most prevalent veneral disease. Lesions usually confined to lower
urogenital tract causing vaginitis and urethritis.
Etiology
Trichomonas vaginalis (a flagellate)

- 63 -

Morphology
The trophozoite form is 15 to 18 m in diameter and is half pear shaped
with a single nucleus, four anterior flagella and a lateral flagellum attached
by an undulating membrane (Fig-1-). Two axostyles are arranged
asymmetrically . The organism does not encyst.

Fig:-1- Trichomonas vaginalis trophozoite
Epidemiology
Trichomonas vaginalis has a world-wide distribution; incidence is as low
as 5% in normal females and as high as 70% among prostitutes.
Transmission and Life cycle
T. vaginalis colonizes the vagina of women and the urethra (sometimes
prostate) of men. Infection occurs primarily via sexual contact. The
organism does not encyst and divides by binary fission which is favored
by low acidity (pH > 5.9; the normal pH is 3.5 to 4.5). There is no non-
human reservoir. Trichomonas vaginalis resides in the female lower
genital tract and the male urethra and prostate (1), where it replicates by
binary fission (2). The parasite does not appear to have a cyst form, and
does not survive well in the external environment. Trichomonas vaginalis
is transmitted among humans, its only known host, primarily by sexual
intercourse (3).

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Clinical features and Pathology
T. vaginalis causes different clinical manifestations in men and women are
more likely to exhibit symptoms which tend to persist longer. The
incubation period typically ranges from 4-28 days. In females the infection
can present as an asymptomatic vaginitis, an acute or chronic
vulvovaginitis, or urethritis. Heavy infections in a high pH environment ,
which may cause mild to severe vaginitis . The onset or exacerbation of
symptoms commonly occurs during or immediately after menstruation.
The most common complaint associated with T. vaginalis infection is a
persitent mild vaginitis associated with a copious, foul-smelling discharge
that is often accompanied by burning or itching. This discharge is most
often gray, but can be yellow or green and is occasionally frothy or blood
- 65 -

tinged. The discharge diminishes as the infection becomes more chronic.
Many women also experience painful or difficult coitus. Urethral
involvement occurs in a large number of cases and is characterized by
dysuria (painful urination) and frequent urination. Males are likely to be
asymptomatic (50-90%) and the infection tends to be self-limiting. The
urethra and prostate and the most common sites of infection. Common
clinical manifestations include (Table-1-): urethral discharge (ranging
from scant to prululent), dysuria, and urethral pruritus (itching). Some
female experience burning immediately after coitus (dyspareunia). Little is
known about the pathophysiology associated with T. vaginalis infection,
but is presumably due to interactions between the parasite and host
epithelial cells. In vitro studies indicate that T. vaginalis can destroy cells
in a contact dependent manner. The vaginal walls are usually
erythematous (ie, red) and may show petechial (a small non-raised spot)
hemorrhages. Punctate hemorrhages of the cervix (called strawberry
cervix) .
Table-1- Common clinical manifestations
Females Males
asymptomatic
(15%*)
vaginal
discharge
(50-75%*)
dyspareunia
(50%*)
pruritus (25-
50%*)
asymptomatic (50-90%*)
urethral discharge (50-60%**)
disuria (12-25%**)
urethral pruritus (25%**)
*% of infected; **% of symptomatic
Laboratory diagnosis
Diagnosis is confirmed by the demonstration of trophozoites in vaginal,
urethral, prostatic secretions, or urine sediment (following prostate
massage). Microscopic examination of wet mounts of fresh vaginal
discharge, preferrably collected with a speculum on a cotton-tipped
- 66 -

applicator, is the most practical method of diagnosis. Specimens should be
diluted in saline and examined immediately. T. vaginalis is recognized by
its characteristic morphological features, and its rapid jerky motility.
Specimens can also be fixed and stained with Giemsa or fluorescent dyes.
The organism may be difficult to recognize on stained slides, though. In
vitro culture will sometimes reveal organisms when direct examination is
negative.
Treatment and Control
Metronidazole (Flagyl) is the recommend treatment for trichomoniasis.
Sexual partners should be treated at the same time to prevent reinfection.
Some drug resistance has been reported. Tinidazole is an alternate drug.
Measures used in the control of other S exual transmitted disease (STD),
such as limiting number of sexual partners and use of condoms, are also
effective in preventing trichomoniasis.
Note; T. vaginalis has been found in up to a third of cases of nonspecific
urethritis in men.











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CHAPTER FIVE (5)
Blood protozoa
Haemoflagellates
The Haemoflagellates, as the name suggests, are flagellates which live
principally in the blood of their hosts. They require the presence of an
arthropod vector (normally a fly or other insect) to complete their
lifecycle. There are normally three stages observed: the Promastigote
found in the arthropod vector, the Tryptomastigote found in the blood and
other fluids, and the Amastigote found in the tissues.
Trypanosomiasis
African Trypanosomiasis/sleeping sickness (Trypanosoma brucei
infection)
African trypanosomiasis or sleeping sickness is a severe disease, often
fatal if untreated, . The disease occurs in scattered foci throughout the
subsaharan. It is closely related to a wide spread cattle infection known as
Nagana, which restricts cattle rearing in many areas of the continent.
Etiology
Protozoan hemoflagellates belonging to the complex Trypanosoma brucei.
Two subspecies that are morphologically indistinguishable cause distinct
disease patterns in humans: a slowly developing disease caused by
Trypanosoma brucei gambiense cause West African sleeping sickness and
a rapidly progressing disease caused by T. brucei rhodesiense causes East
African sleeping sickness. A third subspecies, T.b. brucei is responsible
for the cattle disease, Nagana, but does not infect man.
Morphology
It is pleomorphic (Fig-1-) trypanosome measuring 18-35m in length.T. b.
gambiense and T. b. rhodesiense are similar in appearance: The organism
pleomorphic (showing variety of forms) (see figure-) measures 10-30
micrometers x 1-3 micrometers. It has a single central nucleus and a single
flagellum originating at the kinetoplast and joined to the body by an
- 68 -

undulating membrane . The outer surface of the organism is densely
coated with a layer of glycoprotein, the variable surface glycoprotein
(VSG).

Fig:-1- Trypomastigote in blood .
Epidemiology
T. b. gambiense is predominant in the western and central regions of
Africa, whereas T. b. rhodesiense is restricted to the eastern third of the
continent Number of countries affected: 36. 6,000 to 10,000 human cases
are documented annually. 35 million people and 25 million cattle are at
risk. Regional epidemics of the disease are cause of major health and and
economic disasters.T. b. gambiense is found in foci in large areas of West
and Central Africa. The distribution of T. b. rhodesiense is much more
limited, with the species found in East and Southeast Africa.
Transmission
Protozoan parasites of the genus Trypanosoma, transmitted by tsetse flies.
Tsetse flies (Fig-2-) can acquire a trypanosome infection by feeding on
these infected animals--or on an infected person. Cattle and other large
mammals are important reservoir hosts of trypanosomes. The
trypanosomes are injected into the blood through the bite of an infected
tsetse flies when it feeds again. The trypanosomes then multiply and
invade most tissues. T.b gambiense is usually transmitted by lakeside and
riverine tsetse flies, including G. palpalis, G. fuscipes, and G.tachinoides.
T.b.rhodesiense transmission is associated with woodland and savannah
tsetse flies, including G. morsitans, G..pallidipes, and G.swynnertoni.
- 69 -


Fig:-2- Tsetse (Glossina) fly.
Life Cycle
During a blood meal on the mammalian host, an infected tsetse fly (genus
Glossina) injects metacyclic trypomastigotes into skin tissue. The
parasites enter the lymphatic system and pass into the bloodstream (1).
Inside the host, they transform into bloodstream trypomastigotes (2), are
carried to other sites throughout the body, reach other blood fluids (e.g.,
lymph, spinal fluid), and continue the replication by binary fission (3).
The entire life cycle of African Trypanosomes is represented by
extracellular stages. The tsetse fly becomes infected with bloodstream
trypomastigotes when taking a blood meal on an infected mammalian host
(4), (5). In the flys midgut, the parasites transform into procyclic
trypomastigotes, multiply by binary fission (6), leave the midgut, and
transform into epimastigotes (7). The epimastigotes reach the flys
salivary glands and continue multiplication by binary fission (8). The
cycle in the fly takes approximately 3 weeks. Humans are the main
reservoir for Trypanosoma brucei gambiense, but this species can also be
found in animals. Wild game animals are the main reservoir of T. b.
rhodesiense.

- 70 -


Clinical features
The clinical features of Gambian and Rhodesian disease are the same,
however they vary in severity and duration. Rhodesian disease progresses
more rapidly and the symptoms are often more pronounced. The
symptoms of the two diseases are also more pronounced in Caucasians
than in the local African population. Classically, the progression of
African trypanosomiasis can be divided into three stages: the bite reaction
(chancre), parasitemia (blood and lymphoid tissues), and CNS stage. A
trypanosomal chancre can develop on the site of inoculation. This is
followed by a hemolymphatic stage with symptoms that include fever,
lymphadenopathy, and pruritus. In the meningoencephalitic stage,
invasion of the central nervous system can cause headaches, somnolence,
abnormal behavior, and lead to loss of consciousness and coma , usually
followed by death if untreated . The course of infection is much more
acute with T. b. rhodesiense than T. b. gambiense.
- 71 -

Bite reaction: A non-pustular, firm, tender raised up to 2 cm or more in
diameter, painful, itchy chancre (Fig-3-). Appear 1-3 weeks after the bite
and lasts 1-2 weeks . It apparently does not ulcerate unless secondary
infected. It leaves no scar. During attacks of fever in the early stages of
the disease there may be an irregular blotchy rash, often annular. The
individual patches may be several inches across; they tend to fade in a few
hours and reappear at irregular intervals.

Fig:-3-Chancre at the site of Tsetse bite.
Haemolymphatic stage : Parasitemia and lymph node invasion is marked
by attacks of irregular fever (an irregular fever, usually with evening peaks
and night sweats, is an early finding) which starts 2-3 weeks after the bite
and is accompanied by malaise, lassitude, insomnia, headache,
lymphadenopathy, and edema of the hips, legs, hands, and face that may
accompany the acute stage of African sleeping sickness. In the early stages
of African trypanosomiasis there may be generalized adenopathy; Very
characteristic of Gambian disease is visible enlargement of the glands of
the posterior cervical region (Winterbottom's sign)(Fig-4-). As part of
the generalized lymphoid hyperplasia splenomegaly may be observed .
Febrile episodes may last few months as in Rhodesian disease or several
years as in Gambian disease. Parasitemia is more prominent during the
acute stage than during the recurrence episodes.

Fig:-4- Winterbottom's sign.
- 72 -

CNS Stage: The late or CNS stage (Gambian disease) is marked by
changes in character and personality. They include lack of interest and
disinclination to work, morose and mental retardation and lethargy, low
and tremulous speech, tremors of tongue and limbs, headache, slow and
shuffling gait, altered reflexes, etc. Males become impotent and
amennorhea in female. There is a slow progressive involvement of cardiac
tissue. The later stages are characterized by drowsiness and uncontrollable
urge to sleep. The terminal stage is marked by wasting and emaciation.
Kerandel
,
s sign (Painful sensitivity of palms and ulnar region to
pressure ,may develop in some Caucasians. noted in the stage of central
nervous system involvement in African sleeping sickness. it may be
elicited by pressure on the palm of the hand or over the ulnar nerve and
consists of severe pain that occurs shortly after the pressure has been
relieved). Death results from coma,(in A. trypanosomiasis , coma develops
after a protracted period of increasingly severe symptoms of
meningoencephalitis), intercurrent infection or cardiac failure.The clinical
features of Rhodesian disease are similar but briefer and more acute, often
cause hepatocellular jaundice and mild anaemia, and sever anaemia may
soon develop (may result in part from nutritional causes), slight
enlargement of liver and spleen , lymph nodes enlargement (seldom so
prominent as in T.gambiens) common in inguinal and axillary lymph
glands.Serous effusion , especially into pleural and pericardial spaces, are
common and myocarditis may occur Myocardial involvement is the
commonest cause of death in the early stage. The acuteness and severity of
disease do not allow typical sleeping sickness. Death is due to cardiac
failure within 6-9 months or may follow acute toxaemic stage (congestive
heart failure has been reported in African sleeping sickness , probably in
the Rhodesian form of the disease) before the CNS is involved. When the
CNS is involved , the clinical features resemble stage in T.gambiense but
death is more rapid. T. rhodesiense may be fatal within afew weeks of the
onset. In general , T. gambiense is better adapted to the human host than is
T.rhodesiense. For this reason, T. gambiense is relatively well tolerated:
The illness it causes tends to be subacute or chronic and parasitaemia may
even be asymptomatic.
Pathology and Immunology
An exact pathogenesis of sleeping sickness is not known, although
immune complexes and inflammation have been suspected to be the
mechanism of damage to tissues. The immune response against the
organism does help to eliminate the parasite but it is not protective,
- 73 -

because the parasite has a unique ability of altering its antigens, the
Variant surface glycoprotein (VSG). Estimates are that a single
trypanosome may have as many as 1000 or more VSG genes .
Consequently, there is a cyclic fluctuation in the number of parasites in
blood and lymphatic fluids and each wave of parasite represents a
different antigenic variant. By constantly changing surface proteins
(antigens), trypanosomes are able to evade host defense mechanisms. The
parasite causes polyclonal expansion of B lymphocytes and plasma cells
and an increase in total IgM concentration. Hypergammaglobulinaemia
(IgM level >4 times than normal level).,higher levels of IgM are found in
trypanosomiasis than in any other protozoal infection (these sustained
elevation are thought to be a result of the antigenic variability) , IgG levels
also rise, but not to the same extent . This diversion of the humoral
defences to a useless and inevitably impairs the response to other
pathogens, mainly bacteria. Just as in visceral leishmaniasis, the infected
host becomes much more susceptible to intercurrent infections. It
stimulates the reticuloendothelial function. It also causes severe
depression of cell mediated and humoral immunity to other antigens.
There is generalized lymphoid hyperplasia because parasites multiply in
the lymph nodes. Anaemia is usually noted; the WBC count is essentially
normal, with relatively lymphocytosis. Thrombocytopenia occur as a
cosequense of reticuloendothelial system hyperplasia also due later to
dissiminated intravascular coagulation (DIC). CNS invasion provoke Ag-
Ab reactions and cause progressive meningitis, with perivascular
lymphocyte and plasma cell infiltration. protein level and WBC increased
in Spinal fluid , parasites in CNS.
Laboratory diagnosis
A definitive laboratory diagnosis is made by finding the trypanosomes in
the blood, lymph nodes, and bone marrow in the early disease and in the
spinal fluid in the late disease, while presumptive diagnosis is obtained by
detecting changes in the cerebrospinal fluid and serum IgM.
Direct methods
1-Blood films: stained with a Romanowsky or Giemsa stain , it is most
useful for T.rhodesiense infection.
2- Lymph gland puncture/aspiration: This is much the most useful method
for T.gambiense.
- 74 -

3-Bone marrow aspiration: This is useful in the early stages when other
methods are negative.
4-CSF examination; The deposit from 5-10 ml of centrifuged fluid should
be made into a smear, dried, fixed and stained with Romanowsky stain.
5-Chancre: sometimes trypanosomes can be recoverd by aspiration from
the chancre(midway between its edge and its centre).
6-. Isolation of the parasite by inoculation of rats or mice is a sensitive
method, but its use is limited to T. b. rhodesiense.
Indirect methods
Several serodiagnostic procedures have been used to detect
antitrypanosomal antibodies . such methods may be useful when all
attempts at direct diagnosis have failed.
1-The card agglutination test for trypanosomiasis(CATT) is simple to
carry out.
2-IgM ;The most useful is the detection of very high IgM levels by
immunodiffusion plates, usually 8-16 the normal maximum levels.
Note;The most reliable method to differentiate , whether the infection by
T.gambiense or T.rhodesiense ( inject albino rats with the parasite):
T.rhodesiense produce a fatal infection in 20-50 days; while T.gambiense
either fails to produce infection at all, or leads to a chronic, non-fatal
infection which lasts hundreds of days. This method of no use to the
individual patient. Note;An important guestion for the clinician , to decide
CNS involved or not and how to proceed. The way to decide depends on
examination of the CSF, if blood examination is positive, lumbar puncture
should be precede by treatment to eliminate parasite in the blood
otherwise CSF infection could be introduced by the puncture itself. It is
usual to wait 24 hours after an injection of suramin before performing
lumbar puncture. Finally the diagnosis rests upon demonstrating
trypanosomes by microscopic examination of chancre fluid, lymph node
aspirates, blood, bone marrow, or, in the late stages of infection,
cerebrospinal fluid

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Treatment
Treatment should be started as soon as possible and is based on the
infected persons symptoms and laboratory results. The drug regimen
depends on the infecting species and the stage of infection. Pentamidine
isethionate, and suramin are the drugs of choice to treat the
hemolymphatic stage of West and East African Trypanosomiasis,
respectively. These drugs have been reported also to be effective in
prophylaxis although they may mask early infection and thus increase the
risk of CNS disease. Melarsoprol is the drug of choice for late disease
with central nervous system involvement (infections by T.b. gambiense or
T. b. rhodiense). Treatment of African sleeping sickness has always been
difficult, especially in the later stages of the disease (ie. with central
nervous system involvement). Very recently, a new drug originally
developed as an anticancer agent--DFMO (also known as eflornithine)-has
given very promising results in field trials against gambiense infection, but
seems much less effective against the more virulent rhodesiense form. The
principles of CNS involvement treatment are:1- Improve the general
condition by giving suramin to destroy parasites outside the CNS.2-
Destroy the parasites in the brain with melarsoprol.
Prevention and Control:
Control of African sleeping sickness relies mainly on systematic
surveillance of the population at risk, and treatment of diagnosed cases. In
addition, reduction of the tsetse fly vectors has an important role,
especially against the rhodesiense form of the disease (and against the
cattle disease, Nagana). In the past, this has involved extensive bush
clearance to destroy the flies breeding and resting sites, and widespread
use of insecticides. More recently, efficient traps have been developed,
that can keep tsetse fly populations down to very low levels.
American trypanosomiasis /Chagas' disease (/Trypanosoma cruzi
infection)
Chagas Disease (American Trypanosomiasis) - Chagas disease is caused
by the flagellate protozoa (Trypanosoma cruzi). The infection usually is
transmitted by the feces of blood-sucking insect vectors (reduviid bugs).
The infection is found mostly in small mammals (sylvatic cycle), and the
human disease results from the colonization of the human habitat by some
vector species (domestic cycle). Chagas disease, which occurs only in the
- 76 -

New World, gets its name from Dr Carlos Chagas-a Brazilian doctor who
first described the disease in 1909. Regrettably, the disease remains
incurable, although transmission can be successfully interrupted by control
of the insect vectors in houses and peridomestic habitats.
Etiology:
Chagas' disease is caused by the protozoan hemoflagellate parasite called
Trypanosoma cruzi, a zoonotic disease.
Morphology
Depending on its host environment, the organism occurs in three different
forms. The trypanosomal (trypomastigote) form (Fig-1-) , found in
mammalian blood, it is monomorphic usually C-shaped measuring 12-
30m. morphologically similar to African trypanosomes. The crithidial
(epimastigote) form is found in the insect intestine. The leishmanial
(amastigote) form (Fig-2-), found intracellularly or in pseudocysts in
mammalian viscera (particularly in myocardium and brain), is round or
oval in shape, measures 2-4 microns and lacks a prominent flagellum.

Fig:-1-Trypomastigote form in blood film. Fig:-2- Amastigote form in
the cell.
Epidemiology
American trypanosomiasis, is scattered irregularly from the southern
United States to southern Argentina. Mostly in poor, rural areas of Central
and South America especially in Central and South America, stretching
from parts of Mexico to Argentina . Rare cases have been reported in
Texas, California and Maryland. It is estimated that 16-18 million people
are infected by the parasite and 50 million are at risk. About 50,000 people
die each year from the disease.Chronic Chagas disease is a major health
problem in many Latin American countries. With increased population
movements, the possibility of transmission by blood transfusion has
become more substantial in the United States.
- 77 -

Transmission
Trypanosoma cruzi is transmitted by large bloodsucking 'assassin bugs'(or
kissing bug) of the subfamily Triatominae , family Reduviidae (Fig-3-),
These insects (similar to large bed bugs) commonly live in the cracks and
crevices of poor-quality houses in most rural areas of Latin America. They
emerge from their cracks at night to bite and suck blood from the sleeping
occupants. However, the parasites are not transmitted in the bite of insect.
Instead, they are deposited with the insect faeces onto the skin. Scratching
the bites probably helps the parasites penetrate and enter the bloodstream.
T.cruzi can also be transmitted by blood transfusion from infected people-
this is increasingly a problem in blood banks and hospitals in some areas.
Trypanosoma cruzi can also be transmitted through blood transfusions,
organ transplantation, transplacentally, and in laboratory accidents.

Fig:-3- Triatominae , Reduviidae bug

Life Cycle
An infected insect vector (or kissing bug) takes a blood meal and
releases trypomastigotes in its feces near the site of the bite wound.
Trypomastigotes enter the host through the wound or through intact
mucosal membranes, such as the conjunctiva (1). Inside the host, the
trypomastigotes invade cells, where they differentiate into intracellular
amastigotes (2). The amastigotes multiply by binary fission (3) and
differentiate into trypomastigotes, and then are released into the
circulation as bloodstream trypomastigotes (4). Trypomastigotes infect
cells from a variety of tissues and transform into intracellular amastigotes
in new infection sites. Clinical manifestations can result from this
infective cycle. The bloodstream trypomastigotes do not replicate
(different from the African trypanosomes). Replication resumes only
when the parasites enter another cell or are ingested by another vector.
- 78 -

The kissing bug becomes infected by feeding on human or animal blood
that contains circulating parasites (5). The ingested trypomastigotes
transform into epimastigotes in the vectors midgut (6). The parasites
multiply and differentiate in the midgut (7)and differentiate into infective
metacyclic trypomastigotes in the hindgut (8).



Clinical features
Chagas' disease can be divided into three stages: the primary lesion, the
acute stage, and the chronic stage.


- 79 -

Primary lesion
Chagoma; appearing at the site of infection, within a few hours of a bite,
consists of a slightly raised, flat non-purulent erythematous plaque
surrounded by a variable area of hard edema. It is usually found on the
face, eyelids, cheek, lips or the conjunctiva, but may occur on the
abdomen or limbs. When the primary chagoma is on the face, there is an
enlargement of the pre- and post- auricular and the submaxillary glands on
the side of the bite. Persist for 2 to 3 months. Infection in the eyelid,
resulting in a unilateral conjunctivitis and orbital edema (Ramana's sign)
,it is one of the commonest finding (Fig-4-). It is unilateral palpebral
edema, involving both upper and lower eyelids, appears early in the course
of an infection with T.cruzi. The edema is hard and nonpitting ; it may
remain confined to the eyelids or may spread to involve the cheek and
neck. It may subside promptly or persist for weeks or months.

Fig:-4- Ramana's sign.
Acute stage: The acute stage appears 7-14 days after infection. It is
characterized by restlessness, sleeplessness, malaise, increasing
exhaustion, chills, fever(high remittent fever lasting for several weeks
occurs early in disease) and bone and muscle pains. Other manifestations
of the acute phase are cervical, axillary and iliac adenitis, hepatomegaly,
splenomegaly, erythematous rash and acute myocarditis. There is a
general edematous reaction associated with generalized lymphadenopathy.
Diffuse myocarditis, sometimes accompanied by serious pericarditis and
endocarditis, is very frequent during the initial stage of the disease. In
children, Chagas' disease may cause meningo-encephalitis and coma.
Death occurs in 5-10 percent of infants. Hematologic examination reveals
lymphocytosis (generally seen in chagas disease in early stage followed by
leucopenia). Most acute cases resolve over a period of 2 to 3 months but
more usually the patient survives to enter a symptomless chronic phase
which may last many months or years.
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Chronic stage: The acute stage is usually not recognized and often
resolves with little or no immediate damage and the infected host remains
an asymptomatic carrier. An unknown proportion (10-20%) of victims
develop a chronic disease. They alternate between asymptomatic
remission periods and relapses characterized by symptoms seen in the
acute phase. Cardiac arrhythmia is common. The chronic disease results in
an abnormal function of the hollow organs, particularly the heart,
esophagus and colon. Chronic infection may be seen in patients who have
no history of the acute stage; and if patient are asymptomatic, at times the
infection may be diagnosed by ECG changes, characteristic changes are
seen, tachycardia , where it may be associated with (partial or complete
atrioventricular -AV- block, complete bundle branch block, or premature
ventricular contraction, low voltages of QRS complexes abnormalities of
P and T waves) The cardiac changes include myocardial insufficiency,
disturbances of atrio-ventricular conduction ,and Cardiomegaly.
Symptoms/signs of progressive congestive cardiac failure appear.
Myocardial infection is characteristic ,and is seen in about 50% of chronic
cases. Cardiac failure may come on slowely , although in infants it tends
to occur in the early acute stage. There may be pericardial effusion. Less
common than the cardiac involvement is digestive tract dilatation and
disturbances of peristalsis characteristized by dysphagia and
Megaesophagus and Megacolon (Fig-5-).

Fig:-5- Organomegaly(megaesophagus and megacolon)
During Symptomatic chronic stage the parasites are invading most organs
of the body. So that chronic symptoms eventually develop - often
involving irreversible damage to heart and intestine. In such cases, the
patient becomes progressively weaker, and may die from heart failure.
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Pathology and Immunology
The pathological effects of acute phase Chagas' disease largely result from
direct damage to infected cells. In later stages, the destruction of the
autonomic nerve ganglions of the heart parallels that to Aurebach
,
s plexus
in the walls of the digestive tract, may be of significance. Immune
mechanisms, both cell mediated and humoral, involving reaction to the
organism and to autologous tissues have been implicated in
pathogenesis.The metacyclic trypanosomes, soon after their entrance in
the mammalian host egulfed by the macrophages of Reticuloendothelial
system (RES) , in which they multiply to erupt in 4 or 5 days, some
entering the blood and others penetrating the cells of the various organs.
Within the cells they continue to reproduce until the distended cells
rupture, and trypanosomes liberated and invade other cells (cells of the
RES, cardiac, ,skeletal , smooth muscle and neuron cells are preferentially
parasitized). The chagoma consists of an intense inflammatory reaction
with invasion of histiocytes. As the infection spread beyond the regional
lymph glands trypomastigotes appear in the circulating blood, infecting
other organs, cause diffuse inflamtory reaction with exudates and
proliferation of interstitial connective tissue in these organs , the cells of
these organs react to invasion and hypartrophied . T. cruzi stimulates both
humoral and cell mediated immune responses. Antibody has been shown
to lyze the organism, but rarely causes eradication of the organism,
perhaps due to its intracellular localization. Cell mediated immunity may
be of significant value. While normal macrophages are targeted by the
organism for growth, activated macrophages can kill the organism. Unlike
T. brucei, T. cruzi does not alter its antigenic coat. Antibodies
(autoantibodies) directed against heart and muscle cells have also been
detected in infected patients leading to the supposition that there is an
element of autoimmune reaction in the pathogenesis of Chagas' disease.
The infection causes severe depression of both cell mediated and humoral
immune responses. Immunosuppression may be due to induction of
suppressor T-cells.
Laboratory diagnosis
Clinical diagnosis is usually easy among children in endemic areas.
Cardiac dilation, megacolon and megaesophagus in individuals from
endemic areas indicate present or former infection. Definitive diagnosis
requires the demonstration of trypanosomes by microscopy or biological
tests (in the insect or mice). Antibodies are often detectable by
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complement fixation or immunofluorescence and provide presumptive
diagnosis.
Direct methods
1-Blood film.
2: Demostrating amastigotes in a muscle biopsy (rarely used).
3: Isolation of the agent by: a) inoculation into mice b) culture in
specialized media (e.g. NNN); and c) Xenodiagnosis test (used to detect
very low parasitaemia (clean bugs raised in the laboratory are fed on the
patient. 2-4 weeks later they are killed , and the gut examined for the
presence of epimastigotes or metacyclic trypanosomes)
Indirect method
1- specific antibody detection by (CFT or IFAT)
Note; In certain circumstances, investigational molecular diagnostic tools,
such as PCR, may be useful.
Treatment
There is no curative therapy available. Most drugs are either ineffective or
highly toxic. Recently two experimental drugs, Benznidazol and
Nifurtimox have been used with promising results in the acute stage of the
disease, however their side effects limit their prolonged use in chronic
cases. Medication for Chagas disease is usually effective when given
during the acute stage of infection. The chronic chagas disease stage is
incurable, the treatment involves managing the clinical manifestations of
the disease, e.g., pacemaker for heart block; the decision about whether to
use antiparasitic therapy is debatable.
Prevention and Control
Control therefore relies on insecticides to kill the triatomine bugs in
houses, together with programmes of health education and low-cost
housing improvements to render houses unsuitable for colonization by the
bugs. Moreover, because T. cruzi antigens may stimulate autoimmunity
(immune attack on host tissues) the likelihood of a safe effective vaccine
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now seems very remote. For the traveller, Chagas disease can be avoided
by not sleeping in infested houses, and, if blood transfusion is required,
using blood that has been treated with a blue dye (crystal violet) that
eliminates the parasites from stored blood.
Trypanosoma rangeli
T.rangeli is found Mexico and central / south America . look like T.cruzi
except small kinetoplast . It is non-pathogenic to man or animals.
Transmitted by reduvidii bug. Man is the reservoir host in urban areas,
while monkeys, opossums in rural areas.















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CHAPTER SIX (6)
Other blood and tissue dwelling Protozoa
Leishmaniasis (Leishmania complexes infection)
Leishmania parasites get their name from W.B. Leishman who developed
in 1901 one of the earliest stains specific for this type of parasite.
Although generally known for causing disfiguring lesions, epidemics of
visceral forms of leishmaniasis have caused thousands of deaths.
Etiology and Epidemiology
Leishmaniasis is a vector-borne disease caused by obligate intracellular
protozoa of the genus Leishmania. Human infection is caused by about 21
of 30 species that infect mammals.There are several species of Leishmania
are pathogenic for man:; include the L. donovani complex with 3 species
(L.d. donovani, L.d. infantum, and L.d. chagasi). L. donovani donovani
causes visceral leishmaniasis (Kala-azar, black disease, dumdum fever)
occurs in India, Pakistan, Burma, Chad, Kenya, Uganda, Sudan, Gabon,
Gambia, Niger, China reservoir hosts (rodents and dogs), the vectors
phlebotomus sandflies. Leishmania donovani infantum is found along the
whole Mediterranean littoral- in Europe, middle east, and Africa, occurs in
Hungary, Romania, South of the Russia reported in Serbia and China .
Human Infection are confined almost in the children. Dogs are reservoir
host , Phlebotomus is the vector. Leishmania donovani chagasi ; in central
and south America countries, those affected are primarily children. Foxes
and domestic dogs and cats are naturally infected. The vectors are
lutzomyia sandflies. L. tropica complex with3 main species( L. tropica ,
L. major and L. aethiopica) cause cutaneous leishmaniasis (oriental sore) .
L.tropica produces chronic disease, it is found urban areas, widely
distributed around the Mediterranean littoral,, in russa, Armenia,
Azerbaijan, Turkmenistan, Uzbekistan; it is also seen in Afhanistan , India
and in Kenya. The dogs may be a natural host, but is not thought to be an
effective reservoir for humans. Asimilar chronic disease, seen in the
highlands of Ethiopia, in Kenya, and possibly in south Yemen, is caused
by L. aethiopica. The rock hyrax is a reservoir host of this species. L.
major produces an acute infection , it is found in the rural areas. Occurs in
Russia, Turkmenistan desert, Uzbekistan, and Kazakhstan, in Iran, Syria,
Palestin, and Jordan, in Africa such as Algeria, Libya, Tunisia, Egypt,
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Sudan, Chad, Nigeria, Niger, Burkina Faso, Mali, Senegal, and Kenya,
and reservoir hosts (gerbils and other rodents) are important sources of
human infection. In the new world, cutaneous leishmaniasis is caused by
subspecies of L. mexicana complex of which L.m.mexicana and L. m.
pifanoi are the most important. The chiclero ulcer or Bay sore is caused by
L.m . mexicana. It is found in Guatemala and Yucatan peninsula . A
number of forest rodents are reservoir hosts of this parasite. L.m . pifanoi
occurs in the Amazon basin, Brazil and in venezuela. L. m. amazonensis
is found in the amazon basin of brazil and is the cause of cutaneous and
diffuse cutaneous forms of leishmaniasis. Two other subspecies are L. m.
garnhami, which causes Venezuelan Andean cutaneous leishmaniasis and
L.m.venezuelensis, which causes cutaneous leishmaniasis in a forested
area. Reservoir hosts for this subspecies of L. mexicana are a number of
small forest mammals including rodents, marsupials, and foxes. The
principal vector is Lutzomyia sandfly. and L. braziliensis complex, are
etiologic agents of mucocutaneous leishmaniasis. a subspecies L.
braziliensis are L.b.braziliensis confined in Brazil, Peru, Bolivia, Ecuador,
Colombia, Paraguay, Venezuela and cause a disease known in brazil as
espundia . L.b. peruviana confined in western Peruvian Andes and it
cause Uta disease, the domestic dogs and probably a wild rodent are act as
reservoir hosts, Lutzomyia are the vector. L. b. guyanensis cause pianbois
disease occurs in costa rica, reservoir hosts are sloths and Lutzomyia is the
vectors. L. b. panamensis particularly those travel to the rainforest in costa
rica , it has a variety of reservoir hosts, including sloths, rodents, monkeys,
and procyonids.Lutzomyia and Psychodopygus sandflies are vectors.
Leishmaniasis is prevalent world wide: ranging from south east Asia,
Indo-Pakistan, Mediterranean, north and central Africa, and south and
central America.Leishmaniasis is found in parts of about 88 countries.
Approximately 350 million people live in these areas at risk. 12 million
,Number of new cases per year. Most of the affected countries are in the
tropics and subtropics. The settings in which leishmaniasis is found range
from rain forests in Central and South America to deserts in West Asia.
They are widespread in the New World and Old World (but not in SE
Asia), and human infections are still found in many parts of Europe such
as France, Italy, Greece, Malta, Spain, Portugal, Turkey and southern
USSR. More than 90 percent of the world's cases of visceral leishmaniasis
are in India, Bangladesh, Nepal, Sudan, and Brazil. The different species
are morphologically indistinguishable, but they can be differentiated by
isoenzyme analysis, molecular methods, or monoclonal antibodies.The
several species and subspecies infect man, leading to symptoms ranging
from simple self-healing skin ulcers (eg. due to Leishmania major) to
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severe life-threatening disease (eg. visceral leishmaniasis, known as Kala-
azar, due to L. donovani).
Morphology
Amastigote (leishmanial form) is oval and measures 2-5 m by 1 - 3 m.

Fig:-1- Macrophage filled with amastigotes .
Leishmania tropica amastigotes from an impression smear of a biopsy
specimen from a skin lesion. , an intact macrophage is practically filled
with amastigotes (Fig-1-), several of which have a clearly visible nucleus
and kinetoplast.
Transmission and Life Cycle
Most forms of leishmaniasis are originally infections of small mammals
(known as reservoir hosts) which play a major role in the epidemiology of
this disease. Man becomes infected through the bite of infected
sandflies(tiny sand-coloured biting flies) that breed in moist soil, for
example in forest areas, caves, or in the burrows of small rodents. Old
World forms of Leishmania are transmitted by sand flies of the genus
Phlebotomus, while New World forms are mainly transmitted by sandflies
of the genus Lutzomyia. The sand flies become infected by feeding from
infected reservoir hosts or from infected people.L.donovani can also be
transmitted by blood transfusion.
Leishmaniasis is transmitted by the bite of female phlebotomine sandflies.
The sandflies inject the infective stage, promastigotes, during blood meals
(1). Promastigotes that reach the puncture wound are phagocytized by
macrophages (2)and transform into amastigotes (3). Amastigotes multiply
in infected cells and affect different tissues, depending in part on the
Leishmania species (4). This originates the clinical manifestations of
leishmaniasis. Sandflies become infected during blood meals on an
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infected host when they ingest macrophages infected with amastigotes (5),
(6). In the sandfly's midgut, the parasites differentiate into promastigotes
(7), which multiply and migrate to the proboscis (8).


Clinical features
Visceral leishmaniasis
About 20 species and subspecies of Leishmania are known to infect man.
Each causes a different range of symptoms.Human leishmanial infections
can result in 2 main forms of disease. Visceral leishmaniasis (kala-azar,
Dumdum fever): Man is the chief source of infection .The disease is
chiefly transmitted from man to man ,or from dog to dog to man by
various species of phlebotomus. The infection is chiefly confined to
children (L.infantum see below). Male acquire the disease more
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frequently than female. The incubation period is usually 1 to 4 months but
may be much longer. L. donovani organisms in visceral leishmaniasis are
rapidly eliminated from the site of infection, hence there is rarely a local
lesion, although minute papules have been described in children. They are
localized and multiply in the mononuclear phagocytic cells of (RES)
spleen, liver, lymph nodes, bone marrow, intestinal mucosa and other
organs.Kala-azar is a serious disease, usually fatal if untreated. Common
symptoms after infection, there is occurrence of fever (double remittent or
dromedary fever), which last a few days to several weeks, are separated
by afebrile periods of equal irregularity. Sometimes during the course of a
febrile attack there is usually one or more days during which a double or
triple rise to a temperature of 102-104 degrees F(38-40 C) can be
demonstrated during a 24-hour period., accompanied by chills and
sweating , and the patient may present a malaria like picture with which
leishmaniasis is often confused, later there is malaise, weight loss,
emaciation, and anaemia . Spleen gradually enlarges owing to the
enormous increase of reticuloendothelial cells. The liver & spleen (Fig-
2&3)enlarged owing to proliferation of the kupffer cells, which contain
parasites, liver enzyme (GOT) is increased. And lymph nodes. The main
blood cells count are abnormal. low blood counts (pancytopenia) may
be a consequence of proliferation of infected reticuloendothelial cells in
the bone marrow, including a low red blood cell count (anemia), the
anemia is due to a reduced red cell life span and mild degree of ineffective
erythropoiesis due to bone marrow supression, low white blood cell count
(leucopenia) 4000 mm
3
or less, with relative monocytosis , generally is
seen throughout the course of Kala-azar, sometimes terminating in
agranulocytosis. And low platelet count (thrombocytopenia). With
progression of the diseases to be Chronic disease, renders patients
susceptible to other infections (due to immunosupression). Other
symptoms include cough, diarrhea, dizziness, bleeding gums, pains in the
limbs and weight loss. Later there is progressive enlargement of the spleen
(In Kala-azar the slpeen is said to enlarge downward about an inch per
month, and it may extend into the pelvis. It is not tender and reverts to
normal size after effective therapy), and lymphadenopathy which is more
marked in infection with L.d. infantum. Hepatomegaly and Splenomegaly
occur early in Kala-azar. Ascites occur in chronic cases, probably
secondrary to a nutritional cirrhosis. Dermal leishmanoid is a secondary
cutaneous manifestation of Leishmania donovani infection, occurring a
year or so after supposedly successful treatment of Kala-azar. The lesion
may be flattened or depressed depigmented macules, or erythematous
nodules which, on the face, often occur in butterfly distribution
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reminiscent of lupus erythematosus. Leishmania amastigotes are found in
the lesions. In Kala-azar infiltration of the intestinal submucosa with
leishmania-containing macrophages may lead to mucosal ulceration and
diarrhea. Skin changes are common . Some patients develops
hyperpigmented granulomatous areas of the skin . Local Indian name of
{(Kala-azar=meaning (black disease)}, Kala-azar derives its name from
intensification of the pigmentation of the skin over the cheeks and temples
and around the mouth. It is most obvious in dark-skinned races.General
debility and leucopenia render the patient especially susceptible to
secondry infections, e.g. pulmonary and gastrointestinal infections.

Fig:-2- Boy suffering from visceral leishmaniasis. Fig:-3- Enlarged
spleen and liver.
Visceral leishmaniasis is becoming an important opportunistic infection in
areas where it coexists with HIV. The untreated disease usually progresses
to a fatal termination within 2 years.
Childhood Visceral leishmaniasis (L.infantum)
The clinical manifestations of childhood VL are more or less same as in
the adults. Prolonged fever with anorexia and loss of appetite are the
major presenting features. Marked enlargement of the spleen and liver
(spleen larger than liver (Fig-2&3-) with moderate to severe anaemia and
changes in hair take place. Bacterial infection is a common coinfection
and intestinal parasitic infestations are very common in children with VL.
Liver function tests, blood, urine and stool may show abnormalities.
Note; Glomerular involvement (Glomerulonephritis )with deposition of
subendothelial and mesangial immune complexes (IgA, IgG, IgM,
complement and fibrinogen) .
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Note: In India and occasionally in East Africa, a cutaneous form of
leishmaniasis , affect 20% of patients, can occur 1-2 years after recovery
from visceral leishmaniasis called (Post Kala-azar dermal
leishmaniasis). Hypopigmented and erythematous patches can be found
on the face, trunk, and limbs . These may develop into nodules and
resemble those of lepromatous leprosy. Amastigotes are present in the skin
but ofyen in small numbers.
Cutaneous leishmaniasis ( Old world)
L. tropica (dry oriental sore) transmitted by phlebotomus (sandfly). The
incubation period may be couple of months or as long as 3 years. It is an
urban cutaneous leishmaniasis (with local names such as Bagdad ulcer,
Delhi ulcer, Oriental sore). Endemic in the Middle East and India , eastern
mediterranian countries and north africa. disease with human beings
thought to be the main reservoir of infection (dog probably an incidental
host) .produce chronic disease that, if not treated lasts for years or longer
characterized by dry lesion commonly on the face which ulcerate after
several months. The disease may disseminate in the case of depressed
immune function . At the site of the bite a very small papule develops
which may itch, but is painless, the skin above the papule soon flakes off
and a moist crust forms over a shallow ulcer, usually the crust is dislodged
leaving a crater-like sore with a raised margin (Fig-4-). The sore enlarges
by erosion of its edge until it is usually 25-70 mm in diameter and
secondary papules may appear at its periphery. Infection with L.tropica is
often referred to as a dry urban oriental sore. If there is secondary bacterial
infection with discharge of pus. In some patients, multiple scattered
lesions may be seen, due either to the repeated bites of infected sandflies
or to the spread of parasites by way of the blood or lymphatics. Oriental
sore is usually self-healing after 1-2years leaving disfiguring scar often on
the face, hands (Fig-5-) and leaving the patient firmly immune to re-
infection with the same parasite.

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Fig:-4- crater lesion with a raised margin. Fig:-5- Skin ulcer scar.
leishmaniasis recidivans(LR). The hypersensitive patient is capable of
excellent antibody and cellular responses but canot completely eliminate
the parasites, so as the central lesion heals, active peripheral continue to
form. So there may develop multiple unhealing lesions which strongly
resemble those of tuberculosis of the skin . The condition is referred to as
leishmaniasis recidivans(LR). This type of response, may be seen in any
cutaneous leishmaniasis.
L.major-(wet oriental sore)-infection with L.major species are often
referred to as wet oriental sore, it is a primarily disease of rural areas , and
the reservoir hosts (gerbils and other rodents). The incubation period is
much shorter than L. tropica, as little as 2 weeks. The lesions develop and
heal much more quickly than those of L.tropica. The early papule is often
inflamed and resembles a boil of 5-10mm in diameter which rapidly
develops into a large uneven ulcer which is self healing in as little as 3-6
months. Multiple lesions may occur in non-immune persons. The most
common infection, due to L. major in Africa and Asia, leads to one or
more simple skin lesions (with local names such as 'Delhi boil', 'boutond'
orient , Aleppo boil). These generally heal after a few weeks or months to
leave unsightly scars.
L.aethiopica- Transmitted by phlebotomus (sandflies). Confined to East
Africa highlands where the cave dwelling hyrax is the reservoir. Probably
no interhuman transmission. Cutaneous leishmaniasis as for L.tropica, but
with some some diffuse nodular cutaneous lesions (pseudolepromatous).
It is normaly associated with a lesion similar to typical oriental sore, but
may also give rise to diffuse cutaneous leishmaniasis (DCL) in patients
who produce little or no cell-mediated immunity against the parasite. This
is an incurable condition characterized by the formation of disfiguring
nodules over the surface of the body. The nodules contain large numbers
of amastigotes. L.aethiopeca can also cause mucocutaneous leishmaniasis.
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Note ; In general persons with cutaneous leishmaniasis have one or more
sores on their skin. The sores can change in size and appearance over
time. They often end up looking somewhat like a volcano, with a raised
edge and central crater. The sores can be painless or painful. Some people
have swollen glands near the sores (for example, in the arm pit if the sores
are on the arm or hand).The factors determining the form of disease
include leishmanial species, geographic location, and immune response of
the host.
Mucocutaneous leishmaniasis (New world): common in the new world
with local names such as (Espundia, Uta), Transmitted by lutzomyia
(sandflies). The organisms responsible are L. braziliensis, L. mexicana and
L. peruviana. Forest rodents are reservoir hosts.The initial symptoms of
mucocutaneous leishmaniasis are the same as those of cutaneous
leishmaniasis, except that in this disease the organism can metastasize and
the lesions with start as simple skin ulcers,then can spread to mucoid (oral,
pharyngeal and nasal) tissues and lead to their destruction and hence sever
deformity give hideous tissue destruction (Fig-6-).

Fig:-6- A girl with diffuse mucocutaneous leishmaniasis.
L. braziliensis: It is the commonest species. All forms are zoonoses with
numerous reservoir hosts including forest rodents, marsupials in Brazil
and sloths and monkeys in Panama. Cutaneous and mucocutaneous
leishmaniasis with ulceration and lymphatic spread. The Brazilian form
(Espundia) produces destructive lesions of oronasopharyngeal mucosa
which may lead to death due to secondary infection and pneumonia.
Cutaneous infections known as (chiclero's ulcer) in Latin America is
particularly associated with forest workers who encounter sandflies while
collecting latex from chicle trees (to make chewing gum), the ulcer is
similar to an oriental sore, except when it occurs on the ear, where it may
erode the pinna. L. guyanensis produces forest yaws or (pian bois) , often
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with multiple lesions. L.panamensis is the least pathogenic member of this
group.
Pathology
Visceral leishmaniasis
The pathology of visceral leishmaniasis is due to blockage and destruction
of the reticuloendotheliial system with the most marked effects being seen
in the spleen, liver, lymph glands, bone marrow, and intestines. The spleen
is grossly enlarged and its cell packed with Amastigotes. The liver is
usually enlarged and has a mottled brownish appearance.There is often
fibrosis and cirrhosis of the liver in old untreated cases and there are
usually many parasites in kupffer cells. The bone marrow appears a dark
reddish colour with blood cell production becoming greatly depressed.
The patient becomes anaemic, leucopenic, and thrombocytopenic and
many amastigotes are found in the macrophages. The kidneys and lungs
are not usually heavily parasitized but the villi of the jejunum and
duodenum often become packed with infected macrophages. Lymph
glands are usually enlarged, particularly those of the mesenteries.
Cutaneous leishmaniasis
Following early massive monocytes and histocyte invasion , the ulcer is
then walled off or penetrated by macrophages, plasma cells, and
lymphocytes, usually resulting in a reduction of parasite numbers (partial
protection). This is followed by ulceration of the dermis and healing with
fibrosis and the formation of scar tissue except in those patients who
develop diffuse cutaneous leishmaniasis or leishmaniasis recidivans.
Recovery from infection provides life long immunity to re-infection with
the same parasitic but not necessarily to other Leishmania species or
subspecies.
Immune and blood changes in (visceral leishmaniasis)
In active visceral leishmaniasis there is a lack of a cell-mediated immune
response to leishmanial antigens and therefore the parasites multiply
rapidly. The CMI response is always poor in visceral leishmaniasis, so the
leishmanin test is invariably negative during the disease. It often becomes
positive after successful treatment. The antigenic stimulus of the countless
amastigotes is enormous, and The a humoral response with large amounts
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of polyclonal non-specific immunoglobulin especially IgG being produced
and also specific anti-leishmanial antibody. A high increase in the
production of immunoglobulin (IgM and IgG). Chiefly IgG , and only
some of this is specific (capable of combining with amastigotes) and even
this specifically reactive Ab is lacking in protective effect , perhapse
because most of the amastigotes are inaccessible to Ab because of their
intracellular habitat. The plasma proteins undergo marked changes, with a
reversal of the albumin:globulin ratio due largely to the elevation in the
gamma globulin. At the same time as the IgG level rises, the total globulin
level reflects it , often exceeding 4 or 5 g/dl. The albumin level often falls
at the same time, sometimes sufficiently to lead to oedema. Patients who
have recovered from visceral leishmaniasis are immune from reinfection
but relapse can occur. Anaemia typically feature of visceral leishmaniasis;
it is normochromic and normocytic in type. Although initially mainly due
to secondary hypersplenism, later there may also be marrow depression as
reflected by arelatively low reticulocytes count. There is also a leucopenia
, mainly of granulocytes and sometimes amounting to granulocytosis.
Ninety-five percent of cases when first diagnosed have a total white cell
count of less than 3000/l, and in 75% the count is less than 2000/l . Part
of this granulocytopenia is splenic in origin, part due to the effects of the
parasites on the marrow. The eosinophil count is invariably low. The
platelet count is also usually low, sometimes sufficiently low to lead to
purpura, spontaneous bruising and bleeding, especially from the gums.
Laboratory diagnosis:
Direct methods
Diagnosis is based on a history of exposure to sandfies, symptoms and
isolation of the organisms (amastigote) and identify them by microscopy,
or to culture material containing amastigotes on a medium Novy-Mac
Neal-Nicolle (NNN) which allows their growth and replication as spindle
shape (promastigotes) (Fig-7-), or by animal inoculation from the lesion
aspirate (material is best obtained from the spleen if the organ is large and
firm or bone marrow aspiration) . Splenic puncture in case of visecarl
leishmaniasis, undoubtedly an effective method for securing
reticuloendothelial cells for study , but it is a somewhat risky procedure.
Liver puncture is safer but possibly not productive. Sternal marrow
aspiration may likewise reveal the parasites and is considered by some the
diagnostic procedure of choice. In case of cutaneous leishmaniasis
material must be removed from the active edge of lesion because
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amastigoted available in the active edge only , then the material spread on
a slide dried ,fixed and stained or cultured such as in case of visceral
leishmaniasis.

Fig:-7- Promastigote from a culture(spindle shape).
Indirect methods
1- Leishmanin test (montonegro test) detects a delayed sensitivity
reaction to killed promastigotes injected intradermally. It is read after 48
hr, it is negative in acute stage of cutaneous leishmania , it is positive in a
high percentage of L. tropica infections and in more than 95 % of
L.braziliensis infections, it is negative in active Kala-azar, but it becomes
positive within 2 months following successful treatment . Apositive test
may be very useful in diagnosing recidiva cases, because the routine
histology from these lesions is often indistinguishable from Lupus
vulgaris.
2-Serological tests
Antibody detection can prove useful in visceral
leishmaniasis(IFAT,ELISA) but is of limited value in cutaneous disease,
where most patients do not develop a significant antibody response. Other
diagnostic techniques exist that allow parasite detection and/or species
identification using biochemical (isoenzymes), immunologic
(immunoassays), and molecular (PCR) approaches. Such techniques,
however, are not readily available in general diagnostic laboratories.
Prevention and Treatment: Simple cutaneous leishmaniasis will usually
heal without treatment, leaving the person immune to further infection
with that species of Leishmania. Thus, in many parts of the Middle East
and south Sudan, infections are deliberately encouraged on the buttocks of
babies in order to immunize them against further infections (thus avoiding
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disfiguring scars on the face). However, other forms of leishmaniasis are
extremely difficult to treat, usually requiring a long course of pentavalent
antimony drugs ,Sodium stibogluconate (Pentostam) is the drug of choice.
Treatment with pentamidine, amphotericine or allopurinol Should be to
persons unresponsive antimony compounds. Paromomycin may be
effective.Infection can be prevented by avoiding sandfly bites (eg. using
repellants or insecticides). Many forms of leishmaniasis are related to
specific human activities that bring man directly into contact with
sandflies.
Ciliates
Ciliates are a large and diverse group of protozoa. Most ciliates are free-
living and are found in a variety of habitats. Well-known ciliates include
Paramecium species, which are found in ponds throughout the world, and
Ichthyophthirius multifiliis, an ectoparasite of fish that causes white spot
disease (also called 'ick'). As the name implies, ciliates possess cilia at
some point during their life cycles. The cilia are generally arranged in
longitudinal rows and typically cover the surface of the organism. Ciliates
undergo both an asexual reproduction (ie, binary fission) and a sexual
reproduction involving conjugation .Ciliates are larger protozoans,
growing up to greater than 100m. They tend to have a rigid body shape
and move about by means of thousands of beating hairs called cilia. These
hairs are frequently too small to see, even at high magnification. There is
only one species of pathogenic ciliate known to parasitise humans :
Balantidium coli . This organism lives in the large intestine and causes
diarrhoea. Ciliates are widely spread as pathogens and commensals in
other animals. One species lives in the gut of termites and aids these
animals in digesting wood. Other species live in the stomach (or rumen) of
cattle and helps them digest the grass they eat. There is even a species that
lives in the gut of the cockroach.
Balantidiasis (Balantidium coli infection)
Balantidium coli is a ciliated protozoan, and it is also the largest human
protozoan. It is known to parasitize the colon, and pigs may be its primary
. This is a parasite primarily of cows, pigs and horses. The infection occurs
mostly in farm workers and other rural dwellers by ingestion of cysts in
fecal material of farm animals. Man-to-man transmission is rare but
possible. Balantidium coli , zoonotic intestinal infections protozoan .
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Etiology
Balantidium coli, a large ciliated protozoan parasite.
Morphology
The organism Ciliate (trophozoite) ; is a large (100 x 60 m) ciliate with
a macro- and a micro-nucleus (Fig-1-). Cyst; Large, measuring 50-60
m, thick walled (Fig-2-). Cilia may be seen in younger cysts.
Macronucleus visible in stained preparation.

Fig:-1- Balantidium Ciliate (trophozoite). Fig:-2- Balantidium cyst.
Epidemiology
Worldwide. Because pigs are an animal reservoir, human infections occur
more frequently in areas where pigs are raised. Other potential animal
reservoirs include rodents and nonhuman primates.
Transmission and Life Cycle
Cysts are the parasite stage responsible for transmission of balantidiasis
(1).The host most often acquires the cyst through ingestion of
contaminated food or water (2). Following ingestion, excystation occurs
in the small intestine, and the trophozoites colonize the large intestine (3).
The trophozoites reside in the lumen of the large intestine of humans and
animals, where they replicate by binary fission, during which conjugation
may occur (4). Trophozoites undergo encystation to produce infective
cysts (5). Some trophozoites invade the wall of the colon and multiply.
Some return to lumen and disintegrate. Mature cysts are passed with feces
(1).

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Clinical features and Pathology
B. coli usually lives as a non-pathogenic commensal in the large intestine
and produces no symptoms. The trophozoites will invade the intestinal
epithelium or rare occasions and produce ulceration. Clinically this results
in an acute diarrhea with mucus and blood (ie, dysentery). Symptoms and
pathogenesis of balantidiasis are similar to those seen in entamebiasis,
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including intestinal epithelial erosion. However metastatic lesions do not
occur (liver, lung and brain abscesses are not seen). Most cases are
asymptomatic . Clinical manifestations, when present mainly due to
mucosal ulceration may produce persistent diarrhea, or if the ulceration is
more extensive, dysentery will occur, abdominal pain, and weight loss.
Symptoms can be severe in debilitated persons. The trophozoites cause
colonic ulceration, just as those of E.histolytica.
Laboratory diagnosis
Diagnosis is based on detection of the large , majestically motile
trophozoites on microscopy of direct smear saline preparation of freshly
passed stool specimens or in tissue collected during endoscopy. Cysts are
less frequently encountered. Balantidium coli is passed intermittently and
once outside the colon is rapidly destroyed. Thus stool specimens should
be collected repeatedly, and immediately examined or preserved to
enhance detection of the parasite.
Treatment
The drug of choice is tetracycline, with metronidazole and iodoquinol as
alternatives. Tetracycline is contraindicated in pregnancy and in children
less than 8 years old.







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CHAPTER SEVEN (7)
Sporozoa
The Sporozoa (more correctly known as the Apicomplexans) are a diverse
range of parasites found in all parts of the body and in a wide variety of
animal hosts. They do not have a set body plan like the other parasitic
protozoans we have dealt with, although they are characterised by having
complex life-cycles with an alternation of sexual and asexual generations.
Many species are so small that they are parasites within the cells of their
host.
Blood Sporozoa
Malaria (Plasmodium species infection)
Malaria is a serious infectious disease spread by certain mosquitoes. It is most
common in tropical climates. It is characterized by recurrent symptoms of chills,
fever, and an enlarged spleen. The disease can be treated with medication, but it
often recurs. Malaria is endemic (occurs frequently in a particular locality) in
many third world countries. derived from mala aria (Italian for "bad air") and
formerly called marsh fever in English..It is a type of fever which is a
major cause of morbidity , caused by female Anopheles mosquito bite
which trasmits four types of parasites of genus Plasmodium - vivax, ovale,
falciparum,and malarae. Plasmodium falciparum is the most deadly.(In the
time taken to read this sentence out loud, one child will have died from
falciparum malaria in sub-Saharan Africa) .The recognized species
causing disease in humans are P. falciparum (which alone accounts for
80% of the recognized cases and ~90% of the deaths in infected persons
by malaria ). Other mammals (bats, rodents, non-human primates) as well
as birds and reptiles also suffer from malaria. However, the form of
malaria found in animals is usually different than that found in humans.
Only one form, P. malariae, can cause malaria in both humans and higher
primates. Only female mosquitoes are blood-feeders and therefore
transmit malaria. Males cannot transmit the disease. Malaria remains the
most important of the tropical diseases - widespread throughout the
tropics, but also occurring in many temperate regions. The disease exacts a
heavy toll of illness and death - especially amongst children in endemic
areas. It also poses a risk to business travellers, tourists and immigrants,
and imported cases of malaria are increasingly seen in nonendemic areas
such as Europe and North America, North Africa . Epidemics are frequent
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in rural areas experiencing intense economic development. Treatment and
control have become more difficult with the spread of drug resistant
strains of malaria, and insecticide resistant strains of the mosquito vectors.
Note; Infections with P. knowlesi and P. semiovale are also known to
cause malaria but are of limited public health importance.
Etiology
Single-celled protozoan parasites of the genus Plasmodium are responsible
for human malaria These are Four species infect man : Plasmodium
falciparum(the cause of malignant tertian malaria), Plasmodium vivax (the
most frequent cause of benign tertian malaria) Plasmodium ovale(the
other, less frequent, cause of benign tertian malaria) Plasmodium malariae
(the cause of benign quartan malaria).
Morphology
Malarial parasite ; An early immature trophozoites are generally ring
shaped of all species, but markedly seen in P.falciparum (Fig-1-), 1-2 m
in size. Although other mature forms (ameboid and band) of vivax (Fig-2-
) and malarae respectively easily seen and exist in blood film. The sexual
forms of the parasite (gametocytes) are much larger and 7-14 m in size.
P. falciparum is the largest and is banana shaped (Fig-3-) while others are
smaller and round. P. vivax causes stippling of infected red cells.

Fig:-1- Ring form trophozoit (P.Fal). Fig:-2- Ameboid form trophozoite
(P.vivax).

Fig:-3- P.Falciparm gametocyte (banana form).
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Trophozoite
P.falciparum (ring form) (Fig-1-): small and delicate with thin ring and
dark red staining chromatin dot. May have double chromatin dots.
Note: Parasites may lie on red cell membrane (accole form) .
Note: RBC cells containing late stage trophozoite often show irregular
red-mauve staining Maurers dots (clefts).
Note: In areas where there is drug resistant strains may appear thick and
distorted.
P.vivax : (Fig-2-) Most are large and amoeboid. In thick films the
cytoplasm appears fragmented. Fine pigment granules may be seen in
cytoplasm(Schuffner dots).
P.malariae : Thick, compact and densely staining. Yellow brown pigment
is characteristically seen in late trophozoites. Band-forms (trophozoite
spread across the cell) containing pigment can sometimes be seen in thin
films. Bird-eye form (occasionally seen in which a ring of cytoplasm
surrounds a centrally placed chromatin dot.
P.ovale: Small and compact (resemble P.malariae trophozoite in thick
blood film), but usually very little pigment seen. Schuffner (James) dots
are present surrounding the parasite in RBC, like P.vivax.
Schizont (dividing form)
P.falciparum : Very rarely seen. If seen, they are often small and
immature, containing only two or four merozoites and clumps of dark
coloured pigment.
P.vivax: Large, round or irregular in form. Can be seen easily in blood
film. Mature schizontes contain 24 or more merozoites and a small amount
of pigment.
P.malariae: Small and compact with neatly arranged merozoites. Mature
schizonts contain up to 12 merozoites. Yellow brown pigment is always
seen.
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P.ovale: Small with little pigment. Mature schizonts contain up to 10
merozoites.
Gametocyte
P.falciparum: (Fig-3-) Typically cresent (banana) shaped with rounded or
pointed ends but oval forms may also be seen
P.vivax: Large, round or irregular in form. Small forms may also be seen.
Contain scattered pigment granules.
P.malariae: Small, round or oval, and compact. Nucleus usually lies to
one side. Yellow brown pigment easily seen.
P.ovale: Small and usually round. They are often difficult to distinguish
from late stage trophozoites.
Epidemiology
Malaria generally occurs in areas where environmental conditions allow
parasite multiplication in the vector (Map-1-). Thus, malaria is usually
restricted to tropical and subtropical areas and altitudes below 1,500 m. P.
falciparum (malignant tertian malaria) and P. malariae (quartan malaria)
are the most common species of malarial parasite and are found in Asia
and Africa. P. vivax (benign tertian malaria) predominates in Latin
America, India and Pakistan, whereas, P. ovale (ovale tertian malaria) is
almost exclusively found in Africa .There are an estimated 267 million
global cases of malaria leading a mortality of 1-2 million people per year,.
Estimated number of clinical cases: 107 million per year ,Number of
people considered at risk: 210 million , and Number of countries affected:
103 .

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Map:-1- Malaria endemic countries
Transmission
Malaria parasites are inoculated by the bite of infected female mosquitos
of the genus Anopneles (Fig-4-)(male mosquitos do not bite , feeding on
plant juice). The parasites multiply tremendously in the liver and in
infected red blood cells. Vector mosquitos become infected by feeding on
the blood of infected people, and the parasites then undergo another phase
of reproduction in the infected mosquito.




Fig:-5- Anophelus mosquito (malaria vector)
Life Cycle
The malaria parasite life cycle involves two hosts. During a blood meal,
Infected female Anopheles mosquitoes carry Plasmodium sporozoites in
their salivary glands. Once an infected mosquito pierces a person's skin to
take a blood meal, which they usually do starting at dusk and continuing
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throughout the night, the sporozoites enter the person's body via the
mosquito's saliva, (1). Sporozoites migrate to the liver where they
multiply within hepatic liver cells asexually. Development in the hepatic
cell takes 6 to 15 days depending on the species.
(2) Within hepatic cells the parasite replicates to produce hundreds or
thousands of merozoites , liver schizonts (3), which rupture and release
merozoites following rupture of the hepatic cell (schizonts), are released
into the blood stream and invade red blood cells.
(4). Some of the sporozoites in vivax and ovale malaria do not develop
into hepatic stage merozoites immediately, but produce dormant stage
[hypnozoites] that remain dormant for several months (typically, from 6
to 12 months, but sometimes up to 3 years). After a period of dormancy,
they reactivate and produce merozoites (relapse). Hypnozoites are
responsible for long incubation and late relapses in these two species of
malaria. (exo-erythrocytic schizogony (A). Within the red blood cells
parasites undergo asexual multiplication , periodically breaking out of the
exploited red blood cells to invade red blood cells and start the
amplification cycle anew. The classical description of waves of fever
coming every two (Plasmodium falciparum) or three days (Plasmodium
vivax) arises from simultaneous waves of merozoites breaking out of red
blood cells during the same day. the in the erythrocytes (erythrocytic
schizogony (B). Merozoites infect red blood cells (5). The ring stage
trophozoites mature into schizonts, which rupture releasing merozoites
(6). Some merozoites differentiate into sexual erythrocytic stages
(gametocytes)turn into male and female gametocytes. If a mosquito
pierces the skin of infected person, it potentially picks up gametocytes
with the blood, Some parasites (7). Blood stage parasites are responsible
for the clinical manifestations of the disease.
The gametocytes, male (microgametocytes) and female
(macrogametocytes), are ingested by an Anopheles mosquito during a
blood meal (8). fertilization occurs in the mosquito's gut which means the
mosquito is the definitive host of the disease.The parasites multiplication
in the mosquito is known as the sporogonic cycle (C). While in the
mosquito's stomach, the microgametes penetrate the macrogametes
generating zygotes (9). The zygotes in turn become motile and elongated
(ookinetes) (10)which invade the midgut wall of the mosquito where they
develop into oocysts (11). The oocysts grow, rupture, and release
sporozoites (12), New sporozoites develop and travel to the mosquito's
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salivary gland, completing the cycle. Inoculation of the sporozoites into a
new human host perpetuates the malaria life cycle (1).


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Relapse: Return of signs and symptoms of a disease after a period of
improvement.
Clinical features
Malaria begins as a flu-like illness 8-30 days after the infected mosquito
bite. Typical cycles of fever, shaking chills and drenching sweats may
then develop. The time interval between mosquito bite and development
of malaria is 13-14 days except for P. malariae (35 days) . Initially
symptoms resemble those of a minor viral illness. These include: Lack of
sense of well being ,Headache,Fatigue,Abdominal discomfort,Muscle
aches, pains in the bones and joints, chilly sensations, followed by fever
Nausea and vomiting .The symptomatology of malaria depends on the
parasitemia, the presence of the organism in different organs .
P.falciparum causes sequestration of capillary vasculature in the brain,
gastrointestinal and renal tissues (see below). Chronic malaria results in
splenomegaly, hepatomegaly and nephritic syndromes. Associated
Symptoms mild abdominal ,discomfort Constipation , Diarrhoea. In many
parts of Africa, where malaria has long been highly endemic, people are
infected so frequently that they develop a degree of acquired immunity,
and may become asysmptomatic carriers of the infection.
Common clinical features
All the four malaria species have many clinical features in common
1-Fever: often irregular. The pattern of regularly periodic fever often does
not occur until the illness has continued for a week or more . It depends on
(synchronized schizogony). Pattern of fever may be characteristic in
malaria, but it is a mistake to suppose that they must conform to the
textbook pattern. A daily fever peak corresponding to rupture of the
infected red cells and liberation of merozoites , and are usually seen only
for a few days; apparently within this time all broods of parasites become
synchronized, and thereafter the fever cycle exhibits tertian or Quartan
periodicity depends on species. Falciparum malaria may likewise exhibit
quotidian or irregular periodicity during the first few days of the primary
attack. Tertian fever is characteristic of vivax and ovale malaria. Quartan
fever is seen in malaria caused by P.malariae. Subtertian fever, seen in
falciparum malaria, is so called because the cycle may more nearly
approach 36 than 48 hours. Note: Hyperpyrexia may develop as part of
an attack of cerebral malaria or in the course of an apparently
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uncomplicated attack of falciparum malaria; as the result of injury to the
heat-control center in the hypothalamus there is a rapid rise in temperature
to 107 F (41 C)or higher and death quickly ensues.
2- Anaemia: This is haemolytic in type . It is usually most sever in
P.falciparum because in this infection, RBC of all ages can be invaded ,
and even unparasitized red cell may under go haemolysis . also in
P.falciparum the parasitaemiia much higher than in other malarias , the red
cell count dramatically severly may fall in sever infections. Anaemia is
usually not sever in vivax malaria and is still less pronounced in quartan
infections.
Note-In this condition the reticulocytosis brisk is absent because of bone
marrow suppression due to malaria toxin.
3-Splenomegaly: The spleen enlarges early in the acute attack in all sorts
of malaria. In chronic malaria, when the patient has had many attacks, the
spleen may be of enormous size and lead to secondry hyperslenism.
4-Jaundice: A mild jaundice due to haemolysis may occur in all types of
malaria. Sever jaundice only occurs in P.falciparum infection, and is due
to specific liver involvement. The symptoms of the falciparum malaria
syndrome known as bilious remittent fever include acute epigastric pain,
nausea and vomiting, and marked enlargement and tenderness of the liver,
with jaundice appearing on a bout the second day. Diarrhea , a high
remittent fever, and oliguria are usually seen , and death may result from
renal or hepatic failure.
Important Notes:The symptoms of uncomplicated malaria can be rather
non-specific and the diagnosis can be missed if health providers are not
alert to the possibility of this disease. Since untreated malaria can
progress to severe forms that may be rapidly (<24 hours) fatal, malaria
should always be considered in patients who have a history of exposure
(mostly: past travel or residence in disease-endemic areas). The most
frequent symptoms include fever and chills, which can be accompanied by
headache, myalgias, arthralgias, weakness, vomiting, and diarrhea. Other
clinical features include splenomegaly, anemia, thrombocytopenia,
hypoglycemia, pulmonary or renal dysfunction, and neurologic changes.
The clinical presentation can vary substantially depending on the infecting
species, the level of parasitemia, and the immune status of the patient.
Infections caused by P. falciparum can progress to severe, potentially fatal
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forms with central nervous system involvement (cerebral malaria), acute
renal failure, severe anemia, or even adult respiratory distress syndrome
(see below). Complications of P. vivax malaria include splenomegaly
(with, rarely, splenic rupture), and those of P. malariae include nephrotic
syndrome( which unaffected by the administration of steroids).
Nephrotic syndrome: A condition in which protein leaks through the
damaged walls of glomeruli and is excreted in large amounts in urine .
Loss of protein leads to reduced levels of albumin in the blood which
result in oedema. The nephrotic syndrome is found in glomerulonephritis
associated with permeability of the glomerular basement membrane,
infection with P.malariae, diabetic nephropathy, systemic lupus
erythematosus, and following treatment with certain drugs.
In endemic area malaria is an important cause of stillbirths, infant
mortality and low birth weight in pregnant women infection (see below).
Malaria paroxysm phases
The chill and fever follow a cyclic pattern called paroxysm ; It has an
abrupt onset. Characterised by classical three phases of fever):
The malarial paroxysm is most dramatic and frightening. It begins with
Cold phase A chilly sensation that progresses to teeth chattering, overtly
shaking chill and peripheral vasoconstriction resulting in cyanotic lips and
nails . The chill, varies from moderate sensation of cold to the intense,
bed-shaking chill , lasting up to one 1 hour , and the fever (to 104)(40 C).
At the end of this period. Hot phase - The body temperature begins to
climb and reaches 103-106 degrees F (39- 41degrees C). lasting for 3-4
hours. Fever is associated with hot flushes and severe headache, nausea
(vomiting) and convulsions. Followed by Wet phase The sweating stage
usually lasting for 1-4 hours, characterized by profuse sweat, during the
course of which the temperature falls to normal over a period of an hour or
so. The sweating stage is usually followed by sleep, and when the patient
awakens he generally feels well. Each paroxysm is due to the rupture of
infected erythrocytes and release of parasites. If the infection is left
untreated . Fever paroxysms occur every 48 hours(tertian malaria) in
case of P.vivax, P.ovale,every 72 hours (quartan malaria)in case of P.
malariae. The pattern of fever in P. falciparum infection is erratic.
Hyperpyrexia may complicate malaria, especially in attacks of
P.falciparum . ,Paroxysms with rigors are more common in P. vivax & P.
ovale than in P. falciparum and P. malariae malaria. True rigors are
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unusual in naturally acquired falciparum malaria. As the infection
continues the spleen and liver enlarge and anemia develops. The patient
loses weight. If no treatment is given the natural infection stabilizes for
several weeks or months and then gradually resolves.Without treatment,
all species of human malaria may ultimately result in spontaneous cure
except with P. falciparum which becomes more severe progressively and
results in death.
Note:In rare cases , the patient may be afebrile in the presence of a very
sever P. falciparum infection.
Malaria in Pregnancy; There is increased risk if severe Falciparum
malaria infection in the second and third trimester of pregnancy. It is an
important cause of fetal death and results in high maternal mortality In
areas of intense transmission, it may be associated with low birth weight.
The infected mothers may be asymptomatic.
Malaria in children; The majority of childhood malarial infections
present with fever and malaise. In addition to the clinical features
mentioned for adults malaria in children may lead to Convulsions ,Coma,
Hypoglycaemia Metabolic acidosis and Severe anaemia .
P.Falciparum
It is the most dangerous of all malaria species .Following a single
exposure to infection , the patient will either die in the acute attack
(common event) or survive with the development of some immunity and
residual anaemia. Attacks may recur over the course of the next year (a
phenomenon called Recrudescence {(A new outbreak or the return of a
disease) due to the presence of small numbers of parasitized RBC ,
remaining in the blood from previous attacks , this phenomenon may also
occur in P.malariae over a long period)} . In that event, after 5 years of
repeated challenge, a high degree of immunity to clinical illness develops.




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P.falciparum Symptoms
These symptoms and complication are mainly due to microcirulatory
arrest in many organs (see below) (Table-1-).
Table:-1- Summary of the symptoms and diferential diagnosis
Organs most
affected
Main symptoms or
signs
Typical misdiagnosis
Stomach and
intestines
Vomiting and diarrhea Gastric flu,
cholera(diarrhea is not
bloody
Brain Delirium,
Disorientation, Stupor,
Coma, Convulsion,
Focal neurological signs
Encephalitis, Meningo-
encephalitis
Kidneys Renal failure, with or
without oliguria or
haemoglobinuria
Nephritis
Liver Jaundice and fever Hepatitis
Lung Pulmonary oedema Pneumonia, heart
failure
Complications
Cerebral Malaria
Cerebral malaria is the most severe neurological complication of
Plasmodium falciparum malaria. Even though this type of malaria is most
common in children living in sub-Saharan Africa, it should be considered
in anybody with impaired consciousness that has recently travelled in a
malaria-endemic area. Cerebral malaria has few specific features, but there
are differences in clinical presentation between African children and non-
immune adults. The manifestation develop slowly with increasing
headache and drowsiness over several days or present as a coma , fits or
mental disturbances of sudden onset. Subsequent neurological
impairments are most common and severe in children. In majority of the
cases, examination of thick and thin films of the peripheral blood will
reveal malarial parasites. The presence of malarial pigment in monocytes
is a useful indicator of the diagnosis of malaria, especially in anaemic
children and in patients with severe malaria associated with absent or low
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parasitaemia. Lumbar puncture should routinely be performed to rule out
possibility of bacterial meningitis.
Note: Other factors usually present such as convulsions, acidosis, or
hypoglycaemia can also impair consciousness.
There may be signs of meningeal irritation;. Common . Symptoms are
quite varied, depending on the brain areas affected. If untreated usually
progress to coma, brain stem failure and death, if recovery does occur .
Sequestration of infected erythrocytes within cerebral blood vessels seems
to be an essential component of the pathogenesis.The pathogenesis
remains unclear, but localized disturbances of intracerebral
circulation(microcirculatory arrest see below) seem likely the main
cause. The sudden onset of coma (6-96 hours shorter in children). In a
patient known to be suffering from falciparum malaria, or in an apparently
healthy person who is in or has recently returned from a malarious area,
should always suggest cerebral malaria and requires emergency treatment ,
fatality rate 20%.
Cerebral malaria is also known as 'symmetric encephalopathy' because
of presence of symmetrical upper motor neurone signs. Muscle tone is
increased and tendon reflexes are usually brisk with patellar and ankle
clonus, along with extensor plantar responses. Abdominal reflexes are
usually absent. Extensor posturing suggesting brainstem dysfunction,
either due to cerebral malaria or profound hypoglycaemia, is a common
and important sign. The cause of death is not apparent most of the time.
Progressive deterioration of brainstem function may lead to cardiac and
respiratory arrest.
Note; The studies in Gambia and Thailand on P.falciparum malaria,
demonstrated that in cerebral malaria.
-Retinal hemorrhages are common.
-Hypoglycemia can occur within 2-3 days of treatment with quinine(see
below).
-Septicemia is a common complication requiring urgent treatment.
Malarial infection is associated with immunosuppression (see below).
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-Neurological complications are transient, but 10-18% develop
neurological sequels (see below) , especially in children.
Acute renal failure is an important complication. In falciparum malaria,
proteinuria, with hyaline and granular casts in the urine, is common .
Rarely there may be oliguria or anuria, usually accompanying an attack of
blackwater fever.
Hypoglycemia
Hypoglycaemia is seen commonly in patient treated with iv quinine , but it
may occur in untreated falciparum malaria. It seen particularly in pregnant
women and children (may be due to glycogen depletion).
Blackwater fever
Blackwater fever is the name given to the syndrome which sometimes
occurs in some patients with P.falciparum malaria when sever
intravascular haemolysis is associated with haemoglobinuria and renal
failure. Blackwater fever usually is seen in conjunction with an attack of
falciparum malaria, generally in patients who have had previous attacksof
malaria. The passage of reddish or red-brown urine. It signal a bout
intravascular hemolysis, which may occur once or repeatedly and may
lead to sever renal tubular damage and anuria. The cause is unknown;
hypothesis include quinine sensitivity, G6PD deficiency in person treated
with primaquine and related drugs, and autohemolysis on the basis of
antibodies formed against altered infected red cells. The difference
between blackwater fever and G6PD deficiency (common in Africans) , in
case of blackwater fever the entire red cell mass may be destroyed and the
outlook is obviously grave, in the meantime in G6PD haemolysis usually
only affects the older cells, so ceases when the haemoglobin has dropped
to about 6 g/dl. Jaundice may be marked in both conditions.
Algid syndrome
The patient with sever P.falciparum malaria may go into medical shock,
the so-called (Algid malaria or syndrome), sudden drop in blood pressure
accompanied with impairment of vascular perfusion with hypothermia.
Symptoms of generalized vascular collapse and shock develop quickly.
This syndrome may be due to gram- negative bacterial septicaemia,
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pulmonary edema, massive gastrointestinal hemorrhage, intra-abdominal
hemorrhage as a result of splenic rupture.
Pulmonary edema
This is rare but fatal complication , it frequently develop rapidly in an
oliguric or anuric patient accompanies renal failure common when there is
heavy parasitaemia and during pregnancy.
Dysentry
Plugging of the mucosal capillaries with parasitized red blood cell may
lead , in falciparum malaria , to a watery diarrhea so profuse as to suggest
cholera . Blood containing parasitized red cells may be found in the stools.
The diarrhea or dysentery is usually accompanied by nausea and vomiting.
Shock
When shock complicates falciparum malaria, the patient is pale, with a
cold and clammy skin, thin fast pulse, and low blood pressure. There is
often acute abdominal pain, vomiting, and diarrhea. The cause may be
primary adrenal failure, through parasite-induced ischaemia or infarction,
or it may be secondary to reduced blood volume and blood pressure
caused by widespread vascular injury.
Tropical Splenomegaly Syndrome (Hyper-reactive splenomegaly)
In malaria endemic areas, a chronic form of splenomegaly can be found .
Person with hyper-reactive malaria splenomegaly are immune adults in
malarious areas who have gross and chronic slenomegaly with an over-
production of IgM, high levels of malaria antibody and circulating
immune complexes, and moderately enlarged liver , malaria hyper-
reactive splenomegaly responds to prolonged treatment with anti-malarial
drugs. It is thought to be due to inadequate or defect in suppressor T-
lymphocyte that control B-cell activation. The tropical splenomegaly
syndrome is thought to be due to overactivity of B lymphcytes stimulated
by malaria antigens.


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Pathology and Immunology
The various species of malarial parasites differ in their ability to infect red
cells. Merozoites of P.vivax and P.ovale are able to invade only
reticulocytes, whereas those of P.malariae are limited to senescent cells
nearing the end of their life span. P. falciparum is able to invade all ages
of red cells indifferently, and consequently infections by this parasite
result early in considerable degrees of anemia. Mechanisms of red cell
invasion have been studied by means of electron microscopy. The apical
end of the parasite (merozoite) touch the surface of the erythrocyte, which
invaginates slightly . A junction forms between merozoites and
erythrocyte; it becomes ringlike and expands as the parasite invades the
red cell and then in turn contracts to seal off the parasite within its
vacuole. There is suggestive evidence that anterior organelles within the
merozoite, known as Rhopteries, play an active part in the invasion
process . The entire sequence of attachment and penetration takes only
about 30 seconds. The initial attachment may require specific determinants
on RBC surface. Glcophorin A is apparently involved in the attachment
process of P.falciparum. Human erythrocyte band 3 , amajor membrane
protein, has also been implicated as a receptor for P. falciparum invasion.
Symptoms of malaria are due to the release of massive number of
merozoites into the circulation (Mature schizonts rupture from the red
cells releasing merozoites, malaria pigments and toxins into the plasma.
The entry of toxic metabolites into the blood circulation of the host cause
fever and a malarial attack). Infection results in the production of
antibodies which are effective in containing the parasite load. These
antibodies are against merozoites and schizonts. The infection also results
in the activation of the reticuloendothelial system (phagocytes). The
activated macrophages help in the destruction of infected (modified)
erythrocytes and antibody-coated merozoites. Cell mediated immunity
also may develop and help in the elimination of infected erythrocytes.
Malarial infection is associated with immunosuppression. The parasite is
relatively protected from attack by the body's immune system because for
most of its human life cycle it resides within liver and blood cells and is
relatively invisible to immune surveillance. However, circulating infected
blood cells are destroyed in the spleen.


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Pathogenetic processes (Cerebral malarae)
The nature of the pathogenetic processes leading to the cerebral malarae
complications, though of many theories and debates is still poorly
understood. The specially unpleasant and dangerous effects of
P.falciparum malaria are related to the occurrence of schizogony in deep
capillaries, the red cells which harbour the schizonts become physically
changed , and tend to adhere to the internal lining of the capillaries. This
together with changes in the capillary walls themselves, has the effect of
producing microcirculatory arrest. And the P. falciparum parasite
displays adhesive proteins on the surface of the infected blood cells,
causing the blood cells to stick to the walls of small blood vessels, thereby
sequestering the parasite from passage through the general circulation and
the spleen. Although the red blood cell surface adhesive proteins (called
PfEMP1) are exposed to the immune system they do not serve as good
immune targets because of their extreme diversity; there are at least 50
variations of PfEMP1 within a single parasite. Like a thief changing
disquises or a spy with multiple passports. By the time the human immune
system learns to recognize the protein and starts making antibodies against
it, the parasite has switched to another form of the protein, making it
difficult for the immune system to keep up. In these patients small
cerebral vessels are packed with parasitized red blood cells. The degree of
sequestration of parasitized erythrocytes in the cerebral microvasculature
correlates with the depth of coma. Also Electron-dense knobs are present
on the surface of parasitized red blood cells, close to their point of contact
with endothelial cells. Numerous petechial ring haemorrhages are seen in
the white matter. These haemorrhages result from the rupture of
endarterioles proximal to the occlusive plugs of parasitized red blood
cells. High levels of cytokine 'tissue necrosis factor' (TNF) have been
found in the plasma of patients with malaria. Recent observations suggest
that TNF upregulates the nitric oxide synthetase activity. It is possible that
large amount of nitrous oxide is produced locally at the sites of
sequestered parasites. This nitrous oxide diffuses across the wall of the
affected cerebral vessels into the brain, where it interferes with the activity
of calcium influx mechanisms, inducing coma in a manner analogous to
some anaesthetics. This aspect of P.falciparum pathogenesis is only
signifigant in people with little immunity to the infection.
Microcirculatory arrest in P.falciparum manfest itself in different ways
(see clinical features above).

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Biological resistance to malaria

Sickle cell anemia and other genetic effects;Carriers of the sickle cell
anemia heterozygote gene are protected against malaria because of their
particular hemoglobin mutation; this may explains why sickle cell anemia
is particularly common among people of African origin. They have a
specific variant of the beta-globin gene. Some scientists hypothesize that
another hemoglobin mutation, which causes the genetic disease
thalassemia, may also give its carriers an enhanced immunity to malaria.
Another disease which is linked to protection against malaria is glucose-6-
phosphate dehydrogenase deficiency (G6PD). It protects against malaria
caused by Plasmodium falciparum as the presence of this enzyme is
critical to survival of these parasites within red blood cells. It is thought
that humans have been affected by malaria for about 50,000 years, and
several human genes responsible for blood cell proteins and the immune
system have been shaped by the struggle against the parasite.Resistance to
vivax malaria is naturally found in persons whose red cells lack the red
cell Duffy anti-gens (Fy
a +)
. The glycoprotein receptors which P.vivax
needs to attach to and invade red cells are missing on Duffy negative (Fy
a -
)
red cells. The protection is absolute and afforded only to homozygotes.

Laboratory diagnosis
Direct diagnosis(blood films)
The gold standard for the diagnosis of malaria is microscopic examination
of blood films, because each of the four major parasite species has
distinguising physical characteristics visible under a microscope. Two
sorts of blood films are traditionally used. Thin films are similar to usual
blood films and allow the microscopist to tell what species the malaria is,
because the appearance of the parasite is best preserved in this preparation.
Thick films allow the microscopist to screen a larger volume of blood and
are about eleven times more sensitive than the thin film, so picking up low
levels of infection is easier on the thick film, but the appearance of the
parasite is much more distorted and therefore distinguishing between the
different species can be much more difficult. Microscopic diagnosis can
be difficult because the early trophozoites ("ring form") of all four species
look identical. The biggest pitfall in most laboratories in developed
countries is leaving too great a delay between taking the blood sample and
making the blood films. As blood cools to room temperature, male
gametocytes will divide and release microgametes: these are long sinuous
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filamentous structures that can be mistaken for organisms such as
Borrelia. If the blood is kept at warmer temperatures, schizonts will
rupture and merozoites invading erythrocytes will mistakenly give the
appreance of the accol form of P. falciparum. If P. vivax or P. ovale is
left for several hours in EDTA, the build up of acid in the sample will
cause the parasitised erythrocytes to shrink and the parasite will roll up,
simulating the appearance of P. malariae. This problem is made worse if
anticoagulants such as heparin or citrate are used. Romanovski's stain or a
variant stain is usually used. Some laboratories mistakenly use the same
stain as they do for routine haematology blood films (pH 6.8): malaria
blood films must be stained at pH 7.2, or Schffner's dots and James's dots
will not be seen.
Note: Two new techniques to speed the laboratory diagnosis of malaria
show promise as of late 2002. The first is acridine orange (AO), a staining
agent that works much faster (3-10 min) than the traditional Giemsa stain
(45-60 min) in making the malaria parasites visible under a microscope.
The second is a bioassay technique that measures the amount of a
substance called histadine-rich protein II (HRP2) in the patient's blood. It
allows for a very accurate estimation of parasite development. A dip strip
that tests for the presence of HRP2 in blood samples appears to be more
accurate in diagnosing malaria than standard microscopic analysis.

Important notes:

1- Malaria can not be excluded by a single negative blood film, at least
three , taken at intervals, must be examined.
2- A positive blood film does not prove the patient is suffering from
malaria, because parasitaemia may be entirely asymptomatic in the
indigenous population of endemic areas.
3- white blood cells; leukopenia of 3000 per mm
3
with a relative
monocytosis characterizes the afebrile periods, while there may be
leukocytosis during the paroxysm.
Serodiagnosis
It is of no use for diagnosis of the acute attack. The main use of
serodiagnosis is in excluding malaria in a patient suffering from recurrent
bouts of fever, and malaria parasites not exist (in suspected individuals).
The most commonly method is indirect flurescent antibody test(IFAT).




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Treatment

The treatment of a patient with malaria is supportive and specific.
Ideally patients with sever malaria should be treated in an intensive care
unit . With malaria anemia, exchange transfusion may be life-saving if
25% of erythrocytes are parasitized. Pregnant women , especially
primigravida, are particularly at risk of developing severe malaria.

Supportive treatment

1-Reducing the temperature if hyperpyrexia is present .
2-Rehydration, especially when vomiting and diarrhea have been
prominent.
3-Monitoring renal output and taking corrective measures if necessary.
4-Monitoring the haemoglobin, and look if the patient deserve blood
transfusion.
5- Terminating fits with appropriate anticonvulsant therapy.
6-Monitoring of blood glucose and correction of hypoglycaemia where
necessary.
7- Start antimalarial drugs ( see below)
Specific chemotherapy
Specific treatment is directed to terminating the parasitaemia as rapidly as
possible.
There are several families of drugs used to treat malaria. Chloroquine was
the antimalarial drug of choice for many years in most parts of the world.
However, resistance of Plasmodium falciparum to chloroquine has spread
recently from Asia to Africa, making the drug ineffective against the most
dangerous Plasmodium strain in many affected regions of the
world.Treatment is effective with various quinine derivatives , such drugs
may include quinine sulphate, mefloquine and primaquine, or halofantrine,
depending on resistance patterns in the area where the infection was
contracted. Drug resistance, particularly in P. falciparum and to some
extent in P. vivax is a major problem.
Chloroquine-resistant P.falciparum: oral quinine sulfate combined with
pyrimethamine-sulfadoxine or with a tetracycline or with clindamycin;
oral mefloquine or halofantrine are alternatives; Quick treatment is of the
utmost importance because life-threatening disease can develop within
hours.



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Cerebral malaria treatment

For the treatment of cerebral malaria, antimalarial drugs are given by
intravenous infusion to clear the parasitaemia in the shortest possible
period. Quinine is currently considered the drug of choice. If an
intravenous preparation of quinine is not readily available, quinidine
gluconate can be used to initiate treatment. The practice of using
intravenous route is often difficult to practice in children . One recent
study has confirmed efficacy of intramuscular administration of quinine in
children with cerebral malaria. Another important point in the
management is to achieve therapeutic plasma concentrations of
antimalarial drugs as quickly as possible. This can be done by giving
initial loading dose; which can safely be given in patients with renal and
hepatic dysfunction and in pregnant women. When the patients start taking
orally, antimalarial drugs should be administered by this route .
Artemether and artesunate are two derivatives of traditional Chinese
antimalarial drug qinghaosu (artemisinin). These derivatives are most
rapidly acting and potent of all the antimalarial drugs. Two recently
published reports of controlled studies comparing quinine with artemether
proved superiority of later drug in children as well as in adults.
Artemisinin derivatives are simple to administer by intramuscular route
and have no apparent local or systemic side effects. Quinine causes
hypotension if given too quickly by intravenous injection, and it also
prolongs ventricular repolarization (prolongation of QT interval) seen in
electrocardiography. The intramuscular administration of quinine is often
painful and causes local tissue damage, which sometimes results in
abscess formation and occasionally may produce tetanus. In experimental
studies on primates, artemether produced an unusual and selective pattern
of damage to certain brain-stem nuclei (auditory).
Hypoglycaemia is an important complication of falciparum malaria. It
occurs in three different groups of patients : (1) young patients especially
children with severe disease; (2) patients treated with quinine or quinidine,
as a result of a quinine-induced hyperinsulinaemia; (3) pregnant women,
either on admission or following quinine treatment. The clinical picture
includes deteriorating consciousness, generalized seizures, extensor
posturing, shock and coma. The diagnosis is easily overlooked because all
these clinical features also occur in cerebral malaria itself. Deterioration in
consciousness may be the only sign. On suspicion, the possibility of
hypoglycaemia should be confirmed by biochemical testing, especially in
the high risk groups. In an unconscious patient, glucose should regularily
be given to prevent hypoglycaemia. Use of dexamethasone is contra
- 121 -

indicated in cerebral malaria. In a controlled study there was no evidence
of benefit, but the duration of unconsciousness was prolonged, and there
was an increased incidence of infection and gastrointestinal bleeding in
dexamethasone treated group. Similarly, mannitol has no place in the
management of cerebral malaria, because usually there is no evidence of
cerebral oedema. The successful use of exchange transfusion has been
reported in patients of severe falciparum malaria. Exchange transfuion can
be recommended for patients having parasitaemia exceeding 10%, and
who are severely ill.

In Cerebral malaria treatment we should focus on other serious systemic
complications may contribute to coma, such as hypoglycaemia,
hyperpyrexia, severe anaemia, shock, renal failure and pulmonary oedema.
The prognosis of cerebral malaria is poor, even under optimal conditions
of care. Mortality in children still ranges from 10 to 30% depending upon
the initial coma score. Deaths from cerebral malaria usually occur within
first 24 hours of admission to the hospital, but occasional late deaths are
also encountered. Some patients make a rapid recovery but deterioration in
conscious level and recurrent episodes of convulsions and hypoglycaemia
may occur after an initial period of apparent improvement.
Despite adequate treatment, 10% to 18% of survivors develop
neurological sequelae in the form of psychosis, ataxia, hemiplegia, cortical
blindness, aphasia and extrapyramidal syndrome. These sequelae are more
common in children.
Prevention and control: (1) Avoid bites of anopheline mosquitos by
wearing clothing which limits the amount of exposed skin, and through the
use of repellents, mosquito nets, fumigant coils or insecticidal sprays (2)
When exposure is inevitable, use prophylactic drugs such as chloroquine
or, in areas of high transmission of resistant falciparum parasites,
mefloquine or doxycycline. In endemic areas, malaria control relies on
diagnosis and prompt treatment of infected people, plus measures to
reduce mosquito transmission of infections. Depending on local
conditions, this may include spraying houses with residual insecticides,
and modifying aquatic breeding sites to make them unsuitable for
development of anopheline mosquito larvae.Persons who have been in a
malaria risk area, are not allowed to donate blood for a period of time after
returning from the malarious area. Persons who are residents of
nonmalarious countries are not allowed to donate blood for 1 year after
they have returned from a malarious area. Persons who are residents of
malarious countries are not allowed to donate blood for 3 years after
- 122 -

leaving a malarious area. Persons who have had malaria are not allowed to
donate blood for 3 years after treatment for malaria.

Vaccination

Vaccines for malaria are under development.

Prophylactic drugs

Several drugs, most of which are also used for treatment of malaria, can be
taken preventatively. Generally, these drugs are taken daily or weekly, at a
lower dose than would be used for treatment of a person who had actually
contracted the disease. Use of prophylactic drugs is seldom practical for
full-time residents of malaria-endemic areas, and their use is usually
restricted to short-term visitors and travellers to malarial regions. This is
due to the potentially high cost of purchasing the drugs, because long-term
use of some drugs may have negative side effects, and because some
effective antimalarial drugs are difficult to obtain outside of wealthy
nations. Quinine was used starting in the seventeenth century as a
prophylactic against malaria. The development of more effective
alternatives such as quinacrine, chloroquine, and primaquine in the
twentieth century reduced the reliance on quinine. Today, quinine is still
used to treat chloroquine resistant Plasmodium falciparum, as well as
severe and cerebral stages of malaria, but is not generally for malaria
prophylaxis.
Modern drugs used preventatively include mefloquine (Lariam) and
atovaquone proguanil hydrochloride (Malarone). The choice of which
drug to use is usually driven by what drugs the parasites in the area are
resistant to, as well as side-effects and other considerations. The
prophylactic effect does not begin immediately upon starting taking the
drugs, so people temporarily visiting malarial areas usually begin taking
the drugs one to two weeks before arriving, and continue taking them for a
similar amount of time after leaving (see below).
In choosing an appropriate chemoprophylactic regimen before
travel(seeTable-2-), the traveler and the health-care provider should
consider several factors. Whether the traveler will be at risk for acquiring
drug-resistant P. falciparum malaria should also be determined. Resistance
to antimalarial drugs has developed in many regions of the world. Health-
care providers should consult the latest information on resistance patterns
before prescribing prophylaxis for their patients. The resistance of P.
falciparum to chloroquine has been confirmed in all areas with P.
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falciparum malaria except the Dominican Republic, Haiti, Central
America west of the Panama Canal, Egypt, and some countries in the
Middle East. In addition, resistance to sulfadoxine-pyrimethamine (e.g.,
Fansidar) is widespread in the Amazon River Basin area of South
America, much of Southeast Asia, other parts of Asia, and, increasingly, in
large parts of Africa. Resistance to mefloquine has been confirmed on the
borders of Thailand with Burma (Myanmar) and Cambodia, in the western
provinces of Cambodia, and in the eastern states of Burma (Myanmar).
Note; Malaria chemoprophylaxis with mefloquine or chloroquine; should
begin 1-2 weeks before travel to malarious areas; prophylaxis with
doxycycline, atovaquone/proguanil, or primaquine can begin 1-2 days
before travel. Beginning the drug before travel allows the antimalarial
agent to be in the blood before the traveler is exposed to malaria parasites.
Chemoprophylaxis can be started earlier if there are particular concerns
about tolerating one of the medications. Starting the medication 3-4 weeks
in advance allows potential adverse events to occur before travel. Minor
side effects usually do not require stopping the drug. If unacceptable side
effects develop, there would be time to change the medication before the
traveler's departure.
Chemoprophylaxis should continue during travel in the malarious areas
and after leaving the malarious areas (4 weeks after travel for chloroquine,
mefloquine, and doxycycline, and 7 days after travel for
atovaquone/proguanil and primaquine). In comparison with drugs with
short half-lives, which are taken daily, drugs with longer half-lives, which
are taken weekly, offer the advantage of a wider margin of error if the
traveler is late with a dose. For example, if a traveler is 1-2 days late with
a weekly drug, prophylactic blood levels can remain adequate; if the
traveler is 1-2 days late with a daily drug, protective blood levels are less
likely to be maintained.
Travel to areas without Chloroquine- Resistant P. falciparum
For travel to areas of risk where chloroquine-resistant P. falciparum has
not been reported, once-a-week use of chloroquine alone is recommended
for prophylaxis. Persons who experience uncomfortable side effects after
taking chloroquine may tolerate the drug better by taking it with meals. As
an alternative, the related compound hydroxychloroquine sulfate may be
better tolerated. Travelers unable to take chloroquine or
- 124 -

hydroxychloroquine should take atovaquone/proguanil, doxycycline, or
mefloquine; these antimalarial drugs are also effective against
chloroquine-sensitive parasites.
Chloroquine prophylaxis should begin 1-2 weeks before travel to
malarious areas. It should be continued by taking the drug once a week, on
the same day of the week, during travel in malarious areas and for 4 weeks
after a traveler leaves these areas .
Travel to areas with Chloroquine-resistant P. falciparum
For travel to areas of risk where chloroquine-resistant P. falciparum exists,
three efficacious options are available, listed in alphabetical order below.
In addition, there are new recommendations for the use of primaquine for
prophylaxis in special situations.
Atovaquone / proquanil (Malarone). Atovaquone/proguanil is a fixed
combination of the two drugs, atovaquone and proguanil.
Atovaquone/proguanil prophylaxis should begin 1-2 days before travel to
malarious areas and should be taken daily, at the same time each day,
while in the malarious areas and daily for 7 days after leaving the area.
Doxycycline . Doxycycline prophylaxis should begin 1-2 days before
travel to malarious areas. It should be continued once a day, at the same
time each day, during travel in malarious areas and daily for 4 weeks after
the traveler leaves such areas. Either doxycycline or atovaquone/proguanil
(see above) can be used by travelers to areas with mefloquine-resistant
strains of P. falciparum (the borders of Thailand with Burma (Myanmar)
and Cambodia, western Cambodia, and eastern Burma (Myanmar) .





- 125 -

Table:-2- Drugs used in the prophylaxis of malaria
Drug Usage Adult Dose Pediatric Dose Comments
Atovaquone /
proguanil
(Malarone)
Prophylaxis in
areas with
chloroquine-
resistant or
mefloquine-
resistant P.
falciparum.
Adult tablets
contain 250
mg atovaquone
and 100 mg
proguanil
hydrochloride.

1 adult tablet
orally, daily
Pediatric
tablets contain
62.5 mg
atovaquone and
25 mg
proguanil
hydrochloride.

11-20 kg: 1
tablet

21-30 kg: 2
tablets

31-40 kg: 3
tablets

41 kg or more:
1 adult tablet
daily
Begin 1-2 days
before travel to
malarious areas.
Take daily at the
same time each
day while in the
malarious area
and for 7 days
after leaving
such areas.
Contraindicated
in persons with
severe renal
impairment
(creatinine
clearance <30
mL/min).
Atovaquone /
proguanil should
be taken with
food or a milky
drink. Not
recommended
for prophylaxis
for children <11
kg, pregnant
women, and
women
breastfeeding
infants weighing
<11 kg.
Chloroquine
phosphate
(Aralen and
generic)
Prophylaxis
only in areas
with
chloroquine-
sensitive P.
falciparum.
300 mg base
(500 mg salt)
orally,
once/week
5 mg/kg base
(8.3 mg/kg
salt) orally,
once/week, up
to maximum
adult dose of
300 mg base.
Begin 1-2 weeks
before travel to
malarious areas.
Take weekly on
the same day of
the week while
in the malarious
area and for 4
weeks after
leaving such
areas.

May exacerbate
- 126 -

psoriasis.
Doxycycline
(Many brand
names and
generic)
Prophylaxis in
areas with
chloroquine-
resistant or
mefloquine-
resistant P.
falciparum.
100 mg orally,
daily
8 years of
age: 2 mg/kg
up to adult
dose of 100
mg/day.
Begin 1-2 days
before travel to
malarious areas.
Take daily at the
same time each
day while in the
malarious area
and for 4 weeks
after leaving
such areas.

Contraindicated
in children <8
years of age and
pregnant
women.
Hydroxychloro-
quine sulfate
(Plaquenil)
An alternative
to chloroquine
for prophylaxis
only in areas
with
chloroquine-
sensitive P.
falciparum.
310 mg base
(400 mg salt)
orally,
once/week
5 mg/kg base
(6.5 mg/kg
salt) orally,
once/week, up
to maximum
adult dose of
310 mg base.
Begin 1-2 weeks
before travel to
malarious areas.
Take weekly on
the same day of
the week while
in the malarious
area and for 4
weeks after
leaving such
areas.
Mefloquine
(Lariam and
generic)
Prophylaxis in
areas with
chloroquine-
resistant P.
falciparum.
228 mg base
(250 mg salt)
orally,
once/week
9 kg: 4.6
mg/kg base (5
mg/kg salt)
orally,
once/week

10-19 kg: 1/4
tablet
once/week

20-30 kg: 1/2
tablet
once/week

31-45 kg: 3/4
tablet
once/week

46 kg: 1
Begin 1-2 weeks
before travel to
malarious areas.
Take weekly on
the same day of
the week while
in the malarious
area and for 4
weeks after
leaving such
areas.
Contraindicated
in persons
allergic to
mefloquine or
related
compounds
(e.g., quinine
and quinidine)
- 127 -

tablet
once/week
and in persons
with active
depression, a
recent history of
depression,
generalized
anxiety disorder,
psychosis,
schizophrenia,
other major
psychiatric
disorders, or
seizures. Use
with caution in
persons with
psychiatric
disturbances, or
a previous
history of
depression. Not
recommended
for persons with
cardiac
conduction
abnormalities.
Primaquine An option for
prophylaxis in
special
circumstances.
Call Malaria
Hotline (770-
488-7788) for
additional
information.
30 mg base
(52.6 mg salt)
orally, daily
0.6 mg/kg base
(1.0 mg/kg
salt) up to adult
dose orally,
daily
Begin 1-2 days
before travel to
malarious areas.
Take daily at the
same time each
day while in the
malarious area
and for 7 days
after leaving
such areas.

Contraindicated
in persons with
G6PD
1

deficiency. Also
contraindicated
during
pregnancy and
lactation unless
the infant being
breastfed has a
documented
normal G6PD
- 128 -

level. Use in
consultation
with malaria
experts.
Primaquine Used for
presumptive
anti-relapse
therapy
(terminal
prophylaxis) to
decrease the
risk of relapses
of P. vivax and
P. ovale.
30 mg base
(52.6 mg salt)
orally,
once/day for
14 days after
departure from
the malarious
area.
0.6 mg/kg base
(1.0 mg/kg
salt) up to adult
dose orally,
once/day for 14
days after
departure from
the malarious
area.
Indicated for
persons who
have had
prolonged
exposure to P.
vivax and P.
ovale or both.
Contraindicated
in persons with
G6PD
1

deficiency. Also
contraindicated
during
pregnancy and
lactation unless
the infant being
breastfed has a
documented
normal G6PD
level.
1
Glucose-6-phosphate dehydrogenase. All persons who take
primaquine should have a documented normal G6PD level prior to
starting the medication.
Mefloquine . Mefloquine prophylaxis should begin 1-2 weeks before
travel to malarious areas. It should be continued once a week, on the same
day of the week, during travel in malarious areas and for 4 weeks after a
traveler leaves such areas.
Note: primaquine; may be used for prophylaxis for travel to areas with or
without chloroquine-resistant P. falciparum. This use should generally be
reserved for travelers unable to take any of the other chemoprophylaxis
regimens recommended for the region of travel. The traveler must have a
documented level of G6PD in the normal range prior to being prescribed
primaquine. Primaquine prophylaxis should begin 1-2 days before travel
to malarious areas, be taken daily at the same time each day while in the
malarious areas, and daily for 7 days after leaving such areas. (See Table
for recommended dosages.)
- 129 -

Note: In those who are G6PD deficient, primaquine can cause hemolysis,
which can be fatal. Be sure to document a normal G6PD level before
prescribing primaquine.
Note: No longer recommends chloroquine/proguanil as a preventive
option for persons traveling to areas with chloroquine-resistant P.
falciparum.
Prevention of relapses of P.vivax and P. ovale
P. vivax and P. ovale parasites can persist in the liver and cause relapses
for as long as 4 years or more after departure from the malarious areas.
Travelers to malarious areas should be alerted to this risk and, if they have
malaria symptoms after leaving a malarious area, they should be advised
to report their travel history and the possibility of malaria to a physician as
soon as possible. Presumptive anti-relapse therapy with primaquine
decreases the risk of relapses by acting against the liver stages of P. vivax
or P. ovale. Primaquine presumptive anti-relapse therapy is administered
for 14 days after the traveler has left a malarious area. When chloroquine,
doxycycline, or mefloquine is used for prophylaxis, primaquine is usually
taken during the last 2 weeks of post-exposure prophylaxis, but may be
taken immediately after those medications are completed. When
atovaquone/proguanil is used for prophylaxis, primaquine may be taken
either during the final of atovaquone/ proguanil and then for an additional
7 days, or for 14 days after atovaquone/proguanil is completed. Note; that
the recommended dose of primaquine for terminal prophylaxis has been
increased from 15 mg to 30 mg (base) for adults and from 0.3 mg/kg to
0.6 mg/kg (base) for children. Because most malarious areas of the world
(except Haiti and the Dominican Republic) have at least one species of
relapsing malaria, travelers to these areas have some risk for acquiring
either P. vivax or P. ovale, although the actual risk for an individual
traveler is difficult to define. Presumptive anti-relapse therapy with
primaquine for prevention of relapses is generally indicated only for
persons who have had prolonged exposure in malaria-endemic areas. Most
persons can tolerate this regimen of primaquine (30 mg/day for adults if it
is taken with food); the main exception is for persons who are deficient in
G6PD.
Note:Relapse; The return of signs and symptoms of cancer after a period of
improvement.
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Chemoprophylaxis for Infants, Children, and Adolescents
Infants of any age or weight or children and adolescents of any age can
contract malaria. Therefore, children traveling to malaria-risk areas should
take an antimalarial drug. Pediatric dosages should be carefully calculated
according to body weight but should never exceed adult dosage. Parents
should prepare the child's dose of medication by mixing the drug with
something sweet, such as applesauce, chocolate syrup, or jelly. Giving the
dose on a full stomach may minimize stomach upset and vomiting.
Note:Chloroquine is the drug of choice for children traveling to areas
without

chloroquine-resistant P. falciparum.

Mefloquine is an option for use in infants and children of all ages and
weights who are traveling to areas with chloroquine-resistant P.
falciparum.
Doxycycline may be used for children 8 years of age.
Atovaquone/proguanil may be used for prophylaxis for infants and
children weighing 11 kg ( 24lbs). At this time, insufficient data are
available on the safety and efficacy of atovaquone/proguanil for
prevention of malaria in children weighing <11 kg (<24 lbs).
Atovaquone/proguanil is available in pediatric tablet form; dosage is based
on weight.
Table:-3- Pediatric prophylactic doses of atovaquone/proguanil
Body weight (kg)
Atovaquone/Proguanil
Total daily dose (mg)
Dosage regimen
11-20 62.5/25 1 pediatric tablet
daily
21-30 125/50 2 pediatric tablets
daily
31-40 187.5/75 3 pediatric tablets
daily
41 250/100 1 adult tablet daily
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Chemoprophylaxis during Pregnancy
can be more severe than in nonpregnant women. Malaria can increase
the risk for adverse pregnancy outcomes, including prematurity,
abortion, and stillbirth. For these reasons and because no
chemoprophylactic regimen is completely effective, women who are
pregnant or likely to become pregnant should be advised to avoid travel
to areas with malaria transmission if possible.. If travel to a malarious
area cannot be deferred, use of an effective chemoprophylaxis regimen
is essential. Note:. Pregnant women traveling to areas where
chloroquine-resistant P. falciparum has not been reported may take
chloroquine prophylaxis. Chloroquine has not been found to have any
harmful effects on the fetus when used in the recommended doses for
malaria prophylaxis; therefore, pregnancy is not a contraindication for
malaria prophylaxis with chloroquine phosphate or
hydroxychloroquine sulfate. Mefloquine is currently the only
medication recommended for malaria chemoprophylaxis during
pregnancy with chloroquine-resistant P. falciparum . A review of
mefloquine use in pregnancy from clinical trials and reports of
inadvertent use of mefloquine during pregnancy suggest that its use at
prophylactic doses during the second and third trimesters of pregnancy
is not associated with adverse fetal or pregnancy outcomes. More
limited data suggest it is also safe to use during the first trimester.
Because of insufficient data regarding the use during pregnancy,
atovaquone/proguanil is not currently recommended for the prevention
of malaria in pregnant women. Doxycycline is contraindicated for
malaria prophylaxis during pregnancy because of the risk of adverse
effects of tetracycline, a related drug, on the fetus, which include
discoloration and dysplasia of the teeth and inhibition of bone growth.
Primaquine should not be used during pregnancy because the drug may
be passed transplacentally to a glucose-6-phosphate dehydrogenase
(G6PD)-deficient fetus and cause hemolytic anemia in utero.

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Antimalarial drugs during breastfeeding
Very small amounts of chloroquine and mefloquine are excreted in the
breast milk of lactating women. The amount of drug transferred is not
thought to be harmful to a nursing infant. Because the quantity of
antimalarial drugs transferred in breast milk is insufficient to provide
adequate protection against malaria, infants who require
chemoprophylaxis must receive the recommended dosages of antimalarial
drugs listed in Table Although there are very limited data about the use of
doxycycline in lactating women, most experts consider the theoretical
possibility of adverse events to be remote. No information is available on
the amount of primaquine that enters human breast milk; the mother and
infant should be tested for G6PD deficiency before primaquine is given to
a woman who is breastfeeding. It is not known whether atovaquone is
excreted in human milk. Proguanil is excreted in human milk in small
quantities. Based on experience with other antimalarial drugs, the quantity
of drug transferred in breast milk is likely insufficient to provide adequate
protection against malaria for the infant. Note: Because data are not yet
available on the safety of atovaquone/proguanil prophylaxis in infants
weighing <11 kg (24 lbs), it does not recommend for the prevention of
malaria in women breastfeeding infants weighing <11 kg.
(Atovaquone/proguanil may be used for the treatment of malaria by
women breastfeeding infants weighing >5 kg. However, it can be used for
treatment of women who are breastfeeding infants of any weight when the
potential benefit outweighs the potential risk to the infant, e.g., treating a
breastfeeding woman who has acquired P. falciparum malaria in an area
of multidrug-resistant strains and who cannot tolerate other treatment
options.)
Adverse reactions and contraindications
Following is a summary of the frequent or serious side effects of
recommended antimalarial drugs. The most common adverse effects
reported in persons using atovaquone/proguanil for prophylaxis or
treatments are abdominal pain, nausea, vomiting, and headache.
Atovaquone/proguanil should not be used for prophylaxis in children
weighing <11 kg, pregnant women, women breastfeeding infants
weighing <11 kg, or patients with severe renal impairment (creatinine
clearance <30 mL/min).
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Note; Changing medications during chemoprophylaxis as a result of
side effects
The medications recommended for prophylaxis against malaria have
different modes of action that affect the parasites at different stages of the
life cycle. Thus, if the medication needs to be changed because of side
effects before a full course has been completed, there are some special
considerations. If a traveler starts prophylaxis with a medication such as
mefloquine or doxycycline and then changes to atovaquone/proguanil
during or after travel, the standard duration of prophylaxis for
atovaquone/proguanil might be insufficient. The atovaquone/proguanil
should be continued for 4 weeks after the drug change or 1 week after
returning, whichever is longer, but not beyond 4 weeks after return.
Babesiosis (Babesia microti and Babesia divergens infection)
Apicomplexan parasites belonging to the genus Babesia have long been
known as parasites of domestic and wild animals. Human infection have
been reported from Europe and North America. The organism infect the
red cells, in which they appear as somewhat pleomorphic ringlike
structures. Little is known about the occurrence of Babesia species in
malaria-endemic areas where Babesia can easily be misdiagnosed as
Plasmodium.
Etiology

Babesia microti and Babesia divergens are the only member of the genus
that infects man.
Morphology
The trophozoite is very similar to the ring form of the Plasmodium species
(Fig-1-).

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Fig:-1- Intraerythrocytes Babesia trophozoite .
Epidemiology
Worldwide, but little is known about the prevalence of Babesia in malaria-
endemic countries, where misidentification as Plasmodium probably
occurs. In Europe, most reported cases are due to B. divergens and occur
in splenectomized patients (splenectomized persons susceptible to
infection and the severity of the illness). In the United States, B. microti is
the agent most frequently identified (Northeast and Midwest), and can
occur in non-splenectomized individuals.
Transmision
Transmited by hard tick called (Ixodes dammini)
Life cycle
The Babesia microti life cycle involves two hosts, which includes a
rodent, primarily the white-footed mouse, Peromyscus leucopus. During a
blood meal, a Babesia-infected tick introduces sporozoites into the mouse
host (1). Sporozoites enter erythrocytes and undergo asexual reproduction
(budding) (2). In the blood, some parasites differentiate into male and
female gametes although these cannot be distinguished at the light
microscope level (3). The definitive host is a tick, in this case the deer
tick, Ixodes dammini (I. scapularis). Once ingested by an appropriate tick
(4), gametes unite and undergo a sporogonic cycle resulting in sporozoites
(5). Transovarial transmission (also known as vertical, or hereditary,
transmission) has been documented for large Babesia spp. but not for
the small babesiae, such as B. microti (A). Humans enter the cycle when
bitten by infected ticks. During a blood meal, a Babesia-infected tick
introduces sporozoites into the human host (6). Sporozoites enter
erythrocytes (B)and undergo asexual replication (budding) (7).
Multiplication of the blood stage parasites is responsible for the clinical
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manifestations of the disease. Humans are, for all practical purposes,
dead-end hosts and there is probably little, if any, subsequent transmission
that occurs from ticks feeding on infected persons. However, human to
human transmission is well recognized to occur through blood
transfusions (B).

Note: Deer are the hosts upon which the adult ticks feed and are indirectly
part of the Babesia cycle as they influence the tick population. When deer
populations increase, the tick population also increases, thus heightening
the potential for transmission.
Clinical features and Pathology
Most infections are probably asymptomatic, as indicated by serologic
surveys. Manifestations of disease include fever, chills, sweating,
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myalgias, fatigue, arthralgia, mild hepatosplenomegaly, hemolytic anemia
and jaundice, and liver enzymes slightly raised. Symptoms typically occur
after an incubation period of 1 to 4 weeks, and can last several weeks. The
disease is more severe in patients who are immunosuppressed,
splenectomized, and/or elderly. Infections caused by B. divergens tend to
be more severe (frequently fatal if not appropriately treated) than those
due to B. microti, where clinical recovery usually occurs.
Laboratory diagnosis
Diagnosis is based on symptoms, patient history and detection of
intraerythrocytic parasite in the patient or transfer of blood in normal
hamsters which can be heavily parasitized.
Treatment and Control
Drugs of choice are clindamycin combined with quinine. The patient may
recover spontaneously. One should avoid tick exposure and, if bitten,
remove the tick from the skin immediately.










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CHAPTER EIGHT (8)
Tissue sporozoa (coccidia)
This subclass includes intestinal and tissue coccidian parasites, which have
the following characteristics. A-Reproduce asexually by aprocess called
schizogony and sexually by aprocess called sporogony.B- Transmitted by
ingestion of oocystes but malaria parasites transmitted by mosquitoes. So
these parasites have similar life-cycles (ie. alternation of sexual and
asexual generations), but they do not need another host in order to
reproduce. One species.
Cryptosporidiosis (C.parvum infection)
It is zoonotic disease and an important opportunistic parasite .
Characterized by copious watery diarrhea. Severity and duration of
symptoms are related to immuno-competence. In AIDS patients, the
organism may cause prolonged, severe diarrhea and the organisms may
invade the gallbladder, biliary tract and the lung epithelium.
Etiology
Many species of Cryptosporidium exist that infect humans and a wide
range of animals. Although Cryptosporidium parvum and
Cryptosporidium hominis are the most prevalent species causing disease in
humans, infections by C. felis, C. meleagridis, C. canis, and C. muris have
also been reported.
Morphology
C. parvum oocyst is a small round to oval pink-red stained bodies,
measuring 3 to 5 m .The ooccyst may contain a single deeply stained dot
. Sporozoites are visible inside the oocysts, indicating that sporulation has
occurred. (In comparison, oocysts of Cyclospora cayetanensis, another
important coccidian parasite of humans, are twice larger and upon
excretion are not sporulated, i.e., do not contain Sporozoites .Oocysts of
Cryptosporidium parvum stained by the modified acid-fast method. The
oocysts stand out in a bright red stain. The oocyst of Cryptosporidium is
the form of the organism that survives in the environment. The oocyst of
Cryptosporidium is resistant to chlorination. Note: The trophozoites of
Cryptosporidium are the forms of the organism that colonizes the
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intestinal tract, mainly in the jejunum and ileum and causes the
pathology. The trophozoite of Cryptosporidium is an intra/extra cellular
parasite. The trophozoite is covered by the microvilli, but is not inside the
microvilli.
Epidemiology
Since the first reports of human cases in 1976, Cryptosporidium has been
found worldwide. Outbreaks of cryptosporidiosis have been reported in
several countries, the most remarkable being a waterborne outbreak in
Milwaukee (Wisconsin, USA) in 1993, that affected more than 400,000
people.
Transmission and Life Cycle:
Note; Cryptosporidium has a life cycle that includes sexual and asexual
forms.
Sporulated oocysts, containing 4 sporozoites, are excreted by the infected
host through feces and possibly other routes such as respiratory secretions
(1). Transmission of Cryptosporidium parvum and C. hominis occurs
mainly through contact with contaminated water (e.g., drinking or
recreational water). Occasionally food sources, such as chicken salad, may
serve as vehicles for transmission. Many outbreaks in the United States
have occurred in waterparks, community swimming pools, and day care
centers. C. parvum and C. hominis occur through exposure to infected
animals or exposure to water contaminated by feces of infected animals
(2). Following ingestion (and possibly inhalation) by a suitable host (3),
excystation (a)occurs. The sporozoites are released and parasitize
epithelial cells (b, c) of the gastrointestinal tract or other tissues such as
the respiratory tract. In these cells, the parasites undergo asexual
multiplication (schizogony or merogony) (d, e, f) and then sexual
multiplication (gametogony) producing microgamonts (male) (g)and
macrogamonts (female) (h). Upon fertilization of the macrogamonts by
the microgametes (i), oocysts (j, k) develop that sporulate in the infected
host. Two different types of oocysts are produced, the thick-walled, which
is commonly excreted from the host (j), and the thin-walled oocyst (k),
which is primarily involved in autoinfection. Oocysts are infective upon
excretion, thus permitting direct and immediate fecal-oral transmission.

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Clinical features and Pathology
Cryptosporidium invades the brush border of the epithelia cells of the
intestine
Infection with Cryptosporidium sp. results in a wide range of
manifestations, from asymptomatic infections to severe, life-threatening
illness; incubation period is an average of 7 days (but can range from 2 to
10 days). Sever watery diarrhea may accompanied with (steatorrhea in
immunocompromised persons), is the most frequent symptom, and can be
accompanied by dehydration, weight loss, abdominal pain, fever, nausea
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and vomiting. In immunocompetent persons, symptoms are usually mild
and self-limited , short lived (1 to 2 weeks); they can be chronic and more
severe in immunocompromised patients, especially those with CD4 counts
<200/l. While the small intestine is the site most commonly affected,
symptomatic Cryptosporidium infections have also been found in other
organs in patient with AIDS , in sputum, in lung biopsy material and in
biliary tract and has been associated with malabsorption.
Laboratory diagnosis
Acid-fast staining methods, with or without stool concentration, are most
frequently used in clinical laboratories. For greatest sensitivity and
specificity, immunofluorescence microscopy is the method of choice
(followed closely by enzyme immunoassays). Antibody detection: There
are currently no commercially available serologic assays for the detection
of Cryptosporidium-specific antibodies.
Treatment
Rapid loss of fluids because of diarrhea can be managed by fluid and
electrolyte replacement. Infection in healthy, immunocompetent persons
is self-limited. Nitazoxanide has been approved for treatment of diarrhea
caused by Cryptosporidium in immunocompetent patients.
Immunocompromised persons and those in poor health are at highest risk
for severe illness. The effectiveness of nitazoxanide in immunosuppressed
persons is unclear. For persons with AIDS, anti-retroviral therapy, which
improves immune status, will also reduce oocyst excretion and decrease
diarrhea associated with cryptosporidiosis. There is no approved effective
treatment for cryptosporidiasis, although paromycin is used as an
investigational drug.
Isosporiasis (I. belli infection)
Isosporiasis is a rare infection of normal humans, although it is being seen
in increasing numbers in AIDS patients.
Etiology

The coccidian parasite, Isospora belli, infects the epithelial cells of the
small intestine, and is the least common of the three intestinal coccidia
that infect humans.
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Morphology

The oocyst oval, measuring about 32 x 16 m. When excreted, they are
immature and contain one sporoblast. The oocyst matures after excretion:
the single sporoblast (Fig-1-)divides in two sporoblasts (Fig-2-), which
develop cyst walls, becoming sporocysts, which eventually contain four
sporozoites each.



Fig:-1-Oocyst with single sporoplast. Fig:-2- Oocyst with two
sporoplast.
Epidemiology
Worldwide, especially in tropical and subtropical areas. Infection occurs
in immunodepressed individuals.
Transmission and Life Cycle
At time of excretion, the immature oocyst contains usually one sporoblast
(more rarely two) (1). In further maturation after excretion, the sporoblast
divides in two (the oocyst now contains two sporoblasts); the sporoblasts
secrete a cyst wall, thus becoming sporocysts; and the sporocysts divide
twice to produce four sporozoites each (2). Infection occurs by ingestion
of sporocysts-containing oocysts: the sporocysts excyst in the small
intestine and release their sporozoites, which invade the epithelial cells
and initiate schizogony (3). Upon rupture of the schizonts, the merozoites
are released, invade new epithelial cells, and continue the cycle of asexual
multiplication (4). Trophozoites develop into schizonts which contain
multiple merozoites. After a minimum of one week, the sexual stage
begins with the development of male and female gametocytes
(5). Fertilization results in the development of oocysts that are excreted in
the stool (1). Isospora belli infects both humans and animals.

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Clinical features and Pathology
Infection causes acute, non bloody diarrhea with crampy abdominal pain,
which can last for weeks and result in malabsorption and weight loss. The
disease produces symptoms similar to those of giardiasis. In
immunodepressed patients, and in infants and children, the diarrhea can be
severe with steatorrhea. Eosinophilia may be present (differently from
other protozoan infections).

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Laboratory diagnosis
Microscopic demonstration of the large, typically shaped oocysts, is the
basis for diagnosis. Because the oocysts may be passed in small amounts
and intermittently, repeated stool examinations and concentration
procedures are recommended. If stool examinations are negative,
examination of duodenal specimens by biopsy or string test (Enterotest)
may be needed.
Treatment
In normal individuals, mild infections resolve themselves with rest and
mild diet and heavier infections can be treated with sulpha drugs. The
treatment may have to be carried on for a prolonged period in AIDS
patients. Trimethoprim-sulfamethoxazole is the drug of choice, also
known as Bactrim, Septra, or Cotrim. Supportive measures include
management of fluid and electrolyte balance, and rest.
Cyclosporiasis (Cyclospora infection)
The first known human cases of this illness caused by Cyclospora
infection , were reported in 1979. Cases began being reported more often
in the mid-1980s. In the last several years, outbreaks of cyclosporiasis
have been reported in the United States and Canada.
Etiology
The causal agent has been only recently identified as a unicellular
coccidian parasite.
Morphology
Cyclospora cayetanensis is a parasite composed of one cell, too small to
be seen without a microscope. Stained with modified acid-fast stain. The
oocysts are less perfectly round and have a wrinkled appearance .
Epidemiology
Cyclosporiasis has been reported in many countries, but is most common
in tropical and subtropical areas. Since 1990, at least 11 foodborne
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outbreaks of cyclosporiasis, affecting approximately 3600 persons, have
been documented in the United States and Canada.
Transmission and Life Cycle

When freshly passed in stools, the oocyst is not infective (1)(thus, direct
fecal-oral transmission cannot occur; this differentiates Cyclospora from
another important coccidian parasite, Cryptosporidium). In the
environment (2), sporulation occurs after days or weeks at temperatures
between 22C to 32C, resulting in division of the sporont into two
sporocysts, each containing two elongate sporozoites (3). Fresh produce
and water can serve as vehicles for transmission (4)and the sporulated
oocysts are ingested (in contaminated food or water) (5). The oocysts
excyst in the gastrointestinal tract, freeing the sporozoites which invade
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the epithelial cells of the small intestine (6). Inside the cells they undergo
asexual multiplication and sexual development to mature into oocysts,
which will be shed in stools (7). The potential mechanisms of
contamination of food and water are still under investigation.
Clinical features and Pathology
After an average incubation period of 1 week, symptomatic infections
typically manifest as watery diarrhea, which can be severe. Other
symptoms include anorexia, weight loss, abdominal pain, nausea and
vomiting, myalgias, low-grade fever, and fatigue. Untreated infections
typically last for 10-12 weeks and may follow a relapsing course.
Infections, especially in disease-endemic settings can be asymptomatic.
Laboratory diagnosis
Currently, the most practical diagnostic method consists of the
identification of oocysts in stool specimens by light microscopy.
Treatment
The recommended treatment for cyclosporiasis is a combination of two
antibiotics, trimethoprim-sulfamethoxazole, also known as Bactrim,
Septra, or Cotrim. Supportive measures include management of fluid and
electrolyte balance, and rest.
Pneumocystosis /Pneumocystis Pneumonia (Pneumocystis jiroveci
infection)
Is one of the most common infections in immunosuppressed patients with
AIDS. Other impairements of cellular immunity such as primary
immunodeficiencies, steroid treatment, organ transplantation and cancers
predispose to P.c. infection.
Etiology
Pneumocystis jiroveci. It is often described as an opportunistic parasitic
disease. The organims that causes human pneumocystosis is now named
Pneumocystis jiroveci since 1999(formerly known as Pneumocystis
carinii), in honor of the Czech parasitologist Otto Jirovec. The organism is
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now considered a fungus, based on nucelic acid and biochemical analysis;
nevertheless, on the basis of morpholocic and biologic characterisitcs
Morphology
The organism is pleomorphic, exhibiting, at various stages of its life cycle:
1-2 m sporozoites, 4-5 m trophozoites and 6-8 m cysts. (Fig-1-) 3
cysts in bronchoalveolar material, the rounded cysts contain 6 to 8
intracystic bodies.

Fig:-1- Three P. jiroveci cysts.
Epidemiolgy
The infection has a world-wide distribution and the transmission seems to
occur by airborne route.Cosmopolitan in man, rodents, dogs, and several
domestic animals.
Transmission and life cycle
The organisms are abundant in the pulmonary exudates, and hence,
transmission is probably by droplet to close contacts and multiply by
fission. after inhalation the microorganism reaches the alveoli and adheres
to the type I pneumocytes.
The trophozoites then multiply slowly but extensively in the lungs and
progressively fill the alveoli that are finally stuffed by the foamy exudate.
Clinical features and Pathology
The symptoms of Pneumocystis pneumonia (PCP) include dyspnea,
nonproductive cough, and fever. Chest radiography demonstrates bilateral
infiltrates. Extrapulmonary lesions occur in a minority (<3%) of patients,
involving most frequently the lymph nodes, spleen, liver, and bone
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marrow. Typically, in untreated PCP increasing pulmonary involvement
leads to death. Pneumocystis pneumonia is an infection of
immunosuppressed individuals and is particularly seen in AIDS patients. It
is one of the most common infection seen in patients with AIDS.
Pneumocystis carinii (jiroveci); causes an interstitial plasma cell
pneumonia in new born (chiefly strikes malnourished premature babies,
though full-term infants may be infected) and young children. Infection
characterized by thickened alveolar septum infiltrated with lymphocytes
and plasma cells. The disease begins after an incubation period of 14 to 21
days, with anorexia, failure to thrive, and weight loss, followed shortly by
a progressive dyspnea , affected Infants are generally afebrile , dry cough
,progressive dyspnea, extreme tachypnea, hypoxia, hypercapnia ,cyanosis
and death is due to asphyxia caused by blockage of the alveoli and
bronchioles .
Note:P.jiroveci infiltrates are usually diffuse but atypical presentations
can occur, nodules, cavitation, consolidation, pneumatocele and
pneumotorax (Fig-2-).
Laborator diagnosis:
The specific diagnosis is based on identification of P. jiroveci in
bronchopulmonary secretions obtained as induced sputum or
bronchoalveolar lavage (BAL) material. Microscopic identification of P.
jiroveci trophozoites and cysts is performed with stains that demonstrate
either the nuclei of trophozoites . In addition, immunofluorescence
microscopy using monoclonal antibodies can identify the organisms with
higher sensitivity than conventional microscopy. The X-ray picture is that
of bronchopneumonia ,mainly hilar patchy infiltration (Fig-2-) and spread
. Physical signs and laboratory finding are not helpful . Blood gas
determination may be of value, indicating hypoxia without acidosis or
hypercapnia.

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Fig:-2- Pneumocystis Pneumonia (hilar patchy infiltration)
Note: Fiberoptic bronchoscopy (transbronchial) with BAL is actually the
most commonly used diagnostic procedure. The diagnosis is based on the
observation of cysts and trophozoites.
Clusters of P.jiroveci can be observed in wet mount preparations.
Treatment
Trimethoprim-sulphamethoxazole is the treatment of choice.
Note; P.carinii reportedly has caused ear infection in an otherwise healthy
man with serologic evidence of HIV, hepatitis in a patient with AIDS, and
infection of bone marrow in three patients with either malignant
lymphoma or AIDS.
Toxoplasmosis (T. gondii infection)
Toxoplasmosis is an infectious disease caused by the one-celled protozoan
parasite Toxoplasma gondii. Although most individuals do not experience
any symptoms, the disease can be very serious, and even fatal, in
individuals with weakened immune systems e.g patients with AIDS.
Toxoplasmosis infection is only a danger to developing fetuses ( if a
pregnant woman comes into contact with the parasite, there is a chance
that it will cause birth deformities in her child (eg. brain damage,
blindness, etc).
Etiology
Toxoplasma gondii is the organism responsible for toxoplasmosis.
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Morphology
The obligate intracellular parasites (tachyzoite) are 3x6 m, they are
pyriform - pear-shaped,this parasite has a cell membrane, aspheroid-to-
oval nucleus with a central karyosome, and several organelles of unknown
function (Fig-1). The accumulation of organisms, bounded only by the
plasmalemma of the host cell is known as a Pseudocyst , measuring 10-
100 m in size , plasmalemma a term which is only used in parasitology
for a protective membrane surrounding an organism which has, at least in
part, been produced by the parasite.Oocysts infective stage found in cat
feces are 10-13 m in diameter(Fig-2- ).

Fig:-1- Tachyzoite. Fig:-2- Oocyst.
Epidemiology
Toxoplasmosis is a zoonosis of world wide distribution. In many
populations, 20%-75% of the population is seropositive without any
symptomatic episode. However, the infection poses a serious threat in
immunosuppressed individuals and pregnant females.
Note; However, before you all rush out and abandon your cats, you should
be aware that a current project has found no evidence of oocysts in cat
faeces collected from local catteries - a study in Glasgow showed that a
high proportion of cats were sero-positive for toxoplasma, but again no
oocysts to match the seropositive data.
Transmission transmitted via the faeces of cats - the faeces containing
what appeared to be oocysts - Cats were infected by ingesting oocysts or
cysts in tissues of paratenic hosts, such as mice.
Humans normally become infected either by direct ingestion of oocysts
from a cat or by eating raw or undercooked meat. Cooks or butchers that
handle raw meat are particularly at risk. Man and other animals can be
infected by the congenital route and acute infection . Children can become
infected playing near cat litter trays etc.

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Life cycle
The primary host is domestic cat with the sexual stages of the parasite in
the intestine. Oocyst are passed in the feces and develop in the external
environment to produce infective sporozoites. When the sporozoites are
ingested by awide range of intermediate host, including man , they
undergo asexual development first as intercellular parasites in the
reticuloendothelial tissues and then as cysts in many parts of body,
including brain. Infection is normally acquired by ingestion of cysts in
undercooked meat and transplacentally (see below).
The natural life cycle of T. gondii occurs in cats and small rodents,
although the parasite can grow in the organs (brain, eye, skeletal muscle,
etc.) of any mammal or birds . Cats gets infected by ingestion of cysts in
flesh. Decystation occurs in the small intestine, and the organisms
penetrate the submucosal epithelial cells where they undergo several
generations of mitosis, finally resulting in the development of micro-
(male) and macro- (female) gametocytes. Fertilized macro-gametocytes
develop into oocysts that are discharged into the gut lumen and excreted.
Oocysts sporulate in the warm environment and are infectious to a variety
of animals including rodents and man. Sporozoites released from the
oocyst in the small intestine penetrate the intestinal mucosa and find their
way into macrophages where they divide very rapidly (hence the name
tachyzoites) and form a cyst which may occupy the whole cell. The
infected cells ultimately burst and release the tachyzoites to enter other
cells, including muscle and nerve cells, where they are protected from the
host immune system and multiply slowly (bradyzoites).
Note:Within a pseudocyst, zoites divide rapidly and are known as
tachyzoites (Greek tachos = speed). The host cell eventually bursts and
releases tachyzoites which invade other cells. When this proliferative
phase is slowed down by the influence of developing host immunity and
finally ends, accumulations of zoites form true cysts and the contained
zoites are known as bradyzoites as they develop slowly (Greek brady =
slow).
These cysts may become quite large 60m and can survive for many years
- even the life time of the host. It is these latent infections that can provide
problems in humans.
Note;These cysts are infectious to carnivores (including man). Unless man
is eaten by a cat, it is a dead-end host.
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Note; Toxoplasma can only complete its sexual cycle in the cat. In the
'wrong' host, when oocysts are ingested the sporozoites hatch, cross the
gut wall and invade macrophages and almost any other cell type (except
erythrocytes) and - before any immunity develops - divide rapidly by
endodyogeny until the cell is full of them.

Members of the cat family (Felidae) are the only known definitive hosts
for the sexual stages of T. gondii and thus are the main reservoirs of
infection. Cats become infected with T. gondii by carnivorism (1). After
tissue cysts or oocysts are ingested by the cat, viable organisms are
released and invade epithelial cells of the small intestine where they
undergo an asexual followed by a sexual cycle and then form oocysts,
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which are excreted. The unsporulated oocyst takes 1 to 5 days after
excretion to sporulate (become infective). Although cats shed oocysts for
only 1 to 2 weeks, large numbers may be shed. Oocysts can survive in the
environment for several months and are remarkably resistant to
disinfectants, freezing, and drying, but are killed by heating to 70C for 10
minutes.
Mode of human infection
Human infection may be acquired in several ways:A) ingestion of
undercooked infected meat containing Toxoplasma cysts (2). B) ingestion
of the oocyst from fecally contaminated hands or food (3). C) organ
transplantation or blood transfusion. D) transplacental transmission. E)
accidental inoculation of tachyzoites. The parasites form tissue cysts, most
commonly in skeletal muscle, myocardium, and brain; these cysts may
remain throughout the life of the host.
Clinical features and Pathology (In General)
Toxoplasmosis can be congenital or acquired. Children and adults with a
normal immune system only have minor symptoms if they acquire
toxoplasma. However, neonates can develop hydrocephalus,
periventricular calcifications, and chorioretinitis if exposed in utero.
In HIV infected patients toxoplasma can cause a focal infection in the
brain.
Toxoplasmosis is greatly underdiagnosed because of diverse clinical
features and the need to confirm the diagnosis by laboratory tests which
are not universally available. Toxoplasma gondii is an intracellular
parasite. Cysts form in many organs cell but particularly in the muscles
and brain cells , rupture and sporozoites released to disseminate via blood
stream to invade many other organs and tissues cell. It cause local necrosis
, surrounded by many inflammatory cells like lymphocytes , monocytes
and plasma cells . calcification replace destroyed cells.
The principal clinical forms of toxoplasmosis are as follows:
A-Neonatal ( congenitally acquired) toxoplasmosis
Unlike that in adults , it is severe and often fatal and varies in degree of
severity with the age of the fetus at infection and the antibody protection
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from the mother. Congenital toxoplasmosis is acquired when the mother
suffers from acute toxoplasmosis during pregnancy. Intra-uterine infection
can cause severe and often fatal cerebral damage to a foetus ,usually if
infected at start of gestation period (first trimester). The mother may show
no symptoms but infection can take place across the placenta and the
foetus has a 45% chance of being infected. Congenital infections occur in
about 1-5 per 1000 pregnancies of which 5-10% result in miscarriage and
8-10% result in serious brain and eye damage to the fetus. 10-13% of the
babies will have visual handicaps. Although 58-70% of infected women
will give birth to a normal offspring, but a small proportion of these
babies will develop active retino-chorditis or mental retardation in
childhood or young adulthood. It may lead to stillbirth, abortion or
prematurity if infection occurring in early pregnancy . The newborn may
present the typical syndrome of intracerebral calcification, chorioretinitis,
hydrocephaly,or microcephaly, psychomotor disturbances, and
convulsions (see table-1-).
Table:-1-Possible Signs and Symptoms of Congenital Toxoplasmosis
in Infancy and Later in Life
Abnormal spinal fluid Hepatomegaly Mental retardation
Anemia Hydrocephalus Microcephaly
Chorioretinitis Intracranial calcifications Spasticity and palsies
Convulsions J aundice Splenomegaly
Deafness Learning disabilities Thrombocytopenia
Fever Lymphadenopathy Visual impairment
Growth retardation Maculopapular rash
The commonest clinical features and complications in the newborn
are:
(a) Lymphadenopathy, hepatomegaly, splenomegaly, Convulsion, fever
and jaundice
(b) choriodoretinitis ; Infection of the choroids and retina by toxoplasma,
may produce visual disturbances, which can be profound if the macula is
involved. On ophthalmoscopic examination, a grayish or yellow-white
area surrounded by exudates is seen early; with healing this leaves a white,
atrophic patch bordered by pigment deposits)
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(c) Hydrocephaly, or microcephaly, palsies, deafness and mental
retardation.
(d) Cerebral calcification; when cerebral calcification are found in a
patient who has retinochroiditis, toxoplasmosis is highly probable.
(e) Pneumonitis may be a part of acute toxoplasmosis in infant during the
neonatal period , and more rarely in adults.
Note; Retinchoroiditis and cerebral calcifications, hydrocephalus or
microcephaly is commonly seen in the congenital toxoplasmosis. In
congenital lesions the gliosis and calcifications are usually associated with
profound mental retardation.

B-Acquired (postnatal) toxoplasmosis
This is usually seen following the ingestion of infected inadequate cooked
meat or in laboratory workers who have been exposed to infection. The
incubation period is 7-17 days.After infection and regional lymph node
invasion, the parsite is blood borne to many organs where intracellular
multiplication takes place. Parasitemia persists for several weeks, and with
production of antibody, cyst form in various tissues. Healthy individuals
do not usually display symptoms. When symptoms do occur, they are
usually mild, may be influenza-like resembling infectious mononucleosis,
persisting for several weeks with fever, weakness, malaise, headache,
lymphadenopathy (usually cervical glands), myalgia, anorexia, arthralgia
and occasionally hepatitis, and sometimes a rash. Myocarditis also may be
seen in acute toxoplasmosis in both infants and adults. In adults, if the
infection continues for an extended period of time, chronic toxoplasmosis
can cause an inflammation of the eyes called retinochoroiditis, which can
lead to blindness, severe yellowing of the skin and whites of the eyes
(Jaundice), easy bruising, and convulsions.
Adults with weakened immune systems have a high risk of developing
cerebral toxoplasmosis, including inflammation of the brain
(Encephalitis), one-sided weakness or numbness, mood and personality
changes, vision disturbances, muscle spasms, and severe headaches. If
untreated, cerebral toxoplasmosis can lead to Coma and Death. This form
of encephalitis is the most common in AIDS-related nervous system
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infection that takes advantage of a person's weakened immune system
(opportunistic infection see below).
Note; One of the variants of acute toxoplasmosis is a typhus-like fever,
with a macular rash , prostration, and sometimes stupor and cardiac
decompensation.
Note;Choriodoretinitis may be a complication of both neonatal and
acquired toxoplasmosis. It is usually a unilateral chronic infection and
may be a presenting feature in patients with AIDS.
Laboratory diagnosis
Infection is confirmed directly by demonstrating the parasite in tissues or
by culture, or by animal inoculation, or indirectly by detecting antibodies
or antigens. In acquired toxoplasmosis , blood lymphocytosis is common
finding .
Demonstration of parasites. The tachyzoites or bradyzoites can be seen
in smears from infected tissues after stainining with Giemsa, or they can
be seen in histological preparations stained with hematoxylin and eosin.
Occasionally in acute infection a diagnosis can be confirmed by
identifying toxoplasms in Giemsa or field stained preparations of lymph
gland biopsy, bone marrow aspiration, cerebrospinal fluid, peritoneal or
pleural fluids or even sputum. Note: diagnosis is seldom made by recovery
of the organisms, the only practical laboratory tests of value are the
various serologic procedures that have been employed for diagnostic
purposes.
Serological tests: Serologic diagnosis in congenital toxoplasmosis is
feasible immediately after birth if specific IgM antibodies can be
demonstrated (if such antibodies are present, they must have been formed
by the infant in response to an active infection because IgM antibodies
cannot cross the placenta). The Sabin-Feldman dye test titres are in
excess of 1:1000 in mother and fetus ( This test is sensitive but because it
require the use of live toxoplasms, it is not widely used) and replaced by
other more recently developed tests which do not require the use of viable
parasites such as( IFAT, ELISA).
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Note: At birth if the baby asymptomatic or carry symptoms and signs of
congenital toxoplasmosis (chorioreinitis , hydrocephalus, intracerebral
calcification, and convulsion). Do serology test for specific IgM .
Pregnant women screening
Toxoplasmosis screening only in high-risk persons or those in whom
routine ultrasound examination (or ultrasonography performed for other
reasons) shows findings such as hydrocephalus, intracranial calcifications,
microcephaly, fetal growth retardation, ascites, or hepatosplenomegaly.
Screening tests may have equivocal or false-positive results that could lead
to inappropriate treatment or the termination of pregnancy. However,
women with HIV infection should be screened for toxoplasmosis because
of the risk of T. gondii reactivation and toxoplasmic encephalitis.
Diagnostic tests
When acute T. gondii infection is suspected in a pregnant woman, the
diagnosis should be pursued. Toxoplasmosis usually is diagnosed on the
basis of antibody detection. In acute infection, IgG and IgM antibody
levels generally rise within one to two weeks of infection.
The presence of elevated levels of T. gondiispecific IgG antibodies
indicates that infection has occurred but does not distinguish between
recent infection and infection acquired in the distant past. Detection of T.
gondiispecific IgM antibodies has been used as an aid in determining the
time of infection:
Serologic testing is the mainstay in diagnosing toxoplasmosis.
First trimester - IgM (-), IgG (-)
There is no infection. Testing could be repeated at 22-24 week and before
delivery. In case of seroconversion amniocentesis for detection of
parasites, polymerase change reaction (PCR), after that - treatment of the
mother and infected child.


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IgM (+), IgG (-)
primary infection. Repeat the testing 2 weeks later IgG should then show
seroconversion, otherwise false positive IgM. If IgG positive treatment
should be advised.
IgM (+), Ig G (+).
Because IgM remain positive from 3 months to two years. So, the
interpretation of T. gondii specific IgM-positive results is complicated by
the persistence of IgM antibodies up to 24 months after infection and by
false-positive reactions. IgM-positive test results should be confirmed by a
Toxoplasma reference laboratory . and Avidity test is indicated for
decision of the time of infection.
IgM (-), Ig G (+)
Immunity. There is no need for further investigation and treatment.
Note:When a pregnant woman is found to be infected with T. gondii, the
next step is to determine whether the fetus is infected.
Prenatal diagnosis: of congenital toxoplasmosis may be made by
detecting specific anti-toxoplasma IgM Ab in fetal blood (as mentioned
before). Ultrasound examination of the fetus to detect enlargement of the
cerebral ventricles. Additionally Physicians most often use the polymerase
chain reaction (PCR) has been used to detect a gene sequence specific for
Toxoplasma in sample of amniotic fluid. PCR testing of amniotic fluid is
safer and more sensitive than fetal blood sampling, and it allows earlier
confirmation of fetal infection. Because of the high likelihood of fetal
damage, abortion may be considered if T. gondii infection is confirmed
and infection is thought to have occurred before the 16th week of
pregnancy or if the fetus shows evidence of hydrocephalus.
Opportunistic toxoplasmosis
In immunocompromised persons (including patients with AIDS),
toxoplasmosis is usually the result of a recrudescence of a primary
infection or a newly acquired acute infection. Although Toxoplasma
infection is common, it rarely produces symptoms in normal individuals.
Its serious consequences are limited to pregnant women and
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immunodeficient hosts. In adults toxoplasmosis is almost symptomless but
may result in fever and swelling. The most important factor in
pathogenicity in adults is the immune status of the infected individual.
About 30% of AIDs patients who have toxoplasma-specific antibodies
suggestive of a past infection will develop toxoplasma encephalitis in the
course of their illness - i.e. cysts develop in the brain. It is almost probable
that illness in a result of a reactivated latent infection. That is, cysts with
bradyzoites are present, but do no further damage in the immune
competent person. Once an individual become immuncompromised then
the parasite can emerge again and infect other organs etc. Prognosis for
AIDS patients or immunocompromised individuals, infection results in
generalized parasitemia involvement of brain, liver, lung and other organs,
and often death.
Note: In AIDS patients, the toxoplasma lesion presents as a mass lesion;
in fact, it is the most comman mass lesion of the brain in this disease. It
usually appears as hemorrhagic and necrotic without a capsule but
associated with a considerable amount of edema. In AIDS patients the
toxoplasma abscess with its edema acts as a mass lesion, producing
symptoms according to the area affected. In the left speech areas it may
cause aphasia, in the cerebellum, ataxia etc.
Treatment
Most individuals who contract toxoplasmosis do not require treatment
because their immune systems are able to control the disease. Symptoms
are not usually present. Mild symptoms may be relieved by taking
symptomatic treatment e.g antipyretic and analgesic, such as
acetaminophen (Tylenol) and ibuprofen (Motrin, Advil). Sore throat
lozenges and rest may also ease the symptoms.
Although the treatment of women infected with toxoplasmosis during
pregnancy is controversial, most physicians feel that treatment is justified..
If the presence of acute T. gondii infection in a pregnant woman is
confirmed, treatment with spiramycin (Rovamycine) can be initiated in an
effort to prevent transmission to the fetus. Later in a pregnancy , if the
fetus has contracted the disease, treatment with the antibiotic
pyrimethamine (Daraprim, Fansidar) or sulfonamides may be effective.
If fetal infection is confirmed through amniocentesis, the woman may be
switched to pyrimethamine (Daraprim) and sulfadiazine after the first
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trimester or, according to some experts, after the 18th week of gestation.
Folinic acid (leucovorin) is given with pyrimethamine and sulfadiazine to
protect bone marrow from the suppressive effects of pyrimethamine.
Pyrimethamine generally is not recommended for use in pregnant women
because it is a folic acid antagonist , and can cause bone marrow
suppression in both mother and infant. historical observational studies
suggest that treatment is beneficial, and a recent multicenter observational
study found that treatment in pregnancy was associated with a reduction of
sequelae in infants but not a reduction in maternal-fetal transmission.
Babies born with toxoplasmosis who show symptoms of the disease may
be treated with pyrimethamine, the sulfa drug sulfadiazine (Microsulfon),
and folinic acid (an active form of folic acid). and leucovorin for one year.
Infants are also sometimes given steroids if their vision is threatened or if
the protein level in the spinal fluid is high.
In AIDS patients who have not been infected may be given a drug called
Trimethoprim/sulfametoxazole=TMP/SMX (Bactrim or Septra) to prevent
toxoplasmosis infection. To treat cases of toxoplasmosis in
immunocompromised AIDS patients, a combination of pyrimethamine and
a sulfa-based drug, either sulfadiazine or clindamycin (Cleocin), have
been used together and can be effective in treating this disease.
Note:Intravenous clindamycin has been used to treat toxoplasma
encephalitis in patients with AIDS (see below).
Prevention of Toxoplasmosis
To prevent toxoplasmosis especially pregnant women and other food-
borne illnesses, food should be cooked to a safe temperature (71.1C
[160F]). A food thermometer should be used to ensure that meat is
cooked all the way through. Fruits and vegetables should be peeled or
thoroughly washed before they are eaten. Cutting boards, dishes, counters,
utensils, and hands should be washed with hot soapy water after they have
been in contact with raw meat, poultry, or seafood, or with unwashed
fruits or vegetables. Pregnant women should wear gloves when they are
gardening or touching soil or sand, because of the possible presence of cat
feces. Afterwards, they should wash their hands thoroughly. If possible,
pregnant women should avoid changing cat litter pans. If no one else is
available to change the cat litter, pregnant women should wear gloves for
this task and then wash their hands thoroughly. The litter box should be
changed daily, because Toxoplasma gondii oocysts require more than 1
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day to become infectious. Pregnant women should be encouraged to keep
their cats inside and not to adopt or handle stray cats. Cats should be fed
only canned or dried commercial cat food or well-cooked table food; they
should not be given raw or undercooked meat. Health education for
women of childbearing age should include information about preventing
T. gondii transmission from food and soil. At the first prenatal visit, health
care providers should educate pregnant women about food hygiene and
avoiding exposure to cat feces. Health care providers who care for
pregnant women should be educated about two potential problems
associated with T. gondii serology tests: (1) no assay can determine
precisely when initial T. gondii infection occurred; (2) in populations with
a low incidence of T. gondii infection (e.g., U.S. population), a substantial
proportion of positive IgM test results probably will be false positive. The
government and meat industry should continue efforts to reduce the
presence of T. gondii in meat.
Prognosis
The prognosis is poor when congenital toxoplasmosis is acquired during
the first three months of pregnancy. Afflicted children die in infancy or
suffer damage to their central nervous systems that can result in physical
and mental retardation. Infection later in pregnancy usually results in
only mild symptoms, if any. The prognosis for acquired toxoplasmosis in
adults with strong immune systems is excellent. The disease often
disappears by itself after several weeks. However, the prognosis for
immuniodeficient patients is not as positive. These patients often relapse
when treatment is stopped. The disease can be fatal to all
immunocompromised patients, especially AIDS patients, and particularly
if not treated. As a result, immunocompromised patients are typically
placed on anti-toxoplasmosis drugs for the rest of their lives.
Sarcocystis spp.
These organisms are parasites of carnivorous definitive hosts (dogs,
specifically) and herbivorous intermediate hosts, rodents. Most of the
parasitologist place the genus sarcocystis under the sporozoa. Sarcocystis
were first described in mice in 1843, since that time have been reported
from numerous other mammals, especially sheep, cattle, birds, and pigs,
and rarely horses,. Humans are an accidental intermediate host of several
species of sarcocystis. Previously called Isospora hominis.
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Morphology
Some sarcocystis cyst may measure less than the 100m up to 5 cm. The
limiting membrane may show radial striations. This description
differentiate it from Toxoplasma , upper limit of size of toxoplasma for the
cysts rarely reach 100m , and no striation in the limiting membrane. The
contained trophozoites (bradyzoites) are considerably larger than those of
toxoplasma, measuring 4 to 9 m in breadth and 12 to 16 m in length.
Life Cycle
Sporocysts are released in the feces of the definitive host. These are
consumed by the intermediate host. In the intermediate host, the
sporozoites from the sporocysts penetrate intestinal epithelial tissue and
spread throughout the body via blood vessels to various areas, including
the brain. Some behavioral problems are caused by infection of neural
tissue with Sarcocystis spp. In tissue, sporozoites become schizonts and
then encyst. The definitive host becomes infected with the cysts upon
eating the intermediate host. Then the sporozoites of the oocysts penetrate
the definitive host's small intestine, where gametes are formed. Oocysts
develop and then sporulate. These oocysts are released in the feces of the
definitive host.

Clinical features and Pathology
In the definitive host, the parasite is not very pathogenic. However, in the
intermediate host's brain, muscle, and kidney tissues may be damaged by
infection. Infection of the intermediate host causes a loss of appetite,
fever, weight loss, anemia, and death in severe in infections. It also cause
gait abnormalities, weakening of the limbs, muscle wasting, and head tilt.
The animal may also move in circles. It has been known to cause abortion
in pregnant animals. The number of clinical signs that appear is
proportional to the number of Sarcocystis organisms parasitizing the host.
Most human cases are asymptomatic, except in heavy infection. In some
cases local symptoms such as myositis, characterized by infiltration by
lymphocytes, plasma cells, and eosinophls. Generalized symptoms
including pain and swelling of an isolated muscle, dyspnea, and wheezing,
associated with eosinophilia. In 22 cases of human infection , parasite was
found in the skeletal muscles or in the musceles of larynx, heart, and
tonque.

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Laboratory diagnosis
Sporulated oocysts and sporocysts of Sarcocystis spp. may be found in
fecal flotations of definitive hosts (cats, dogs, and other carnivorous
animals). They are about 12 microns in length and are oblong or
cylindrical in shape. Within the sporocysts, long and sort of teardrop-
shaped sporozoites may be seen. In the intermediate host, schizonts may
be found in the skeletal muscle or in brain tissue . A western blot may be
performed to test for antibodies in blood serum and cerebrospinal fluid
last. They have a somewhat thick covering and contain several
bradyzoites, which resemble coccidian merozoites (elongated, somewhat
dark structures).
Treatment
Rest and bland diet. Chemotherapy is not available and probably is
unnecessary, since the infection is self limited. Sulfonamides and
nitrofurantoin are curative in poultry and domestic animal infection.











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CHAPTER NINE (9)
Microsporidiosis( Encephalitozoon cuniculi/helen etc infection)
Microsporidia is obligate intracellular protozoan parasites belonging to the
phylum microsporidia. Microsporidia are tiny protozoan parasites ,about
which very little is known. Because they are so difficult to diagnose, very
little work has been done into their importance in human disease,
Etiology
More than 1,200 species belonging to 143 genera have been described as
parasites infecting a wide range of vertebrate and invertebrate hosts. There
are at least 14 microsporidian species that have been identified as human
pathogens: Brachiola algerae, B. connori, B. vesicularum,
Encephalitozoon cuniculi, E. hellem, E. intestinalis, Enterocytozoon
bieneusi Microsporidium ceylonensis, M. africanum, Nosema ocularum,
Pleistophora sp, Trachipleistophora hominis, T. anthropophthera,
Vittaforma corneae. Encephalitozoon intestinalis was previously named
Septata intestinalis, but it was reclassified as Encephalitozoon intestinalis
based on its similarity at the morphologic, Microsporidia have also been
implicated in causing disease in immunocompromised hosts.
Morphology
The microsporidia spores of species associated with human infection
measure from 1 to 4 m and that is a useful diagnostic feature. The spores
measure from 0.8 to 1.4 m in the case of Enterocytozoon bieneusi, and
1.5 to 4 m in Brachiola algerae, Encephalitozoon spp., Vittaforma
corneae, and Nosema spp. Microsporidia, are characterized by the
production of resistant spores that vary in size, depending on the species.
Epidemiology
Microsporidia are being increasingly recognized as opportunistic
infectious agents worldwide. Cases of microsporidiosis have been
reported in developed as well as in developing countries, including:
Argentina, Australia, Botswana, Brazil, Canada, Czech Republic, France,
Germany, India, Italy, Japan, The Netherlands, New Zealand, Spain, Sri
Lanka, Sweden, Switzerland, Thailand, Uganda, United Kingdom, United
States of America, and Zambia.
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Transmission and Life cycle

The infective form of microsporidia is the resistant spore and it can
survive for a long time in the environment (1). The spore extrudes its
polar tubule and infects the host cell (2). The spore injects the infective
sporoplasm into the eukaryotic host cell through the polar tubule (3).
Inside the cell, the sporoplasm undergoes extensive multiplication either
by merogony (binary fission) or schizogony (multiple fission) (4). This
development can occur either in direct contact with the host cell cytoplasm
(e.g., E. bieneusi) or inside a vacuole termed parasitophorous vacuole
(e.g., E. intestinalis). Either free in the cytoplasm or inside a
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parasitophorous vacuole, microsporidia develop by sporogony to mature
spores (5). During sporogony, a thick wall is formed around the spore,
which provides resistance to adverse environmental conditions. When the
spores increase in number and completely fill the host cell cytoplasm, the
cell membrane is disrupted and releases the spores to the surroundings (6).
These free mature spores can infect new cells thus continuing the cycle.
Clinical features and Pathology
Human microsporidiosis represents an important and rapidly emerging
opportunistic disease, occurring mainly, but not exclusively, in severely
immunocompromised patients with AIDS. Additionally, cases of
microsporidiosis in immunocompromised persons not infected with HIV
as well as in immunocompetent persons also have been reported. The
clinical manifestations of microsporidiosis are very diverse, varying
according to the causal species with diarrhea being the most common
(Table-1-).
Note; Enterocytozoon bieneusi, infect enerocytes , has been shown to
cause a persistent watery diarrhea in patients with AIDS.
Table:-1- The common Microsporidia clinical features.
Brachiola algerae Keratoconjunctivitis, skin and deep
muscle infection
Enterocytozoon bieneusi Diarrhea, acalculous cholecystitis
Encephalitozoon cuniculi and
Encephalitozoon hellem
Keratoconjunctivitis, infection of
respiratory and genitourinary tract,
disseminated infection
Encephalitozoon intestinalis (syn.
Septata intestinalis)
Infection of the GI tract causing
diarrhea, and dissemination to
ocular, genitourinary and
respiratory tracts
Microsporidium (M. ceylonensis
and M. africanum)
Infection of the cornea
Nosema sp. (N. ocularum),
Brachiola connori
Ocular infection
Pleistophora sp. Muscular infection
Trachipleistophora
anthropophthera
Disseminated infection
Trachipleistophora hominis Muscular infection, stromal
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keratitis, (probably disseminated
infection)
Vittaforma corneae (syn. Nosema
corneum)
Ocular infection, urinary tract
infection
Laboratory diagnosis
There are several methods for diagnosing microsporidia:
Light microscopic examination The most widely used staining technique
is the Chromotrope 2R method or its modifications. This technique stains
the spore and the spore wall a bright pinkish red. This technique, however,
is lengthy and time consuming and requires about 90 min. A recently
developed Quick-Hot Gram Chromotrope technique however, cuts
down the staining time to less than 10 min and provides a good
differentiation from the lightly stained background fecal materials so that
the spores stand out for easy visualization. The spores stain dark violet.
Transmission electron microscopy (TEM) is still the gold standard and
is necessary for the identification of the microsporidian species. However,
TEM is expensive, time consuming, and not feasible for routine diagnosis.
Immunofluorescence assays (IFA) using monoclonal and/or polyclonal
antibodies are being developed for the identification of microsporidia in
clinical samples.
Molecular methods (mainly Polymerase Chain Reaction, PCR) is an
alternative method for the laboratory diagnosis of microsporidiosis. PCR
is available only in research laboratories and has been successfully used
for the identification ofBrachiola algerae, Enterocytozoon bieneusi,
Encephalitozoon intestinalis, Encephalitozoon hellem, and
Encephalitozoon cuniculi. .
Treatment
The treatment of choice for ocular microsporidiosis (Brachiola algerae,
Encephalitozoon hellem, E. cuniculi, Vittaforma corneae) is oral
albendazole plus topical fumagillin. Corneal infections with V. corneae
often do not respond to chemotherapy and may require keratoplasty. Oral
fumagillin has been effective to treat Enterocytozoon bieneusi infections,
but it has been associated with thrombocytopenia. Albendazole is the drug
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of choice to treat gastroenteritis caused by Encephalitozoon intestinalis
and to treat disseminated microsporidiosis (E. hellem, E. cuniculi, E.
intestinalis, Pleistophora sp., Trachipleistophora sp., Brachiola
vesicularum) and skin and deep muscle infection (Brachiola algerae).


















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CHAPTER TEN (10)
Helminths
Helminth is a general term meaning worm. The helminths are
invertebrates characterized by elongated, flat or round bodies. In
medically oriented schemes the flatworms or platyhelminths (platy from
the Greek root meaning "flat") include flukes and tapeworms.
Roundworms are nematodes (nemato from the Greek root meaning
"thread"). These groups are subdivided for convenience according to the
host organ in which they reside, e.g., intestinal tapeworms, roundworms,
extraintestinal tapeworms, and flukes . Helminths develop through egg,
larval (juvenile), and adult stages. Nematodes and Platyhelminths that
infect humans have similar anatomic features that reflect common
physiologic requirements and functions. The outer covering of helminths
is the cuticle or tegument. Prominent external structures of cestodes are
acetabula (suckers) or bothria (false suckers). Male nematodes of several
species possess accessory sex organs that are external modifications of the
cuticle. Internally, the alimentary, excretory, and reproductive systems can
be identified by an experienced observer. Tapeworms are unique in
lacking an alimentary canal. This lack means that nutrients must be
absorbed through the tegument. The blood flukes and nematodes are
bisexual. All other flukes and tapeworm species that infect humans are
hermaphroditic. With few exceptions, adult flukes, cestodes, and
nematodes produce eggs that are passed in excretions or secretions of the
host. The various stages and their unique characteristics will be reviewed
in more detail as each major group of helminths is considered (see below).












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Flukes (Trematodes)

Introduction
The structure of flukes is summarized in dorsoventrally flattened body,
bilateral symmetry. Flukes are leaf-shaped, ranging in length from a few
millimeters to 7 to 8 cm. Flukes possess an oral sucker around the mouth
and a ventral sucker or acetabulum that can be used to adhere to host
tissues. A body cavity organs are embedded in specialized connective
tissue or parenchyma. Flukes have a well-developed alimentary canal with
a muscular pharynx and esophagus. The intestine is usually a branched
tube (secondary and tertiary branches may be present) consisting of a
single layer of epithelial cells. The main branches may end blindly or open
into an excretory vesicle. Except for the blood flukes, trematodes are
hermaphroditic, having both male and female reproductive organs in the
same individual. Fluke eggs, except for those of schistosomes, are
operculated (have a lid).The blood flukes or schistosomes are the only
bisexual flukes that infect humans. Although the sexes are separate, the
general body structure is the same as that of hermaphroditic flukes. Within
the definitive host, the male and female worms inhabit the lumen of blood
vessels and are found in close physical association. The female lies within
a tegumental fold, the gynecophoral canal, on the ventral surface of the
male. The medically important flukes belong to the taxonomic category
Digenea. This group of flukes has a developmental cycle requiring at least
two hosts, one being a snail intermediate host. Depending on the species,
other intermediate hosts may be involved to perpetuate the larval form that
infects the definitive human host. Flukes go through several larval stages,
each with a specific name, before reaching adulthood. A generalized life
cycle of digenetic flukes runs the following course. Eggs are passed in the
feces, urine, or sputum of humans and reach an aquatic environment. The
eggs hatch, releasing ciliated larvae, or miracidia, which either penetrate
or are eaten by a snail intermediate host. In rare instances land snails may
serve as intermediate hosts. A saclike sporocyst or redia stage develops
from a miracidium within the tissues of the snail. The sporocyst gives rise
either to rediae or to a daughter sporocyst stage. In turn, from the redia or
daughter sporocyst, cercariae develop asexually and migrate out of the
snail tissues to the external environment, which is usually aquatic. The
cercariae, which may possess a tail for swimming, develop further in one
of three ways. They either penetrate the definitive host and transform
directly into adults, or penetrate a second intermediate host and develop as
encysted metacercariae, or they encyst on a substrate, such as vegetation,
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and develop there as metacercariae. When a metacercarial cyst is ingested,
digestion of the cyst liberates an immature fluke that migrates to a specific
organ site and develops into an adult worm.


Generalized life cycle of flukes. All cycles involve snails as intermediate
hosts. Hermaphroditic flukes - Clonorchis sinensis, Fasiolopsis buski,
Paragonimys westermani, and Heterophytes heterpphyes. Metacercaria are
infective for humans. Bisexual flukes: Schistosoma japonicum, S mansoni,
and S hematobium. Cercariae are infective for humans.

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Schistosomiasis/Bilharziasis (Schistosoma species infection)
Schistosomiasis is also known as bilharzia or bilharziasis after german
pathologist Theodor Bilharz who first discovered the parasites in Egypt in
1851. The infection is wide spread with a relatively low mortality rate but
very high morbidity rate-causing severe debilitating illness in millions of
people. It is often associated with water development projects, such as
dams and irrigations schemes, where the snail intermediate hosts of the
parasite breed in water where people swim, wash and fishing.
Etiology
Schistosomiasis is caused by blood trematodes. The three main species
infecting humans are Schistosoma haematobium, S. japonicum, and S.
mansoni. Two other species, more localized geographically, are S.
mekongi and S. intercalatum. In addition, other species of schistosomes,
which parasitize birds and mammals, can cause cercarial dermatitis in
humans see below.
Morphology
Mature S.haematobium flukes; The male fluke is short and cylindrical,
measuring 10-15x 0.8 1.0 mm. The female is longer and thinner,
measuring 20-26 x 0.25 mm and appears darker than the male. The body
surface of the male is covered with small tubercles (rounded knobs).
Mature S. mansoni flukes; The male flukes is short and cylindrical,
measuring 6-13 x 1.0mm. The female is longer and thinner and darker the
male measuring 7-17x0.25 mm. The body surface of the male is covered
with prominent tubercles.
Epidemiology
Schistosomiasis is a prevalent parasitic infection, with an estimated 200
million people worldwide affected. Estimated mortality rate: <200
000/year .Number of people considered at risk: 500-600 million ,Number
of countries affected= 76. 80-85% of current disease now found in sub-
Saharan Africa, the number of people infected is not decreasing.
Schistosoma mansoni is found in parts of South America and the
Caribbean, Africa, and the Middle East; S. haematobium in Africa and the
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Middle East; and S. japonicum in the Far East. S. intercalatum in small
foci in Africa, and S. mekongi in the Mekong river basin of SE Asia).
Transmission
In water, larval stages of schistosomes (known as cercaria) are shed from
infected snails and penetrate the skin of people in the water. Bulinus
snails, is an intermediate host for Schistosoma haematobium.
Biomphalaria , Oncomelania snails are an intermediate hosts for S.
mansoni and S. japonicum respectively.
Life Cycle
Eggs are eliminated with feces or urine (1). Under optimal conditions the
eggs hatch and release miracidia (2), which swim and penetrate specific
snail intermediate hosts (3). The stages in the snail include 2 generations
of sporocysts (4)and the production of cercariae (5). Upon release from
the snail, the infective cercariae swim, penetrate the skin of the human
host (6), and shed their forked tail, becoming schistosomulae (7). The
schistosomulae migrate through several tissues and stages to their
residence in the veins (8), (9). Adult worms in humans reside in the
mesenteric venules in various locations, which at times seem to be specific
for each species (10). For instance, S. japonicum is more frequently found
in the superior mesenteric veins draining the small intestine (A), and S.
mansoni occurs more often in the superior mesenteric veins draining the
large intestine (B). However, both species can occupy either location, and
they are capable of moving between sites, so it is not possible to state
unequivocally that one species only occurs in one location. S.
haematobium most often occurs in the venous plexus of bladder (C), but it
can also be found in the rectal venules. The females (size 7 to 20 mm;
males slightly smaller) deposit eggs in the small venules of the portal and
perivesical systems. The eggs are moved progressively toward the lumen
of the intestine (S. mansoni and S. japonicum) and of the bladder and
ureters (S. haematobium), and are eliminated with feces or urine,
respectively (1). Various animals, such as dogs, cats, rodents, pigs, hourse
and goats, serve as reservoirs for S. japonicum, and dogs for S. mekongi.
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Clinical features
Clinical manifestations range from cercarial dermatitis (a maculopapular
eruption due to cercariae migrating through the epidermis) to acute
schistosomiasis ( Katayama fever, consisting of fever, generalized
adenopathy, and eosinophilia) to chronic schistosomiasis (due to adult
worms in the venules of particular organs).
Adult male and female schistosomes live together in blood vessels of
different organs; they release eggs--some of which are passed out in the
urine (S. haematobiurn) or stools (S. mansoni, S. japonicum), but some
eggs become lodged in the tissues. Reactions to schistosome eggs lodged
in the tissues are the cause of disease in schistosomiasis. Penetration of
schistosome cercaria through the skin causes (Swimmer itch) localized
edema and pruritus, mild in case of human schistosomes, more severe by
bird schistosome cercaria.which is quite common in north Europe, north
America and south east Asia (see below).
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Many infections are asymptomatic. In schistosomiasis japonicum the
early symptoms tend to be quite sever in heavily infected persons, with
abrupt onset of fever, chills, and cough, abdominal pain, diarrhea,
hepatospenomegaly, and eosinophilia. Occur from 4 to 6 weeks after
infection. There is often a significant mortality at this stage of the disease.
In Intestinal schistosomiasis (see complications below)(due to S.
mansoni, S. japonicum or S. mekongi) the disease slower to develop. There
is progressive enlargement of the liver and spleen as well as damage to the
intestine, due to fibrotic lesions around the schistosome eggs (granuloma)
lodged in these tissues and hypertension of the abdominal blood vessels.
Repeated bleeding from these vessels leads to blood in the stools, and can
be fatal.
Occasionally central nervous system lesions occur: cerebral
granulomatous disease may be caused by ectopic S. japonicum eggs in the
brain, and granulomatous lesions around ectopic eggs in the spinal cord
from S. mansoni and S. haematobium infections may result in a transverse
myelitis with flaccid paraplegia. Continuing infection may cause
granulomatous reactions and fibrosis in the affected organs, which may
result in manifestations that include: colonic polyposis with bloody
diarrhea (Schistosoma mansoni mostly). Hepatic perisinusoidal egg
granulomas, Symmers pipe stem periportal fibrosis, portal hypertension
with hematemesis and splenomegaly (S. mansoni, S. japonicum); In
schistosomiasis mansoni and japonicum, there is diarrhea, presumably of
toxic origin , associated with nausea, vomiting, hepatic tenderness, fever,
eosinophilia.. Somewhat later, with the beginning of egg deposition in the
intestinal wall , there may be profuse diarrhea or dysentery.
In Urinary schistosomiasis (see complication below)(due to S.
haematobiurn), damage to the urinary tract is revealed by blood in the
urine (haematuria), so common among adolescent boys in the Nile river
vally as to have been widely considered phenomenon analogous to the
menarche in girls. Haematuria beginning as early as 3 months after
infection or sometimes not until several years later, there may be
intermittent hematuria. Eosinophiluria is a constant finding and chronic
bacteriuria is common. Urination becomes painful and there is progressive
damage to the bladder, ureters, and then to the kidneys. cystitis and
ureteritis usually with terminal hematuria, which can progress to bladder
cancer, Bladder cancer is quite common in advanced cases Note;
Pulmonary hypertension (S. mansoni, S. japonicum, more rarely S.
haematobium). A nephritic syndrome is occasionally seen in both
S.mansoni and S.haematobium infection; immune comlex nephropathy
has occasionally been demonstrated.
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Note: Occasional embolic egg granulomas in brain or spinal cord (see
ectopic below) .Rarely, with a very low dietary iron intake, iron deficiency
anaemia may result.

Swimmer itch

A local cutaneous itch can occur where cercariae penetrate. Slight
erythema and pruritic papules develop. This is well known with S.
mansoni, S. haematobium and with S. japonicum. The itch is more
frequent and violent in infections with animal schistosomes, probably
because the cercariae die after penetration in humans (e.g. avian
schistosomiasis, which also occurs in areas with a moderate climate) (see
below).

Katayama fever

Acute schistosomiasis, called Katayama fever in Japan and safari's fever in
Africa, is an immunoallergic reaction due to transcutaneous penetration of
infective cercaria.
The Katayama valley in Japan was an area that was hyperendemic for S.
japonicum. [Note; Do not confuse Katayama fever with Kawasaki
syndrome]. The name of this place is now used to indicate acute
schistosomiasis in general. A severe disease syndrome was often observed
among immigrants in this valley and became known as Katayama fever.
The theory is that as the worm begin to lay eggs, soluble antigen leaks out
of the eggs and into the circulation . This Ag/Ab complex formation , with
the development of generalized immune complex disease called
{(katayama fever) see below}. Spontaneous recovery may be related to
restoration of Ag/Ab balance as the infection matures and antibody
production increases.The disease is caused by primary infection with
schistosomes and a violent reaction to products (Antigens) released from
the eggs. Signs of acute japonicum or mansoni schistosomiasis can occur 4
to 8 weeks after initial infection. It takes the form of fever, general
discomfort, abdominal pain, diarrhoea, vomiting, flu-like syndrome with
muscle and joint pain, severe dry cough, wheezing, urticaria and
sometimes lymph node enlargement and hepatosplenomegaly. There is
marked eosinophilia. Katayama fever is less frequent and milder in S.
haematobium infections.



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Diagnosis and treatment of Katayama fever
Katayama fever tends to occur in patients who are not previously
exposed, although in the case of S. japonicum this syndrome can
also occur on re-infection.
History of recent exposure, freshwater contact in endemic area
Respiratory disorder and abdominal discomfort with fever and
eosinophilia (DD trichinellosis, fascioliasis, filariasis, Strongyloides
hyperinfection, etc.)
Note :that the eggs usually only appear later in the faeces. Failure
to detect eggs thus does not rule out Katayama fever.
Serology is initially still negative in early samples, but will become
positive a couple of weeks later.
Treatment consists of praziquantel and steroids. Repeat the course
of praziquantel after a few months. Praziquantel is only active
against adult worms.
Pathological processes and complication

the main pathological reactions related to the retained eggs . This reaction
which follows sensitization to egg antigens, is a circumoval Granuloma.
It results from combined humoral and cell mediated immunity (CMI)
attack on the egg, and granuloma occupies several hundred times the
volume of the egg itself. Its characteristics are: (Epitheloid and giant cells,
lymphocytes and eosinophils) arranged in concentric fashion around the
egg. The cellular contents diminishes with the time to be replaced by
fibroblasts and a collagenous scar. Precipitation of Ag/Ab complex on the
egg surface helps activate inflammation. The duration of vigorous cellular
response to a single egg lasts a few week. If egg-laying is stopped by
chemotherapy , the cellular component of the granuloma usually resolve in
2 or 3 months. Large numbers of eggs reaching the periportal regions
cause a granulomatous response which leads to gradual occlusion of the
intrahepatic portal veins .
Circumoval tissue proliferation leading to extensive fibrosis of the liver in
S.mansoni and S.japonicum infections may lead eventually to cirrhosis.
Sever and longstanding S. mansoni infections cause a characteristic liver
disease called Symmers pip stem fibrosis (This fibrous tissue may finally
come to surround the branches of the portal vein in a thick white layer,
visible grossly as the clay pipestem). Eggs are laid in the bladder , not
singly, but usually in (clutches). The eggs give rise to a granulomatous
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lesion up to several centimeters in diameter (Fig-1-). Most commonly
these fleshy lesions form simulate tumour and so called
(pseudopapilloma). They may be sessile (flat) or pedunculated (on stalks).
Smaller deposits cause lesions a few millimeters in diameters resembling
tubercles (sandy patches), and there may be areas of ulceration. Not all
granulomata lead to scars. These pathological processes occur , with
variation , in all the schistosome infections. They help to explain the
following features or complications in schistosomiasis:




Fig:-1- Schistosoma mansoni eggs granuloma in the liver.

A-S.haematobium complications
1-obstructive uronephropathy: When granulomata form near the ureteric
orifices or in the ureters themselves, the ureters may become obstructed
and the secondary effects of this obstruction are hydroureter and later
hydronephrosis, pyelonephritis and nephritic syndrome may occur due to
immune complex deposition . In the most sever cases , kidney drainge
may be so impaired as to cause uraemia.
2- Calcification of the bladder
This is common due to calcification of the eggs, not of the bladder itself.
Also the ureter may be calcified in heavy infection . these calcification
reduce bladder capacity due to thickening and rigidity of its wall.
Carcinoma (sequamous cell type) in the bladder and kidney stones
associated with chronic obstruction are also common in urinary
schistosomiasis.
3- Cor pulmonale
Eggs escaping from the pelvic veins into the caval circulation reach the
lungs. And granuloma may cause obstruction in pulmonary arterioles.
Pulmonary hypertension, right ventricular hypertrophy and congestive
heart failure may follow.
4-Elephantiasis
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Extensive egg deposition may lead to fibrosis that block lymphatic
drainge, and to subsequent elephantiasis of the penis.
B-S. mansoni /japonicum complications
Most patients with S.mansoni infections have few or no symptoms. blood
loss may contribute to iron deficiency anaemia.
1-Pseudopolyposis of the colon
Granulomata in the large intestine may develop into papilloma like
outgrowths of the mucosa. They may ulcerate and bleed, and cause
symptoms of dysentery.
2-Liver fibrosis/cirrhosis
Lead to Portal hypertension and its complications, haematemesis-bleeding
from oesophageal varices). In late cases , hepatic perfusion may be so
impeded that the peripheral liver ischaemia occurs. Then features of true
cirrhosis may develop (oedema, ascites and even anasarca due to
hypoalbuminaemia and water retention. Impaired synthesis of coagulation
factors leads with oesophageal varices to gastrointestinal hemorrhage etc)
(Fig-2-). When portocaval shunts are well established, the eggs of
S.mansoni may by pass the liver in large numbers, and so reach the lungs
and lead to cor pulmonale.



Fig:-2- A boy have ascites due to portal hypertension, liverfibrosis.
Bilharzia. Schistosomiasis. Schistosoma mansoni (note; distended
abdomen). Photo Dr Van den Enden.
Note: Cirrhosis - Definition Cirrhosis represents the final common
histologic pathway for a wide variety of chronic liver diseases. The term
cirrhosis was first introduced by Laennec in 1826. It is derived from the
Greek term scirrhus and is used to describe the orange or tawny surface of
the liver seen at autopsy.Many forms of liver injury are marked by
fibrosis. Fibrosis is defined as an excess deposition of the components of
extracellular matrix (ie, collagens, glycoproteins, proteoglycans) within
the liver.
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Ectopic eggs
The most important site for ectopic eggs is the CNS
1-CNS: Sometimes eggs or adult worms can cause lesions of the spinal
cord, known as transverse myelitis (principally S. haematobium and S.
mansoni), or of the brain (principally S. japonicum).
All three species of schistosome may be found in the paravertebra venous
plexus, the worms lay eggs and granulomata develop lead to spinal cord
compression or space occupying lesion. S.japonicum egg is most often
ectopic in the brain because its worm lay more eggs and smaller than other
species also S.jabonicum without spine which may delay its distribution. .
In S.japonicum infection, there may be severe neurologic symptoms,
including coma and paresis, during the incubation period or first few
weeks after. A large localized granuloma produces symptoms and signs
indistinguishable from cerebral tumour. Whereas in
S.mansoni/haematobium, eggs are found more frequently in the spinal
cord than in the brain.
2-Subserosal: other sites for ectopic eggs is subserosal veins of the
abdomen , leading to peritoneal granulomata resembling tumours, and the
female genital tract where granulomata of the fallopian tubes may cause
sterility.
3- skin: Sometimes eggs can reach the skin, where they can cause papular
dermatitis. This rare condition can only be diagnosed by biopsy.
4- Pneumonitis: In schistosomiasis there may likewise be a transitory
cough , sometimes with haemoptysis and frequently with dysnea, during
the stage of migration through the lungs.
5-Vocal cords: Even more rare is egg localisation in the vocal chords, with
nodules and hoarseness.

Salmonella infection
Patients with schistosomiasis (S. mansoni, S. haematobium and S.
japonicum) are at increased risk of being Salmonella carriers. Various
Salmonella spp. Can escape the hosts immune defences and attack in
people harbouring schistosomiasis infections by antibiotics. This may
due to the bacilli lurk in the granulomata, it is impossible to eradicate the
salmonella infection until the schistosomiasis has been treated. This
association explain recurrent bacterial urinary tract infections,in patients
suffering from S.hamatobium infection.
Note:These bacteria are found in the intestinal tract of the worm.

Laboratory diagnosis
A-Direct method
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Microscopic identification of eggs in stool or urine is the most practical
method for diagnosis.
1-Urine for S.haematobium
Most eggs are voided around midday. Specimens collected between
midday and 3 pm are most likely to contain eggs. The methods for finding
eggs depend on their high specific gravity (sedimentation) or their size
(filtration). Egg of S.haematobium (yellow-brown, oval in shape, 145x
55m, has acharacteristic small spine at one end (terminal spine) (Fig-3-)



Fig:-3- Egg of S.haematobium.

2-Stool for S.mansoni and S.japonicum
Direct smear examination is not sufficiently sensitive, so concentration
technique should be used. Egg of S.mansoni (yellow-brown, oval in shape,
150x 60m, has acharacteristic lateral small spine ( Fig-4-). Egg of
S.japonicum (colourless or yellow-brown, large and round to oval in
shape, 90x 65m, has acharacteristic lateral small tubercle (rudimentary
spine) (Fig-5-).




Fig:-4- S.mansoni (lateral small spine). Fig:-5- S.japonicum (lateral
small tubercle).






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3-Rectal biopsy

Asmall piece of rectal mucosa is removed by biopsy forceps or curette
under direct proctoscopic vision. Then placed on a slide under a coverslip
and examined with a 10 objective.

4-Ultrasonography for schistosomal fibrosis of the liver

B-Indirect methods
1-Skin test
There is an immediate sensitivity reaction following within 15 min of the
intradermal injection of Ag, which is usually an extract of adult
Schistosome worms: a wheal and flare. It is insensitive and non-specific so
it is useless.
2-Immunodiagnosis

(CFT, IFAT, ELISA)

C-Circumstantial diagnosis of schistosomiasis
In endemic area the radiological changes in the urinary tract may be very
suggestive (calcification in the wall of the bladder, hydronephrosis,
hydroureter). Radiological changes in cor pulmonale , dilation of the
pulmonary artery and its main branches, right ventricular hypertrophy.The
presence of colonic polypi in an endemic area incriminates shistosome
infection as the most likely cause. The most useful clue , in cases with
disease due to ectopic worms or metastatic eggs is the presence of
eosinophilia (marked eosinophilia 20 to 70% or more) is most frequently
seen in schistosomiasis. Eosinophiluria is constant finding in urinary
schistosomiasis. Eosinophilic meningitis can be associated with
schistosomiasis.

Treatment

Safe and effective drugs are available for the treatment of schistosomiasis.
The drug of choice is praziquantel effective in a single dose against all
species of schistosome species. Oxamniquine(single dose, but only
effective against S. mansoni) . in some areas in which praziquantel is less
effective. Metrifonate (cheap, but requires 3 spaced doses, only effective
against S. haematobium).

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Prevention and Control
1-Avoid contact with streams and ponds where infected snails live.2-
Never defecate or urinate in or near open waters, so that snails have less
chance of becoming infected.3- Support for development of national
control plans specific for particular endemic situations.4- Prevent
morbidity and reduce transmission by systematic drug treatment of
infected people.5- Health education to discourage people from urinating
and defaecating in or near open waters.6- Encourage and support the use
of simple diagnostic tests. (eg. indicators of haematuria for S.
haematobium infection) . 7- Destroying the snail intermediate hosts by
using molluscides in water.
Schistosoma mekongi: Its name derived from Mekong river basin in
Cambodia , it resemble S.japonicum, it differ from S.japonicum , its
infection to human is milder than S.japonicum , eggs are consistently
smaller , and it has a different snail intermediate host (lymnea aperta lives
in water on soil debris).
Schistosoma intercalatum: Also it cause intestinal schistosomiasis but
less pathogenic than S. mansoni/japonicum/mekongi. Occurs in human in
western and central Africa. Its eggs with terminal bend spine . It differs
from other species ,the eggs can be found in the stool and urine.
Cercarial dermatitis (Cercaria of Schistosoma species infection)
Etiology
Cercarial dermatitis is caused by the cercariae of certain species of
schistosomes whose normal hosts are birds and mammals other than
humans. These cercariae seem to have a chemotrophic reaction to
secretions from the skin and are not as host-specific as other types of
schistosomes. They attempt to, and, sometimes may actually, enter human
skin. The penetration causes a dermatitis which is usually accompanied
with intense itching, but the cercariae do not mature into adults in the
human body. Cases of cercarial dermatitis can occur in both fresh and
brackish water environments. One species of schistosome often implicated
in cases of cercarial dermatitis is Austrobilharzia variglandis, whose
normal hosts are ducks. The snail, Nassarius obsoletus, is the
intermediate host for this species and can be found at marine beaches in
temperate climates. Cercarial dermatitis should not be confused with
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seabather's eruption, which is caused by the larval stage of cnidarians
(e.g., jellyfish). The areas of skin affected by seabather's eruption is
generally under the garments worn by bathers and swimmers where the
organisms are trapped after the person leaves the water. Cercarial
dermatitis occurs on the exposed skin outside of close-fitting garments.
Morphology
cercaria (Austrobilharzia variglandis) which can cause cercarial
dermatitis. Diagnostic characteristics include Forked-tail, presence of eye
spots.(Fig-1-).

Fig:-1-Cercaria with forked tail.
Epidemiology
Cercarial dermatitis occurs worldwide with cases reported from every
continent except Antarctica. In the United States, cases are commonly
reported from the Great Lakes region.
Life Cycle
Typically, hosts of avian schistosomes are migratory water birds,
including shorebirds, ducks, and geese. Adult worms are found in the
blood vessels and produce eggs that are swallowed and passed in the feces
(1). On exposure to water, the eggs hatch and liberate a ciliated
miracidium that infects a suitable molluscan intermediate host (2). The
parasite develops in the intermediate host, usually a certain species of snail
(3), to produce free-swimming cercariae that are released under
appropriate conditions and penetrate the skin of the birds to complete the
cycle (4). Humans are inadvertent and inappropriate hosts; cercariae may
penetrate the skin but do not develop further (5). A number of species of
dermatitis-producing cercariae have been described from both freshwater
and saltwater environments, and exposure to either type of cercariae will
sensitize persons to both.
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Clinical features and Pathology
Cercarial dermatitis (Swimmer's itch); is a cutaneous inflammatory
response usually associated with penetration of the skin by cercariae of
bird schistosomes. Symptoms include reddening and itching of exposed
skin in the water or immediately after emerging. This is an indication of
initial penetration of the cercariae. After a period of approximately 12
hours, pruritic papules may become vesicular. Scratching the affected
areas may result in secondary bacterial infections. An interesting note is
that previous contact with cercariae can lead to a more immediate and
intense immune response.
Laboratory diagnosis
Specific snails that would be suitable hosts for these particular avian
schistosomes (such as Nassarius obsoletus, the intermediate host for the
duck schistosome Austrobilharzia variglandis) need to be collected from
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the area where cases of cercarial dermatitis have been reported. The snails
need to be checked to verify if they are shedding cercariae by standard
methodology. Sunlight may be preferred over using artificial light to
stimulate shedding. Another method is to crush the snails and examine the
body for parasite sporocysts and/or cercariae. The cercariae then must be
identified as being a type that can cause cercarial dermatitis by using
appropriate reference material.
Treatment
Most cases do not require medical attention. Topical use of corticosteroid
cream may be used for relief. In addition, cool compresses, bathing with
baking soda, applying baking soda paste to the rash, and anti-itch lotion
may also be tried. Scratching the affected area may cause the rash to
become infected
Clonorchiasis (Clonorchis sinensis infection)
Etiology
The trematode Clonorchis sinensis (Chinese or oriental liver fluke). The
name . Opisthorchis sinensis is also used.
Morphology
Mature adult worm C. sinensis measuring 10 to 25 mm by 3 to 5 mm.
Epidemiology
Endemic areas are in Asia including Korea, China, Taiwan, and Vietnam.
Clonorchiasis has been reported in non endemic areas (including the
United States). In such cases, the infection is found in Asian immigrants,
or following ingestion of imported, undercooked or pickled freshwater fish
containing metacercariae.
Transmission and Life cycle
Embryonated eggs are discharged in the biliary ducts and in the stool (1).
Eggs are ingested by a suitable snail intermediate host (2); there are more
than 100 species of snails that can serve as intermediate hosts. Each egg
releases a miracidia (2a), which go through several developmental stages
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(sporocysts (2b), rediae (2c), and cercariae (2d). The cercariae are
released from the snail and after a short period of free-swimming time in
water, they come in contact and penetrate the flesh of freshwater fish,
where they encyst as metacercariae (3). Infection of humans occurs by
ingestion of undercooked, salted, pickled, or smoked freshwater fish (4).
After ingestion, the metacercariae excyst in the duodenum (5)and ascend
the biliary tract through the ampulla of Vater (6). Maturation takes
approximately 1 month. The adult flukes reside in small and medium
sized biliary ducts. In addition to humans, carnivorous animals can serve
as reservoir hosts.



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Clinical features and Pathology
Most pathologic manifestations result from inflammation and intermittent
obstruction of the biliary ducts. In the acute phase, abdominal pain,
nausea, diarrhea, and eosinophilia can occur. In long-standing infections,
cholangitis, cholelithiasis, pancreatitis, and cholangiocarcinoma can
develop, which may be fatal.
Note; An acute irregularly spiking fever with hepatic tenderness,
suggestive of cholangitis, may be seen in acute clonorchiasis.
Laboratory diagnosis
Microscopic demonstration of eggs in the stool or in duodenal aspirate is
the most practical diagnostic method.The egg indistinguishable from
O.viverrini The adult fluke can also be recovered at surgery.

Fig:-1- Clonorchis sinensis egg.
Clonorchis sinensis egg:. These are small operculated eggs. Size 27 to 35
m by 11 to 20 m. The operculum, at the smaller end of the egg, is
convex and rests on a visible "shoulder". The miracidium is visible inside
the egg(Fig-1-).
Treatment
Praziquantel or albendazole are the drugs of choice.
Opisthorchiasis (Opisthorchis viverrini/ O. felineus infection)
Etiology

Trematodes (flukes) Opisthorchis viverrini (Southeast Asian liver fluke)
and O. felineus (cat liver fluke).
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Morphology

Mature adult flukes of O. viverrini ( 5 mm to 10 mm by 1 mm to 2 mm; O.
felineus( 7 mm to 12 mm by 2 mm to 3 mm).
Epidemiology
O. viverrini is found mainly in northeast Thailand, Laos, and Kampuchea.
O. felineus is found mainly in Europe and Asia, including the former
Soviet Union.
Transmission and Life Cycle

The adult flukes deposit fully developed eggs that are passed in the feces
(1). After ingestion by a suitable snail (first intermediate host) (2), the
eggs release miracidia (2a), which undergo in the snail several
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developmental stages (sporocysts (2b), rediae (2c), cercariae (2d).
Cercariae are released from the snail (3)and penetrate freshwater fish
(second intermediate host), encysting as metacercariae in the muscles or
under the scales (4). The mammalian definitive host (cats, dogs, and
various fish-eating mammals including humans) become infected by
ingesting undercooked fish containing metacercariae. After ingestion, the
metacercariae excyst in the duodenum (5)and ascend through the ampulla
of Vater into the biliary ducts, where they attach and develop into adults,
which lay eggs after 3 to 4 weeks (6). The adult flukes reside in the
biliary and pancreatic ducts of the mammalian host, where they attach to
the mucosa.
Clinical features

Most infections are asymptomatic. In mild cases, manifestations include
dyspepsia, abdominal pain, diarrhea or constipation. With infections of
longer duration, the symptoms can be more severe, and hepatomegaly and
malnutrition may be present. In rare cases, cholangitis and cholecystitis,
accompanied with an irregular fever . And chlolangiocarcinoma may
develop. In addition, infections due to O. felineus may present an acute
phase resembling Katayama fever (schistosomiasis), with fever, facial
edema, lymphadenopathy, arthralgias, rash, and eosinophilia. Chronic
forms of O. felineus infections present the same manifestations as O.
viverrini, with in addition involvement of the pancreatic ducts.
Laboratory diagnosis
Diagnosis is based on microscopic identification of eggs in stool
specimens. However, the eggs of Opisthorchis are practically
indistinguishable from those of Clonorchis. The egg is yellow-brown and
small measuring about 30x16m. it is shaped like an electric light bulb
and contain a ciliated miracidium but this is difficult to see through the
surface of the egg.
Treatment
Praziquantel is the drug of choice to treat Opisthorchiasis.



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Metagonimiasis (Metagonimus yokogawai infection)

Etiology

Metagonimus yokogawai, a minute intestinal fluke (and the smallest
human fluke).

Morphology

Metagonimus yokogawai, adult fluke. These minute intestinal flukes (1
mm to 2.5 mm by 0.4 mm to 0.75 mm) resemble Heterophyes heterophyes
(Fig-1-). An important distinctive feature is the position of the ventral
sucker.




Fig:-1- Metagonimus yokogawai adult worm.

Epidemiology

Mostly the Far East, as well as Siberia, Manchuria, the Balkan states, and
Spain.
Transmission and Life Cycle
Adults release fully embryonated eggs each with a fully-developed
miracidium, and eggs are passed in the hosts feces (1). After ingestion by
a suitable snail (first intermediate host), the eggs hatch and release
miracidia which penetrate the snails intestine (2). Snails of the genus
Semisulcospira are the most frequent intermediate host for Metagonimus
yokogawai.
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The miracidia undergo several developmental stages in the snail, i.e.
sporocysts (2a), rediae (2b), and cercariae (2c). Many cercariae are
produced from each redia. The cercariae are released from the snail
(3)and encyst as metacercariae in the tissues of a suitable fresh/brackish
water fish (second intermediate host) (4). The definitive host becomes
infected by ingesting undercooked or salted fish containing metacercariae
(5). After ingestion, the metacercariae excyst, attach to the mucosa of the
small intestine (6)and mature into adults (7). In addition to humans, fish-
eating mammals (e.g., cats and dogs) and birds can also be infected by M.
yokogawai (8).
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Clinical features
The main symptoms are diarrhea and colicky abdominal pain. Migration
of the eggs to extraintestinal sites (heart, brain) can occur, with resulting
symptoms.
Laboratory diagnosis
The diagnosis is based on the microscopic identification of eggs in the
stool. However, the eggs are indistinguishable from those of Heterophyes
heterophyes and resemble those of Clonorchis and Opisthorchis. The egg
differs from an opisthorchis egg in being more oval with a less distict
operculum, lacking shoulders, and in being without an outer indistinct
coat. Specific diagnosis is based on identification of the adult fluke
evacuated after antihelminthic therapy, or found at autopsy.
Treatment
Praziquantel is the drug of choice.
Paragonimiasis(Paragonimas. Westermani infection)
Etiology

More than 30 species of trematodes (flukes) of the genus Paragonimus
have been reported which infect animals and humans. Among the more
than 10 species reported to infect humans, the most common is P.
westermani, the Oriental lung fluke.

Morphology

Mature adult worm measuring (7.5 to 12 mm by 4 to 6 mm) , it is reddish
brown, small and oval covered with short spines.

Epidemiology
While P. westermani occurs in the Far East, other species of Paragonimus
are encountered in Asia, the Americas, and Africa.



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Transmission and Life Cycle

The eggs are excreted unembryonated in the sputum, or alternately they
are swallowed and passed with stool (1). In the external environment, the
eggs become embryonated (2), and miracidia hatch and seek the first
intermediate host, a snail, and penetrate its soft tissues (3). Miracidia go
through several developmental stages inside the snail (4): sporocysts (4a),
rediae (4b), with the latter giving rise to many cercariae (4c), which
emerge from the snail. The cercariae invade the second intermediate host,
a crustacean such as a crab or crayfish, where they encyst and become
metacercariae. This is the infective stage for the mammalian host (5).
Human infection with P. westermani occurs by eating inadequately
cooked or pickled crab or crayfish that harbor metacercariae of the
parasite (6). The metacercariae excyst in the duodenum (7), penetrate
through the intestinal wall into the peritoneal cavity, then through the
abdominal wall and diaphragm into the lungs, where they become
encapsulated and develop into adults (8). The worms can also reach other
organs and tissues, such as the brain and striated muscles, respectively.
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However, when this takes place completion of the life cycles is not
achieved, because the eggs laid cannot exit these sites. Time from
infection to oviposition is 65 to 90 days. Infections may persist for 20
years in humans. Animals such as pigs, dogs, and a variety of feline
species can also harbor P. westermani.
Clinical features and Pathology
The acute phase (invasion and migration) may be marked by diarrhea,
abdominal pain, fever, cough, urticaria, hepatosplenomegaly, pulmonary
abnormalities, and eosinophilia. Extrapulmonary locations of the adult
worms result in more severe manifestations, especially when the brain is
involved.
A- Pulmonary Paragonimiasis
Here fibrotic tissue forms a cyst around the parasites in the lungs. This
cyst is surrounded by a cellular infiltrate. Symptoms, which may be severe
in infections with high worm densities, include pleurisy, pneumothorax, a
bad cough, bronchitis, blood in the sputum (hemoptysis), mild anaemia
and weariness and may be confused with tuberculosis or pneumonia. and
chest radiographic abnormalities (patchy infiltrate) rounded shadows
suggestive (resemble)of coin lesions.
B- Extrapulmonary Paragonimiasis
In this case disease is caused by ectopic parasites in aberrant locations.
These may vary from parasites encysted in the abdominal wall, to more
serious cerebral infections. Depending on the location of these ectopic
parasites symptoms will vary. If in the intestinal wall there may be
diarrhoea and abdominal pain. Cerebral involvement may occur in many
cases, with symptoms such as visual disturbances, headaches, and in more
serious cases embolisms and epilepsy.
Laboratory diagnosis
Diagnosis is based on microscopic demonstration of eggs in stool or
sputum (Fig-1-). Egg of Paragonimus westermani. The average egg size
is 85 m by 53 m (range: 68 to 118 m by 39 to 67 m). They are
yellow-brown, ovoidal or elongate, with a thick shell, and often
asymmetrical with one end slightly flattened. At the large end, the
operculum is clearly visible. The opposite (opercular) end is thickened.
The eggs of P. westermani are excreted unembryonated
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Fig:-1- Paragonimus westermani egg.
Treatment
Praziquantel is the drug of choice to treat paragonimiasis. Bithionol is an
alternative drug for treatment of this disease.
Poikilorchis congolensis
The trematode Poikilorchis congolensis ,found in Central Africa
(Congo), Nigeria and Sarawak. The life cycle is unknown. This parasite
causes retro-auricular cysts and abscesses (Fig-1-). The eggs which are
found in the pus are similar to Paragonimus eggs, but are smaller.
Treatment is surgical. It is not known whether praziquantel is of any
benefit.


Fig:-1-Retro-auricular swelling due to infection with Poikilorchis
congolense
Heterophyiasis (Heterophyes heterophyes infection)
Etiology

The trematode Heterophyes heterophyes, a minute intestinal fluke.
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Morphology

The mature worm are small measuring (measuring 1.0 to 1.7 mm by 0.3 to
0.4 mm) and covered with small spines. They have a characteristic large
spined genital sucker situated just below a large ventral sucker.

Epidemiology
Egypt, the Middle East, and Far East.
Transmission and Life Cycle

Adults release embryonated eggs each with a fully-developed miracidium,
and eggs are passed in the host's feces (1). After ingestion by a suitable
snail (first intermediate host), the eggs hatch and release miracidia which
penetrate the snails intestine (2). Genera Cerithidia and Pironella are
important snail hosts in Asia and the Middle East respectively. The
miracidia undergo several developmental stages in the snail, i.e.
sporocysts (2a), rediae (2b), and cercariae (2c). Many cercariae are
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produced from each redia. The cercariae are released from the snail
(3)and encyst as metacercariae in the tissues of a suitable fresh/brackish
water fish (second intermediate host) (4). The definitive host becomes
infected by ingesting undercooked or salted fish containing metacercariae
(5). After ingestion, the metacercariae excyst, attach to the mucosa of the
small intestine (6)and mature into adults (7). In addition to humans,
various fish-eating mammals (e.g., cats and dogs) and birds can be
infected by Heterophyes heterophyes (8).
Clinical features
The main symptoms are diarrhea and colicky abdominal pain. Migration
of the eggs to the heart, resulting in potentially fatal myocardial and
valvular damage, has been reported from the Philippines. Migration to
other organs (e.g., brain) has also been reported.
Laboratory diagnosis
The diagnosis is based on the microscopic identification of eggs in the
stool. However, the eggs are indistinguishable from those of Metagonimus
yokogawai and resemble those of Clonorchis and Opisthorchis. The egg s
differs from Opisthorchis egg in being more oval with less distinct
operculum, lacking shoulders and in being without an outer indistinct coat.
Treatment
Praziquantel is the drug of choice.
Fascioliasis ( Fasciola hepatica /Fasciola gigantica infection)
Fascioliasis is an infection caused by flukes of the class Trematoda, most
often characterized by fever, eosinophilia, and abdominal pain, although
as many as half of these cases may be asymptomatic. Humans are
incidental hosts for Fasciola hepatica (Fh), commonly known as the sheep
liver fluke, and Fasciola gigantica (Fg); these flukes cause similar illnesses
in those who become infected by ingesting contaminated watercress or
water. The illness occurs worldwide, particularly in regions with intensive
sheep or cattle.


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Etiology

The trematodes Fasciola hepatica (the sheep liver fluke) and Fasciola
gigantica, parasites of herbivores that can infect humans accidentally.

Morphology

Adult worm Fasciola hepatica measuring : up to 30 mm by 13 mm; F.
gigantica:may attain a length of up to 75 mm , it is parasite of herbivores,
particularly camels, cattle, and water buffalo in Africa and the orient.
Human cases reported from several regions. Both are grey-brown in
colour.
Epidemiology
Fascioliasis occurs worldwide. Human infections with F. hepatica are
found in areas where sheep and cattle are raised, and where humans
consume raw watercress, including Europe, the Middle East, and Asia.
Infections with F. gigantica have been reported, more rarely, in Asia,
Africa, and Hawaii.
Transmission and Life Cycle
Immature eggs are discharged in the biliary ducts and in the stool (1).
Eggs become embryonated in water (2), eggs release miracidia (3), which
invade a suitable snail intermediate host (4), including many species of the
genus Lymnae. In the snail the parasites undergo several developmental
stages (sporocysts (4a), rediae (4b), and cercariae (4c). The cercariae are
released from the snail (5)and encyst as metacercariae on aquatic
vegetation or other surfaces. Mammals acquire the infection by eating
vegetation containing metacercariae. Humans can become infected by
ingesting metacercariae-containing freshwater plants, especially
watercress (6). After ingestion, the metacercariae excyst in the duodenum
(7)and migrate through the intestinal wall, the peritoneal cavity, and the
liver parenchyma into the biliary ducts, where they develop into adults
(8). In humans, maturation from metacercariae into adult flukes takes
approximately 3 to 4 months. The adult flukes reside in the large biliary
ducts of the mammalian host. Fasciola hepatica infect various animal
species, mostly herbivores.

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Clinical features and Pathology
Acute Fascioliasis :During the acute phase (caused by the migration of
the immature fluke through the hepatic parenchyma), manifestations
include abdominal pain, hepatomegaly, fever, vomiting, diarrhea, urticaria
and eosinophilia, and can last for months.
As a pathological is more commonly seen in sheep, and is not usually a
feature of fascioliasis in man or other animals. It occurs when very large
numbers of metacercaria (>10 000) have been ingested at once. In these
cases as the resulting large numbers of migrating larvae invade the liver
they cause a traumatic hepatitis, frequently resulting in death. In some
cases the liver capsule may rupture into the peritoneal cavity causing death
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due to peritonitis. More commonly, on ingestion of fewer metacercaria, a
period of fever and eosinophilia is seen.
Chronic Fascioliasis
In the chronic phase (caused by the adult fluke within the bile ducts), the
symptoms are more discrete and reflect intermittent biliary obstruction and
inflammation (cholangitis and cholycystitis with irregular spiking
fever). This form of the disease is much more common in all of its host,
particularly man. Here the infection is only rarely fatal, but, at least in
domesticated animals, is of economic importance. In man the presence of
the flukes causes a number of fairly non-specific symptoms including
malaise, an intermittent fever, mild jaundice and anaemia, eosinophilia
and, frequently, pain under the right costal margin. In addition, as
described above, as Fasciola does not appear to be fully adapted to using
man as a definitive host, the flukes may often give rise to ectopic
infections, particularly in the lungs and subcutaneous tissues, where they
may be found encysted.
Occasionally, ectopic locations of infection (such as intestinal wall, and
pharyngeal mucosa) can occur. Halzoun; It is a pharyngeal form of
F.hepatica, has been descriped in the Middle East and results from eating
raw animal liver infected with Fasciola. Young adult worms attach to the
pharyngeal mucosa, causing pain, bleeding, and edema that sometimes
interferes with respiration.
Black disease
In addition to these two major forms of fascioliasis, in some cases a
condition known as 'black disease' is a complication, usually fatal, of the
infection. Here a secondary infection due to the bacterium Chlostridium
oedematiens, proliferating in necrotic lesions produced by the young
larvae migrating in the liver.
Note: F. gigantica is very similar in clinical picture to F. hepatica.
Laboratory diagnosis
Microscopic identification of eggs is useful in the chronic (adult) stage.
Eggs can be recovered in the stools or in material obtained by duodenal or
biliary drainage. The egg of Fasciola (gigantica and hepatica) resembles
the egg of Fasciolopsis buski except for the operculum which is less
distict, the egg of F. gigantica is larger than that of F. hepatica. False
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fascioliasis (Pseudofascioliasis) refers to the presence of eggs in the stool
resulting not from an actual infection but from recent ingestion of infected
livers containing eggs. This situation (with its potential for misdiagnosis)
can be avoided by having the patient follow a liver-free diet several days
before a repeat stool examination. Antibody detection tests are useful
especially in the early invasive stages, when the eggs are not yet apparent
in the stools, or in ectopic fascioliasis.

Fig:-1- Fasciola (gigantica and hepatica) egg.
Fasciola hepatica eggs. The eggs are ellipsoidal. They have a small,
barely distinct operculum. The operculum can be opened , for example
when a slight pressure is applied to the coverslip. The eggs have a thin
shell which is slightly thicker at the abopercular end. They are passed
unembryonated. Size range: 120 to 150 m by 63 to 90 m(Fig-1-) .
Treatment
Unlike infections with other flukes, Fasciola hepatica infections may not
respond to praziquantel. The drug of choice is triclabendazole with
bithionol as an alternative.
Fasciolopsiasis (Fasciolopsis buski infection)
Etiology

The trematode Fasciolopsis buski, the largest intestinal fluke of humans.




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Morphology
Adult worm vary in size measuring (20 to 75 mm by 3-7 mm thick) , oval
and covered with rows of small spines.
Epidemiology
Asia and the Indian subcontinent, especially in areas where humans raise
pigs and consume freshwater plants.
Transmission and Life cycle
Immature eggs are discharged into the intestine and stool (1). Eggs
become embryonated in water (2), eggs release miracidia (3), which
invade a suitable snail intermediate host (4). In the snail the parasites
undergo several developmental stages (sporocysts (4a), rediae (4b), and
cercariae (4c). The cercariae are released from the snail (5)and encyst as
metacercariae on aquatic plants (6). The mammalian hosts become
infected by ingesting metacercariae on the aquatic plants. After ingestion,
the metacercariae excyst in the duodenum (7)and attach to the intestinal
wall. There they develop into adult flukes in approximately 3 months,
attached to the intestinal wall of the mammalian hosts (humans and pigs)
(8). The adults have a life span of about one year.





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Clinical features
Most infections are light and asymptomatic. In heavier infections,
symptoms include diarrhea, abdominal pain, fever, ascites, anasarca and
intestinal obstruction. Diarrhea, which usually has its onset about a month
after infection takes place, is characterized by the passage of stools
containing much undigested food; severe infections are accompanied by
symptoms of severe malnutrition, edema of the face, abdominal wall and
lower extremities, ascites, and prostration.
Laboratory diagnosis
Microscopic identification of eggs (it is pale yellow-brown, large and oval,
measuring about 140 x 85 m, contains an unsegmented ovum surrounded
by many yolk cells . These are practically indistinguishable from those of
Fasciola hepatica. with a thin shell, and a usually small, indistinct
operculum. In this particular egg, the operculum is open. . Or more rarely
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of the adult flukes, in the stool or vomitus is the basis of specific
diagnosis.
Treatment
Praziquantel is the drug of choice.
.

















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CHAPTER ELEVEN (11)
Tapeworms (Cestodes)
Introduction
As members of the platyhelminths, the cestodes, or tapeworms, possess
many basic structural characteristics of flukes, but also show striking
differences. shows the general features of the structure and development
of tapeworms. Whereas flukes are flattened and generally leaf-shaped,
adult tapeworms are flattened, elongated, and consist of segments called
proglottids. Tapeworms vary in length from 2 mm to 10 m, and may have
three to several thousand segments. Anatomically, cestodes are divided
into a scolex, or head, which bears the organs of attachment, a neck that is
the region of segment proliferation, and a chain of proglottids called the
strobila. The strobila elongates as new proglottids form in the neck region.
The segments nearest the neck are immature (sex organs not fully
developed) and those more posterior are mature. The terminal segments
are gravid, with the egg-filled uterus as the most prominent feature. The
scolex contains the cephalic ganglion, or "brain," of the tapeworm nervous
system. A rostellum is a retractable, conelike structure that is located on
the anterior end of the scolex, and in some species is armed with hooks. A
characteristic feature of adult tapeworm is the absence of an alimentary
canal, which is intriguing since all of these adult worms inhabit the small
intestine. The lack of an alimentary tract means that substances enter the
tapeworm across the tegument. This structure is well adapted for transport
functions, since it is covered with numerous microvilli resembling those
lining the lumen of the mammalian intestine. Cestodes are hermaphroditic,
each proglottid possessing male and female reproductive systems . The
eggs are released only when the tapeworms shed gravid proglottids into
the intestine. Some proglottids disintegrate, releasing eggs that are voided
in the feces, whereas other proglottids are passed intact. The eggs of
pseudophyllidean tapeworms (D. Latum) are operculated, but those of
cyclophyllidean species (T.solium, saginata, H. nana and E.granulosus)
are not. Eggs of all tapeworms, however, contain at some stage of
development an embryo or oncosphere. The oncosphere of
pseudophyllidean tapeworms is ciliated externally and is called a
coracidium. The coracidium develops into a procercoid stage in its micro-
crustacean first immediate host and then into a plerocercoid larva in its
next intermediate host which is a vertebrate. The plerocercoid larva
develops into an adult worm in the definitive (final) host. The oncosphere
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of cyclophyllidean tapeworms, depending on the species, develops into a
cysticercus larva, cysticercoid larva, coenurus larva, or hydatid larva (cyst)
in specific intermediate hosts. These larvae, in turn, become adults in the
definitive host.
Generalized life cycle of tapeworms. Hymenolepsis nana, H .diminuta,
Taenia saginata, T solium, Diphyllobothrium latum, Dipylidium craninum.
- 207 -

Note; hexacanth embryos. Cysticercus larva in cow and pig; procercoid
larva in copepod, plerocercoid (sparganum) larva in fish; cysticercoid
larva in insect.
Taeniasis (Taenia saginata/Taenia solium infection)
Etiology
Cestode (tapeworm) Taenia saginata (beef tapeworm) is the main cause of
human taeniasis. Cestode (tapeworm) Taenia solium (pork tapeworm) is
the main cause of human cysticercosis.
Morphology
Adult worm
T.saginata adults are ribbonlike, flattened, segmented, hermaphroditic
flatworms 5 m or less , however may reach up to 25 m long, consisting of
scolex (has 4 suckers, but no hooks (Fig-1-). These segments are muscular
and can crawl caterpillar-fashion through the anal sphincter to the outside
environment which renders them available to their herbivore
intermediate hosts. Adult T. solium, measures up to 2 to 7 m in length and
consists of 800-1000 segments. The scolex is round, measuring about 1
mm in diameter, and has four suckers and a crown of hooks in two rows
(Fig-2-).

Fig:-1- Scolex of T. saginata Fig:-2- Scolex of T. solium
Gravid segment (proglottide)
Appears white and opaque and measures about 20 mm long by 6 mm wide
when freshly passed. T. saginata uterus has more than 13 main side
branches on each side (15-20 branches) (Fig-3-). The main branches are
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subdivided into smaller branches. While T. solium Appears grey-blue and
translucent and measures about 13 mm long by 8 mm wide , when freshly
passed. It is shorter than a gravid segment of T.saginata. Uterus has a
central stem whish has up to 13 main side branches (7-13 on each
side)(Fig-4-).

Fig:-3- proglottids of T. saginata . Fig:-4- proglottids of T. solium.
Larva
T.saginata Called Cysticercus bovis is a pea-sized, fluid-filled cyst, which
develops in the muscles of the intermediate host. Within the cyst is a
single inverted scolex, formed from a germinative portion of the inner cyst
wall.
T.solium larva Called Cysticercus cellulosae measures 5-18 x 5mm and
consists of a fluid filled bladder containing a small invaginated scolex
which has a ring of hooks as well as suckers.
Egg
T.solium / saginata eggs are similar (Fig-5-) , it is round or round to oval ,
measuring 33 -43 m in diameter, thick , brown , radially striated wall
Inside each shell is an embryonated oncosphere with 6 hooks.
.
Fig:-5- Taeniid eggs.

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Epidemiology
Taenia saginata, the commonest large tapeworm of humans, is transmitted
as cysticerci in beef ("measly beef"). Partially cooked, smoked, or pickled
beef can be infective, although raw beef (steak tartare) is the commonest
bearer of infection, as witnessed by the frequency of taeniasis in countries
such as Ethiopia and Argentina where raw or undercooked beef is often
eaten.Eggs may also be found in pastures flooded by human sewage or on
which human sewage is used as fertilizer. Taenia solium is found
worldwide. Because pigs are intermediate hosts of the parasite,
completion of the life cycle occurs in regions where humans live in close
contact with pigs and eat undercooked pork. cysticercosis are very rare in
Muslim countries.
Transmission and Life cycle (T. saginata and T.solium )
Humans are the only definitive hosts for Taenia saginata and Taenia
solium. Eggs or gravid proglottids are passed with feces (1); the eggs can
survive for days to months in the environment. Cattle (T. saginata) and
pigs (T. solium) become infected by ingesting vegetation contaminated
with eggs or gravid proglottids (2). In the animal's intestine, the
oncospheres hatch (3), invade the intestinal wall, and migrate to the
striated muscles, where they develop into cysticerci. A cysticercus can
survive for several years in the animal. Humans become infected by
ingesting raw or undercooked infected meat (4). In the human intestine,
the cysticercus develops over 2 months into an adult tapeworm, which can
survive for years. The adult tapeworms attach to the small intestine by
their scolex (5)and reside in the small intestine (6). Length of adult worms
is usually 5 m or less for T. saginata (however it may reach up to 25 m)
and 2 to 7 m for T. solium. The adults produce proglottids which mature,
become gravid, detach from the tapeworm, and migrate to the anus or are
passed in the stool (approximately 6 per day). T. saginata adults usually
have 1,000 to 2,000 proglottids, while T. solium adults have an average of
1,000 proglottids. The eggs contained in the gravid proglottids are
released after the proglottids are passed with the feces. T. saginata may
produce up to 100,000 and T. solium may produce 50,000 eggs per
proglottid respectively.
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Clinical features and Pathology
The clinical manifestations of infection with adult T saginata tapeworms
are confined to occasional nausea or vomiting, appetite loss, epigastric or
umbilical pain, and weight loss. Moderate eosinophilia may develop. A
disturbing manifestation of T saginata infection is the active crawling of
the muscular segments out of the anus. Rarely, intestinal perforation may
occur from the scolex of Taenia, or proglottides may be vomited and then
aspirated. Rarely, intestinal blockage have been reported. The most
striking feature consists of the passage (active and passive) of
proglottids. Occasionally, appendicitis or cholangitis can result from
migrating proglottids. Because of its limited contact with the epithelial
lining, the gut-dwelling adult tapeworm induces little host inflammatory,
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allergic, cell-mediated, or humoral response. The sucking action of the
scolex appears to have relatively limited immunogenic effect. The long
life span of the worm suggests the absence of an effective inhibitory
mechanism.Taenia saginata taeniasis produces only mild abdominal
symptoms. Taenia solium taeniasis is less frequently symptomatic than
Taenia saginata taeniasis. The main symptom is often the passage of
proglottids. The most important feature of Taenia solium taeniasis is the
risk of development of cysticercosis. The hooked scolex of T solium may
cause greater intestinal disturbance, pain, and inflammatory response than
that caused by T saginata, but symptoms are still generally mild and the
pathology minor. However, T solium larval infection (Cysticercosis see
below) .
Laboratory diagnosis
Microscopic identification of eggs and proglottids in feces is diagnostic
for taeniasis, but is not possible during the first 3 months following
infection, prior to development of adult tapeworms. Repeated examination
and concentration techniques will increase the likelihood of detecting light
infections. Nevertheless, speciation of Taenia is impossible if solely
based on microscopic examination of eggs, because all Taenia species
produce eggs that are morphologically identical. Eggs of Taenia sp. are
also indistinguishable from those produced by cestodes of the genus
Echinococcus (tapeworms of dogs and other canid hosts). Adult infections
can be diagnosed by Microscopic identification of gravid proglottids (or,
more rarely, examination of the scolex) allows species determination. The
species of Taenia can be identified only by the segments, because their
eggs are identical.
Treatment
Treatment is readily available for the intestinal adult worms. Niclosamide,
is a nonabsorbed oxidative phosphorylation inhibitor that kills the scolex
and anterior segments on contact, after which the worm is expelled.
Praziquantel, a synthetic isoquinoline-pyrazine derivative, is an equally
effective and relatively nontoxic cesticidal compound. Since the scolex is
usually but not always destroyed, and a new worm can regenerate if the
scolex and a minute portion of the neck survive, the patient should be
observed for several months, as egg-bearing segments can reappear in 10-
12 weeks.
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Note: Because Niclosamide disintegrate segments and release viable eggs
in the intestine, there is a risk of causing extensive cysticercosis. If it is
used a purgative should be given one hour after treatment.
Prevention and Control
Inspection of beef for cysticerci is the best preventive measure. Beef must
be thoroughly cooked in endemic areas to at least 56C throughout the
meat, which may be difficult to accomplish with large cuts of fatty meat,
particularly pork. Freezing at 10C for 10 days usually is lethal to Taenia
cysticerci, but they can withstand 70 days at 0C. Ingestion of eggs can be
avoided by personal hygiene and by not eating food which may be
contaminated with T.solium eggs such as raw vegetables grown on land
fertilized with untreated human faeces.
Cysticercosis (Cestode larva infection)
The common larval stage of tapeworms of the genus Taenia is known as a
cysticercosis.
Etiology
The cestode (tapeworm) Taenia solium (pork tapeworm) is the main cause
of human cysticercosis. In addition, the larval stage of other Taenia
species (e.g., multiceps, serialis, brauni, taeniaeformis, crassiceps) can
infect humans in various sites of localization including the brain,
subcutaneous tissue, eye, or liver.
Morphology (see Cysticercus cellulosae)
Epidemiology
Taenia solium is found worldwide. Because pigs are intermediate hosts of
the parasite, completion of the life cycle occurs in regions where humans
live in close contact with pigs and eat undercooked pork. So Cysticercosis
are very rare in Muslim countries.


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Transmission and life cycle



Cysticercosis is an infection of both humans and pigs with the larval
stages of the parasitic cestode, Taenia solium. This infection is caused by
ingestion of eggs shed in the feces of a human tapeworm carrier (1). Pigs
and humans become infected by ingesting eggs or gravid proglottids (2).
Humans are infected either by ingestion of food contaminated with feces,
or by Autoinfection. In the latter case, occur after ingestion of eggs,
either from exogenous sources or from their own stools. Although not
proved , it is thought that reverse peristalsis may carry intestinal contents
with eggs to the upper portions of the duodenum, where after hatching the
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oncospheres penetrate directly into the intestinal wall. Once eggs are
ingested, oncospheres hatch in the intestine (3), invade the intestinal wall,
and migrate to striated muscles, as well as the brain, liver, and other
tissues, where they develop into cysticerci. In humans, cysts can cause
serious sequellae if they localize in the brain, resulting in
neurocysticercosis. The parasite life cycle is completed, resulting in
human tapeworm infection, when humans ingest undercooked pork
containing cysticerci (4). Cysts evaginate and attach to the small intestine
by their scolex (5). Adult tapeworms develop, (up to 2 to 7 m in length
and produce less than 1000 proglottids, each with approximately 50,000
eggs) and reside in the small intestine for years (6).
Clinical features and Pathology
The symptoms of cysticercosis are caused by the development of
cysticerci in various sites. In human, cysticerci are most commonly found
in the central nervous system; in heavier infection the chance of cysts
lodging in the brain (Fig-1-)or eye, where they most likely to cause
symptoms, is increased . 60% of patient with cysterci are found in the
brain , and 3 % in the eye. Though a large percentage of persons with
known cerebral infections are asymptomatic. cerebral cysticercosis (or
neurocysticercosis), can cause diverse manifestations including seizures,
mental disturbances, focal neurologic deficits, and signs of space-
occupying intracerebral (headach, nausea, vomiting, papiledema),
secondary hydrocephalus,psychotic episodes, diplopia, vertigo, cranial
nerve palsies, and behavior . Death can occur suddenly. Extracerebral
cysticercosis can cause ocular, cardiac, or spinal lesions with associated
symptoms. Asymptomatic subcutaneous nodules and calcified
intramuscular nodules can be encountered (Fig-2-). Though the majority
of intramuscular (Note;larva can develop in any voluntary muscle)
infection are asymptomatic , invasion of muscle by the larvae may give
rise to myositis, accompanied with fever and eosinophilia rarely can cause
pseudohypertrophy of the muscle but frequently larvae die and become
calcified. Subcutaneous easily to palpate, because it resemble small
lipoma. Cysticeri may be found in either anterior or posterior eye chamber
and cause visual difficulties, retinal edema, hemorrhage or even
detachment. Racemose cysts are aberrant cysticerci, which found and
developing in the ventricle or subarachnoid space. Such larvae form no
scolex, and the cyst wall grows in an irregular branching and budding
fashion to a diameter of several centimeters. It cause unphysiologic
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enlargement within the ventricles system and contain fluid same spinal
fluid density.
Laboratory diagnosis
The definitive diagnosis consists of demonstrating the cysticercus in the
tissue involved. Demonstration of Taenia solium eggs and proglottids in
the feces diagnoses taeniasis and not cysticercosis. While suggestive, it
does not necessarily prove that cysticercosis is present. Persons who are
found to have eggs or proglottids in their feces should be evaluated
serologically since autoinfection, resulting in cysticercosis, can occur.
Calcified cysts in the subcutaneous tissues, muscle, brain can be
discovered by X-ray (Fig-2-) ,and also Ultrasound /CTscan/MRI (Fig-1-
)are important for diagnosis of the cysts.

Fig:-1-MRI-scan of the brain, showing neurocysticercosis.

Fig:-2-Radiograph of an arm, showing elongated oval calcifications,
typical of cysticercosis (calcified cysts in muscle).


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Treatment
Infections are generally treated with antiparasitic drugs in combination
with antiinflammatory drugs. Surgery is sometimes necessary to treat
infection in the eyes, brain. Cases that are not responsive to drug
treatment, or to reduce brain edema. Not all cases of cysticercosis are
treated and the use of albendazole and praziquantel is controversial.
Diphyllobothriasis (D. latum infection)
Etiology
The cestode Diphyllobothrium latum (the fish or broad tapeworm), the
largest human tapeworm. Several other Diphyllobothrium species have
been reported to infect humans, but less frequently; they include D.
pacificum, D. cordatum, D. ursi, D. dendriticum, D. lanceolatum, D.
dalliae, and D. yonagoensis.
Morphology
Adult worm Mature D.latum tapeworm is grayish white and long,
measuring 3-10 meters can reach even more than 10 m with 3000-4000
segments. The elongated scolex almonde shape, has two slit-like suckers
with grooves but no hooks.
Gravid segment (proglottid)
It is not often found in the faeces because they tend to disintegrate in the
intestine. These proglottids tend to be passed in strands of variable length
in the stool. Undamaged mature segments are wider than they are longer
(Fig-1-) , measuring 10-20mm across by 3-7mm long.Uterus coiled in
rosette appearance; genital pore at the center of the proglottid.

Fig:-1- D. latum mature segments are wider than they are longer.
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Larva
D.latum larva called plerocercoid (sparganum), it is white and tape like,
measuring about 10 mm long by 2 mm wide. When full developed it
contains a head with sucking grooves.
Egg
It is pale yellow and oval in shape, measuring about 70 x 45 m, has
operculum (lid ,see the arrow)(Fig-2-).Which is usually difficult to see. It
contain a mass of granulated yolk cells surrounding an undeveloped ovum.

Fig:-2-D.latum egg (Note; operculum).
Epidemiology
Diphyllobothriasis occurs in the Northern Hemisphere (Europe, newly
independent states of the former Soviet Union [NIS], North America,
Asia) and in Uganda and Chile. Freshwater fish infected with
Diphyllobothrium sp. larva may be transported to and consumed in
geographic areas where active transmission does not occur, resulting in
human diphyllobothriasis. For example, cases of D. latum infection
associated with consumption of imported fish have been reported in
Brazil.
Transmission and Life Cycle
Immature eggs are passed in feces (1). Under appropriate conditions, the
eggs mature (approximately 18 to 20 days) (2)and yield oncospheres
which develop into a coracidia (3). After ingestion by a suitable
freshwater crustacean (the copepod first intermediate host) the coracidia
develop into procercoid larvae (4). Following ingestion of the copepod by
a suitable second intermediate host, typically minnows and other small
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freshwater fish, the procercoid larvae are released from the crustacean and
migrate into the fish flesh where they develop into a plerocercoid larvae
(sparganum) (5). The plerocercoid larvae are the infective stage for
humans. Because humans do not generally eat undercooked minnows and
similar small freshwater fish, these do not represent an important source of
infection. Nevertheless, these small second intermediate hosts can be
eaten by larger predator species, e.g., trout, perch, walleyed pike (6). In
this case, the sparganum can migrate to the musculature of the larger
predator fish and humans can acquire the disease by eating these later
intermediate infected host fish raw or undercooked (7). After ingestion of
the infected fish, the plerocercoid develop into immature adults and then
into mature adult tapeworms which will reside in the small intestine. The
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adults of D. latum attach to the intestinal mucosa by means of the two
bilateral groves (bothria) of their scolex (8). The adults can reach more
than 10 m in length, with more than 3,000 proglottids. Immature eggs are
discharged from the proglottids (up to 1,000,000 eggs per day per worm)
(9)and are passed in the feces (1). Eggs appear in the feces 5 to 6 weeks
after infection. In addition to humans, many other mammals can also
serve as definitive hosts for D. latum.
Note:Diphyllobothrium latum is the only adult cestode of humans that has
an aquatic life cycle.
Clinical features and Pathology
Infection with this tapeworm usually produces no pathology, although the
minor symptoms noted above are occasionally present. Megaloblastic
anemia ("tapeworm anemia"), which is exacerbated by the worm's uptake
of vitamin B12, is now seldom seen, as a result of improved diet, prenatal
care, and ready treatment. This condition was formerly most common in
Finland. Diphyllobothriasis can be a long-lasting infection (decades).
Most infections are asymptomatic. Manifestations may include abdominal
discomfort, diarrhea, vomiting, and weight loss. Infected persons may
develop macrocytic hyperchromic anemia and megaloblastic bone marrow
on the basis of Vitamin B
12
. The worm compete with the host by uptake
this vitamin. Pernicious anemia , occur in many persons have a genetic
predisposition to pernicious anemia (intrinsic factor deficiency), such as
finland population. Suggesting that B
12
deprivation through D.latum
infection is seldom sufficient to produce clinical symptoms in an
otherwise normal patient. Massive infections may result in intestinal
obstruction. Migration of proglottids can cause cholecystitis or
cholangitis.The edema of the face and legs, with protuberant abdomen
seen in severe diphyllobothriasis may be related to malnutrition.
Laboratory diagnosis
Microscopic identification of eggs in the stool is the basis of specific
diagnosis. Eggs are usually numerous and can be demonstrated without
concentration techniques. Examination of proglottids passed in the stool
is also of diagnostic value.

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Treatment
Praziquantel is the drug of choice. Alternatively, Niclosamide can also be
used to treat diphyllobothriasis.
Sparganosis (Sparganum/Plerocercoid infection)
Sparganosis is a tissue infection with the sparganum (or plerocercoid) of
Spirometra, a genus related to Diphyllobothrium. These two genera have
similar life cycles, but Spirometra usually utilizes frogs, reptiles, or
various small mammals as intermediate hosts, whereas Diphyllobothrium
uses fish. In the Southeast Asia, frog flesh (rather than beef steak) is used
as a poultice over a wound or black eye, which allows the sparganum to
crawl into the wound or orbit, initiating a severe inflammatory response.
Humans can also acquire the infection as a result of drinking water
containing infected Cyclops and possibly from undercooked snake or
other infected meat. The procercoids from Cyclops invade the gut wall of
the human or animal intermediate host and usually migrate to
subcutaneous tissues to form a sparganum, which induces in humans
formation of a fibrous 2-cm nodule that encloses and destroys the worm.
The nodule can usually be removed surgically or can be treated with
praziquantel if the cyst is inaccessible to surgery.
Etiology
Accidental infection with the larval stages of spirometra
(Diphyllobothrium) tapeworms , like (Spirometra mansonoides) and
other diphyllobothriid tapeworms that are not normally parasitic in human
is known as or causes sparganosis. Spirometra species are closely related
to diphyllobothrium species, few details are known of the life cycle of
most spirometra tapeworms. Definitive hosts are known to include cats,
dogs and possibly birds. First intermediate hosts are crustaceans and
second intermediate hosts are frogs, birds and snakes. Plerocercoid larvae
(spargana) are unable to develop into adult tapeworms in a human host.
Morphology
The adult worm S.mansonoides resembles D.latum but smaller.The larva
is white and tape-like. Measuring 10-35 mm long by 2-7 mm wide. The
body is transversely wrinkled with a longitudinal groove.
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Epidemiology
Sparganosis in human is cosmopolitan , but it occurs mainly in the Far
East. Southeast Asia and parts of Africa.
Transmission and life cycle
The definitive hosts are dogs, cats, and wild carnivore. The primary
intermediate hosts are species of cyclops, and the secondary intermediate
hosts include various small animals, snakes, and frogs. The life cycle
follows the same pattern as that of D.latum. Infection is by ingesting a
Cyclops infected with a procercoid. The larva migrates and develops into a
plerocercoid (Sparganum) in subcutaneous tissue and muscles.
Sparganosis of the eye is commonly caused by the application of infected
frog tissue to eye sores. The plerocercoid migrates out of the tissue into
the orbit of the eye Infection with a plerocercoid may also occur by
ingesting undercooked food prepared from secondary intermediate hosts.
The plerocercoids of some Spirometra species are able to multiply in a
human host, usually in subcutaneous tissue where they encyst, forming
large nodules.
Clinical features and Pathology
Sparganosis may cause serious symptoms including painful inflamed
swelling and occasionally widespread cystic lumps in muscles, lymph
nodes, and subcutaneous tissue. Spargana form subcutaneous nodules,
somewhat elongate and several centimeters in length, which may resemble
lipomas, but they may move through the subcutaneous tissues at irregular
intervals and often cause pain. Spargana proliferum may develop as
branched or multiple nodules and invade the viscera. Ocular sparganosis
can cause serious damage to the eye. Ocular sparganosis is not uncommon
in some areas where eye lesions are poulticed with split raw infected
frogs. In the subcutaneous tissues around the eye, the sparganum produces
a violent tissue reaction with edema; retrobulbar development of the
sparganum may cause protrusion of the eyeball and consequent corneal
ulceration. Occasoonally serious symptoms can develop if spargana
become sited in the other vital organs like CNS (may give rise to
epileptiform seizures).

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Laboratory diagnosis
Sparganosis diagnosed clinically or after removal of a larvae or nodule.
Treatment and Control
Surgical removal of one or a few sparganum larvae is usually possible.
Praziquantel is apparently effective. In areas of endemic infection , people
should be advised of the dangers of drinking water from ponds and
ditches, which may contain infected copepods (cyclop). The use of
potentially infected animals for medicinal purposes must be discourged.
Dipylidiasis (Dipylidium caninum infection)
Etiology
Dipylidium caninum (the double-pored dog tapeworm) mainly infects
dogs and cats, but is occasionally found in humans.
Morphology
Adult worm
It measures 60cm in length and 3 mm in width . The scolex has 4 oval
suckers and several rows of hooks which can be retracted.
Gravid segment (proglottid)
The segment are elongate and resemble rice grains (Fig-1-). They measure
approximately 12 mm x 3 mm in length. A genital pore is present on each
side of the segment (Fig-2-). This is acharacteristic feature of Dipylidium
tapeworm.


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Fig:-1- D.caninum (resemble rice grain). Fig:-2-D.caninum (Note ;
genital pore).
Egg capsule
A typical capsule measures about 60 x 100m. It contain up to 20 eggs
(Fig-4-). Each egg contains an embryo which has 3 pairs of hooklets and
measures about 35 m in diameter.

Fig:-4- D.caninum Egg capsule.
Epidemiology
Worldwide. Human infections have been reported in Europe, the
Philippines, China, Japan, Argentina, and the United States.
Transmission and Life Cycle
Gravid proglottids are passed intact in the feces or emerge from the
perianal region of the host (1). Subsequently they release typical egg
packets (2). On rare occasions, proglottids rupture and egg packets are
seen in stool samples. Following ingestion of an egg by the intermediate
host (larval stages of the dog or cat flea Ctenocephalides spp.), an
oncosphere is released into the flea's intestine. The oncosphere penetrates
the intestinal wall, invades the insect's hemocoel (body cavity), and
develops into a cysticercoid larva (3). The larva develops into an adult,
and the adult flea harbours the infective cysticercoid (4). The vertebrate
host becomes infected by ingesting the adult flea containing the
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cysticercoid (5). The dog is the principal definitive host for Dipylidium
caninum. Other potential hosts include cats, foxes, and humans (mostly
children) (6), (7). Humans acquire infection by ingesting the cysticercoid
contaminated flea. This can be promulgated by close contact between
children and their infected pets. In the small intestine of the vertebrate
host the cysticercoid develops into the adult tapeworm which reaches
maturity about 1 month after infection (8). The adult tapeworms
(measuring up to 60 cm in length and 3 mm in width) reside in the small
intestine of the host, where they each attach by their scolex. They produce
proglottids (or segments) which have two genital pores (hence the name
"double-pored" tapeworm). The proglottids mature, become gravid,
detach from the tapeworm, and migrate to the anus or are passed in the
stool (1).


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Clinical features
Most infections with Dipylidium caninum are asymptomatic. Pets may
exhibit behavior to relieve anal pruritis (such as scraping anal region
across grass or carpeting). Mild gastrointestinal disturbances may occur.
The most striking feature in animals and children consists of the passage
of proglottids. These can be found in the perianal region, in the feces, on
diapers, and occasionally on floor covering and furniture. The proglottids
are motile when freshly passed and may be mistaken for maggots or fly
larvae.
Laboratory diagnosis
The diagnosis is made by demonstrating the typical proglottids or egg
packets in the stool
Treatment
Treatment for both animals and humans is simple and very effective.
Praziquantel is given either orally or by injection (pets only). The
medication causes the tapeworm to dissolve within the intestines. Since
the worm is usually digested before it passes, it may not be visible in the
dog's stool. These drugs are generally well tolerated. Flea control of pets
would largely eliminate the infection from household pets and children
Coenuriasis (Multiceps Multiceps infection)
These cestodes belong to the Taeniidae. Multiceps multiceps (synonym
Taenia multiceps), M. brauni (synonym T. brauni), M. glomeratus
(synonym T. glomeratus), M. longihamatus (synonym T. longihamatus)
and M. serialis (synonym T. serialis) are tapeworms which may
occasionally infect humans.
Etiology
Multiceps Multiceps is a taeniid worm of moderate size, it is found in the
dogs and other canidae. The larval stage of this worm called Coenurus
cyst found in a variety of herbivorous mammals, and have been reported
occasionally from human in various parts of the world.

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Morphology
The worm 40- 60 cm in length and has pyriform scolex with double crown
of 22 to 32 large and small hooks.The coenurus larva is larger than a
cysticercus (up to 2 cm diameter); semitransparent, glistening white, and
filled with fluid.Numerous denser white spots on the wall indicate the
position of the attached scolices.
Epidemiology
M.multiceps is found in North and South Africa .
Mode of infection
Egg ingestion of Multiceps species, the oncosphere hatches in the small
intestine and makes its way into a blood vessel in the intestinal wall, the
embryo carried in the blood stream to various parts of the body but and
frequently to the Central nervous system (CNS) especially the brain . The
definitive hosts of Multiceps species are dogs and jackls. The intermediate
hosts of M. multiceps are sheep , but the intermediate hosts for M.brauni
/M. serials / M.glomeratus are rodents and lagomorphs (rabbits, hares) are
intermediate hosts and various carnivores are the normal final hosts.
Clinical features and Pathology
In sheep , the parasite produces blind staggers disease known as gid
(unstable gait, or giddiness) . When a human accidentally swallows an egg
of M. multiceps or M. brauni, the larva may develop into a coenurus larva.
Localisation in the eye and the brain may occur in M. multiceps and M.
brauni. These worms are responsible for the most serious pathology. A
visceral larva migrans syndrome may result. M. serialis may cause cysts in
the tissues. M. glomeratus may become established in the muscles. M.
longihamatus occurs as an adult worm in the lumen of the small intestine.
Coenrus disease In human have had coenuri in the brain or spinal cord
give space occupying lesion symptoms or if within the ventricular system,
internal hydrocephalus.The symptoms requiring several years to develop,
depend upon the exact location of the coenurus, symptoms of increased
intracranial pressure, including loss of consciousness, convulsion,
temporary anesthesia, paresis, occasional diplopia, staggering gait, and
positive Romberg sign. Note; lipoma-like subcutaneous nodules. In almost
half the recorded human cases of coenurus infection, the larvae have been
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found in the subcutaneous tissue; others have been recorded from the
brain, spinal cord, the eye.
Note: In sheep, the most common intermediate host, the parasite produces
a disease known as gid, from the unstable gait, or giddiness, that marks the
infected animals.
Laboratory diagnosis
Preoperative diagnosis unlikely (CTscan, MRI-indicate space occupying
lesion) . Only by the surgical removal of the larvae. Because there are no
specific serological test for it.
Treatment and Prevention
As with many cestodes, the parasites are sensitive to praziquantel.
Treatment of coenurosis is surgical. In endemic ares prevention requires
the protection of food and hands from the feces of dogs.
Echinococcosis/hydatidosis/ hydatid disease(Echinococcus granulosus infection)
A tissue infection caused by the larval stage of the Echinococcus
granulosus worm.
Etiology
Echinococcus granulosus causes cystic echinococcosis, the form most
frequently encountered; E. multilocularis causes alveolar echinococcosis;
E. vogeli causes polycystic echinococcosis. E. oligarthrus is a very rare
cestode which cause. Intra-orbital and cardiac cysts have been described.
Morphology
Adult worm
Mature E.granulosus tapeworm, small measuring (3 to 6 mm long up to
9mm), E. multilocularis (1.2 to 3.7 mm) and E .vogeli (up to 5.6 mm long)
usually with only 3 to 4 segments. The scolex scolex has 4 suckers and a
crown of hooks in two rows.

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Larva
Two larva morphological forms caused by E.granulosus are found in
humans: the unilocular hydatid cyst and the osseous hydatid cyst. A third
form in humans is the alveolar hydatid cyst, caused by Echinococcus
multilocularis. The unilocular hydatid cyst (Fig-1-) .Consists of an outer
thick laminated cyst wall (connective tissue and fibres )and an inner, thin
nucleated germinal layer. From the germinal layer, brood capsules are
produced inside which small protoscoleces form. Daughter cysts form
within the main cyst when parts of the germinal layer become detached.
The detached brood capsules and individual protoscoleces, form what is
called hydatid sand swimming in colorless hydatid fluid (Fig-1-). The
Alveolar hydatid cyst of E. multilocularis similar to E. granulosus
except the limiting (outer ) membrane is thin and the germinal epithelium
may bud externally, to proliferate in any direction or even to metastasize,
full of connective tissue and a jelly-like material. The liver is the primary
focus of the disease for both Unilocular and Alveolar hydatid cysts. In
case of E.vogeli the germinal membrane proliferates both inward, in the
original cyst,forming septa that divide it into many sections, and outward,
to form new cysts. The vesicles forming a polycystic hydatid are
relatively large and filled fluid. Note: Cysts may never produce brood
capsules, or the brood capsules may fail to produce protoscolices. In other
cases , hydatids may become sterile because of secondary bacterial
infection or they may die and become calcified.

Fig:-1- A section through a unilocullar cyst.

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Protoscolex
It is colourless and round to oval in shape, with focusing the hooks of the
invaginated scolex can be easily seen (Fig-2-).

Fig:-1- Protoscolex.
Note: "Hydatid sand". Fluid aspirated from a hydatid cyst will show
multiple protoscolices (size approximately 100 m), each of which has
typical hooklets. The protoscolices are normally invaginated (left), and
evaginate (middle, then right) when put in saline.
Egg
Indistiguishable from those of Taenia species (T. solium/saginata)
Epidemiology
Hydatid disease due to E. granulosusis endemic in cattle-and sheep-
raising regions of the world such as Central Europe, the Mediterranean
countries, the Middle East, South America,Australia, New Zealand, and
South Africa.

E. granulosus occurs practically worldwide, and more
frequently in rural, grazing areas where dogs ingest organs from infected
animals. Alveolar echinococcosis is a parasitic disease, one of the most
dangerous of human infections caused by E. multilocularis. The fox is the
main host for the adult parasite also known as E. alveolaris. This organism
is a parasite known in Northern Hemisphere regions including Alaska ,
Canada , Siberia and former Soviet Union , north and northwest China ,
several north central states of the USA , Island of Hokkaido, Japan ,
eastern Turkey , Bulgaria , Poland and the Alps but it has recently been
increasingly observed in the more temperate regions of central Europe ,
Nebraska, and Illinois , western Turkey . However ,in general E.
multilocularis occurs in the northern hemisphere of the world. Man is
infected either by direct contact with foxes or contamination from plants
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or water. E. vogeli in Central and South America. E. oligarthrus is a very
rare cestode which occurs in Brazil and Venezuela. Note; A single case of
infection of a human by E.oligarthrus has been reported from Venezuela .
The hydatid cyst was orbital , producing a proptosis. The definitive hosts
are pumas, jaguars, and wildcats, and the intermediate hosts pacas,
agouits, spiny rats, and opossums.
Transmission and Life Cycle
The adult Echinococcus granulosus (1)resides in the small bowel of the
definitive hosts, dogs or other canids. Gravid proglottids release eggs
(2)that are passed in the feces. After ingestion by a suitable intermediate
host (under natural conditions: sheep, goat, swine, cattle, horses, camel),
the egg hatches in the small bowel and releases an oncosphere (3)that
penetrates the intestinal wall and migrates through the circulatory system
into various organs, especially the liver and lungs. In these organs, the
oncosphere develops into a cyst (4) that enlarges gradually, producing
protoscolices and daughter cysts that fill the cyst interior. The definitive
host becomes infected by ingesting the cyst-containing organs of the
infected intermediate host. After ingestion, the protoscolices (5)evaginate,
attach to the intestinal mucosa (6), and develop into adult stages (1)in 32
to 80 days.
The same life cycle occurs with E. multilocularis, with the following
differences: the definitive hosts are foxes, and to a lesser extent dogs, cats,
coyotes and wolves; the intermediate host are small rodents; and larval
growth (in the liver) remains indefinitely in the proliferative stage,
resulting in invasion of the surrounding tissues. With E. vogeli, the
definitive hosts are bush dogs and dogs; the intermediate hosts are rodents;
and the larval stage (in the liver, lungs and other organs) develops both
externally and internally, resulting in multiple vesicles. Humans become
infected by ingesting eggs (2), with resulting release of oncospheres (3)in
the intestine and the development of cysts (4) in various organs. E.
oligarthrus, Felis sp. are the definitive hosts. Rodents are intermediate
hosts. Humans are infected by swallowing an egg.

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Clinical features
The clinical features depend on four processes:
1-Mechanical effects such as non tender enlargement of the liver (the
commonest presentation), cough and breathlessness (cysts may compress
bronchi and cause collapse of a lobe), symptoms suggesting brain tumour
(intracerebral cysts).
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Note: Jaundice and portal hypertension can result from pressure effects of
a cyst in the liver; hemoptysis and dyspnea from a lung cyst.
2-Allergic processes due to escape of allergenic hydatid fluid into the
circulation, such as urticaria and anaphylaxis.
3-Cyst rupture
a- Ruptur causing anaphylactic shock and sudden death.
b- Rupture causing spread to other organs or serous cavities due to seeding
with viable germinal epithelium.
Note: In endemic areas, hydatid cysts are often much the commonest
cause of intra-abdominal masses and solid-looking pulmonary shadows.
Some cysts will continue to grow until they rupture and lead to the
patients death. Some will stop growing , the germinal epithelium will die,
and the gradual involution of the cyst leaves only a harmless calcified
remnant behind (Fig-2-). The fate of an individual cyst is unpredictable,
and some cysts seem to be (sterile) from the start.

Fig:-2- Calcified Echinococcus granulosus (hydatid) cyst in the liver is
visible on a plain radiograph of the abdomen.
c- Secondary infection of the cyst.
4- Cyst location
Although hydatid cysts are known commonly to affect the liver and lung,
but it can also affect the brain, bone ,heart, kidney, ureter, spleen, uterus,
fallopian tube, mesentery, pancreas, diaphragm, and muscles. Brain
involvement, which is more commonly seen in children, is encountered in
12% of the patients and the cysts are usually solitary and have an
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intraparenchymal localization.

Cardiac involvement with echinococcosis is
uncommon (0.02%-2%); the left ventricular wall is the most frequent site,
but the interventricular septum, right ventricle and left or right atrium may
also be involved with varying degrees of complications. Major
complications of cardiac hydatid disease result from rupture of the cyst
either into the heart or pericardium and death may occur subsequent to
anaphylactic shock, cardiac tamponade and systemic or pulmonary
hypertension.

Pancreatic involvement has been reported in 0.250.75% of
adult cases.
Note: Echinococcus granulosus infections remain silent for years before
the enlarging cysts cause symptoms in the affected organs.
Hepatic involvement can result in abdominal pain, a mass in the hepatic
area, and biliary duct obstruction. In Pulmonary involvement , cough is
usually the first symptom and can produce chest pain . There may be
increasing dyspnea; with erosion of blood vessels there will be
hemoptysis, and with obstruction there results secondary bacterial
infection and fever. If the cyst rupture into a bronchus, the contents may
be coughed up or the patient become asphyxiated.
Note; hydatid cyst may develop in the central nervous system, where they
may produce symptoms related t aspace occupying lesion or, if within
ventricular system, internal hydrocephalus.
Note; Hydatid thrill; in large unilocular echinococcus cysts of the
abdominal viscera that are situated close to the abdominal wall, a
characteristic thrill may be elicited by quick palpation or percussion. This
phenomenon may be simulated by percussion of a balloon filled with
water.
Echinococcus multilocularis ; affects the liver as a slow growing,
destructive tumor, with abdominal pain, biliary obstruction, and
occasionally metastatic lesions into the lungs and brain. In human the
hydatid cyst of the E.multilocularis(alveolar) is invasive and spreads like a
malignant tumour because (The cyst produces daughter cysts by external
and not internal budding and it is not encapsulated like the hydatid cyst of
E.granulosus) so causing cavities and necrosis. Their symptoms are related
to the pressure from expanding tissue. Growth into the Vena cava or portal
veins may lead to metastasis, usually to the lungs or the brain. Surgical
removal is rarely possible and the diseaseis usually fatal.
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E.vogeli polycystic larval stage in rodents , human cases reported . It acts
as a slow growing tumor; secondary cystic development is common.
Commonly found in the liver also lung , pleura, pericardium and even in
the heart, dighragm, stomach and mesenteries.
Pathology
The pathology in man depends upon the location of the cyst. Up to 70%
found in the right lobe of the liver , lung 20%, 1% in the brain also in the
kidneys, and other tissues such as(bone, muscles, spleen, eye,heart and
thyroid). The unilocular cyst evokes an inflammatory reaction of the
surrounding tissues that produces an encapsulating fibrous adventitia. The
expanding hydatid cyst causes pressure necrosis of the surrounding
tissues, and erosion of blood vessels leads to hemorrhage. The Osseous
cyst produces a pseudotuberculous reaction with, extensive intramedullary
erosion. In diaphysis it causes destruction of trabeculae, necrosis, and
spontaneous fracture with thickening of cortex . Eosinophilia elicits if
there is slow leakage of hydatid fluid, if the cyst rupture it carries grave
risk of anaphylactic shock and the spread of the infection. There is no
fibrous wall in hydatid cyst of the bone and therefore the cyst spreads and
leading to pathological frature.Rupture of pulmonary cyst into bronchus
may be marked by sever allegic symptoms and coughing of blood-flecked
fluid.
Laboratory diagnosis
The diagnosis of echinococcosis relies mainly on findings by X-ray as in
the case of pulmonary cyst(Fig-3-) . Well defined, rounded masses may be
seen in the lung parenchyma; sometimes a fluid level is visible within
them. Hepatic cysts are easy to be visible if calcification of the wall has
taken place (Fig-2-). Hydatid cyst of the bone produce extensive
intramedullary erosion. Preoperative diagnosis can be made ultrasonically
and confirmed by other imaging techniques (CTscan) supported by
positive serologic tests. Furthermore, echocardiography and magnetic
resonance imaging (MRI) are of great value in diagnosing and determining
the anatomic extent and relationship of the cyst in cardiac hydatidosis.

The
MRI is also of considerable value in cases of intracranial hydatidosis. In
seronegative patients with hepatic image findings compatible with
echinococcosis, ultrasound guided fine needle biopsy may be useful for
confirmation of diagnosis but it is highly risky procedures so during such
procedures precautions must be taken to control allergic reactions or
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prevent secondary recurrence in the event of leakage of hydatid fluid or
protoscolices.

Fig:-3-Pulmonary hydatid cyst in lung, paracardial on the right side,
Echinococcus granulosus.
Special tests: 30% of patients have an absolute eosinophilia. The Casoni
test (currently rarely used) is negative in about 15% of cases. Several
serological tests used to detct atihydatid Ab such as the ELISA test, also
often give false negatives.
Aspiration:. Many surgeons consider that you should not try to confirm
the diagnosis by aspiration, because this may make the cyst leak, and may
be fatal. Aspiration is safer if a cyst is superficial, and unlikely to leak into
a serous cavity. If you are aspirating what you think is an abscess, and you
aspirate water-clear fluid, it is almost certainly a hydatid cyst. Continue
aspirating to dryness, before you remove the needle. It will then be less
likely to leak. If you decide to aspirate the cyst in a patient's liver, do so
under anaesthesia, so that it can be kept still for a few seconds, while you
insert the needle.
Caution: Dont try try to tap hydatid cyst merely to make it smaller.
Differential diagnosis:Febrile? (hepatoma or amoebic abscess). Fever and
a tender mass? (amoebic abscess). Liver diffusely enlarged and very
tender? (amoebic hepatitis). Mass hard and nodular with loss of weight?
(hepatoma). Craggy, irregular knobbly liver? (secondaries). A history of
anything less than years, suggests that the mass is not a hydatid.


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Treatment:
The treatment of hydatid cysts is principally surgical. However, pre- and
post-operative 1-month courses of Albendazole and 2 weeks of
Praziquantel should be considered in order to sterilize the cyst, decrease
the chance of anaphylaxis, decrease the tension in the cyst wall (thus
reducing the risk of spillage during surgery) and to reduce the recurrence
rate post-operatively.
Surgery is the most common form of treatment for accessable
echinococcosis cyst , although removal of the parasite mass is not usually
100% effective , if the cyst is ruptured during surgery, death from
anaphylaxis or the delayed results of dissemination may follow. If the
surgeon canot excise a cyst, it can be sterilized by withdrawing 10-20 ml
of cyst fluid and replacing it with an equal volume of 10% formalin , or
0.5% silver nitrate solutions before opening the cavities tends to kill the
daughter cysts and therefore prevent further spread or anaphylactic
reaction.This is withdrawn 5 min later, and the contents repeatedly washed
out with sterile saline preceding aspiration to dryness. Multiple cysts
confined to one lobe of the liver are best dealt with by hemi-hepatectomy.
Lobectomy is the corresponding procedure for a cyst in the lung. After
surgery, medication may be necessary to keep the cyst from recurring. The
drug of choice for treatment echinococcosis is albendazole (Echinococcus
granulosus). Some reports have suggested the use of albendazole or
mebendazole for Echinococcus multilocularis infections.
.Prevention and Control
1- Practising personal hygiene, especially the washing of hands after
handling dogs and before eating. 2- Avoiding unnecessary handling of
dogs that are in contact with sheep, and informing herdmen and others at
risk of the dangers of infection, 3- Regular deworming of dogs. 4-
Eliminating stray dogs. 5- Not feeding dogs with uncooked meat or offal.
6- Preventing dogs from entering places where sheep and other
intermediate hosts are slaughtered and also inspecting carcasses for
infection.7- Prevent dogs reaching intermediate hosts infected organs so
burry or burn it .
Hymenolepiasis(Hymenolepis nana /Hymenolepis dimnuta)
Etiology
Hymenolepiasis is caused by two cestodes (tapeworm) species,
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Hymenolepis nana (the dwarf tapeworm) and Hymenolepis dimnuta (rat
tapeworm). Hymenolepis diminuta is a cestode of rodents infrequently
seen in humans and frequently found in rodents.
Morphology
Adult worm
H-nana measuring (15 to 40 mm in length) consists of 100-200 short
wide segments, a long neck and a scolex which has suckers and hooks.
H. diminuta (adults measuring 20 to 60 cm in length), the greates length
reported for an adult specimen of H.diminuta from a person is 1m, the
scolex bears four suckers and a small rostellum without hooks.
Egg
H. nana is colourless, oval or round, measuring 30-45m in diameter
(Fig-1-). Hooklets are present in the embryo and at each end of the egg
thread-like structures called polar filaments are usually visible. The
oncosphere has six hooks . Compared with H. nana, the egg of H.
diminuta is yellow-brown and larger, measuring 60-80 m. It is without
polar filaments. The oncosphere has six hooks (of which at least four are
visible at this level of focus).

Fig:-1-H.nana egg.
Epidemiology
H. nana is the most common cause of all cestode infections, and is
encountered worldwide. In temperate areas its incidence is higher in
children and institutionalized groups. H. diminuta, while less frequent,
has been reported from various areas of the world.
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Transmission and Life Cycle (H. nana)
Eggs of Hymenolepis nana are immediately infective when passed with
the stool and cannot survive more than 10 days in the external
environment (1). When eggs are ingested by an arthropod intermediate
host (2)(various species of beetles and fleas may serve as intermediate
hosts), they develop into cysticercoids, which can infect humans or
rodents upon ingestion (3)and develop into adults in the small intestine. A
morphologically identical variant, H. nana var. fraterna, infects rodents
and uses arthropods as intermediate hosts. When eggs are ingested (4)(in
contaminated food or water or from hands contaminated with feces), the
oncospheres contained in the eggs are released. The oncospheres
(hexacanth larvae) penetrate the intestinal villus and develop into
cysticercoid larvae (5). Upon rupture of the villus, the cysticercoids return
to the intestinal lumen, evaginate their scoleces (6), attach to the intestinal
mucosa and develop into adults that reside in the ileal portion of the small
intestine producing gravid proglottids (7). Eggs are passed in the stool
when released from proglottids through its genital atrium or when
proglottids disintegrate in the small intestine (8). An alternate mode of
infection consists of internal autoinfection, where the eggs release their
hexacanth embryo, which penetrates the villus continuing the infective
cycle without passage through the external environment (9). The life span
of adult worms is 4 to 6 weeks, but internal autoinfection allows the
infection to persist for years.

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Transmission and Life Cycle (H. diminuta)
Eggs of Hymenolepis diminuta are passed out in the feces of the infected
definitive host (rodents, man) (1). The mature eggs are ingested by an
intermediate host (various arthropod adults or larvae) (2), and oncospheres
are released from the eggs and penetrate the intestinal wall of the host (3),
which develop into cysticercoid larvae. Species from the genus Tribolium
are common intermediate hosts for H. diminuta. The cysticercoid larvae
persist through the arthropod's morphogenesis to adulthood. H. diminuta
infection is acquired by the mammalian host after ingestion of an
intermediate host carrying the cysticercoid larvae (4). Humans can be
accidentally infected through the ingestion of insects in precooked cereals,
or other food items, and directly from the environment (e.g., oral
exploration of the environment by children). After ingestion, the tissue of
the infected arthropod is digested releasing the cysticercoid larvae in the
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stomach and small intestine. Eversion of the scoleces (5)occurs shortly
after the cysticercoid larvae are released. Using the four suckers on the
scolex, the parasite attaches to the small intestine wall. Maturation of the
parasites occurs within 20 days and the adult worms can reach an average
of 30 cm in length (6). Eggs are released in the small intestine from gravid
proglottids (7)that disintegrate after breaking off from the adult worms.
The eggs are expelled to the environment in the mammalian host's feces
(1).

Clinical features and Pathology
Hymenolepis nana infections are most often asymptomatic. Heavy
infections with H. nana can cause weakness, headaches, anorexia,
abdominal pain, and diarrhea. Toxins released from the worms can cause
allergic reactions. Little or no pathology occurs from development of
cysticercoids in the villi, and only after a heavy infection (perhaps
produced by autoinfection) do symptoms develop from the adult worms.
Children may be particularly subject to massive worm loads and show the
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most severe intestinal symptoms. Also H. diminuta infections are most
often asymptomatic. But occasional patients may present with mild
gastrointestinal complaints such as nausea, anorexia, abdominal pains, and
diarrhea.
Laboratory diagnosis
The diagnosis depends on the demonstration of eggs in stool specimens.
Concentration techniques and repeated examinations will increase the
likelihood of detecting light infections.
Treatment
Praziquantel is the drug of choice.













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Table-1-Summary in the most common serious tape worms
Treatment Diagnosis Symptoms Transmission Organism
Praziquantel Proglottids or
eggs in stool or
perianal area
Epigastric
pain,
vomiting,
diarrhea
Cyst in beef Tenia saginata
Praziquantel Proglottids or
eggs in stool or
perianal area
Epigastric
pain,
vomiting,
diarrhea
Cyst in pork Tenia solium
Praziquantel Roentgenography,
anti-cysticercal
antibody (EIA)
Muscle pain
and
weakness,
ocular and
neurologic
problems
Oro-fecal T. solium
Cysticercosis
Praziquantel Proglottids or
eggs in stool or
perianal area
Abdominal
pain, loss of
weight,
anorexia,
malnutrition
and B12
deficiency
problems
Cyst in fish D. latum
Surgery,
formalin
injection
and
drainage,
Praziquantel
,
Albendazole
Roentgenography,
anti-hydatid fluid
antibody (EIA),
Casoni skin test
Large cysts
produce
various
symptoms
depending on
the location
of the
organism.
Oro-fecal






E. granulosus
Surgery,
Albendazole
As above As above Oro-fecal E.
multiloculoris




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CHAPTER TWELVE (12)

Nematodes (Roundworms)
Introduction
In contrast to platyhelminths, nematodes are cylindrical rather than
flattened; hence the common name roundworm. The body wall is
composed of an outer cuticle that has a noncellular, chemically complex
structure, a thin hypodermis, and musculature. The cuticle in some species
has longitudinal ridges called alae. The bursa, a flaplike extension of the
cuticle on the posterior end of some species of male nematodes, is used to
grasp the female during copulation. The alimentary canal of roundworms
is complete, with both mouth and anus. The mouth is surrounded by lips
bearing sensory papillae (bristles). The esophagus, a conspicuous feature
of nematodes, is a muscular structure that pumps food into the intestine; it
differs in shape in different species. Nematodes are usually bisexual.
Males are usually smaller than females, have a curved posterior end, and
possess (in some species) copulatory structures, such as spicules (usually
two), a bursa, or both. Copulation between a female and a male nematode
is necessary for fertilization except in the genus Strongyloides. Most
nematodes that are parasitic in humans lay eggs that, when voided, contain
either an uncleaved zygote, or a completely formed larva. Some
nematodes, such Trichinella spiralis, produce larvae that are deposited in
host tissues. The developmental process in nematodes involves egg, larval,
and adult stages. Each of four larval stages is followed by a molt in which
the cuticle is shed. The larvae are called second-stage larvae after the first
molt, and so on. The nematode formed at the fifth stage is the adult.
Blood and Tissue Nematodes
Filariasis
Filariasis - Filariasis is a disease group affecting humans and animals that
is caused by nematode parasites of the order Filariidae, commonly called
filariae. Filarial parasites may be classified according to the habitat of the
adult worms in the vertebral host. The lymphatic group includes
Wuchereria bancrofti, Brugia malayi, and Brugia timori. The cutaneous
group includes Loa loa, Onchocerca volvulus, and Mansonella
streptocerca. The body cavity group includes Mansonella perstans and
Mansonella ozzardi.

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Lymphatic Filariasis can be caused by the following species:
Wuchereria bancrofti

Brugia malayi
Brugia timori
Bancroftian Filariasis (W. bancrofti infection)
Bancroftian Filariasis - Bancroftian filariasis refers specifically to filarial
infection with the nematode parasite Wuchereria bancrofti. Adult worms
usually reside in the large lymphatics of the human host.
Morphology
Adult female W. bancrofti found in lymph nodes and lymphatic channels
are 80 to 100 mm in length and 0.24 to 0.30 mm in diameter, whereas
males are only half that size measure about 40 mm by .1 mm. Microfilaria
found in blood are only 244 to 296 m by 7.5 to 10 m. The microfilaria
is sheathed (Fig-1-), its body is gently curved, and the tail is tapered to a
point. The nuclear column (the cells that constitute the body of the
microfilaria) is loosely packed, the cells can be visualized individually and
do not extend to the tip of the tail.

Fig:-1- W. bancrofti microfilaria.
Epidemiology
W. bancrofti is distributed throughout the tropical regions of Asia, Africa,
China, the Pacific and isolated locations in the Americas. Current
estimates (WHO, 1994) suggest that 100 million people are infected with
lymphatic filariae of all types, and most of these cases are bancroftian
filariasis. Nocturnally periodic forms occur indigenously in almost every
tropical and subtropical country and are very widespread. However they
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show focal and periodic distribution patterns which are dependent on their
vector of transmission.
Transmission and Life Cycle
Different species of the following genera of mosquitoes are vectors of W.
bancrofti filariasis depending on geographical distribution. Among them
are: Culex (C. annulirostris, C. bitaeniorhynchus, C. quinquefasciatus, and
C. pipiens); Anopheles (A. arabinensis, A. bancroftii, A. farauti, A.
funestus, A. gambiae, A. koliensis, A. melas, A. merus, A. punctulatus and
A. wellcomei); Aedes (A. aegypti, A. aquasalis, A. bellator, A. cooki, A.
darlingi, A. kochi, A. polynesiensis, A. pseudoscutellaris, A. rotumae, A.
scapularis, and A. vigilax); Mansonia (M. pseudotitillans, M. uniformis);
Coquillettidia (C. juxtamansonia). Culcicine or anopheline mosquitoes
are the main vectors of the nocturnally periodic forms of W. bancrofti,
while day biting Aedes polynesiensis transmit the subperiodic form in
various pacific islands . During a blood meal, an infected mosquito
introduces third-stage filarial larvae onto the skin of the human host,
where they penetrate into the bite wound (1). They develop in adults that
commonly reside in the lymphatics (2). The female worms produce
microfilariae which are sheathed and have nocturnal periodicity, except
the South Pacific microfilariae which have the absence of marked
periodicity. The microfilariae migrate into lymph and blood
channels moving actively through lymph and blood (3). A mosquito
ingests the microfilariae during a blood meal (4). After ingestion, the
microfilariae lose their sheaths and some of them work their way through
the wall of the proventriculus and cardiac portion of the mosquito's midgut
and reach the thoracic muscles (5). There the microfilariae develop into
first-stage larvae (6)and subsequently into third-stage infective larvae (7).
The third-stage infective larvae migrate through the hemocoel to the
mosquito's prosbocis (8)and can infect another human when the mosquito
takes a blood meal (1).


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Clinical features
The early symptoms develop 6 or more months after initial infection, and
are due to lymphangitis. The adult worms in the proximal lymphatics
draining the limbs and external genitalia cause an intermittent sterile
lymphanitis and lymphadenitis. The commonest features are recurrent
attack or bouts of high fever every 8 to 10 weeks which lasts 3 to 7 days,
associated with heat, redness, pain and tenderness overlying a lymphatic
vessel. The local lymph nodes are usually enlarged and tender too. If it can
be observed (in a fair-skinned patient) the lymphangitis may be seen to
spread distally. This is the opposite to direction of spread in patient with
lymphangitis secondary to a peripheral septic lesion. There is progressive
lymphadenitis due to an inflammatory response to the parasite lodged in
the lymphatic channels and tissues. As the worm dies, the reaction
continues and produces a fibro-proliferative granuloma which obstructs
lymph channels and causes lymphedema and Elephantiasis {filarial
elephantiasis is a chronic enlargement of a limb, the scrotum, a breast, or
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the vulva, with hyperplasia of the connective tissue and skin, awoody
nonpitting edema, and thickened, coarsened skin, often with verrucous
changes (Fig-2-)}. In Malayan and Timoran filariasis, elephantiasis is less
severe and generally is confined to the lower limbs below the knee.

Fig:-2- Filarial elephantiasis.
The most frequently affected sites are:
1-Leg (thigh and groin).
2-Arm (upper arm/axilla)
3-Breast (in women)
4- Epididymitis (in man); it is an early complication of bancroftian
filariasis, often associated with orchitis, and with or without
accompanying lymphangitis and fever.
5-Funiculitis ; inflammation of the spermatic cord is frequently an early
sign of bancroftian filariasis.
6- Hydrocele ; common finding in areas where filariasis is endemic,
developing as a sequel to repeated attacks of orchitis. If lymphatic varices
develop in the cord and rupture into the scrotal sac, a condition known as
lymphocele results.
7- Lymph varices ; Dilatations of the lymphatic vessels , frequently seen
in the inguinal and femoral areas, but other lymphatic tracts may be
affected. The soft lobulated swellings may rupture , when this occurs on
the scrotum, a chronic condition known as lymph scrotum may develop.
The stretched skin is susceptible to traumatic injury and infections.
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Microfilaria cause eosinophilia. Not all infections lead to elephantiasis.
Prognosis, in the absence of elephantiasis, is good. As more attacks occur,
there is an increasing amount of residual damage to lymphatic system
which does not resolve between the attacks. In the early stage the swelling
is due to fluid only, and can be relieved by elevating the affected part or
by the application of pressur bandage. Due to overgrowth of the skin and
subcutaneous in elephantiasis make the skin rugose, with an exaggerated
pattern of creases and folds. Bacteria causing secondary infection find a
hospital environment in these closely apposed skin folds with their lymph-
rich tissue fluid. They tend to multiply and invade the vulnerable tissues.
Repeated bacterial infection lead to cellulites , in which often contribute to
further damage to the lymphatic system, and significantly add to the
patients misery. Streptococci are most often involved. Abscesses of the
pelvis of the kidney (pyelonephritis), retroperitoneal tissues, inguinal
nodes, and iliopsoas muscles may result from the dead and degenerating
worms , it may be sterile but frequently pyogenic bacteria are present.
Chyluria; The formation of lymphatic varices, consequent to repeated
attacks of filarial lymphangitis and obstruction of lymphatic drainge, may
lead to passage of lymphatic fluid in the urine if varices rupture into any
part of the urinary tract . The urine may be milky white and contain
microfilaria. , the chyle consist of lymph and partcles of digested fat
(soluble in ether). The urine containing chyle appears creamy white. When
blood present the urine appears pinkish-white.
Pathology
Following infection with third stage larvae there is usually a period of
vigorous immune response to the invading larvae. If the larvae are not
cleared from the body during this period then the various pathologies
associated with filarial infection can develop. Most of these conditions do
not appear to arise from the effects of the nematodes themselves but from
immune reactions to their presence. The most pronounced of these is the
damage to the lymphatic vessels which is mediated by the immune
system's response to the adult worms living in them. These immune
responses (Lymphangitis) are characterized by inflammation of the
affected area (which are usually extremities) and fever. Repeated episodes
of lymphangitis lead to the formation of fibrous and calcified tissues in
and around the lymphatic vessels. This can then result in gross
enlargement of the effected lymph nodes and the pictures below. The
microfilariae in the blood and lungs can also cause an IgE mediated
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allergic response which results in asthma like symptoms. This condition is
called (Tropical pulmonary eosinophilic syndrome) It is a syndrome
characterized by persistent hypereosinophilia, nocturnal cough and
wheezing with scanty production of sputum, low grade fever, weight loss,
and adenopathy. Eosinophil counts are over 3000 per mm
3
blood, IgE
levels are 1000 units per ml or greater, and high titers of antifilarial
antibodies are present both in the blood and in fluid obtained by
brochoalveolar lavage. Microfilaria are not found in peripheral blood, but
may be found in biopsy specimens from the lung and elsewhere.
Radiography shows increased bronchovascular markings and diffuse
coarse interstitial infiltrates, but the radiograph may be normal in up to
30% of cases. Pulmonary function testing reveals a predominant restrictive
pattern together with mild reversible airway obstruction in the majority of
patients. diagnosis can be established by response to DEC, which is
generally prompt. The suggested dose is 2 mg/kg three times daily for 7 to
10 days.),and is treatable with microfilaricides. This syndrome must be
distinguished from other eosinophilic syndromes; this is generally not
difficult, given the geographic distribution of the disease and rapid clinical
and radiologic response to therapy with diethylcarbamazine. Cases of TPE
have typically been reported to present as "refractory bronchial asthma"
usually in nonimmune individuals (visitors to endemic regions). Despite a
3-week course of diethylcarbamazine, low-grade alveolitis persists in
almost half of such patients and may be the cause of progressive
pulmonary fibrosis seen in many inadequately treated patients. Relapses
can occur and are treated with repeat courses of the same drug.
Corticosteroids may be helpful in treating the chronic forms of TPE.
Laboratory diagnosis
Blood
Direct method
Diagnosis is based on history of mosquito bites in endemic areas, clinical
findings and presence of microfilaria in blood samples collected at night.
Mf begin to appear in the blood a year or more after infection . They are
rarely found when the lymphatic have become obstructed. Blood must be
collected at the correct time , during the hours when the greatest number
of mf are likely to be present .The most commonly used method is the
Giemsa-stained thick blood film. Most W.bancrofti infections show
marked nocturnal periodicity. This means most of the mf appear at night,
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with apeak (periodic nocturnal) between 2200 and 0100. (subperiodic
nocturnal) between 2000-2200. During the day the mf are very scanty or
cannot be found at all on ordinary blood films. When not circulating in the
blood , the mf are sequestered in the lungs. , mf can be flushed by giving
a single dose of 50mg of diethylcarbamazine (DEC), to detect nocturnal
periodic mf during the day. The pacific strains of W.bancrofti show
diurnal periodicity , more mf being found in the blood in the day than in
the night ,the periodicity is described as (diurnally subperiodic) time
between 1200-1800h.
Indirect methods
This is only needed where filariasis is suspected, but mf cannot be found
in the blood. It can be very useful in patients with elephantiasis of
unknown cause. Antibody may be detected in the blood using the usual
array of methods. Most common are the CFT, IFAT, ELISA. All the
indirect Ab tests suffer from the usual disadvantages of lack of sensitivity
or specificity.
Others
1- Skin test can also be used by using adult worm extract , the
development of a wheal 15 mins after the intradermal injection is positive
and indicates the presence of Ab.
2-Urine examination: in chronic bancroftian filariasis a condition called
chyluria(chyle in urine) can occur . Mf can often be found in the fibrin
clots which form (10-20 ml ofurine specimen collect in the early
morning).
Treatment
Diethylcarbamazine (DEC) quickly kills the adults worms or sterilizes the
female. The drug itself is extremely well tolerated , but it commonly
causes reactions in patients with filariasis , due to the liberation of
antigens from the mf in the early days of treatment, and to reactions
around the dead worms later. The early reactions are fever ,
malaise,headache, nausea, vomiting, and sometimes urticaria. Later there
may be lymphangitis, funiculitis, painful lymphadenopathy and abscess
formation around the dead worms . The severity of these initial reaction is
reduced if drug started with small dose. Steroids help alleviate
inflammatory symptoms. Cooler climate reduces the inflammatory
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reaction. Lymphatic filariasis has for many years been treated with
diethylcarbamazine (DEC), but this drug is not always easy to administer
and often has unpleasant side-effects. Ivermectin is now entering field
trials against lymphatic filariasis in Brazil and parts of Africa, India, SE
Asia and the Western Pacific region.
Prevention and Control
Mass treatment of infected people (using diethylcarbamazine at present) to
reduce morbidity .Transmission of lymphatic filariasis can also be reduced
by Reduce man-vector contact, (eg. using repellents, bednets, insecticides)
. Improve sanitation in urban areas of endemic areas because the
important mosquito vectors such as Culex quinquefasciatus often breed in
polluted urban waters (such as blocked drains and sewers), so urban
sanitation can make an important contribution to reducing the risk of this
disease.
Brugia malayi
Morphology
Adult B. malayi are only half the size of W. bancrofti but their microfilaria
are only slightly smaller than W. bancrofti.
Female worms measure 43 to 55 mm in length by 130 to 170 m in width,
and males measure 13 to 23 mm in length by 70 to 80 m in width.
Adults produce microfilariae, measuring 177 to 230 m in length and 5 to
7 m in width, The microfilaria of B. malayi can be distinguished from
those of W. bancrofti by the two isolated nuclei at the tip of the tail and the
absence of nuclei in the cephalic spaces . The mf are sheated. Differently
from Wuchereria, the microfilariae in this species are more tightly coiled,
and the nuclear column is more tightly packed, preventing the
visualization of individual cells.
Epidemiology
The endemic range of Brugia malayi is confined to South and South-East
Asia from India in the west to Korea in the east. Like W. bancrofti its
distribution is dependent on its mosquito vectors. The nocturnally periodic
form is found in areas with rice fields and the nocturnally subperiodic
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form is found in rural villages and plantations along the lower reaches of
major rivers in swamp forests.
Transmission and Life Cycle
B. malayi is almost identical to that of Wuchereria bancrofti. However B.
malayi is transmitted by different mosquito vectors in the Mansoniodes
(mansonia species) and some Anopheles species transmit the infection in
towns. The typical vector for Brugia malayi filariasis are mosquito species
from the genera Mansonia and Aedes. During a blood meal, an infected
mosquito introduces third-stage filarial larvae onto the skin of the human
host, where they penetrate into the bite wound (1). They develop into
adults that commonly reside in the lymphatics (2). The adult worms
resemble those of Wuchereria bancrofti but are smaller. Adults produce
microfilariae, which are sheathed and have nocturnal periodicity. The
microfilariae migrate into lymph and enter the blood stream reaching the
peripheral blood (3). A mosquito ingests the microfilariae during a blood
meal (4). After ingestion, the microfilariae lose their sheaths and work
their way through the wall of the proventriculus and cardiac portion of the
midgut to reach the thoracic muscles (5). There the microfilariae develop
into first-stage larvae (6)and subsequently into third-stage larvae (7). The
third-stage larvae migrate through the hemocoel to the mosquito's
prosbocis (8)and can infect another human when the mosquito takes a
blood meal (1).

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Clinical features
The clinical feature of B. malayi infection is somewhat different than that
of W. bancrofti. The symptoms of Brugian filariasis begin earlier than
those of Bancroftian filariasis, often within a month or less. The basic
pathology is the same as that of W.bancrofti. And the clinical features are
similar but less severe. The elephantiasis of Malayan filariasis is usually
confined to below the knee (Fig-1&2-), and scrotal involvement is not so
gross. Chyluria is rare.
Pathology
Immune responses to the worms quickly lead to lymphoedema and
swelling of the legs is a prominent early symptom. Bouts of fever and
lymphangitis are common and often more frequent than those found in
patents infected with W. bancrofti. Unlike bancroftian infection the
lymphoedema in the legs is below the knees and in the arms below the
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elbows. Gross elephantiasis is very uncommon. However, when it does
occur it generally develops more quickly in Brugian (1 to 2 years) than the
Bancroftian (3 or more years) filariasis. The pictures below show both
early (Fig-1-) and late (Fig-2-) stages of Brugian elephantiasis.


Fig:-1- Early stage Fig:-2-Late stage of Brugian elephantiasis
(Note; swelling below the knee)
Laboratory diagnosis

Same lab procedures for W.bancrofti . Collection time for brugia malayi
(Periodic B.malayi: collect blood between 2200-0400 hrs) and
( Subperiodic B.malayi: collect blood between 2000-2200 hrs).

Treatment

Same treatment for W.bancrofti.
Brugia timori
Morphology
The microfilariae have several distinguishing features: they are longer
with a cephalic space length to width of about 3:1. In addition the sheath
does not stain pink with Giemsa stain like B. malayi and W. bancrofti. The
adults also differ morphologically from B. malayi.
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Epidemiology
Brugia timori is found in the lesser Sunda islands of the Indonesian
archipelago, such as Timor . Like B. malayi it is locally confined to areas
endemic to its mosquito vector .
Transmission and Life Cycle:
The life cycle of B. timori is almost identical to that of Wucheria bancrofti
and B. malayi. It is nocturnally periodic and is transmitted by the mosquito
Anopheles barbirostris which breeds in rice fields.
Clinical features and Pathology

The clinical and pathological features of timorian filariasis is very similar
to malayan filariasis with acute recurrent lymphagitis and filarial
abscesses in the lymphatic trunk in the leg are common (Fig-1-).
Subsequent scaring over thick hard, cord like lymphatics are a hallmark of
the disease. Elephantiasis resulting from timorian infection is rare.





Fig:-1- Subsequent scaring.

Laboratory diagnosis

Same lab procedures for W.bancrofti. Collection time for brugia timori
(Periodic B.timori: collect blood between 2200-0400 hrs).

Treatment

Same treatment for W.bancrofti
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Nonfilarial Elephantiasis

An elephantiasis of nonfilarial origin is not uncommon in northern and
central east Africa, where it is overlaps with that of bancroftian filariasis.
It is confined in areas where soil contains large quantities of iron and
aluminium salts. The affected persons go barefoot so these material were
frequently absorbed through abrasions on the feet. The crystals of silicate,
with iron and aluminium salts will accumulate and obstruct the lymphatic
circulation of these persons and lead to lymphoedema (same picture of
elephantiasis) , starts distally and proceed upward rarely extends above the
knee.

Subcutaneous Filariasis can be caused by the following species:
Onchocerca volvulus

Loa loa

Mansonella streptocerca

Onchocerciasis/Blinding filariasis/ river blindness (O.volvulus infection)
Onchocerciasis (syn. onchocercosis) is a disease resulting from infection
by the nematode Onchocerca volvulus. The principal characteristics of the
condition are pruritic dermatitis, subcutaneous nodules and ocular lesions.
Skin lesions were described at the end of the nineteenth century in Africa
by Leuckart (1993) and by the Briton, John O'Neil (1875). Robles in 1915
discovered the disease in Guatemala. He was the first to associate the
subcutaneous nodules with eye lesions. The disease is found in a wide
band across equatorial Africa. As the disease is a major cause of blindness,
the WHO and the countries most affected are cooperating in an attempt to
eradicate the infection from huge areas of West and Central Africa.
Etiology

Human onchocerciasis is caused by the filarial parasite Onchocerca
volvulus whose life cycle occurs in two different hosts: black flies, and
human.
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Morphology
Females measure 33 to 50 cm in length and 270 to 400 m in diameter,
while males measure 19 to 42 mm by 130 to 210 m. The microfilariae,
measuring 220 to 360 m by 5 to 9 m and unsheathed, and with sharply
pointed, curved tails (sharply angled at the end) , the tail is free of nuclei.
Whereas nuclei extend to the tip of M.streptocerca mf tail.
Epidemiology
Human onchocerciasis is found in both the Old and New World but about
96% of all cases are in Africa and mostly in Western Africa. Of the 36
countries where the disease is endemic, 30 are in sub-Sahara Africa (plus
Yemen) and six are in the Americas. Indeed, important foci exist also in
Mexico, Guatemala, Venezuela and Ecuador. A total of 18 million people
are infected with the disease and have dermal microfilariae, of whom 99%
are in Africa.
Transmission
The infective larvae are normally transmitted by the bite of Simulium flies
(Fig-1-).

Fig:-1- Simulium (Black) fly.
Life Cycle
During a blood meal, an infected blackfly (genus Simulium) introduces
third-stage filarial larvae onto the skin of the human host, where they
penetrate into the bite wound (1). In subcutaneous tissues the larvae
(2)develop into adult filariae, which commonly reside in nodules in
subcutaneous connective tissues (3). Adults can live in the nodules for
approximately 15 years. Some nodules may contain numerous male and
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female worms. In the subcutaneous nodules, the female worms are
capable of producing microfilariae for approximately 9 years. have a life
span that may reach 2 years. They are occasionally found in peripheral
blood, urine, and sputum but are typically found in the skin and in the
lymphatics of connective tissues (4). A blackfly ingests the microfilariae
during a blood meal (5). After ingestion, the microfilariae migrate from
the blackfly's midgut through the hemocoel to the thoracic muscles (6).
There the microfilariae develop into first-stage larvae (7)and subsequently
into third-stage infective larvae (8). The third-stage infective larvae
migrate to the blackfly's proboscis (9)and can infect another human when
the fly takes a blood meal (1).


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Note;Simulium flies larvae (Fig-2-)breed in fast flowing rivers i.e well
oxygenated water, because their larvae have an obligatory aquatic stage
during which they require high oxygen tension. Hence, Onchocerciasis is
associated with fast flowing rivers including rapids. That's why the
blindness Onchocerciasis can lead to is often referred to as 'river
blindness'.

Fig:-2- Simulium flies larvae.
Note;The microfilariae can be found free in the fluid within the nodules
and in the dermal layers and subcutaneous tissues of the skin spreading
away from the nodules containing the adults. Rarely may be found in
urine, or sputum,blood and eye during heavy infections. They infect their
fly vectors while the flies are feeding on the human host and mature into
third stage infective larvae in the flies' flight muscles (about 10 days total).
Clinical features and Pathology
One early sign of infection with Onchocerca is the raised nodules that can
be seen under the skin Onchocercoma (Fig-3-) (adult worms lie in coiled
masses beneath the skin, completely enclosed in a fibrous tissue capsule.
They are from a few millimeters to several centimeters in diameter,
generally freely movable , and resemble lipoma. In America they
frequently occur beneath the patients scalp; in Africa most frequently
occur on other parts of the patients body). These are most often seen in
areas over bony prominence . It is suggested that this phenomenon occurs
because the larvae are immobilized in these locations. In the skin there is
destruction of the elastic tissues and the formation of redundant folds (see
below) (Fig-4-). There is also often a loss of pigmentation and the
histological appearance of advanced cases often resembles the skin of very
old normal subjects

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Fig:-3- Onchocercoma (Onchocerciasis nodule) on iliac crest Fig:-4-
Redundant skin folds ;Hanging groin.
During the incubation period of 10 to 12 months, there is eosinophilia and
urticaria. Ocular involvement consists of trapping of microfilaria in the
cornea, choroid, iris and anterior chambers, leading to photophobia,
lacrimation and blindness.
Note: Most of the pathology of onchocerciasis results from the migration
of microfilariae into the skin and eyes, leading to intense itching and
disfiguring dermatitis, and ocular damage including blindness. So the
main Symptoms and pathological changes are occur in (Eye) and (Skin).
The Ocular lesions
The earliest symptoms of eye involvement are redness and irritation,
sometimes associated with lachrymation. At this stage there are often no
visible lesions.Chronic conjunctivitis is seen in Onchocercal infection ,
with, photophobia, and gradual development of corneal opacities; acute
exacerbations of conjunctivitis and photophobia may be associated with
attacks of onchocercal dermatitis. Ocular lesions only occur after many
years of severe infection and are therefore usually not present before the
age of 30. They are more frequent in savanna regions than in the
rainforest. Ocular lesions can be exacerbated by DEC therapy, but not by
ivermectin. Microfilariae can be seen in the anterior chamber with a
slitlamp. When microfilariae die, opaque fine 0.5 mm wide corneal lesions
occur: keratitis punctata. This is a corneal inflammation with small spots
on the cornea accompanied by redness of the conjunctiva. Sclerosing
keratitis occurs later (hazy cornea with pannus formation) as well as iritis
and uveitis, resulting in blindness (river blindness!). Eventually this leads
to virtually complete blindness, and when corneal opacification is
complete, the patient may not be able to perceive light. More rarely, there
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is involvement of the posterior part of the eye: chorioretinitis and optic
nerve atrophy. In chorioretinitis, an active exudative form and a chronic
atrophic form are recognised. There is initially a loss of retinal pigment
which assumes a greyish-yellow patchy appearance, mostly in an arch
around the macula (temporally to the macula and nasally to the optic disk).
Pigment clumps, atrophy and subretinal fibrosis occur subsequently. Mild
infections may continue for many years without causing any symptoms
other than minor itching, . In general only when there is repeated
reinfection over a period of two or more decades do serious eye
complications develop. There are many parts of tropical and subtropical
Africa where the disease is endemic but the rate of blindness is very low.
On the other hand , there are parts of Africa where the transmission rate is
so high and mf densities so large, that complications in the eye can be seen
before the patient reaches the age of 30 years. There is some evidence that
African forest strains of the parasite are less pathogenic to the eye than
are savannah strains.
The Pathogenesis mainly due to mf migration and death in the eye tissue.
The pathology progresses the vision becomes gradually reduced. The
microfilariae can also enter the eye by passing along the sheaths of the
ciliary vessels and nerves from under the bulbar conjunctiva directly into
the cornea, via the nutrient vessels into the optic nerve, and via the
posterior perforating ciliary vessels into the choroid. Dead microfilariae in
the eye lead to an inflammatory immune response and the eventual
formation of secondary cataracts (lens opacity) and ocular lesions.
Note: Blindness;On a global scale, the main causes of blindness are:
cataract (clouding of the lens), trachoma (infection with the bacterium;
Chlamydia trachomatis), glaucoma (increased intra-ocular pressure with
damage to the optic nerve), xerophthalmia (vitamin A deficiency with
night blindness first of all, followed by dry eyes and corneal softening),
onchocerciasis, diabetes, leprosy, maculopathy and trauma.
The skin lesions
The commonest and early symptom of skin in Onchocerciasis is itching.
Pruritus occurs locally or systemically. There are scratch lesions often
with bacterial surinfection. The chronic itching has given rise to the terms
"gale filarienne" . In severe cases, the itching may be so intolerable that
the patient can not sleep at night, and it has even been known to lead to
suicide. If untreated, the dermatitis assumes the form of a pruritic papular
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dermatitis, progressing to a chronic rough, coarse, papular dermatitis,
often with postinflammatory hyperpigmentation, followed by
lichenification, atrophy and finally patchy depigmentation (Leopard
skin). Pea- to plum-sized subcutaneous nodules (Onchocercoma) are
found predominantly over bony protuberances such as the hip, pelvis, ribs,
shoulderblades and skull. For every palpable nodule, there are 4 non-
palpable nodules (forest onchocerciasis) or 10 non-palpable nodules
(savanna onchocerciasis). Though not always found (in Africa in only 30
to 60% of positive people), enlargement of the inguinal nodes is
sometimes also present, with redundant skin folds , resulting in what is
known as (Hanging groin Fig-3&4-see below). Onchocerciasis causes
Elephantiasis (lymphoedema) in a number of cases. More severe skin
disease is produced by numerous mf, and the skin changes in Africa are
usually most severe in the lower half of the body. This is almost certainly
because the flies bite in the lower half of the body and more adult worms
are found in the lower half of the body than in the upper. Whereas In
central A merica the flies bite on the head, and nodules on the scalp are
common.
Note: In Yemen, a syndrome of unilateral or bilateral maculopapular
pruritic onchocerca dermatitis of the legs is found with hyperpigmentation
and inguinal lymph node enlargement, known as "Sowda".
The Pathogenesis of O.volvulus in the skin is almost entirely due to
microfilaria (mf), and the adult worms normally cause no symptoms. Mf
cause pathology when they die, and form a small focus of inflammation.
In Onchocerciasis, the presence of Mf in the skin sometimes elicits an
acute pruritic inflammatory reaction cause diffuse reddish swelling of the
tissues, called (Erysipelas de la costa) may result from intense mf
infiltration, especially in children. Repeated acute attacks may result in a
chronic lichenification, with hyperpigmentation (usually on the face, neck,
or ears) and fissuring. Itching is commonly followed by papular rash,
aggravated by consequent scratching. Secodary infection of excoriations
may be severe. Often the itchy skin looks normal, especially when the
infection is light. Prolonged heavy infection leads to irreversible structural
changes in the skin. The skin loses pigment, most commonly in the shins .
There is destruction of the elastic tissues and the formation of redundant
folds. And the histological appearance of advanced cases often resembles
the skin of very old normal subjects. Wrinkles form, and skin sometimes
becomes so redundant as to hang dowen , This condition is especially
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prominent in the inguinal areas and around the scrotum often called the
('Hanging groin' ) (Fig-4-).
Laboratory diagnosis
Diagnosis is based on symptoms, history of exposure to black flies and
presence of microfilaria.
Direct method
Detection of microfilariae in a skin snip
Various techniques may be used for detecting microfilariae in the skin. A
skin snip is often used. A needle is used to raise the skin and a fine piece
is shaved off with a razor blade. The piece of tissue is placed in some
physiological saline. The specimen is then examined 15 minutes to 3 hours
later to see whether or not microfilariae have emerged.
Detection of microfilariae at other sites
Occasionally O. volvulus microfilariae are found in the blood and in the
urine.
Nodulectomy
This is both diagnostic and curative if all the nodules would be resected.
The macrofilariae are found in the nodule.
Slitlamp examination
This is a non-invasive test, but requires considerable experience. It is best
to get the patient to lay his/her head on his/her knees for at least 2 minutes
before the examination to allow more microfilariae to come into the
anterior eye chamber.
Indirect methods
Serology cannot distinguish between the various species of filariae. The
antigen used is usually extracted from a different worm: Litosomoides
sigmodontis.
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Antigen detection
This is a fairly recent technique which is relatively complicated and needs
to be assessed further. The benefit for individual patients in endemic areas
is probably limited.
Mazzotti test
If the diagnosis is doubtful, the patient may be given 50 mg DEC orally. If
microfilariae are present, a severe itching reaction will occur within 2
hours. This is caused by an allergic reaction to the proteins released after
the rapid breakdown of microfilariae. Because this is very unpleasant, this
test should be used only when strictly necessary. Topical use of a DEC-
containing cream has also been described (DEC patch test), in response to
which a limited local skin reaction can occur.
Treatment
Drugs
1-Ivermectin: The treatment of onchoerciasis has been revolutionized by
the arrival of ivermectin, unlike DEC it has a prolonged suppressive effect
on mf production by acting on the reproductive system of the adult female
worms. The ivermectin had made the use of DEC obsolete.
2-Diethylcarbamazine: is effective in killing the worm.
Destruction of microfilaria produces extreme allergic reaction which can
be controlled with corticosteroids.
Nodulectomy (see diagnosis)
Prevention and Control : measures include vector control, treatment of
infected individuals and avoidance of black fly. Control of blackfly
vectors by use of biodegradable insecticides to kill blackfly larvae in their
riverine breeding sites.




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Mansonelliasis (M. streptocerca infection)
Morphology
Adult streptocercae are thin sinuous worms, the males averaging
17x0.05mm and the females 27x0.075 mm. mf measure (180-240 x 2.5-5
m). The microfilaria are unsheathed and have a characteristic pattern of
nuclei posterior to the clear cephalic space with four oval nuclei followed
by seven to ten smaller, more rounded nuclei and an oval rounded terminal
nucleus in a characteristic curved posterior portion of the worm producing
the 'walking stick' or 'shepherds crook' tail. These features distinguish
them from M. ozzardi and perstans .
Epidemiology
in Ghana, Mansonella streptocerca is distributed through the western
portion of Africa. It is especially common in Ghana and Zaire.
Transmission and Life Cycle:
The third-stage infective larva are transmitted by the midge Culicoides
grahami ,and once inside a human host the larvae move to the upper
thorax and shoulders where they mature in the dermis. When the adults
have mated they produce microfilaria which also inhabit the dermis.
During a blood meal, an infected midge (genus Culicoides) introduces
third-stage filarial larvae onto the skin of the human host, where they
penetrate into the bite wound (1). They develop into adults that reside in
the dermis, most commonly less than 1 mm from the skin surface (2). The
adults females produce unsheathed and non-periodic microfilariae, which
reside in the skin but can also reach the peripheral blood (3). A midge
ingests the microfilariae during a blood meal (4). After ingestion, the
microfilariae migrate from the midge's midgut through the hemocoel to
the thoracic muscles (5). There the microfilariae develop into first-stage
larvae (6)and subsequently into third-stage larvae (7). The third-stage
larvae migrate to the midge's proboscis (8)and can infect another human
when the midge takes another blood meal (1).

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Clinical features and Pathology
In many cases there are no clinical or pathological features of
streptocercian infection. IgE mediated immune responses to filarial
antigens can occur against dead worms and microfilariae. They are similar
but usually less severe than those caused by onchocerciasis and the eye is
never affected. The incubation and maturation time of the third-stage
infective larvae is three to four months. Persons with symptoms often have
an itching dermatitis over the thorax and shoulders. The skin is thickened
and there are hypopigmented macules. The axillary lymph glands can also
be enlarged.
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Laboratory diagnosis
Microfilaria are found primarily in the skin but also in the blood
Treatment

Diethylcarbamazine (DEC).
Loiasis/eye worm(Loa Loa infection)
Morphology
The female worms measure 40 to 70 mm in length and 0.5 mm in
diameter, while the males measure 30 to 34 mm in length and 0.35 to 0.43
mm in diameter. Adults produce microfilariae measuring 250 to 300 m
by 6 to 8 m. Microfilariae of Loa loa is sheathed, with a relatively dense
nuclear column; its tail tapers and is frequently coiled, and nuclei extend
to the end of the tail. Mansonella perstans is smaller, has no sheath, and
has a blunt tail with nuclei extending to the end of the tail.
Epidemiology
Human loiasis is confined to the rain forest and swamp forest areas of
West Africa. It is especially common in Cameroon and on the Ogowe
river.
Transmission and Life Cycle
The life cycle of Loa loa is identical to that of onchocerca except that the
vector for this worm is the deer fly. Loa loa which is transmitted to
humans by day-biting Chrysops flies (Fig-1-). The vector are flies from
two species of the genus Chrysops, C. silacea and C. dimidiata.




Fig:-1- deer fly.
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During a blood meal, an infected fly (genus Chrysops, day-biting flies)
introduces third-stage filarial larvae onto the skin of the human host,
where they penetrate into the bite wound (1). The larvae develop into
adults that commonly reside in subcutaneous tissue (2). The female
worms produce microfilariae have diurnal periodicity. Microfilariae have
been recovered from spinal fluids, urine, and sputum. During the day they
are found in peripheral blood, but during the noncirculation phase, they
are found in the lungs (3). The fly ingests microfilariae during a blood
meal (4). After ingestion, the microfilariae lose their sheaths and migrate
from the fly's midgut through the hemocoel to the thoracic muscles of the
arthropod (5). There the microfilariae develop into first-stage larvae
(6) and subsequently into third-stage infective larvae (7). The third-stage
infective larvae migrate to the fly's proboscis (8)and can infect another
human when the fly takes a blood meal (1).

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Clinical features
Circumscribed subcutaneous swellings (Calabar swelling) are seen in
loiasis. They are usually intensely pruritic and may be quite painful if they
develop in areas where there is little loose subcutaneous tissue, such as the
elbows and knees. They appear rapidly , developing within an hour or so
to a diameter of several centimeters measuring 5 to 10 cm , and persist for
several days; if in an area subject to repeated trauma they may last a week
or longer. The adult worm migrates under the skin at a rate of up to an
inch every two minutes. Consequently, indicated by a thin raised reddened
line , a few centimeters in length. the The worm usually causes no serious
problems, except when passing through the orbital conjunctiva or the nose
bridge.Note ;Unilateral circumorbital edema, with local pruritus and
sometimes intense pain, results from passage of the adult worm across the
eyeball or lid. Passage of the worm across the eyeball can take less than
half a minute to as long as 10 minutes; the resulting inflammatory changes
usually persist for several days.
Pathology
Most of the pathological problems observed in people infected with Loa
loa are connected to periods when the migrating adult worms appear near
the surface of the skin. The worms often appear around the eye (Fig-2-)
where they can be easily seen and extracted (Fig-3-) before they damage
the conjunctiva. Immune reactions to the migrating worms can also cause
calabar swellings in the arms and legs. Recurrent swelling can lead to the
formation of cyst like enlargements of the connective tissues around the
tendon sheaths. These swellings can be extremely painful when moved.
Dying worms can also cause chronic abscesses followed by
granulomatous reactions and fibrosis. Once inside the body the infective
larvae develop slowly into a mature adult (the process takes about a year).
During this period it lives and moves around the fascial layers of the skin.

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Fig:-2- L.loa adult worm in the conjunctiva. Fig:-3- Worm extraction.
Laboratory diagnosis
The diagnosis is based on symptoms, history of deer fly bite. Mf in
peripheral blood and presence of eosinophilia. Recovery of worms from
the conjunctiva is confirmatory.
Treatment
Treatment and control are the same as those for onchocerciasis. X-ray may
reveals calcified worms may be seen in the tissues. Surgical removal of
the migrating adult worms. DEC is effective.
Serous Cavity Filariasis
This nonpathological condition is caused by the following species:
Mansonella perstans

Mansonella ozzardi

Mansonelliasis (M. perstans infection)

It is common parasite of humans and apes .
Morphology
The size range for female worms is 70 to 80 mm in length and 120 m in
diameter, and the males measure approximately 45 mm by 60 m. Adults
produce unsheathed and subperiodic microfilariae, measuring 200 by 4.5
m that reach the blood stream. Nuclei extend to the end of the tail and
there is alarge nucleus at the tip. Tip of the tail is rounded.
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Epidemiology
Mansonella perstans is widely distributed throughout central Africa. In
certain locations in Zaire, Nigeria, Ghana, Sierra Leone, Ivory Coast,
Zambia, and Uganda extremely high proportions of the inhabitants show
signs of infection. It is also found in the new world in Venezuela,
Trinidad, Guyana, Surinam, northern Argentina and Amazonia.
Transmission and Life Cycle

M. perstans is transmitted to humans by the midges Culicoides grahami
and C. austeni. Once inside the body the infective larvae move to serous
cavities (pleural and peritoneal), mesentery, peri-renal spaces,
retroperitoneal spaces or the pericardium and mature into adults. The
mated adults produce microfilariae. They possess the power of elongation
and contraction so they can vary in measurement and form. They are
nonperiodic and circulate in the blood in equal amounts through out the
day and night. The microfilariae can also often be found in the
cerebrospinal fluids. During a blood meal, an infected midge (genus
Culicoides) introduces third-stage filarial larvae onto the skin of the
human host, where they penetrate into the bite wound (1). They develop
into adults that reside in body cavities, most commonly the peritoneal
cavity or pleural cavity, but less frequently in the pericardium (2). Adults
produce unsheathed and subperiodic microfilariae, that reach the blood
stream (3). A midge ingests microfilariae during a blood meal (4). After
ingestion, the microfilariae migrate from the midge's midgut through the
hemocoel to the thoracic muscles of the arthropod (5). There the
microfilariae develop into first-stage larvae (6)and subsequently into third-
stage infective larvae (7). The third-stage infective larvae migrate to the
midge's proboscis (8)and can infect another human when the midge takes
a blood meal (1).
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Clinical features and Pathology
The vast majority of infections with M. perstans are asymptomatic. Some
individuals do show symptomless eosinophilia, pleuritis, abdominal pain,
and transient skin swellings. However, to date most studies have not found
any serious conditions connected with perstanian infection. Note;Scattered
symptomatic cases are reported in the endemic areas such as Calabar-like
swellings, pruritus, fever, and headache. In Uganda, a condition known as
Kampala eye worm (eyelids swelling- periorbital edema), as a result to
the invasion of conjunctiva or periorbital connective tissue. Granuloma
were formed around the death worm with considerable edema and
inflammatory changes . Joints pain , lymphadenits and hydrocele reported
in cases with mansonelliasis perstans in south America.
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Treatment
A combination of mebendazole with levamisole hydrochloride is effective
. But treatment Unnessary in most cases.
Mansonelliasis (M. ozzardi infection)

Morphology

The size range for females worms is 65 to 81 mm in length and 0.21 to
0.25 mm in diameter but unknown for males. Adults worms recovered
from experimentally infected Patas monkeys measured 24 to 28 mm in
length and 70 to 80 m in diameter (males) and 32 to 62 mm in length and
,130 to .160 mm in diameter (females). The unsheathed mf about 207-232
x 3-4 m in size, nuclei of the body of the mf do not extend to the tip of
the as in M. streptocerca. The microfilaria is typically small, unsheathed,
and has a slender, tapered tail that is hooked ("button hook").
Epidemiology
The only filarial that parasitizes humans that is confined to the new world.
Mansonella ozzardi is endemic to many tropical locations throughout the
New World. Locations include various parts of Mexico, Panama, Brazil,
Colombia, Argentina, as well as many islands in the Caribbean.
Transmission and Life Cycle:
M. ozzardi consists of two biological forms. One is transmitted by black
flies of the Simulium family and is mainly found in the Amazon and parts
of the South American mainland. The other form is transmitted by midges
of the Culicoides family and is endemic to beach areas in the Caribbean
where these pests are common. Once in the human host the larvae move
into the peritoneal cavities. The adults then mate and produce
microfilariae . The microfilaria closely resemble those of M. perstans
except they have a sharp tail. They are nonperiodic like their vectors and
can be found in the blood and skin at all times.
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During a blood meal, an infected arthropod (midges, genus Culicoides, or
blackflies, genus Simulium) introduces third-stage filarial larvae onto the
skin of the human host, where they penetrate into the bite wound (1).
They develop into adults that commonly reside in subcutaneous tissues
(2). Adult worms are rarely found in humans .Adults produce unsheathed
and non-periodic microfilariae that reach the blood stream (3). The
arthropod ingests microfilariae during a blood meal (4). After ingestion,
the microfilariae migrate from the arthropod's midgut through the
hemocoel to the thoracic muscles (5). There the microfilariae develop into
first-stage larvae (6)and subsequently into third-stage infective larvae (7).
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The third-stage infective larvae migrate to arthropod's proboscis (8)and
can infect another human when the arthropod takes a blood meal (1).
Clinical features and Pathology
The adult worms cause little damage to the connective tissue of
peritoneum.Most infected people are completely symptomless. However,
joint pains, headaches, fever, and marked eosinophilia , coldness of the
legs. Occasionally a hydrocele , enlarged lymph node is noted, and itchy
red spots have been described in conjunction with infection.
Laboratory diagnosis
Microfilaria are found primarily in the skin but also in the blood
Treatment
Asymptomatic cases do not require treatment. DEC is the drug of choice .

Note: Mansonella species rarely cause serious disease and they can be
found in areas where pathogenic filarial also occur so its microfilaria
require differentiation from those of the major pathogenic filarial.


Dracunculiasis /Guinea worm(D.medinensis infection)

A parasitic disease caused by the largest parasite that plagues people and
bores into their tissues .
Etiology
Dracunculiasis (guinea worm disease) is caused by the nematode
(roundworm) Dracunculus medinensis. Species of skin-infecting, yard-
long nematodes, formerly incorrectly classed as Filaria; adult worms live
anywhere in the body of humans .
Morphology
The adult female worm measures (length: 70 to 120 cm) by 1 mm and the
male is half that size.
Epidemiology
Dracunculiasis is the only parasitic disease that may be eradicated from
the globe in the near future. Although widely distributed at the beginning
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of the 20th century, it is now confined to sub-Saharan Africa. The
countries known to harbor the guinea worm are Benin, Burkina Faso,
Central African Republic, Ethiopia, Ghana, Ivory Coast, Mali, Mauritania,
Niger, Nigeria, Sudan, Togo and Uganda, southwestern Asia, the West
Indies . Two-thirds of the world's estimated 100,000 annual cases of
dracunculiasis occur in war-torn Sudan, where peace is needed before aid
workers can reach affected areas, mainly in the south.
Transmission and Life cycle


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Humans become infected by drinking unfiltered water containing
copepods (small crustaceans) which are infected with larvae of D.
medinensis (1). Following ingestion, the copepods die and release the
larvae, which penetrate the host stomach and intestinal wall and enter the
abdominal cavity and retroperitoneal space (2). After maturation into
adults and copulation, the male worms die and the females migrate in the
subcutaneous tissues towards the skin surface (3). Approximately one
year after infection, the female worm induces a blister on the skin,
generally on the distal lower extremity, which ruptures. When this lesion
comes into contact with water, a contact that the patient seeks to relieve
the local discomfort, the female worm emerges and releases larvae (4).
The larvae are ingested by a copepod (5)and after two weeks (and two
molts) have developed into infective larvae (6). Ingestion of the copepods
closes the cycle (1).
Clinical features and Pathology
The female guinea-worm lives in the connective tissues of the limbs and
trunk where it usually does not cause any noticable pathological
conditions . Although heavy infestations in the joint can cause arthritic
conditions and require the removal of the worms . most pathology is
associated with infection occuring when the female dies after discharging
its larvae. If the worm does not reach the skin, it dies and causes little
reaction. The course of the worm tunnel is marked with induration and
edema. In superficial tissue, it liberates a toxic substance that produces a
local inflammatory reaction in the form of a sterile blister with serous
exudation (Fig-1-). Contamination of the blister produces abscesses,
cellulitis, extensive ulceration and necrosis. D. medinensis has also been
found coiled in the hernial sac and retroplacentally causing bleeding in
pregnancy. However, chills fever and local painful swellings commonly
precede the emergence of the worm. The worm emerges as a whitish
filament (Fig-2-) (duration of emergence: 1 to 3 weeks)


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Fig:-1- Female D.medinensis induces painful blister. Fig:-2- Worm
extraction.
Laboratory diagnosis
The clinical presentation of dracunculiasis is so typical, and well known to
the local population, that it does not need laboratory confirmation. The
outline of the worm under the skin may be revealed by reflected light. In
addition, the disease occurs in areas where such confirmation is unlikely to
be available. Examination of the fluid discharged by the worm can show
rhabditiform larvae. No serologic test is available.
Treatment and Prevention
Local cleansing of the lesion and local application of antibiotics, if
indicated because of bacterial superinfection. Mechanical, progressive
extraction of the worm by rolling it a few centimeters per day over a
period of several days or preferably by multiple surgical incisions under
local anaesthesia. No curative antihelminthic treatment is available.
Niridazole is reported to be effective in killing the worm , but it may cause
hemolytic anaemia in person with G6PD deficiency , alternative
metronidazole, and thiabendazole. Protection of drinking water from being
contaminated with Cyclops and larvae are effective preventive measures.
The provision of safe water including appropriate water supply systems,
filtering devices and the chemical treatment of water to eliminate the
vector and health education.
Dirofilariasis (D.immitis/D.repens infection)
Dirofilariasis - The zoonotic filariae, Dirofilaria immitis and Dirofilaria
(Nochtiella) repens, have become increasingly recognized worldwide as
inadvertent human pathogens. The normal hosts of these infective
nematodes usually are domestic and wild carnivores, dogscats, foxes, and
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other mammals are the natural hosts of Dirofilaria species.Human
infection presents with either subcutaneous nodules or lung parenchymal
disease that may be asymptomatic. Dirofilariasis infection in dogs and cats
can produce a potentially fatal heart condition called heartworm. In
humans, however, dirofilariasis infection is generally benign and
asymptomatic. The significance of infection in man is that pulmonary and
some subcutaneous lesions commonly are labeled as malignant tumors
requiring invasive investigation and surgery before a correct diagnosis is
made. Dirofilariasis is derived from the Latin words diro and filum,
meaning "evil thread." In humans, it is the result of accidental zoonotic
infection, with the distribution of infection in humans roughly paralleling
the distribution of infection in animal hosts. mosquitoes are the vector-
intermediate hosts, and humans are the dead-end hosts. Given that man is
a dead-end host, worms rarely reach maturity in humans.
Etiology
The agents of dirofilariasis include members of the Dirofilaria genus
within the Nematoda phyla. Human dirofilariasis is caused by. Dirofilaria
immitis (dog heartworm), Dirofilaria tenuis (raccoon parasite),
Dirofilaria repens (dog parasite), Dirofilaria ursi (bear parasite). The
mainly two Species which have been reported as causing pulmonary or
subcutaneous disease in humans include:
1-Dirofilaria immitis, which is associated with pulmonary dirofilariasis
and some rare cases of extrapulmonary dirofilariasis , and 2-Dirofilaria
repens, which is mainly associated with subcutaneous and conjunctival
dirofilariasis. Other members of the genus that have been found to be the
infectious agents of subcutaneous dirofilariasis in humans include:
Dirofilaria ursi, Dirofilaria tenuis, Dirofilaria striata, Dirofilaria
lutrae,and Dirofilaria subdermata.
Note; D. repens and D. tenuis have also been called D. conjunctiva and
Loa extraocularis due to their propensity for infecting the conjunctiva or
other locations near the eye
Morphology

In the natural host, the adult worm varies in size from a few centimeters to
35 centimeters in D. immitis. The females are generally larger than the
males, and females from different species are often indistinguishable.
However, in human infections, mature worms are rarely found. The actual
size of the parasite in human infection ranges from 100 to 600m in
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diameter. Many of the subcutaneous Dirofilaria found in humans are
characterized by the presence of morphologically distinct longitudinal
ridges on the cuticle, which become visible under a light microscope.

Epidemiology
Since human dirofilariasis infection is rare and generally occurs in isolated
cases, the epidemiology of human dirofilariasis is not well understood.
However, several factors are known to influence the frequency and
distribution of infection, including: 1-The size of the natural host
population in a particular area, 2-The prevalence of infection in the natural
host population, 3-The density of the vector population (mosquitoes of
various species), and 4-The degree of human exposure to the bite of
infected mosquitoes .
D. immitis; infections have been reported from japan, Australia, southern
and eastern USA, and parts of South America.
D. tenuis; infections have occurred in southern USA.
D. repens; infections have been reported from India, Asia, and Europe.
D. ursi: D. ursi infection is found in the northern United States and
Canada in the perirenal fat and mediastinum of bears.
D. subdermata: D. subdermata infection is found in the northern United
States and Canada in porcupines.
D. striata: D. striata infection is found in deep tissues and muscular
fascia of some species of wild cats on the American continent.

Transmission and Life Cycle
Little is known about the transmission of dirofilariasis infection to
humans. It is generally understood to occur by accidental infection by the
agency of the same insects that infect the parasite's natural hosts, namely
various species of mosquito. Transmission occurs via the blood when the
mosquito vector takes its blood meal from an infected animal that has
circulating microfilariae. Microfilariae enter through the insect's
proboscis, and then develop into infective juvenile larvae inside the
insect's salivary gland. These infective juveniles are introduced into a new
animal host when the mosquito feeds again. Since the insect vector is
generally indiscriminate in its blood meal host, a mosquito carrying the
parasite can potentially transmit the infective juvenile larvae to humans by
depositing the infective larvae on the skin as it takes its blood meal from
the human. Humans are a dead-end host for Dirofilaria. The larvae will
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either die at the site of inoculation or migrate into the subcutaneous
tissues, where they will incompletely mature. In the case of pulmonary
filariasis, incompletely matured worms migrate to the right side of the
heart. However, since they are unable to complete maturation, they die
and embolize to the pulmonary vasculature, causing solitary pulmonary
nodules to form. Since the worms are unable to achieve sexual
maturation, microfilaremia is not seen in human infections.
Note;Both D. immitis and D. repens are transmitted via the common
mosquito vectors, Anopheles, Culex, and Aedes. However, more than 60
species of mosquitoes from six different genera are capable of acting as
the vector-intermediate host. Also, it is believed that some species of
fleas, lice, and ticks also act as vectors of D. immitis . D. ursi is
transmitted by blackflies, and D. tenuis is transmitted by the black salt
marsh mosquitoes, Aedes taeniorhynchus and Anopheles quadrimaculatus
.
Clinical features and Pathology in Humans

Human Pulmonary Dirofilariasis (HPD)

Human pulmonary dirofilariasis develops when the larval form of D.
immitis dies, embolizes to the lung, and lodges in a small pulmonary artery
branch. HPD is characteristically manifested by a solitary pulmonary
nodule, which is easily confused with malignancy. The majority of
patients (about 60%) with pulmonary dirofilariasis are asymptomatic.
Symptomatic patients commonly experience chest discomfort, cough,
fever, chills, malaise, hemoptysis, and eosinophilia. Chest x-ray
examination will usually reveal a noncalcified, well-circumscribed,
pulmonary nodule (Coin lesion) in the periphery of the lungs (Fig-1&2-).
The nodule will usually be less than 4 centimeters in diameter, although it
may be as large as 4.5 centimeters in diameter. Although there is great
morphologic variation seen, the lesion is generally characterized by a
central necrotic area surrounded by a granulomatous inflammation and a
fibrous wall. Dead or dying worms at different stages of necrosis and
calcification are found in the lesion. The lesion is often marked by an
inflammatory reaction, with abundant histiocytes, eosinophils,
lymphocytes, and plasma cells infiltrating the infected area.
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Fig:-1- Chest x-ray showing a pulmonary "coin" lesion caused by
Dirofilaria immitis Infection in an adult man.


Fig :-2- CT scan of a solitary, noncalcified, left upper lobe pulmonary
nodule caused by infection by D. immitis.
Subcutaneous Dirofilariasis
Subcutaneous dirofilariasis manifests itself clinically by a 1 to 3 cm
nodule anywhere in the body, with common sites of infection including:
subcutaneous tissue, pectoral muscle, genitals, breast tissue, urinary
bladder, portacaval shunt, peritoneal cavity, ocular cavity, and eyelids.
The clinical manifestations of the infection and morphological appearance
of the lesions are similar in infecton by all species of subcutaneous
Dirofilaria. It is rare for an infected patient to present with multiple
nodules.
In the first several months of infection, the nodule is usually painless and
does not give rise to inflammation. It may also disappear and reappear in
a new location. As the infection progresses and the nodule grows,
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however, pain and inflammation may result. Other symptoms may
include: edemas, arthritis, subcutaneous swellings, and eosinophilia.
Abdominal wall infection by D. repens in a Kuwaiti man resulted in
symptoms of abdominal swelling and pain, as well as detection of an
apparent bulge and mild redness in the area of infection . When the
parasite infects the subconjuctiva in the eye, intense irritation, or
conjunctivitis may result. In a case of eyelid infection by D. repens in a
Spanish woman, subcutaneous migratory movement of the worm was
detected upon close examination. Surgical removal of the worm usually
recovers the organism within the nodule itself at various stages of
degeneration. In the majority of extrapulmonary dirofilariasis cases, the
recovered worm is in immature (larval) stages. In more rare cases, adult
worms of small size and incomplete sexual maturation are recovered.

Laboratory diagnosis
Since dirofilariasis infection is often asymptomatic, diagnosis most
frequently occurs during routine chest x-ray or physical examination.
Upon x-ray, the nodule is often misdiagnosed as a carcinoma. In such
cases, only after surgical removal of the nodule, is the nematode pathogen
identified. Upon removal of the worm, microscopic evaluation of tissue
cross-sections and study of macroscopic characteristics of the worm serve
as the main methods of dirofilariasis diagnosis. Another important
diagnostic factor is the geographic area where the infection is believed to
have been acquired. Even though dirofilariasis infection is rare, much of
the medical community is in agreement that extrapulmonary dirofilariasis
should be considered in the differential diagnosis of nodular inflammatory
infection, and pulmonary dirofilariasis should be considered in the
differential diagnosis of solitary pulmonary nodules. Human dirofilariasis
infection, especially human pulmonary dirofilariasis, is often a benign and
self-limiting condition that does not necessitate immediate treatment.
However, it is often confused with life-threatening diseases, (such as
tumors, tuberculosis, fungal infections, and hamartomas). Misdiagnosis
occasionally leads to inappropriate and bodily harmful therapeutic
interventions. For example, this may occur if dirofilariasis infection in the
breast were mistaken for breast cancer and chemotherapy were prescribed
to treat the cancer. It would be beneficial to develop noninvasive, reliable
diagnostic tests for dirofilariasis infection so that misdiagnosis could be
prevented, infected individuals could be informed of the nature of the
infection before having to go through the invasive process of having the
worm surgically removed, and accurate diagnosis of the specific
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Dirofilaria species for the purpose of epidemiological studies could
consistently and easily be achieved.
Diagnostic methods
Serological detection: Serology is an attractive alternative to
invasive diagnosis because it avoids surgery. Serological detection
of human antibodies to dirofilariasis has been reported, but with poor
sensitivity and specificity. The efficacy in using ELISA to
quantitatively detect dirofilarial antibodies has been debated due to
the presence of cross-reacting antibodies.
Detection by PCR: Early protocols for PCR-based detection of D.
repens DNA failed to amplify dirofilariae DNA from formalin
preserved human biopsies. One report published in 1999, however,
presented an improved PCR protocol and discussed its potential
application to routine clinical diagnosis in humas and large scale
epidemiological studies in dogs .
Histologic Examination: Routine histologic stains generally are not
effective for Dirofilaria identification. However in general,
Dirofilaria specimens stained with calcofluor can be easily
recognized in tissue sections The characteristic morphologic features
that are examined include: diameter of body, thickness and structure
of cuticle, presence or absence of external cuticular ridges.
Treatment

Identified nodules are surgically removed. The drugs used to treat other
filarial infections, such as diethylcarbamazine (DEC) and ivermectin, are
not used.

Angiostrongyliasis (Angiostrongylus cantonensis & A. costaricensis infection)

Etiology
Angiostrongylus cantonensis is a natural parasite of rodents and is often
referred to as the rat lungworm lives in (pulmonary arterioles). In humans
it can cause eosinophilic meningoencephalitis, And causing intestinal
disease.
A. costaricensis adult worm in habits the mesenteric arteries of the cotton
rat (sigmodon hispidus) and several other species of wild rodents.


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Morphology
A. cantonensis ;Adult female 12.8 mm, male 7.7mm

A. costaricensis; Anonymous

In humans, eggs and larvae are not normally excreted, but remain
sequestered in tissues. Both eggs and larvae (occasionally adult worms) of
A. costaricensis can be identified in biopsy or surgical specimens of
intestinal tissue. The larvae need to be distinguished from larvae of
Strogyloides stercolaris however, the presence of granulomas containing
thin shelled eggs and/or larvae serve to distinguish A. costaricensis
infections.

Epidemiology

A. cantonensis has been reported from many of the Pacific Islands, the
Philippines, Sumatra, and parts of South-East Asia especially Thailand ,
found in Egypt, New Orleans (USA).
A. costaricensis has been reported from Costa Rica and South America.

Transmission and life cycle

Adult worms of A. cantonensis live in the pulmonary arteries of rats. The
females lay eggs that hatch, yielding first-stage larvae, in the terminal
branches of the pulmonary arteries. The first-stage larvae migrate to the
pharynx, are swallowed, and passed in the feces. They penetrate, or are
ingested by, an intermediate host (snail or slug). After two molts, third-
stage larvae are produced, which are infective to mammalian hosts. When
the mollusk is ingested by the definitive host, the third-stage larvae
migrate to the brain where they develop into young adults. The young
adults return to the venous system and then the pulmonary arteries where
they become sexually mature. Of note, various animals act as paratenic
(transport) hosts: after ingesting the infected snails, they carry the third-
stage larvae which can resume their development when the paratenic host
is ingested by a definitive host. Humans can acquire the infection by
eating raw or undercooked snails or slugs infected with the parasite; they
may also acquire the infection by eating raw produce that contains a small
snail or slug, or part of one. There is some question whether or not larvae
can exit the infected mollusks in slime (which may be infective to humans
if ingested, for example, on produce). The disease can also be acquired by
ingestion of contaminated or infected paratenic animals (crabs, freshwater
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shrimps). In humans, juvenile worms migrate to the brain, or rarely in the
lungs, where the worms ultimately die. The life cycle of Angiostrongylus
(Parastrongylus) costaricensis is similar, except that the adult worms
reside in the arterioles of the ileocecal area of the definitive host. In
humans, A. costaricensis often reaches sexual maturity and release eggs
into the intestinal tissues. The eggs and larvae degenerate and cause
intense local inflammatory reactions and do not appear to be shed in the
stool



Clinical features and Pathology

A. cantonensis; The main feature of human infection by A.cantonensis is
an eosinophilic meningoencephalitis which develops in response to toxins
released from dead and degenerating worms, headache, and stff neck,
often sensorial changes occur. A radiculomyeloencephalitis, with pains,
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weakness of the limbs, and partial facial palsy and parasthesias of the
lower trunk and legs, bowel and bladder dysfunction and one death . CSF
pleocytosis of more than 500 per mm
3
occurred in 80% of infected
persons/ the CSF usually contain 100 to 200 WBC per mm
3
, generally
accompanied by marked eosinophilia, blood eosinophilia also common.
Other reported symptoms include abdominal pain,constipation, nausea,
vomiting, Fever. Eye invasion is marked by visual impairment, ocular pain
, blepharospasm, circumcorneal injection, keratitis, iritis , and retinal
edema.
A. costaricensis ; The presence of adult worms provkes an inflammatory
reaction that damages the endothelium of the occupied vessels, causing
localized thrombosis and necrosis of the tissues perfused by the
thrombosed vessels. Granuloma formation occurs around the eggs and
larvae. In the most common form , with localization of the worms in the
regionof the cecum, there is usually pain in the right iliac fossa and
tenderness to palpation. Atumorlike mass is often palpable, may mimic
that of malignancy by barium enema. May also mimic appendicitis and
intestinal obstruction may occur. If the worm block spermatic arteries will
cause necrosis, with acute testicular pain. In most cases leukocytosis of
15,000 to 40,000 cells per mm
3
And 20 to 50 % eosinophil.

Laboratory diagnosis

A. cantonensis;Apresumptive diagnosis may be made in patients from
areas where the disease is endemic on the basis of meningitis with blood
and spinal fluid eosinophilia. CTscan , with serologic confirmation of the
infection by ELISA.
The commonest laboratory finding in angiostrongyliasis are as follows:

Cerebrospinal fluid (CSF) analysis: Cell count is usually over 500
cells/l with 50 -75 % of cells being eosinophilic (there is also blood
eosinophilia). Protein is raised, Glucose is reduced and very occasionally
larvae are found.

A. costaricensis; Askin test antigen has been prepared and is reported to
give good results. A precipitin test has also been developed. Neither of
these tests available. Diagnosis is usually made by surgery .




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Treatment
A. cantonensis;The disease is self limited, watchful waiting is advised,
corticosteroid reserved for cases with ocular infection.
Thiabendazole and mebendazole both are effective drugs , DEC reported
to be effective.

A. costaricensis; Surgical intervention.

Prevention and Control

This is by avoiding eating raws or insufficiently cooked slugs , land
snails,crabs, or fresh wter prawns that may be infected. The larvae can be
killed by being boiled or frozen at -15 C for 12 hrs. The contamination of
fresh vegetables by carnivorous land planarians that have fed on infected
snails appears to be another important source , so vegetables should be
cleaned well in endemic areas.

Gnathostomiasis (Gnathostoma spinigerum infection)

Etiology

Gnathostoma spinigerum It is normally found in the stomach wall of cats ,
tigers, lion, leopard, dogs, and other animals where it causes tumours. The
larvae of the parasite can infect humans.

Morphology
Scanning electron micrographs of a Gnathostoma spinigerum female
worm depicting the cuticular armature of the body surface. The cuticular
armature is important for identification of Gnathostoma spp. Head bulb.
Cuticular spines the body part (Fig-1-).

Fig:-1- Head part of Gnathostoma spinigerum adult worm.
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Epidemiology

Human infections have been reported from South-east Asia especially
Thailand and also from the Philippines, Bangladesh, India, and China.

Transmission and life cycle




In the natural definitive host (pigs, cats, dogs, wild animals) the adult
worms reside in a tumor which they induce in the gastric wall. They
deposit eggs that are unembryonated when passed in the feces (1). Eggs
become embryonated in water, and eggs release first-stage larvae (2). If
ingested by a small crustacean (Cyclops, first intermediate host), the first-
stage larvae develop into second-stage larvae (3). Following ingestion of
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the Cyclops by a fish, frog, or snake (second intermediate host), the
second-stage larvae migrate into the flesh and develop into third-stage
larvae (4). When the second intermediate host is ingested by a definitive
host, the third-stage larvae develop into adult parasites in the stomach wall
(5). Alternatively, the second intermediate host may be ingested by the
paratenic host (animals such as birds, snakes, and frogs) in which the
third-stage larvae do not develop further but remain infective to the next
predator (6). Humans become infected by eating undercooked fish or
poultry containing third-stage larvae, or reportedly by drinking water
containing infective second-stage larvae in Cyclops (7).
Clinical features and Pathology

Migration of the larvae in cutaneous tissues causes recurring allergic
swelling. The inflamed swelling are often painful and itchy. Migration of
the larvae through the intestinal wall and into the abdominal cavity may
produce epigastric pain, fever, vomiting, and anorexia. Occasionally ,
worms enter the eye, mucous membrane , respiratory tract, central nervous
system, or abdominal organs where they can cause serious inflammatory
reactions, haemorrhage, and fibrosis.Circumscribed patches of edema,
usually on the abdomen , may last a few days and recur at different sites,
depending on the path of the migrating worm. An eosinophilic
meningoencephalitis may result from invasion of the CNS by migration of
the worms along nerve tracts.

Laboratory diagnosis

Made on the basis of clinical symptoms and patients history in relation to
food habits and residence. Most infection are diagnosed by a skin test.

Treatment

Surgical removal of the worms from subcutaneous and other accessible
loci. Mebendazole, has been reported to give good results in skin and eye
lesions.

Prevention and Control

Infection can be prevented by boiling fish which may be infected .
Alternatively the fish can be immersed in vinegar for 5-6 hrs which will
also kill any larvae present.
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Toxocariasis (Toxocara canis & Toxocara catis infection)
Toxocariasis is considered an aberrant infection because humans are
Paratenic, accidental,and incidental hosts, and the parasites cannot
completely mature in the human body. Instead, the invasive larvae migrate
for months through different organs until they are overcome by the human
inflammatory reaction and die. The larvae can survive in tissues for at
least 9 years and, possibly, for the life of the host.
Etiology
Toxocariasis is caused by Toxocara canis and, less frequently, Toxocara
catis, which are intestinal nematodes (roundworms) in dogs and cats.
Most frequently, human toxocariasis is caused by T canis, a canine
roundworm. Adult T canis female worms are usually found in young
puppies and lactating female dogs.Less frequently, caused by Toxocara
catis. These are roundworms larva of dogs and cats but they can infect
humans and cause damage of the visceral organs. Toxocara species are not
the only causes of Ocular larva migrans (OLM) and Visceral larva
migrans (VLM); others include Baylisas Gnathostoma spinigerum,
Trichinella spiralis, and Angiostrongylus and Anisakis species, Ascaris
suum (especially in Japan); Angiostrongylus cantonensis or
Angiostrongylus costaricensis; and, much less commonly, ascarids from
salt-water fishes, such as members of the genera Phocanema, Anisakis,
and Contracaecum.

Morphology

The adult worms of T. cati/canis, similar to Ascaris lumbricoides in
appearance but only a quarter to half its size.
Epidemiology
Experts in the United States estimate that about 20% of dogs pass
Toxocara eggs into their stool. In Great Britain, 24% of soil samples taken
from public parks contained Toxocara eggs. Toxocariasis cannot be spread
from person to person.


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Transmission
Eggs from the Toxocara worms pass into the stools of dogs and cats and
can contaminate pet areas around the home where children play. The eggs
can be swallowed by children, especially those who:
are 1 to 4 years old
often put things in their mouths
don't often wash their hands
Once Toxocara eggs (Fig-1-) enter a child's body, they hatch into larvae
that penetrate through walls of the digestive tract and may migrate to a
child's liver, lungs, eyes, and elsewhere.

Fig:-1- Eggs of Toxocara canis. The egg to the left is fertilized but not
yet embryonated, while the egg to the right contains a well developed
larva. The latter egg would be infective if ingested by a human
(frequently, a child).
Life cycle
The adult T canis female worms can excrete as many as 200,000 eggs per
day. When a dog ingests the infective eggs, the larvae hatch in the small
intestine, penetrate the intestinal wall, and gain access to the blood and
lymphatic circulation. The larvae invade the liver, lungs, and other tissues.
In most dogs, the larval maturation process is arrested in most tissues, but
in a pregnant female, T canis resumes development and migrates across
the placenta, infecting the fetus. After the birth of the puppies, the larvae
continue their maturation process, migrating from the lungs to the
gastrointestinal tract via the trachea; they achieve their mature forms in the
puppies' intestinal tracts. Female dogs then become reinfected while
caring for their puppies. The main sources of eggs, therefore, are puppies
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younger than 3 months and lactating female dogs. Humans are paratenic
hosts for T canis.

Note; Paratenic hosts are (transport hosts in which the larvae never
develop into adult worms). The infection is acquired by ingesting T canis
embryonated eggs. Sources of these eggs are in areas, such as parks,
where dogs defecate.
The cat roundworm, T catis, has a life cycle similar to that of T canis
except that vertical transmission is due to lactation more than
transplacental transmission. T catis causes fewer cases of human infection
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than T canis, probably because of the defecation patterns of cats, which
make environmental infestation less frequent.
Toxocara canis accomplishes its life cycle in dogs, with humans acquiring
the infection as accidental hosts. Following ingestion by dogs, the
infective eggs yield larvae that penetrate the gut wall and migrate into
various tissues, where they encyst if the dog is older than 5 weeks. In
younger dogs, the larvae migrate through the lungs, bronchial tree, and
esophagus; adult worms develop and oviposit in the small intestine. In the
older dogs, the encysted stages are reactivated during pregnancy, and
infect by the transplacental and transmammary routes the puppies, in
whose small intestine adult worms become established. Thus, infective
eggs are excreted by lactating bitches and puppies. Humans are paratenic
hosts who become infected by ingesting infective eggs in contaminated
soil. After ingestion, the eggs yield larvae that penetrate the intestinal wall
and are carried by the circulation to a wide variety of tissues (liver, heart,
lungs, brain, muscle, eyes). While the larvae do not undergo any further
development in these sites, they can cause severe local reactions that are
the basis of toxocariasis.
Clinical features
Three clinical forms of toxocariasis are traditionally described; these
include visceral larva migrans (VLM), ocular larva migrans (OLM), and
covert toxocariasis.
The 3 clinical forms of toxocariasis that are traditionally described include
the following:
A- Visceral larva migrans forms
1-General: The classic Visceral larva migrans (VLM) syndrome consists
of episodes of fever, coughing and wheezing, anemia, eosinophilia,
hepatomegaly, and positive Toxocara titers. The patient usually has
malaise, asthenia, and vague abdominal symptoms. VLM is diagnosed
mainly in children aged 1-7 years. Many organs can be involved in VLM.
2-Dermatologic: Skin lesions, such as urticaria and nodules, have been
described. Toxocariasis can cause chronic idiopathic urticaria, especially
when it is associated with eosinophilia. Well syndrome is an eosinophilic
cellulitis of unknown origin. A report describes 2 cases with clinical and
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histologic features of Well syndrome with positive anti-Toxocara titers.
Not only did the symptoms respond to treatment with albendazole, but
also, the antibody titer also normalized.
3-Pulmonary: Wheezing is a common sign of VLM. Progression to
eosinophilic pneumonia and respiratory failure has been reported. Isolated
reports describe diffuse noncavitating pulmonary nodules and pleural
effusions. Asthma is common in VLM infection, in which there is usually
an accompanying hepatomegaly and marked eosinophilia and leukocytosis
of up to 80,000 mm
3
.
4-Hepatic and lymphatic: VLM usually is associated with hepatomegaly.
When histologic results are available, they usually reveal granulomatous
hepatitis. Reports of pyogenic liver abscess concomitant with Toxocara
hepatitis also exist. The spleen is enlarged less often than the liver.
Generalized lymphadenopathy is an infrequent manifestation of
toxocariasis. A report exists of a 24-month-old boy in whom lymphedema
was the main clinical manifestation of toxocariasis.
5-Rheumatologic: Frequently, manifestations such as arthralgias,
monoarthritis, migratory cutaneous lesions, and small-vessel vasculitis
coincidentally occur with VLM. One case report describes Henoch-
Schnlein purpura in a 17-year-old male in association with anti-Toxocara
immunoglobulin G (IgG) and immunoglobulin E (IgE) that resolved
spontaneously.
6-Cardiac: Although infrequently involved, all layers of the heart can be
affected. The most common presentation is myocarditis. Endomyocarditis
and even pericardial tamponade.
7-Central nervous system: Toxocariasis is one of the causes of
eosinophilic meningitis, a form of aseptic meningitis in which the white
blood cells in the cerebrospinal fluid mainly consist of eosinophils. Other
less common entities described in association with VLM are encephalitis,
larval invasion of the brain parenchyma, solitary mass lesions that cause
seizures, static encephalopathy, arachnoiditis, and spinal cord lesions.
Although Toxocara organisms are the most common causes of VLM, case
reports exist of other zoonotic nematodes causing VLM, including Ascaris
suum, Baylisascaris procyonis (raccoon ascarid)
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B-Ocular larva migrans (OLM) form
1-This refers to eye (usually retinal - retinitis) involvement during
Toxocara infection. By chance, the larvae migrate to the eyes, where they
induce an eosinophilic inflammatory reaction (may also produce a
retinochoroiditis). Most of the time, it is unilateral.
2-Patients with OLM are older than those with VLM. They lack systemic
symptoms, such as fever, cough, and abdominal pain, and they do not have
significant eosinophilia.
3-OLM manifests as a loss of visual acuity, leukocoria, strabismus, and
eye pain.
4-Other presentations of OLM include endophthalmitis with secondary
retinal detachment, uveitis, vitreous abscess, and optic neuritis.
Note; It can be confused with a Retinoblastoma when fundus of the eye
examined.
C-Covert toxocariasis form
1-Most cases of toxocariasis are asymptomatic. 2-Usual symptoms are
chronic or recurrent abdominal pain, hepatomegaly, coughing, wheezing,
sleep disturbances, headache, malaise, anorexia, and failure to thrive,
among others. Eosinophilia is less frequent and less pronounced with this
form Toxocara antibody titers are low.
Pathology:
The traveling larva through the tissues produces tracks marked by
haemorrhage, necrosis, and infiltration of lymphocytes and eosinophil.
Granulomatous foci are produced around dead larvae.
Tissue damage has most been in the liver and consists of a gray, elevated,
circumscribed area approximately 4 mm in diameter. And it is due to the
host inflammatory reaction more than the infection itself. The larvae
produce glycosylated proteins, usually referred to as Toxocara excretory
secretory antigens. Toxocara larvae have been found in liver, brain, eye,
spinal cord, lungs, cardiac muscle, kidney, and lymph nodes.
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Ocular toxocariasis is usually seen in the absence of other signs or
symptoms of VLM , this suggested by researchers that it is more likely to
occur in persons initially exposed to small numbers of larvae, which are
able to migrate freely with little restraint from the hosts immune
mechanism.
Laboratory diagnosis
Humans do not produce or excrete eggs, and therefore eggs are not
a diagnostic finding in human toxocariasis. With Toxocara
infection there is an eosinophilic leucocytosis and
hyperglobulinaemia. A doctor can usually diagnose a case of
toxocariasis by physical exam and blood tests. VLM usually is
suspected in a young child with fever, wheezing, and
hepatomegaly whose complete blood cell count reveals
leukocytosis and marked eosinophilia (as high as 80%). Diagnosis
is based on serologic findings. The best serological test to diagnose
Toxocara infection by an ELISA . The sensitivity of ELISA is
approximately 75%, and its specificity is greater than 90%.
Western blotting appears to be more specific, but it is more labor-
intensive. The main pitfall of serologic tests is that they cannot be
used to distinguish between current and past infections. Other
nonspecific laboratory findings are hypergammaglobulinemia
(particularly IgM). The diagnosis of VLM can be definitively
confirmed only by finding larvae in the affected tissue at histologic
examination or by assessing the digestion of tissue. Biopsy is
performed rarely, and the larvae are not always found. Patients
with OLM have low or even negative titers. Toxocara titers in the
vitreous and aqueous humor are elevated relative to serum
levels.The diagnosis of OLM usually relies on clinical. A
definitive test for covert toxocariasis does not exist. Positive anti-
Toxocara titers in the presence of malaise, chronic weakness,
abdominal pain, or allergic signs accompanied by eosinophilia and
absence of response to allergens support the diagnosis of covert
toxocariasis.Recently, the polymerase chain reaction (PCR) has
been introduced as a diagnostic tool. Examination of stools has no
role in the evaluation of toxocariasis.Chest radiography is
indicated in patients with wheezing and eosinophilia in whom
eosinophilic pneumonia is suspected. It also can be used to identify
pleural effusions and cardiomegaly.Echocardiography is used to
evaluate myocardial function, which is depressed in myocarditis,
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and to identify pericardial fluid and intracardiac
pseudotumors.Abdominal ultrasonography is a good screening test
to identify granulomas in the liver.CT scanning and MRI also have
been used. Neuroimaging relies on CT scanning and MRI.
Treatment
Treatment is controversial, regarding whether or not one should treat the
infection and, if so, when and how. Mebendazole, thiabendazole,
albendazole, and diethylcarbamazine, among others, are agents used in the
treatment. Corticosteroids also have a significant role in therapy. Doctors
may not prescribe any medication to treat a child with mild symptoms of
toxocariasis. Severe toxocariasis involving the lungs, eye, or other
important organs may be treated with antiparasitic drugs to kill the
Toxocara larvae. For severe lung toxocariasis, doctors sometimes
also prescribe anti-inflammatory drugs. Treatment with anthelmintic
agents is indicated for severe complications such as those involving the
brain, lung, and heart. Because anthelmintic treatment can lead to an
increased inflammatory reaction, corticosteroids sometimes are used with
or without specific therapy. Treatment of covert toxocariasis should be
individualized. The decision to treat depends on the age of the patient,
severity of the symptoms, and certainty of the diagnosis. An experienced
ophthalmologist should be involved in the treatment of patients with
OLM. Treatment of this entity does not require anthelmintic therapy but
relies on local corticosteroids and surgery. Surgical care may be necessary
for OLM. Correction of underlying causes of pica may prevent reinfection.
Prevention
You can help prevent your child from being exposed to toxocariasis by:
1-keeping your child away from areas where dogs or cats play
2-washing your toddler's hands frequently
3-Reminding your older child to wash his or her hands often,
especially after playing with a pet dog or cat.
4-discouraging your toddler from putting dirty hands in his or
her mouth.
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5-keeping pets away from your child's sandbox and covering the
sandbox when it's not being used.
6-taking household pets to the veterinarian to be dewormed,
especially puppies younger than 6 months old.
Cutaneous larva migrans /creeping eruption(Ancylostoma braziliense
&A.caninum infection)

Cutaneous larva migrans (CLM) is the most common tropically acquired
dermatosis whose earliest description dates back more than 100 years. It
manifests as an erythematous, serpiginous, pruritic, cutaneous eruption
caused by accidental percutaneous penetration and subsequent migration
of larvae of various nematode parasites.

Etiology

Common etiologies and where the parasites are most commonly found
include the following:Ancylostoma braziliense (hookworm of wild and
domestic dogs and cats) is the most common cause. It can be found in the
central and southern United States, Central America, South America, and
the Caribbean.Ancylostoma caninum (dog hookworm) is found in
Australia.Uncinaria stenocephala (dog hookworm) is found in Europe.
Bunostomum phlebotomum (cattle hookworm).Rare etiologies include the
following:Ancylostoma ceylonicum.Ancylostoma tubaeforme (cat
hookworm),Necator americanus (human hookworm).Strongyloides
papillosus (parasite of sheep, goats, and cattle).Strongyloides westeri
(parasite of horses).Ancylostoma duodenale

Epidemiology

It is most commonly found in tropical and subtropical geographic areas
and the southwestern United States.

Life cycle
The life cycle of the parasites begins when eggs are passed from animal
feces into warm, moist, sandy soil, where the larvae hatch. They initially
feed on soil bacteria and molt twice before the infective third stage. By
using their proteases, larvae penetrate through follicles, fissures, or intact
skin of the new host. After penetrating the stratum corneum, the larvae
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shed their natural cuticle. Usually, they begin migration within a few days
In their natural animal hosts, the larvae are able to penetrate into the
dermis and are transported via the lymphatic and venous systems to the
lungs. They break through into the alveoli and migrate to the trachea,
where they are swallowed. In the intestine they mature sexually, and the
cycle begins again as their eggs are excreted.
Clinical features
The organism is primarily a hookworm of dogs and cats but the filariform
larvae in animal feces can infect man and cause skin eruptions. The CLM
reaction is characterized by a reddened papule at the site of entry; the larva
forms a reddened sepiginous tunnel, at first covered with vesicles, later
dry and crusted, which advances at the rate of a few millimeters to
centimeters a day. The area itches intensely; without treatment, the
symptoms last the duration of larval persistence which ranges from 2 to 10
weeks. Light infection can be treated by freezing the involved area. Most
children with toxocariasis have no symptoms or only mild symptoms, and
most cases are never diagnosed and do not cause problems.
Pathology
Humans are accidental hosts, and the larvae are believed to lack the
collagenase enzymes required to penetrate the basement membrane to
invade the dermis. Therefore, the disease remains limited to the skin when
humans are infected. Penetration of skin may take place , but the larvae
are then unable to complete their migratory cycle. The traped larvae of
A.braziliense may survive for some weeks or even months, migrating
through the subcutaneous tissues, whereas those of A.caninum encyst and
remain dormant in skeletal muscle after a shorter cutaneous migratory
period.
Laboratory diagnosis
Diagnosis is mostly based on the classic clinical appearance of the
eruption.
A minority of patients demonstrate peripheral eosinophilia on a
CBC count and increased IgE levels on total serum
immunoglobulin determinations.
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Procedures:
A skin biopsy sample, taken just ahead of the leading edge of a
tract, may show a larva. basal layer tracts, spongiosis with
intraepidermal vesicles, necrotic keratinocytes, and an epidermal
and upper dermal chronic inflammatory infiltrate with many
eosinophils.
Note :Some toxocariasis cases are diagnosed during a routine eye exam or
an X-ray study done for some other reason.
Treatment
Thiabendazole is currently considered the agent of choice. Topical
application is used for early, localized lesions. The oral route is preferred
for widespread lesions or unsuccessful topical treatment. Other effective
alternative treatments include albendazole, mebendazole, and ivermectin.
The treatment course includes decreased pruritus within 24-48 hours and
lesions/tracts resolve in 1 week. Antibiotics are indicated in secondary
bacterial superinfections if they occur. As alternative therapy, use liquid
nitrogen cryotherapy for progressive end of larval burrow.










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CHAPTER THIRTEEN (13)
Intestinal Nematodes
Intestinal nematodes of importance to man are Ascaris lumbricoides
(roundworm), Trichinella spiralis (trichinosis), Trichuris trichiura
(whipworm), Enterobius vermicularis (pinworm), Strongyloides
stercoralis (Cochin-china diarrhea), Ancylostoma duodenale and Necator
americanes (hookworms) . E. vermicularis and T. trichiura are exclusively
intestinal parasites. Other helminths listed above have both intestinal and
tissue phases.



Generalized life cycle of intestinal nematodes.


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Enterobiasis/oxyuriasis/pinworm/seatworm(E. vermicularis infection)

Etiology
Humans are considered to be the only hosts of Enterobius vermicularis. A
second species, Enterobius gregorii, has been described and reported from
Europe, Africa, and Asia. For all practical purposes, the morphology, life
cycle, clinical presentation, and treatment of E. gregorii is identical to E.
vermicularis.
Morphology
The female worm measures 8 mm x 0.5mm; the male is smaller
Epidemiology
The worldwide infection is about 210 million. It is an urban disease of
children in crowded environment (schools, day care centers, etc.). Adults
may get it from their children. Enterobiasis is by far one of the most
common helminthic infection in world. The incidence in whites is much
higher than in blacks.
Transmission and Life Cycle
The gravid females, containing more than 10,000 eggs migrate, at night, to
the perianal region and deposit their eggs there. Eggs mature in an
oxygenated, moist environment and are infectious 3 to 4 hours later,Eggs
are deposited on perianal folds (1). Self-infection occurs by transferring
infective eggs to the mouth with hands that have scratched the perianal
area (2). Person-to-person transmission can also occur through handling
of contaminated clothes or bed linens. Enterobiasis may also be acquired
through surfaces in the environment that are contaminated with pinworm
eggs (e.g., curtains, carpeting). Some small number of eggs may become
airborne and inhaled. These would be swallowed and follow the same
development as ingested eggs. Following ingestion of infective eggs, the
larvae hatch in the small intestine (3)and the adults establish themselves in
the colon (4). The time interval from ingestion of infective eggs to
oviposition by the adult females is about one month. The life span of the
adults is about two months. Gravid females migrate nocturnally outside
the anus and oviposit while crawling on the skin of the perianal area (5).
The larvae contained inside the eggs develop (the eggs become infective)
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in 4 to 6 hours under optimal conditions (1). Retroinfection, or the
migration of newly hatched larvae from the anal skin back into the rectum,
may occur but the frequency with which this happens is unknown.

Clinical features and Pathology
The most common symptom is perianal, perineal and vaginal irritation
caused by the female migration. The itching results in insomnia and
restlessness and may lead to excoriations and bacterial superinfection. The
local pruritus and discomfort produce a chain of secondary reflex
symptoms ,poor apetite (anorexia), loss of sleep (insomnia), weight loss,
hyperactivity, enuresis, grinding of the teeth, abdominal pain, nausea,
vomiting that tend to deblitiate the patient-due to disturbed sleep.
Eosinophilia can occur but unusual. Occasionally, migration of the gravid
female to female genital tract cause vulvovaginitis and may imbedded and
die with granuloma formation, in uterus, the fallopian tubes, peritoneal
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cavity , and even urinary bladder frequently found in the appendix (Fig-
1&2-), but seldom cause appendicitis . and pelvic or peritoneal
granulomas can occur. The nocturnal pruritus that accompanies pinworm
infection varies considerably in degree, probably depending upon
hypersensitivity of the host. In some persons there is no noticeable itching,
whereas in others it may be sufficiently severe to interfere with rest.

Fig:-1- E. vermicularis worms. And Fig:-2- E. vermicularis eggs
can be seen in
Cross-section of human appendix containing.
Laboratory diagnosis
Diagnosis is made by finding the adult worm or eggs (Fig-3&4) in the
perianal area, particularly at night. Scotch tape or a pinworm paddle is
used to obtain eggs. This must be done in the morning, before defecation
and washing, by pressing transparent adhesive tape ("Scotch test",
cellulose-tape slide test) on the perianal skin and then examining the tape
placed on a slide. Alternatively, anal swabs (a paddle coated with
adhesive material) can also be used. . Eggs (60 micrometers x 27
micrometers) are ovoid but asymmetrically flat on one side , it iscolourless
and has a clear shell, oval in shape and usually flattened on one side and
contains a larva. Eggs can also be found, but less frequently, in the stool,
and occasionally are encountered in the urine or vaginal smears. Adult
worms are also diagnostic, when found in the perianal area, or during ano-
rectal or vaginal examinations. A single swabbing reveals only about50%
of the infections, three swabbing about 90%, and examinations on 7
consecutive days are necessary before the patient is considered free from
infection.
- 306 -


Fig:-3- Enterobius egg . Fig:-4-.Enterobius eggs on cellulose tape..
Treatment and Control
The drug of choice is pyrantel pamoate.Two doses Pyrental Pamoate two
weeks apart gives a very high cure rate. Mebendazole is an alternative.
The whole family should be treated, Measures to prevent reinfection, such
as personal hygiene and laundering of bedding. Bedding and
underclothing must be sanitized between the two treatment doses. Personal
cleanliness provides the most effective in prevention.
Ascariasis (A. lumbricodes infection)
Ascariasis - Ascariasis is the most common helminthic infection, with an
estimated worldwide prevalence of 25% (>1.25 billion people). Usually
asymptomatic, infections are most prevalent in tropical and developing
countries, where they are perpetuated by contamination of soil by human
feces or use of untreated feces as fertilizer. Symptomatic disease may be
manifested by growth retardation, pneumonitis, intestinal obstruction, or
hepatobiliary and pancreatic ducts occlusion.
Etiology
Ascaris lumbricoides is the largest nematode (roundworm) parasitizing the
human intestine.
Morphology
The male is smaller. (Adult females: 20 to 35 cm; adult male: 15 to 30
cm.)
Epidemiology
Worldwide distribution. Highest prevalence in tropical and subtropical
regions, and areas with inadequate sanitation. Occurs in rural areas of the
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southeastern United States.The annual global morbidity due to ascaris
infections is estimated at 1 billion with a mortality of 20,000. Ascariasis
can occur at all ages, but it is more prevalent in the 5 to 9 years age group.
The incidence is higher in poor rural populations.The most common
human helminthic infection.
Transmission and Life Cycle

Note:The infection occurs by ingestion of food contaminated with
infective eggs which hatch in the upper small intestine. The infection is
man to man. Auto infection can occur.
Adult worms (1)live in the lumen of the small intestine. A female may
produce approximately 200,000 eggs per day, which are passed with the
feces (2). Unfertilized eggs may be ingested but are not infective. Fertile
eggs embryonate and become infective after 18 days to several weeks (3),
depending on the environmental conditions (optimum: moist, warm,
shaded soil). After infective eggs are swallowed (4), the larvae hatch (5),
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invade the intestinal mucosa, and are carried via the portal, then systemic
circulation to the lungs (6). The larvae mature further in the lungs (10 to
14 days), penetrate the alveolar walls, ascend the bronchial tree to the
throat, and are swallowed (7). Upon reaching the small intestine, they
develop into adult worms (1).
Note:Adult worms can live 1 to 2 years. Between 2 and 3 months are
required from ingestion of the infective eggs to oviposition by the adult
female.
Note; The eggs are resistant to chemical disinfectant and survive for
months in sewage, but are killed by heat (40 degrees C for 15 hours).
Clinical features and Pathology
Symptoms are related to the worm burden. Ten to twenty worms may go
unnoticed except in a routine stool examination. The commonest
complaint is vague abdominal pain. In more severe cases, the patient may
experience listlessness, weight loss, anorexia, distended abdomen,
intermittent loose stool and occasional vomiting. Infections may cause
stunted growth High worm burdens may cause abdominal pain and
intestinal obstruction or perforation lead to generalized peritonitis (pain,
marked distention , generalized abdominal tenderness , and free air under
the diaphragm ) , continuing their migration, they may come out through
the body wall, usually at the umbilicus in children and the inguinal region
in adults. It causes volvulus and intussuception especially in children,
three fourths of children with bowel obstruction presented with fever and
generalized malaise. Migrating adult worms may cause symptomatic
occlusion of the biliary tract and pancreatic duct or oral expulsion, and
other complications include liver abscesses and appendicits caused by
migrating worms. During the lung phase of larval migration, pulmonary
symptoms can occur eosinophilic pneumonitis - Loefflers syndrome or
verminous pneumonia {during the lung migration, the larvae may produce
host sensitization which results in allergic manifestations, such as
pulmonary infiltration, asthmatic attacks , such as fever, wheeze, dyspnea
and sub-sternal discomfort , in sever cases. X-ray shadows, and
eosinophilia, and edema of the lips and even hemoptysis as a result of the
larva breaks out of alveolar capillaries). And in sever cases there may be
complete consolidation of one or more lobes . The sudden development of
asthma in a previously nonasthmatic person who has traveled to an area
with poor sanitation should raise suspicion of ascariasis. Ascaris infections
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can produce symptomatic lactose maldigestion or intolerance in preschool.
Most symptoms are due to the physical presence of the worm.
The pathogenesis ;An impressive eosinophilia is not characteristic of
ascariasis , but is usually peaks during the period of tissue migration,
declining after the worms reenter the gut . Increased levels of IgG, and
especially IgE , are seen in infected persons. Aside from the immune
responses, the damage caused by ascarids seems largely related to their
size. The larvae, 20 m in diameter, trapped in 10 m alveolar capillaries,
break out with consequent (usually minor) haemorrhage. The large and
muscular adult worms do not attach to the intestinal wall but maintain
their position by constant movement. It is not surprising that they
occasionally forces their way into extraintestinal sites, or if present in
large numbers form tangled masses that occlude the bowel.
Pica ( see hookworm below).
Laboratory diagnosis
Diagnosis is based on identification of eggs (Fig-1-). Usually fertilized
eggs are found in the faeces but occasionally unfertilized eggs are passed
when the worms in the intestine are.mostly female

Fig:-1-Egg containing a larva, which will be infective if ingested.
Fertilized egg; It is yellow-brown and the shell is covered by an uneven
albuminous coat, oval or round and measures 60 x 40 m , contains a
central granular mass which is the unsegmented ovum (Fig-2-).
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Fig:-2- 3 fertilized eggs (one decorticated, on the right) of Ascaris
lumbricoides.
Note; Decorticated egg ( the term is used to describe an egg that has a
smooth shell without albumious coat.
Unfertilized egg; It is darker in colour and has a more granular albuminous
covering than a fertilized egg, more elongated than a fertilized egg,
measuring 90 x 45 m and contains acentral mass of large refractile
granules (Fig-3-).

Fig:-3-Unfertilized egg. Prominent mammillations of outer layer.
Note; in X- ray evidence of ascaris , adult worms may be seen as
cylindrical empty spaces in the barium-filled bowel in asmall bowel series.
Treatment and Prevention
Albedazole is drug of choice , Mebendazole, for 3 days is effective as an
alternative, and pyrantel pamoate are also effective drugs. Good hygiene is
the best preventive measure.

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Simple Pulmonary Eosinophilia (Leffler's Syndrome)
The roundworm Ascaris lumbricoides and the hookworms Ancylostoma
duodenale and Necator americanus may cause pulmonary symptoms
during their migration through the lung. This acute disorder also known as
Lffler's syndrome is most commonly caused by infection with Ascaris
spp. It is characterized by migratory pulmonary infiltrates accompanied by
peripheral blood eosinophilia and minimal pulmonary symptoms. Ascaris
is transmitted by the ingestion of the fertilized eggs, while hookworm
transmission occurs via oral or skin penetration by infective larvae. The
migration of the parasite larvae from the pulmonary capillaries results in
low-grade fever, blood-streaked sputum, cough, wheezing, dyspnea, and
substernal chest discomfort. These symptoms are caused by transient
allergic pneumonitis in response to parasite antigens. Lffler's syndrome
generally tends to occur 1 to 2 weeks after ingestion of the larval eggs.
The sputum examination reveals eosinophilia and Charcot-Leyden
crystals. The chest radiograph shows fleeting infiltrates that resolve over
days. Ascaris or hookworm ova may be absent from stool at the time of
pneumonitis, but larvae can often be seen in sputum or gastric lavage. The
appearance of Ascaris or hookworm ova in the stool within 3 months of
self-limited eosinophilic pneumonitis suggests this diagnosis. Although
severity of symptoms correlates with larval burden, this disorder is self-
limited and tends to resolve spontaneously. Symptomatic patients may be
treated with bronchodilators. Prevention of infection and treatment of the
intestinal phase are the mainstays of management.
Hookworm diseases (Ancylostoma duodenale & Necator americanus infection)
Hookworm is the common name for blood-sucking nematodes of the
Ancylostomatidae family; the 2 species that most commonly infect
humans are Ancylostoma duodenale and Necator americanus.Members of
the Ancylostoma genus cause the following 3 clinical entities in
humans:Classic hookworm disease is a gastrointestinal (GI) infection with
chronic blood loss leading to iron deficiency anemia and protein
malnutrition.






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Ancylostomiasis(Ancylostoma duodenale infection)

Necatoriasis(Necator americanus infection)

Etiology
human hookworms include two nematode (roundworm) species,
Ancylostoma duodenale and Necator americanus. A smaller group of
hookworms infecting animals can invade and parasitize humans (A.
ceylanicum). Or can penetrate the human skin (causing cutaneous larva
migrans), but do not develop any further (A. braziliense, A. caninum,
Uncinaria stenocephala). Occasionally A. caninum larva may migrate to
the human intestine causing eosinophilic enteritis; this may happen when
larva is ingested rather than through skin invasion.
Morphology
Adult females: 10 to 13 mm (A. duodenale), 9 to 11 mm (N. americanus);
adult males: 8 to 11 mm (A. duodenale), 7 to 9 mm (N. americanus). The
anterior end of N. americanes is armed with a pair of curved cutting
plates(Fig-1-) whereas A. duodenale is equipped with one or more pairs of
teeth (Fig-2-).


Fig:-1- Adult worm of Necator americanus. showing mouth parts with
cutting plates.

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Fig:-2-Adult worm of Ancylostoma duodenale. showing cutting teeth.
Epidemiology
The second most common human helminthic infection (after ascariasis).
Worldwide distribution, mostly in areas with moist, warm climate.The
hookworm (HW) is widespread in the tropics and subtropics and can even
persist in North Europe if suitable microclimate exists, such as in mines.
The worms inhabit the small intestine of man and suck blood. Adult
worms live several years. Ancylostomiasis is the most prevalent
hookworm infection and is second only to ascariasis in infections by
parasitic worms. N. americanes (new world hookworm) is most common
in the Americas, central and southern Africa, southern Asia, Indonesia,
Australia and Pacific Islands. A. duodenale (old world hookworm) is the
dominant species in the Mediterranean region and northern Asia.
Transmission and Life Cycle
Eggs are passed in the stool (1), and under favorable conditions (moisture,
warmth, shade), larvae hatch in 1 to 2 days. The released rhabditiform
larvae grow in the feces and/or the soil (2), and after 5 to 10 days (and two
molts) they become become filariform (third-stage) larvae that are
infective (3). These infective larvae can survive 3 to 4 weeks in favorable
environmental conditions. On contact with the human host, the larvae
penetrate the skin and are carried through the veins to the heart and then to
the lungs. They penetrate into the pulmonary alveoli, ascend the bronchial
tree to the pharynx, and are swallowed (4). The larvae reach the small
intestine, where they reside and mature into adults. Adult worms live in
the lumen of the small intestine where they attach to the intestinal wall
with resultant blood loss by the host (5). Most adult worms are eliminated
in 1 to 2 years, but longevity records can reach several years.Some A.
duodenale larvae, following penetration of the host skin, can become
dormant (in the intestine or muscle). In addition, infection by A.
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duodenale may probably also occur by the oral and transmammary route.
N. americanus, however, requires a transpulmonary migration phase.





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Clinical features and Pathology
Symptoms of hookworm infection depend on the site at which the worm is
present and the burden of worms. Light infection may not be noticed
(Table-1-).
Table:-1- Clinical features and pathology summary.
Site Symptoms Pathogenesis
Dermal Local erythema, macules,
papules (ground itch)
Cutaneous
invasion and
subcutaneous
migration of
larva
Pulmonary Bronchitis, eosinophilic
pneumonitis and,
sometimes, eosinophilia
Migration of
larvae through
lung, bronchi,
and trachea
Gastro- intestinal Anorexia,pica, epigastric
pain , diarrhea and gastro-
intestinal hemorrhage
Attachment of
adult worms
and injury to
upper intestinal
mucosa
Hematologic Iron deficiency, anemia
(microcytic
hypochromic),eosinophilia
hypoproteinemia, edema
(face and legs) may be
related to malnutrition and
cardiac failure.
Intestinal blood
loss
The hookwors attach to the mucosa of the small intestine by their buccal
capsules. The favorite site is the upper small intestine, they suck blood of
the hosts . The worm secrets anticoagulant substances which facilitate
blood sucking. A. duodenale withdrawn approximately of 0.15 to 0.26 ml
whereas N.americans 0.03 ml of blood by worm per day. The most
prominent characteristic in moderate or heavy chronic infection is
progressive, secondary, microcytic hypochromic anemia . Anemia
primarily due to the continuous loss of blood. The pathology and
symptomatology are proportional to the number of worms and the
nutritional intake of the patient. Malnutrition not only may produce
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anemia but also may weaken the natural protective mechanism of the host
so more worms may become established. The anaemic patient (decrease
2.0g/100ml of the standard range) will complaining dyspnea on exertion,
weakness, and dizziness, the appetite may be enormous or poor and
associated with pica. The heart show hypertrophy, hemic murmur is
present, and the pulse is rapid. There is edema of varying degrees, and
albumin is present in the urine. Heavely infected children may be
physically ,mentally and sexually retarded. Eosinophlia and leukocytosis
are marked in early infection then both decrease but anemia persist. The
stools may contain gross blood , and occult blood is readily found.
Pica; A craving for unnatural foods (such as soil, charcoal etc) as seen in
hysteria, pregnancy, and in malnourished children, its causes broadened to
include anaemia, and especially the anemia of hookworm disease.
Consumption of soil, may increase exposure to such infections as
ascariasis, toxocariasis, toxoplasmosis and definitely hookworm.
Note; In previously uninfected persons, the onset of a heavy hookworm
infection may be marked by nausea, vomiting, epigastric or midabdominal
tenderness, and diarrhea. The diarrhea is presumably caused by toxicity or
hypersensitivity, although mechanical irritation may play some part.
Laboratory diagnosis
Diagnosis is made by identification of hookworm eggs in fresh or
preserved feces. Species of hookworms cannot be distinguished by egg
morphology. Hookworm eggs are 60m x 35 m, colourless with a thin
shell which appears as a black line around the ovum, oval in shape,
contains ovum which is usually appears segmented (Fig-3-).

Fig:-3- hookworm egg.


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Treatment and Control
Mebendazole (vermox) is effective. Sanitation is the chief method of
control: sanitary disposal of fecal material and avoidance of contact with
infected fecal material.In countries where hookworm is common and
reinfection is likely, light infections are often not treated. In the United
States, hookworm infections are generally treated with albendazole.
Mebendazole or pyrantel pamoate can also be used.
Trichostrongyliasis (pseudo-hookworms: Trichostrongylus colubriformis
infection)
Etiology
Trichostrongylus nematodes, occasionally refered to as pseudo-
hookworms, are mainly parasites of ruminants, equines, and rodents. But
several species can infect humans like Trichostrongylus colubriformis
(synonym T. instabilis)
Morphology
Trichostrongylus are related to the hookworms , and the adults are rather
similar in appearance. Adult worms are approximately 5 mm long.
Fertilised female worms produce quite large eggs (85 x 115 m). These
are rather longer and more pointed than the eggs of Ascaris. They contain
a morula. The head is without cutting teeth or plates.
Epidemiology
These are small red worms which have a cosmopolitan distribution and
infect birds, ruminants, rabbits and rodents. T. probolurus parasitises a
gazelle and camels. T. colubriformis normally parasitises the small
intestine of sheep and goats. In some regions (Iran, Central Africa, Egypt,
Java, India) humans in rural areas are frequently infected.
Transmission and life cycle
Once outside the body the eggs hatch. At an ambient temperature of 22C
the rhabditiform larva takes 6 days to change into an infectious filariform
larva. The infectious larvae of T. colubriformis are found on ground
vegetation and are resistant to drying out. They can be differentiated from
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hookworm larvae and Strongyloides larvae by the typical small nodule at
the tail. The larvae can penetrate the skin, but faeco-oral transmission is
also possible. The parasites penetrate the intestinal mucosa and
subsequently migrate back to the intestinal lumen. The larvae do not
undergo a pulmonary migration but when swallowed attach themselves to
intestinal mucosa and grow to adulthood in 3 to 4 weeks.
Clinical features and Pathology
Most infections are asymptomatic. It is important, however, to
differentiate between infections by hookworms or by Strongyloides
stercoralis. Trichostrongylus worms suck blood from their host. Only in
heavy infection blood loss (anaemia) is significant and emaciated. The
clinical features of Trichostrogyliasis, are less sever than those of
hookworm.
Laboratory diagnosis
Diagnosis by finding eggs in the stool (it is longer than a hookworm egg ,
measuring 85-115 m in length. It is more pointed at one or both ends.
Treatment
Mebendazole is the drug of choice. Albendazole is also active against
these worms.
Haemonchus contortus
The sheep wire worm , belong to the Trichostrongylus family, it is
cosmopolitan parasite of economic importance in sheep, cattle, and other
ruminant, has been reported as an incidental parasite of man in Brazil and
Australia. It measures 10 -30 mm in length and has attenuated anterior
end. The egg resemble trichostrongylus species eggs. Infection take place
through the digestive tract. Heavy infections produce an anaemia
resembling that of hookworm infection.
Ternidens deminutus
T. deminutus is a nematode which resembles a hookworm. It belong to
Strongylidae family. It is normally parasitic in monkeys and baboons but
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can infect man . Human inections have been reported mostly from South
Africa and East Africa.
Transmission
Probably by ingestion of third stage larvae. The worms are found in the
large intestine. Like hookworms ,
Clinical feature and Pathology
T. deminutus worms also suck blood from their host and anaemia may
develop in heavy infections. Diagnosis by finding eggs in the faeces. The
egg have similar featuresto hookworm except that they are longer,
measuring up to 85 m in length.
Trichuriasis (Trichuris trichiura /whipworm infection)
Etiology
Trichuris trichiura (whipworm)

Morphology

The female organism is 50 mm long with a slender anterior end (100 m)
and a thicker (500 m diameter) posterior end (Fig-1-). The male is
smaller and has a coiled posterior end.




Fig:-1- Trichuris trichiura (whipworm), adult worm.



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Epidemiology
Trichuriasis is a tropical disease of children (5 to 15 yrs). 65% of cases in
rural Asia. It is, however, seen in the two Americas, mostly in the South
and is concentrated in families and groups with poorer sanitary habits.
Transmission and Life cycle

The unembryonated eggs are passed with the stool (1). In the soil, the
eggs develop into a 2-cell stage (2), an advanced cleavage stage (3), and
then they embryonate (4); eggs become infective in 15 to 30 days. After
ingestion (soil-contaminated hands or food), the eggs hatch in the small
intestine, and release larvae (5)that mature and establish themselves as
adults in the colon (6). The adult worms (approximately 4 cm in length)
live in the cecum and ascending colon. The adult worms are fixed in that
location, with the anterior portions threaded into the mucosa. The females
begin to oviposit 60 to 70 days after infection. Female worms in the
cecum shed between 3,000 and 20,000 eggs per day. The eggs are less
resistant to desiccation, heat and cold than ascaris eggs. The embryo is
killed under desiccation at 37 degrees C within 15 minutes. Temperatures
- 321 -

of 52 degrees C and -9 degrees C are lethal. The life span of the adults is
about 1 year.
Clinical features and Pathology
The anterior ends of the worms, interlaced in the colonic mucosa, produce
little damage, and is thought to increase the risk infection with bacterial
and even parasitic at site of worm mucosa penetration such as pathogenic
enterobacteria (e.g shigella species) and E. histolytica. Symptoms are
determined largely by the worm burden: Light infection ,less than 10
worms are asymptomatic. A characteristic clinical picture of heavier
infections (e.g., massive infantile trichuriasis) are characterized by sever
anemia , chronic profuse mucus and bloody diarrhea, tenesmus with
abdominal pains with distension , weight loss , nausea , vomiting , slight
fever and headach may occur and occasional edematous prolapsed rectum
(Rectal prolpse). The infection may result in malnutrition, weight loss
,and growth retardation in children with heavy infection, anemia (usually
microcytic hypochromic), with moderate eosinophilia and sometimes
death. Appendicitis may occur due to appendix lumen blockage by the
worm and mucosal oedema .
Note: prolapsed rectal mucosa result from straining at the frequent stools
and tenesmus.
Note: The worms apparently suck the blood of their host , and hemorrhage
may occur at the site of their attachment, approximately 0.005 ml of blood
is lost per day by each worm.
Laboratory diagnosis

Diagnosis is based on symptoms and the presence of eggs in feces The
Trichuris eggs are lemon or football shaped and have terminal plugs at
both ends. The external layer of the shell of the egg is yellow-brown in
contrast to the clear polar plugs. It measures (50 to 55 x 20 to 25 m)
(Fig-2-).

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Fig:-2- Trichuris egg.
Treatment and Control
Mebendazole, for 3 days is effective. Accompanying infections must be
treated accordingly. Improved hygiene and sanitary eating habits are most
effective in control.
Trichinellosis/Trichinosis/ Trichiniasis (Trichinella spiralis infection)

Etiology

Trichinella spiralis
Morphology
The adult female measures 2.2 mm in length, males 1.2 mm . The larvae in
the tissue (100 m x 5 m ) are coiled in capsule (Fig-1-).

Fig:-1- Trichinella spiralis, coiled larva.
Epidemiology
Trichinosis is related to the quality of pork and consumption of poorly
cooked meat. Autopsy surveys indicate about 2 percent of the population
is infected. The mortality rate is low.

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Transmission and Life cycle
Trichinellosis is acquired by ingesting meat containing cysts (encysted
larvae) (1)of Trichinella. After exposure to gastric acid and pepsin, the
larvae are released (2)from the cysts and invade the small bowel mucosa
where they develop into adult worms (3)(female life span in the small
bowel: 4 weeks). After 1 week, the females release larvae (4)that migrate
to the striated muscles where they encyst (5). Trichinella pseudospiralis,
however, does not encyst. Encystment is completed in 4 to 5 weeks and
the encysted larvae may remain viable for several years. Ingestion of the
encysted larvae perpetuates the cycle. Rats and rodents are primarily
responsible for maintaining the endemicity of this infection.
Carnivorous/omnivorous animals, such as pigs or bears, feed on infected
rodents or meat from other animals. Different animal hosts are implicated
in the life cycle of the different species of Trichinella. Man is the terminal
host. The reservoir includes most carnivorous and omnivorous animals .

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Clinical features
Trichinosis symptoms depend on the severity of infection: mild infections
may be asymptomatic. A larger bolus of infection produces symptoms
according to the severity and stage of infection and organs involved
(Table-1-).
Table:-1- Trichinosis Clinical features.
Intestinal
mucosa
(24-72
hrs)
Circulation and
muscle
(10-21 days)
Myocardium(myocarditi
s)
(10-21 days)
Brain and
meninges
(14-28 days)
Nausea,
vomiting
diarrhea(5
-15
time/day
of
nonblood
y /non
mucoid) ,
abdominal
pain,
headache.
Edema, peri-
orbital
conjunctivitis,
photo phobia,
fever, chill,
sweating, muscle
pain, spasm,
eosinophilia,
leukocytosis,
hyperglobulinaemi
a E is
characteristic.
Chest pain, tachycardia,
ECG changes, edema of
extremities, vascular
thrombosis.
Headache
(supraorbital
), vertigo,
tinnitus,
deafness,
mental
apathy,
delirium,
coma, loss of
reflexes.
Hemiplegia
and focal
epileptic
attacks
reported
Note; sever myositis is characteristic of the larval stage migration. If
accompanied by circumorbital edema, eosinophilia, and a history of
consumption of insufficiently cooked pork, the diagnosis may be made
with some certainity. Myositis, usually involving a single muscle group.
Splinter hemorrhages; Sometimes occurring during the stage of active
larval migration in trichinosis, minute linear hemorrhages in the nail beds
are a sign of vascular injury.
Pathology and Immunology
The female, after fertilization, burrows deeply in the small intestinal
mucosa, whereas the male is dislodged (intestinal stage). On about the 5th
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day eggs begin to hatch in the female worm and young larvae are
deposited in the mucosa from where they reach the lymphatics, lymph
nodes and the blood stream (larval migration). Larval dispersion occurs 4
to 16 weeks after infection. The larvae are deposited in muscle fiber and,
in striated muscle, they form a capsule which calcifies to form a cyst. In
non-striated tissue, such as heart and brain, the larvae do not calcify; they
die and disintegrate. The cyst may persist for several years. One female
worm produces approximately 1500 larvae.Trichinella pathogenesis is due
the presence of large numbers of larvae in vital muscles and host reaction
to larval metabolites. The muscle fibers become enlarged edematous and
deformed. The paralyzed muscles are infiltrated with neutrophil,
eosinophils and lymphocytes. The worm induces a strong IgE response
which, in association with eosinophils, contributes to parasite death.
Laboratory diagnosis
Diagnosis is based on symptoms, recent history of eating raw or
undercooked meat and laboratory findings (eosinophilia, increased serum
creatine phosphokinase and lactate dehydrogenase and antibodies to
T. spiralis). X-ray may show calcified encysted larvae in the muscle.
Muscle biopsy; demonstration of living larvae in a fragment of patients
muscle confirms the diagnosis, a small piece of muscle is removed by
biopsy from the gastrocnemius, usually near the tendinous attachments,
compressed between two slides and examined under microscope.
Treatment and Control
Steroids are use for treatment of inflammatory symptoms and
Mebendazole is used to eliminate worms. Elimination of parasite infection
in hogs and adequate cooking of meat are the best ways to avoid infection.
Capillariasis (C. philippinensis, C. hepatica, andC. aerophila infection)
Etiology
The nematode (roundworm) Capillaria philippinensis causes human
intestinal capillariasis. Two other Capillaria species parasitize animals,
with rare reported instances of human infections. They are C. hepatica,
which causes in humans hepatic capillariasis, and C. aerophila, which
causes in humans pulmonary capillariasis.

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Morphology

The adults of C. philippinensis measure (males: 2.3 to 3.2 mm; females:
2.5 to 4.3 mm).
Epidemiology
Capillaria philippinensis is endemic in the Philippines and also occurs in
Thailand. Rare cases have been reported from other Asian countries, the
Middle East, and Colombia. Rare cases of human infections with C.
hepatica and C. aerophila have been reported worldwide.
Transmission and Life Cycle
Typically, unembryonated eggs are passed in the human stool (1)and
become embryonated in the external environment (2); after ingestion by
freshwater fish, larvae hatch, penetrate the intestine, and migrate to the
tissues (3). Ingestion of raw or undercooked fish results in infection of the
human host (4). The adults of Capillaria philippinensis reside in the
human small intestine, where they burrow in the mucosa (5). The females
deposit unembryonated eggs. Some of these become embryonated in the
intestine, and release larvae that can cause autoinfection. This leads to
hyperinfection (a massive number of adult worms) (6). Capillaria
philippinesis is currently considered a parasite of fish eating birds, which
seem to be the natural definitive host (7).
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Note:Capillaria hepatica adult worms reside in the liver of various
animals, especially rats. The females produce eggs that are retained in the
liver parenchyma. When the infected animal is eaten by another animal,
the eggs are released by digestion, excreted in the feces of the second
animal, and become embryonated in the soil. Alternately, the eggs can be
released following the death and decomposition of the first animal, and
mature in the soil. Following ingestion by a subsequent host, these
infective eggs release larvae in the intestine that migrate through the portal
circulation to the liver, where they develop into adults.
Capillaria aerophila adult worms reside in the epithelium of the tracheo-
bronchial tract of various animals. Eggs are produced, coughed up,
swallowed by the animal, and excreted in its feces. The eggs become
embryonated in the soil. Ingestion of infective eggs completes the cycle.
Transport or paratenic hosts may also intervene in the cycle.
Clinical features and Pathology
Intestinal capillariasis (caused by C. philippinensis) manifests as
abdominal pain and diarrhea, which, if untreated, may become severe
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because of autoinfection. A protein-losing enteropathy can develop which
may result in cachexia and death. Hepatic capillariasis (C. hepatica)
manifests as an acute or subacute hepatitis with eosinophilia, with possible
dissemination to other organs. It may be fatal. Pulmonary capillariasis
(C. aerophila) may present with fever, cough, asthma, and pneumonia,
and also may be fatal.
Laboratory diagnosis
The specific diagnosis of C. philippinensis is established by finding eggs
(It is similar and smaller than T.trichuria, measuring about 45 x 21 m,
yellow-brown but less elliptical in shape and the plugs are one at each end
of the egg are smaller and do not protrude like those of T. trichuria) (Fig-
1-), larvae and/or adult worms in the stool, or in intestinal biopsies.
Unembryonated eggs are the typical stage found in the feces. In severe
infections, embryonated eggs, larvae, and even adult worms can be found
in the feces.
The specific diagnosis of C. hepatica infection is based on demonstrating
the adult worms and/or eggs in liver tissue at biopsy or necropsy. Note:
identification of C. hepatica eggs in the stool is a spurious finding, which
does not result from infection of the human host, but from ingestion by
that host of livers from infected animals. The specific diagnosis of C.
aerophila is based on demonstrating eggs in stool or in lung biopsy.
A B
Fig:-1- Capillaria hepatica eggs: (A)The egg has a typically striated shell
and shallow polar prominences. (B) in tissue.
Treatment
The drug of choice is mebendazole, and albendazole is an alternative.
Strongyloidiasis (S.stercoralis infection)
Strongyloides stercoralis ( dwarf threadworm) . It is a worm inhabitating
the small bowel of man in large areas of the tropics and subtropics and it
- 329 -

can occur in mines in temprate climate.infection has been recorded in a
british girl who acquired it from running barefoot in an Englis park in
summer. Almost all infection cause trivial symptoms or none at all. The
infection only becomes important in patients immunosuppressed by reason
of intercurrent disease, malnutrition or medication.
Etiology
The nematode (roundworm) Strongyloides stercoralis. Other
Strongyloides include S. flleborni, which infects chimpanzees and
baboons and may produce limited infections in humans.
Morphology
The size and shape of threadworm varies depending on whether it is
parasitic or free-living. The parasitic female is larger (2.2 mm x 45 m)
than the free-living worm (1 mm x 60 m) . The eggs, when laid are 55
m by 30 m .
Epidemiology
Tropical and subtropical areas, but cases also occur in temperate areas
(including the South of the United States). More frequently found in rural
areas, institutional settings, and lower socioeconomic groups. Threadworm
infection, estimated at 50 to 100 million cases worldwide, is an infection
of the tropical and subtropical areas with poor sanitation. In the United
States, it is prevalent in the South and among Puerto Rica.
Transmission and Life Cycle
The Strongyloides life cycle is more complex than that of most nematodes
with its alternation between free-living and parasitic cycles, and its
potential for autoinfection and multiplication within the host. Two types
of cycles exist:
Free-living cycle: The rhabditiform larvae passed in the stool (1)(see
"Parasitic cycle" below) can either molt twice and become infective
filariform larvae (direct development) (6)or molt four times and become
free living adult males and females (2)that mate and produce eggs (3)from
which rhabditiform larvae hatch (4). The latter in turn can either develop
(5)into a new generation of free-living adults (as represented in (2), or into
infective filariform larvae (6). The filariform larvae penetrate the human
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host skin to initiate the parasitic cycle (see below) (6).
Parasitic cycle: Filariform larvae in contaminated soil penetrate the
human skin (6), and are transported to the lungs where they penetrate the
alveolar spaces; they are carried through the bronchial tree to the pharynx,
are swallowed and then reach the small intestine (7). In the small intestine
they molt twice and become adult female worms (8). The females live
threaded in the epithelium of the small intestine and by parthenogenesis
produce eggs (9), which yield rhabditiform larvae. The rhabditiform
larvae can either be passed in the stool (1)(see "Free-living cycle"
above), or can cause autoinfection (10). In autoinfection, the rhabditiform
larvae become infective filariform larvae, which can penetrate either the
intestinal mucosa (internal autoinfection) or the skin of the perianal area
(external autoinfection); in either case, the filariform larvae may follow
the previously described route, being carried successively to the lungs, the
bronchial tree, the pharynx, and the small intestine where they mature into
adults; or they may disseminate widely in the body. To date, occurrence
of autoinfection in humans with helminthic infections is recognized only
in Strongyloides stercoralis and Capillaria philippinensis infections. In
the case of Strongyloides, autoinfection may explain the possibility of
persistent infections for many years in persons who have not been in an
endemic area and of hyperinfections in immunodepressed individuals.
Note:Transmammary transmission of Strongyloides larvae can also occur,
i.e. larvae are transmitted from mother to infant in breast milk.
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Clinical features and Pathology

Light infections are asymptomatic. It is impossible to overemphasize that
most infections are asymptomatic. But the following symptoms do
sometimes occur: Skin penetration causes itching and red blotches. Larva
currens ; {This is a characteristic virtually pathognomonic- skin
eruption. It is caused by the migration of larva through the skin during
autoinfection. The eruption typically: is a serpiginous wheal (a raised
wiggly line ) surrounded by a flare; it is evanescent (comes and goes in a
few hours); it is very itchy , confined to the trunk between the neck and
the knees; and tends to appear in corps at irregular and unpredictable
intervals}. During migration, the organisms cause bronchial verminous
pneumonia (pneumonitis) and, Pulmonary symptoms (including
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Loefflers syndrome) can occur during pulmonary migration of the
filariform larvae. Invading the mucosal wall, may cause a severe
duodenitis or jejunitis (a burning mid-epigastric pain and tenderness
accompanied by nausea and vomiting), symptoms suggestive of duodenal
ulcer disease. In S. stercoralis infections there may be mild diarrhea
alternating with periods of constipation, or the diarrhea may be severe and
prostrating.
In heavy infections ulceration and sloughing of intestinal mucosa may take
place, with dysentery and often with secondry bacterial infection and
fever. Heavy, chronic infections result in anemia, weight loss and chronic
bloody dysentery. Secondary bacterial infection of damaged mucosa may
produce serious complications. Leukocytosis early in the course of
infection and then usually decline and may be followed by leucopenia.
Infection may run the gamut from a complete absence of symptoms to
those infections of the duodenum and jejunum that are so extensive as to
produce ulceration of the mucosa , with blood loss to the
Point of clinical anemia, and with melena. Especially in
immunosuppressed patients, the coincidental finding of anemia with
melena and a significant eosinophilia should stimulate a through search for
this sometimes elusive parasite.
Note; Many Strongyloides infections are mild and go unnoticed. Moderate
infections may cause a burning pain in your abdomen. You may have
nausea and vomiting and alternating diarrhea and constipation. Severe
infections result in anemia, weight loss, and chronic diarrhea.
Disseminated strongyloidiasis in severely immunocompromised people
can cause a variety of symptoms, including an ARDS-like pneumonia
(Acute Respiratory Distress Syndrome).
Note:Disseminated strongyloidiasis occurs in immunosuppressed patients,
can present with abdominal pain, distension, shock, pulmonary and
neurologic complications and septicemia, and is potentially fatal. Blood
eosinophilia is generally present during the acute and chronic stages, but
may be absent with dissemination.
Hyperinfection syndrome
This occurs when the body loses its defences against autinfection and
there are enormous numbers of successful filariform larvae reinvading the
body. In its most fulminating form it has been reported in patients
receiving corticosteroid treatment, in those with multiple diseases and
malnutrition (The beggar syndrome), in malignant lymphoma and
following renal transplantation. The features are:
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1- Diarrhea. (This may take the form of sever steatorrhea leading to death
in a few weeks if not recognized. If the colon is severly affected , there
may be numerous haemorrhagic lesions leading to dysentery like picture.
2- Paralytic ileus with diffuse inflammatory thickening of the gut.
3-Gram-negative septicaemia.
4-Serous effusion and bacterial peritonitis.
5- Pulmonary symptoms (cough, wheeze, dyspnoea, haemoptysis) due to
massive migration of larvae through the lungs.
6-Specific organ involvement such as when many larvae in the brain cause
encephalitis and pyogenic meningitis. In the hyperinfection syndrome
there is never eosinphilia, and as the eosinophils are the cells mainly
concerned with killing the migrating larvae, this is scarcely surprising.
Hyperinfection is largely the result of the eosinopenia. Treatment with
thiabendazole in the hyperinvasion syndrome is often unsuccessful. It is
too early to say whether albendazole will be more effective or not.
Laboratory diagnosis
Diagnosis rests on the microscopic identification of larvae (rhabditiform
and occasionally filariform) in the stool or duodenal fluid , similar to those
of hookworms but can be distinguished by their very short buccal
cavity. The presence of free rhabditiform larvae in the feces is diagnostic.
Larva are often found in the mucus passed with the stool , it is actively
motile , measuring 200-300m x 15 m and is unsheathed,its buccal
cavity shorter than hookworm larva buccal cavity . With sever diarrhea
egg may be present in the stool (It is colourless, oval in shape 50x 35 m,
and it contain a partially developed larva) Culture of stool for 24 hours
will produce filariform larvae in agar plates.Examination of serial samples
may be necessary, and not always sufficient, because stool examination is
relatively insensitive.
The stool can be examined in wet mounts:
directly
after concentration (formalin-ethyl acetate) or by Baermann funnel
technique
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The duodenal fluid can be examined using techniques such as the
Enterotest string or duodenal aspiration. Larvae may be detected in
sputum from patients with disseminated strongyloidiasis.
Note: A characteristic x-ray picture is reported in severe infection, with
loss of mucosa pattern, rigidity, and tubular narrowing.
Treatment and Control
The drug of choice for the treatment of uncomplicated strongyloidiasis is
ivermectin with albendazole or thiabendozole as the alternative.
Direct and indirect infections are controlled by improved hygiene and
auto-infection is controlled by chemotherapy.
All patients who are at risk of disseminated strongyloidiasis should be
treated.
Strongyloides fuelleborni
It is a natural parasite of monkeys and dogs but it can also infect humans.
This worm differs from S.stercoralis morphologically and also in the fact
that eggs and not larvae are found in the feces of the infected host , found
in central Africa. Another similar worms , but some morphological.
Differences were observed in the free-living adults commonly found in
Papua Guina. Human S. fuelleborni and S. fuelleborni-like infections have
been reported from tropical Africa and Papua New Guinea respectively,
especially in young children and infants. In Papua New Guinea,
S.fuelleborni like infections are associated with an acute infantile disease
known a Swollen Belly Syndrome. Characterized by respiratory distress ,
abdominal distension, generalized edema, and hypoproteeinemia, which in
the past was almost uniformly fatal. The discovery of Stronyloides eggs in
vast numbers in the stools of these infants prompted the use of
thiabendazole.
Summary in the most common and important Intestinal and Tissue
Nematods
Organism Transmission symptoms Diagnosis Treatment
Ascaris
lumbricoides
Oro-fecal Abdominal pain,
weight loss,
distended
abdomen
Stool: corticoid
oval egg (40-
70x35-50 m)
Albedazol
e,
Mebenda
zole
Trichinella Poorly cooked Depends on Medical corticoste
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spiralis pork worm location
and burden:
gastroenteritis;
edema, muscle
pain, spasm;
eosinophilia,
tachycardia,
fever, chill
headache,
vertigo, delirium,
coma, etc.
history,
eosinophilia,
muscle biopsy,
serology
roid and
Mebenda
zole
Trichuris
trichiura
Oro-fecal Abdominal pain,
bloody diarrhea,
prolapsed rectum
Stool: lemon-
shaped egg
(50-55 x 20-
25m)
Mebenda
zole,
Albedazol
e
Enterobius
vermicularis
Oro-fecal Peri-anal pruritus,
rare abdominal
pain, nausea
vomiting
Stool:
embryonated
eggs (50-
60x20x32 m),
flat on one side
Pyrental
pamoate ,
Albedazol
e and,
Mebenda
zole
Strongyloides
stercoralis
Soil-skin,
autoinfection
Itching at
infection site,
rash due to larval
migration,
verminous
pneumonia, mid-
epigastric pain,
nausea, vomiting,
bloody dysentery,
weight loss and
anemia
Stool:
rhabditiform
larvae (1mmx
60m)
Ivermecti
n or
Thiabend
azole
Necator
americanes;
Ancylostoma
duodenale
(Hookworms)
Oro-fecal (egg);
skin penetration
(larvae)
Maculopapular
erythema (ground
itch), broncho-
pneumonitis,
epigastric pain,
GI hemorrhage,
anemia, edema
Stool: oval
segmented
eggs (60 x
35m)
Mebenda
zole
Dracunculus
medinensis
Oral: cyclops in
water
Blistering skin,
irritation,
inflammation
Physical
examination
Mebenda
zole
Wuchereria
bancrofti; W.
brugia malayi
(elephantiasis)
Mosquito bite Recurrent fever,
lymph-adenitis,
splenomegaly,
lymphedema,
elephantiasis
Medical
history,
physical
examination,
microfilaria in
blood (night
sample)
Mebenda
zole;
Diethyl-
carbamazi
ne
- 336 -

Onchocerca
volvulus
Black fly bite Nodular and
erythematous
dermal lesions,
eosinophilia,
urticaria,
blindness
Medical
history,
physical
examination,
microfilaria in
nodular
aspirate
Ivermecti
n,
Diethyl-
carbamazi
ne (DEC)
and
Mebenda
zole,
Loa loa Deer fly Calabar swelling,
Unilateral
circumscribed
edema
Medical
history,
physical
examination,
microfilaria in
blood (day
sample)
Surgical
removal,
DEC

Anasakiasis (Anisakis simplex or Pseudoterranova decipiens infection)
Etiology
Anisakiasis is caused by the accidental ingestion of larvae of the
nematodes (roundworms) Anisakis simplex or Pseudoterranova decipiens
also called teranova and Phocanema.
Morphology
Such larvae may reach a length of 50 mm and a diameter of 1 to 2mm.
Epidemiology
Worldwide, with higher incidence in areas where raw fish is eaten (e.g.,
Japan, Pacific coast of South America, the Netherlands).
Transmission and life cycle
Adult stages of Anisakis simplex or Pseudoterranova decipiens reside in
the stomach of marine mammals, where they are embedded in the mucosa,
in clusters. Unembryonated eggs produced by adult females are passed in
the feces of marine mammals (1). The eggs become embryonated in
water, and first-stage larvae are formed in the eggs. The larvae molt,
becoming second-stage larvae (2a), and after the larvae hatch from the
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eggs, they become free-swimming (2b). Larvae released from the eggs
are ingested by crustaceans (3). The ingested larvae develop into third-
stage larvae that are infective to fish and squid (4). The larvae migrate
from the intestine to the tissues in the peritoneal cavity and grow up to 3
cm in length. Upon the host's death, larvae migrate to the muscle tissues,
and through predation, the larvae are transferred from fish to fish. Fish
and squid maintain third-stage larvae that are infective to humans and
marine mammals (5). When fish or squid containing third-stage larvae are
ingested by marine mammals, the larvae molt twice and develop into adult
worms. The adult females produce eggs that are shed by marine mammals
(6). Humans become infected by eating raw or undercooked infected
marine fish (7). After ingestion, the anisakid larvae penetrate the gastric
and intestinal mucosa, causing the symptoms of anisakiasis.
- 338 -


Clinical features and Pathology
Within hours after ingestion of infected larvae, violent abdominal pain,
nausea, and vomiting may occur. Occasionally the larvae are coughed up.
If the larvae pass into the bowel, a severe eosinophilic granulomatous
response may also occur 1 to 2 weeks following infection, causing
symptoms mimicking Crohn's disease.


- 339 -

Laboratory diagnosis
Diagnosis can be made by gastroscopic examination during which the 2
cm larvae are visualized and removed, or by histopathologic examination
of tissue removed at biopsy or during surgery.
Treatment
The treatment of choice is surgical or endoscopic removal.













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CHAPTER FOURTEEN (14)
Other worms
Pentastomida, Armillifer sp.
Armillifer armillatus, A. moniliformis and A. grandis belong to the
Pentastomida or tongue-worms. The taxonomical classification of these
organisms is not clear, Pentastomes are related to arthropods, although
they also hacesome annelids-like features. These are worm like parasites
that live in the respiratory passages of carnivorous reptiles, birds, and
mammals. Pentastomids are hermaphroditic.
Morphology
They are often referred to as tongue worms because of the generalized
tongue like shape, they are cylindrical. The head bears five ventral
opening (actually the mouth and four hooks), hence the parasite name.
They also have some annelid-like features.
Epidemiology
Human infections reported in many parts of the world , Africa, Europe,
Asia, and the America, they more common in central Africa and Malaysia.
Infection with A. armillatus frequently occurs in foci, certainly in Congo.
Transmission and Life cycle
Various mammals are intermediate hosts. Pythons and adders are the
normal final hosts. The parasites are found in the respiratory passages of
these reptiles. People become infected by eating an infected snake, by
taking infected food or water. Infection acquired by ingesting raw
vegetables or contaminated water with pentastomes eggs (passed with
sputum or feces of definitive host) or by uncooked infected snake meat or
sheep liver. The eggs hatch and larvae penetrate the intestinal wall and
migrate to liver, spleen, lungs, eye , and lymph nodes where they develop
to become nymph and encapsulated (Comma or C shaped , less than 1 cm,
and may calcify).

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Clinical features
The nymphs are found in the liver, spleen, lungs and under the
conjunctiva. Comma-shaped calcifications may be observed on an X-ray
of the abdomen. The infection is also known as porocephalosis . Common
symptoms/signs are inflamed and enlarged mesenteric lymph nodes,
abdominal pain, jaundice, and ocular lesions. and is usually without
symptoms if the parasites are only located in the abdomen.
Note; in Lebanon, a clinical condition known as Halzoun (same condition
caused by F. hepatica ) . This condition caused by nymph present in the
liver and visceral lymph nodes of sheep , the nymph may attach to the
nasopharyngeal mucous membrane when infected raw meat is eaten. The
attachched nymph provoke pharyngitis (pain , coughing, sneezing, and
vomiting (Fig-1-).

Fig:-1-Pentastomiasis. Linguatula serrata. Causes halzoun in humans.
Treatment
No need for treatment if the parasite in the abdomen and asymptomatic , it
is usually asymptomatic. If located in the eye the parasite should be
surgically removed.
Annelida (segmented worms)
Leeches
These are ectoparasites , the species of medical importance are either
aquatic or terrestrial. It occur in different sizes, muscular, pigmented, oval
in shape with tough cuticle, suckers at both ends, hard jaws, and
pharyngeal pharynx.
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The Aquatic leeches; species of Limnatis usually cause injuy to man, It is
strong blood sucker of the bathers , if ingested in drinking water , infest
the upper respiratory or digestive passages. It may invade vagina, urethra,
and eyes of the bathers.
The Terrestrial leeches; species of Haemadipsa found and live in damp
tropical forest, where they attach to travelers. It cause painless and
unnoticed wound caused by the bite bleeds readily because of an
anticoagulant secretion, and heals slowely. Removed by applying local
anaesthesia, strong salt solution, or a lighted match. Travelers in endemic
areas may be protected by impregnating their cloths with a repellent such
as dimethyl phthalate.














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CHAPTER FIFTEEN (15)
Opportunistic parasite
Persons whose immune systems are weakened for any of these following
reasons may more readily become infected with certain parasites. The
important cause of immunodefiency in human is human
immunodeficiency virus (HIV), produce the acquired immunodeficiency
syndrome (AIDS). There are other acquired cause such various
malignancies and their treatment by (cytotoxic drugs, radiation)
prolonged corticosteroid therapy, drugs used to prevent organ transplant
rejection.Some innate deficiencies, such as achlorhydria and
hypogammaglobulinemia, also malnutrition, may also be important factor
in facilitating parasitic infection. Chronic diseases with some parasites
have profound effect on immune system and produce immunosuppression
(Malaria, Trypanosomiasis, Schistosomiasis, and filariasis) .
Protozoa
Leishmania donovani- exacerbated in immunocompromised patients.
T.cruzi (is reported cause acute diffuse meningoencephalitis in
immunocomromised patients).
G.lamblia- common and the infection prolonged but symptoms not
increase. Levels of IgG, IgM ,and IgA antibodies to Giardia are depressed
in (AIDS) patients.
Acanthamoeba- The course of acanthamoebiasis more acute in patient
whose immune status is compromised by AIDS.
Toxoplasma gondii- generalized form of the disease seen almost
exclusively in immunocompromised persons. Cerebral toxoplasmosis is
the most common form also toxoplasma affecting the spinal cord reported
in AIDS patients .
Cryptosporidium parvum- In AIDS patients cause sever gastrointestinal
symptoms, and extraintestinal symptoms , including the respiratory tract
and ears.
- 344 -

Isospora belli- causes sever diarrhea in immunocompromised patients.
May also cause extraintestinal disease (having been found in the
mesenteric, periaortic, and mediastinal lymph nodes in patients with
AIDS.
Malaria- no evidence to suggest that malaria either more common or more
sever in immunocompromised persons. There is a single report of
blackwater fever apparently caused by P. vivax in ptient with AIDS.
Burkitts lymphoma which is caused by Epstein bar virus quite common in
endemic areas of malaria. In malaria infected children the T4-T8 ratio is
reduced to levels usually seen only with AIDS.
Encephalitozoon cuniculi- human disease by this microsporidia almost
entirely recognized in immunocompromised persons such as
keratoconjunctivitis. Peritonitis caused by this organism was reported in a
patient with AIDS.
Encephalitozoon bieneusi- has been reported only from patients with
AIDS.
Nematode
S.stercolaris- it is the only nematode cause special problems in
immunocompromised patients. It have the ability to multiply (endogenous
multiplication) so the infection persist for many years especially in
immunocompromised persons and cause disseminated strongyloidiasis, in
which injury may occur to virtually every organ and tissue.
C. philippinensis are also capable of completing their life cycles within a
single human host, and may produce a hyperinfection syndrome in
immunocompetent persons. So might be expected , to produce more
expolsive hyperinfection syndrome in immunocompromised hosts (but
have not reported yet).
Pseudoparasites
Many things may be mistaken for parasites when microscopy is used in
diagnosis. Below are descriptions of some of these pseudoparasites.
- 345 -

Air bubbles
When seen in the microscope, air bubbles look like little black tires. If the
air bubble is large, be sure not to identify it as some kind of cell wall.
Crystals
Crystals usually have some kind of geometric shape. If crystals are seen in
a sample, most of them should have the same shape (depending on the
chemical composition). If you are unsure of an object, increase
magnification and check the shape. It may be a crystal.
Mites
There are several species of mites that are parasitic. Occasionally,
however, mites are non-pathogenic. Species are commensalistic and may
occur on plants. When making a diagnosis, it is important to find out the
diet of the animal, where it is kept, and where it has travelled. Mites are
ectoparasites; if they are found in the stool and are suspected of being
parasitic, check the fur and skin of the animal.
Plant hair
Easily confused with worms, this pseudoparasite looks like one but lacks
internal material. Most plant material is missing either a distinct anterior
worm end, a distinct posterior worm end, or both ends. This material may
also have a thin spiral structure.
Pollen
Under the microscope, pollen looks like a hat worn by Disney's
"Mousekateers."
Yeast
Yeast may look similar to a parasite; however, it has no internal structure.
Generally, the organism is elongated and it may undergo budding.


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CHAPTER SIXTEEN (16)
Antiparasites drugs
Antitrematodals
Quinoline derivatives
Praziquantel
Praziquantel produces contraction and paralysis of helminths by affecting
membrane permeability to calcium. It also leads to vacuolisation and
disintegration of the integument of susceptible parasites.
Indications: Schistosomiasis (agent of choice); intestinal tapeworm
infestations (T.solium, T.saginata, D.latum and H.nana); cysticercosis
caused by T.solium.
Contraindications: Ocular cysticercosis - irreparable ocular lesions may
result from local destruction of parasites.
Pregnancy: Safety has not been established; avoid in the first trimester,
and use thereafter only if the benefits outweigh the possible risk to the
fetus.
Lactation: Excreted in breast milk to reach 25% of maternal serum levels;
discontinue breast- feeding on the day of therapy and for 72 hours
thereafter.
Paediatrics: Has been used in children over 2 years of age without
evidence of adverse age- related reactions.
Adverse effects: These are usually mild and transient. Frequent - malaise,
non-specific gastrointestinal disturbances, headache, drowsiness and
dizziness.
Less frequent - urticaria, eosinophilia and arthralgia.
Inflammatory responses to dead and dying parasites in neurocysticercosis
may cause fever, brain oedema, raised intracranial pressure and
convulsions.
- 347 -

Special Prescriber's Points
*Patients with cerebral cysticercosis are at risk of developing reactive
cerebral oedema and are best treated in hospital with expert advice and
supervision. Concomitant steroid therapy, e.g. dexamethasone or
prednisolone, is often indicated. There is recent evidence that concomitant
corticosteroids lower plasma levels of praziquantel.
* Calcified cysts do not respond to treatment.
* Hospital treatment is recommended when treating schistosomiasis or
adult tapeworms in patients with concomitant cysticercosis.
* Patients should be warned that the drug may cause temporary
drowsiness and dizziness, affecting the ability to drive or perform other
tasks requiring mental alertness. Alcohol may aggravate these effects.
* Dose reduction may be required in patients with severely impaired
hepatic function.
Adult dose: (taken unchewed with some liquid after a meal).
S.haematobium and S.mansoni: 40 mg/kg in a single dose.
T.solium, T.saginata and D.latum: 10-20 mg/kg as a single dose.
Cysticercosis: 50 mg/kg/day in 3 divided doses for 15 days.
Paediatric dose: Children over 2 years may receive doses according to
body weight as for adults.
Preparations include:
Praziquantel Biltricide - tablets, 600 mg .Cysticide-tablets, 500 mg
Oxamniquine
Oxamniquine is active against mature as well as early developmental
stages of S.mansoni. Adult male worms are thought to be more susceptible
than females. Mode of action is not clear; worms migrate from the
- 348 -

mesenteric veins to the liver where they are destroyed. It is ineffective
against S.haematobium.
Contraindications: Relative - epilepsy, history of epilepsy or seizures. Use
with caution under close supervision.
Pregnancy: Embryotoxic in animals. Potential effects on the human fetus
are not known; avoid during the first 16 weeks of pregnancy.
Lactation: Problems have not been reported. Use with caution only if
essential; abstain from nursing for 72 hours.
Adverse effects: Frequent - transient dizziness, drowsiness, headache,
nausea, vomiting and diarrhoea.
Rare - skin rashes, fever, hallucinations and convulsions (usually in
patients with a history of epilepsy).
Eosinophilia has developed 2-3 days after therapy.
Special Prescriber's Points
* Gastrointestinal intolerance may be markedly improved by taking the
drug with food.
* May cause a non-significant orange or red discoloration of urine.
* As patients may become drowsy or dizzy, they should be warned not to
drive or operate machinery.
Adult dose: Oral, 15 mg/kg twice daily for 2 days. Dosage range and
duration depends on the geographical location and the strain of S.mansoni.
Paediatric dose: As for adults.
Preparations include:
Vansil

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Organophosphorous compounds
Metrifonate
Indications: Treatment and prophylaxis of schistosomiasis caused by
S.haematobium.
Contraindications: Recent exposure to insecticides; severe liver disease.
Pregnancy and Lactation: Contraindicated.
Adverse effects: Nausea, colic, weakness, bronchospasm, tremor,
sweating, fainting, headache and vertigo; usually mild and subside
spontaneously.
Adult dose: Therapy: Oral, 7.5-10 mg/kg in a single dose, repeated 3 times
at intervals of 2-weeks.
Prophylaxis: Oral, 7.5 mg/kg once every 4 weeks.
Paediatric dose: Oral, 7.5-10 mg/kg in a single dose, repeated every 2
weeks for 3 doses.
Preparations include:
Bilarcil
Antinematode
The following agents are included in the WHO essential drug list.
.Ivermectin has a broad spectrum of activity and is now considered the
drug of choice in onchocerciasis. It is given as a single dose according to
body weight and produces a prolonged reduction in microfilarial levels.
Retreatment is required at intervals of 6-12 months, depending on
symptoms, until adult worms have died out. It is associated with fewer and
less severe systemic and ocular reactions than diethylcarbamazine.


- 350 -

Benzimidazole derivatives
Albendazole
a new member of the benzimidazole group, has the broadest spectrum of
activity in the single dose oral treatment of intestinal helminth infestation.
It is challenging the position of mebendazole as the drug of choice in
mixed worm infestation. Albendazole blocks glucose uptake in susceptible
helminths, depleting the energy level until it becomes inadequate for
survival.
Indications: Single or mixed intestinal parasite infestations - effective
against roundworm, pinworm (threadworm), whipworm, hookworm,
Strongyloides stercoralis and Taenia spp.(tapeworm). Hydatid disease -
chemotherapeutic agent of choice in inoperable cases and prophylactically
before and after surgery. Also effective in neurocysticercosis, cutaneous
larva migrans, and visceral larva migrans (one study).
Pregnancy: Teratogenicity and embryotoxicity have been demonstrated in
animals; should not be taken at any stage of pregnancy nor by women
likely to become pregnant during or shortly after the course of therapy.
Lactation: No data available on excretion in breast milk; not
recommended.
Paediatrics: Has not been fully evaluated in children under 2 years of age,
but use in 1-2 year-olds in intestinal nematode infestations has been
reported.
Adverse effects: The dose recommended for intestinal worms is very well
tolerated. Epigastric pain, diarrhoea, headache, nausea, dizziness,
vomiting, constipation, pruritus ani and dry mouth have been reported in a
small percentage of patients. Leucopenia has occurred with large doses
and/or long periods of therapy. Abnormalities in liver function,
gastrointestinal symptoms, allergic reactions and alopecia have been
reported with the higher doses used in hydatid disease and
neurocysticercosis.
Special Prescriber's Points
- 351 -

* Frequent white cell counts should be done when given in large doses or
for long periods.
* In neurocysticercosis supervision is recommended as there may be
inflammatory reactions in response to the death of the parasite, which if
severe may require steroids.
* Tablets may be chewed, swallowed or crushed and mixed with food.
* No fasting or purging is necessary; however, since food increases
systemic availability, it would seem preferable to take the medicine on an
empty stomach when a high intraluminal concentration is desirable for
treating intestinal worms.
Adult dose: Oral, 400 mg as a single dose.
Strongyloidiasis, taeniasis and heavy mixed infestations involving
trichuris: Efficacy is improved by giving 400 mg daily for 3 consecutive
days. If a cure is not achieved the same dose can be given after 3 weeks.
Hydatid disease: Oral, 10-15 mg/kg/day. The regimen most frequently
used has been 400 mg twice daily for three 28- day cycles with 14 days'
rest between cycles. Long- standing cysts or those in biologically less
accessible sites such as bone and brain may require more prolonged
therapy.
Neurocysticercosis: 15 mg/kg/day in 3 divided doses for one month has
been used in most studies. Recently shorter courses (8 days or 3 days)
have also been shown to be effective.
Cutaneous larva migrans: Oral, 400 mg/day either once or for 3
consecutive days has been reported to be effective and well tolerated.
Visceral larva migrans: 5 mg/kg twice daily for 5 days has been used in
one study.
Paediatric dose: Children over 2 years of age see adult dose above.
Children 1-2 years (or less than 10 kg): 200 mg as a single dose has been
used safely and effectively in single and mixed intestinal nematode
infestation.
- 352 -

Preparations include: Zentel -tablets, 200 mg and suspension, 20 mg/mL.
Mebendazole
a benzimidazole derivative, is a useful broad spectrum anthelmintic and a
drug of choice for mixed worm infestations. Mebendazole causes selective
inhibition of glucose uptake in susceptible helminths.
Indications: Roundworm, hookworm, pinworm (threadworm), whipworm
and Strongyloides stercoralis infestations.
Contraindications: Relative - Crohn's disease, ulcerative colitis and other
ulceration of GI tract (increased absorption and possible toxicity);
impaired hepatic function.
Pregnancy: Crosses the placenta; teratogenicity has been demonstrated in
animals; should not be used during the first trimester, and only if essential
during the later trimesters. Category C.
Lactation: Not known if excreted in breast milk; no problems recorded.
Paediatrics: Some authorities recommend that it should not be given to
children under 2 years old. However, in practice it is used and the
manufacturers do not contraindicate it in this age group. One report of
serious toxicity in an 8-week, 5.1 kg infant.
Adverse effects: Uncommon with doses recommended for intestinal
worms.
Occasionally - gastrointestinal discomfort; abdominal pain, nausea and
diarrhoea are usually associated with severe infestations and upward
migration of worms. Rarely - itching, pyrexia, dizziness, drowsiness and
headache. High doses used for hydatid disease have been associated with
bone marrow depression and hepatotoxicity; allergic reactions and
alopecia may also occur.
Special Prescriber's Points
* Leucocyte counts should be done at regular intervals if used in high
doses for hydatid disease; it has been superseded by albendazole.
- 353 -

* Caution should be exercised where hepatic metabolising capacity is
impaired as high plasma mebendazole concentrations may develop with
potential drug toxicity.
* Upward migration of round worms may occur, with parasites being
expelled through the nose and mouth of heavily infested persons.
* No fasting or purging is required.
Adult dose: Oral, 100 mg twice daily for 3 days.
Pinworm (Enterobius): 100 mg as a single dose, repeated after 2 weeks, is
also effective.
Strongyloidiasis: 200 mg twice daily for 3 days.
Hookworm: 200 mg twice daily for 4 days has been used.
Tapeworm (Taenia spp.): 100 mg twice daily for 6 days. There are reports
of high success rates with higher doses for shorter periods such as 200 mg
twice daily for 4 days or 300 mg twice daily for 3 days.
* Treatment may be repeated after 2 weeks if necessary.
Hydatid disease: 40-50 mg/kg/day in divided doses (up to 200 mg/kg/day)
has been used. Treatment may be needed for 3 months or longer.
Paediatric dose: Oral, 100 mg twice daily for 3 days.
Pinworm (Enterobius): 100 mg as a single dose, repeated after 2 weeks, is
also effective.
Tapeworm (Taenia spp.): 100 mg twice daily for 6 days.
Preparations include:
Vermox-tablets, 100 mg and suspension, 100 mg/5 mL
Also: Anthex and Vermazide.

- 354 -

Tiabendazole
Another benzimidazole, is the drug of choice against strongyloidiasis,
cutaneous larva migrans and may be of some value in therapy of visceral
larva migrans.
The action of tiabendazole is uncertain but may involve interference with
the source of energy of susceptible helminths.
Indications: Strongyloidiasis, visceral and cutaneous larva migrans,
guinea-worm and porkworm (T.spiralis).
Contraindications: Absolute - history of hypersensitivity to tiabendazole.
Use with caution in hepatic and renal impairment.
Pregnancy: Teratogenicity has been reported in animals and safety in
humans has not been established; best avoided.
Lactation: No data available on excretion into breast milk; potential for
adverse effects in the nursing infant.
Paediatrics: Clinical experience in children weighing less than 15 kg is
limited.
Adverse effects: Frequent - anorexia, nausea, vomiting and dizziness.
Less frequent - pruritus, skin rashes, headache, drowsiness, tinnitus,
disturbances of vision, effects on the liver, leucopenia, crystalluria,
malodour of urine, hyperglycaemia, bradycardia, hypotension and
collapse. Erythema multiforme, including fatal Stevens-Johnson
syndrome, toxic epidermal necrolysis, convulsions and effects on mental
state have also been recorded. Fever, chills, angioedema and
lymphadenopathy have occurred, but may represent allergic response to
dead parasites rather than to the drug.
Special Prescriber's Points
* Therapy should be discontinued at the first sign of hypersensitivity.
- 355 -

* As drowsiness may occur, patients should be warned not to drive or
operate machinery.
* Despite the frequent and unpleasant side-effects it remains the treatment
of choice for strongyloidiasis.
* Not suitable for mixed infestation with Ascaris as it may cause these
worms to migrate.
* Tablets should be taken after meals and chewed before swallowing.
Adult dose: Oral, 25 mg/kg twice daily (maximum 3 g/day).
Strongyloidiasis: The above dose is given for 2 successive days, and for at
least 5 days if the infestation is disseminated.
Cutaneous larva migrans: Two consecutive days of treatment are
recommended; may be repeated 2 days later if active lesions are still
present.
Topical application (approximately 17%) four times daily has been
reported to successfully eliminate the larvae in about a week.
Visceral larva migrans: 25 mg/kg may be given twice daily for 7 days.
Guineaworm: 25 mg/kg twice daily for 2-3 days.
Paediatric dose: Children and adolescents weighing more than 15 kg as for
adults above.
Preparations include:
Mintezol-tablets, 500 mg
Piperazine and derivatives
Piperazine
It is used in ascariasis and enterobiasis; it is relatively
inexpensive.Piperazine causes paralysis of roundworms by blocking the
- 356 -

action of acetylcholine at the neuromuscular junction. Its mechanism in
enterobiasis is not clear.
Indications: Roundworm and pinworm (threadworm) infestations.
Contraindications: Absolute - patients with a history of epilepsy or other
neurological disorders, severe malnutrition or anaemia.
Relative - impaired renal or hepatic function.
Pregnancy: After a long history of use without reported adverse effect,
there have been two recent reports of fetal abnormalities. Avoid use during
the first trimester and preferably delay treatment until after parturition.
Lactation: Excreted in breast milk; use with caution if essential during
lactation. Manufacturers advise that the infant be fed immediately before
maternal dosing, then milk expressed and discarded during the next 8
hours.
Paediatrics: Has been widely used in children of all ages. Manufacturers'
recommended dosages are from 9 months old.
Adverse effects: These are generally rare and dose-related. Mild nausea
and abdominal pain may develop. Neurotoxicity with vertigo, ataxia,
nystagmus and hyporeflexia are seen mostly in children and in patients
with neurological or renal disease. Hypersensitivity reactions have been
reported.
Special Prescriber's Points
* Roundworm infestation: If constipation is a problem, an effective
purgative should be taken on the morning after the dose of piperazine to
expel the worms before the effect of the drug wears off.
* Efficacy is improved by giving a second dose 24 hours after the first.
* Piperazine citrate 125 mg is equivalent to 100 mg piperazine hydrate.
Adult dose: Doses are for piperazine hydrate.
Roundworm: Oral, 4 g as a single dose with the evening meal.
- 357 -

Pinworm (threadworm): Oral, 2 g daily for 7 days.
Paediatric dose: Roundworm: Oral, 120 mg/kg (maximum 4 g ) as a single
dose.
Pinworm: Oral, over 12 years, 2 g daily in 2-3 divided doses; 6-12 years,
1.5 g daily; 1-5 years, 250 mg/day per year of age. Treatment should be
continued for 7 days. A second course after a 1-week interval may be
required.
Preparations include:
Pipralen - syrup, piperazine hydrate 750 mg/5 mL (as citrate)
Also: Ascarient , Pip-A-Ray , Wormelix , Padax, and Piprine tabs
Diethylcarbamazine
a piperazine derivative, is mainly indicated for the treatment of filariasis
due to W.bancrofti, B.malayi and L.loa.
Indications: Filariasis due to W.bancrofti, B.malayi, L.loa; visceral larva
migrans.
Contraindications: Relative - impaired renal function, hypertension,
tuberculosis or malnutrition; onchocerciasis.
Pregnancy: Treatment is best deferred until after delivery.
Paediatrics: No adequate, well-controlled studies done; no specific
problems documented.
Adverse effects: Minor effects include headache, weakness and anorexia.
Sleepiness, nausea and vomiting sometimes occur. Prolonged use may
lead to ocular damage.
* Allergic responses to killed organisms vary with the infecting species:
W.bancrofti and B.malayi: Headache, fever, skin rashes, weakness,
arthralgia, malaise and gastrointestinal symptoms and precipitation of
asthma.
- 358 -

Loiasis: Risk of encephalitis. Onchocerciasis: Potentially fatal `Mazotti'
reaction, generally occurring within 24 hours after beginning therapy and
usually subsiding after 3-7 days, with intense skin reactions, tachycardia,
hypotension and fever. Lymph glands draining affected areas may become
painful and enlarged.
Special Prescriber's Points
* Ivermectin is preferred in onchocerciasis.
* To diminish adverse reactions due to the destruction of microfilariae,
particularly those of L.loa, it is advisable to use a small initial dose.
Corticosteroids may be needed in cases of severe reaction. Close medical
supervision is necessary, particularly in loiasis where in rare instances
there may be severe cerebral reactions.
* Swelling and itching of the eyes, or any other sign of an allergic reaction
should be reported to the prescriber.
* Ocular damage may require corticosteroid therapy.
* Dosage should be adjusted in impaired renal function.
Adult dose: W.bancrofti, B.malayi and L.loa (recommended regimen):
Day 1, single dose of 50 mg; Day 2, 50 mg for 3 doses; Day 3, 100 mg for
3 doses ; thereafter 2 mg/kg 3 times daily for total 21 days. In loiasis,
some authorities recommend 3 mg/kg 3 times daily from day 4 to day 21
in all age groups.
Visceral larva migrans (Toxocara): Initially 1 mg/kg 3 times daily,
increased if well tolerated to 2-3 mg/kg three times daily for 21 days.
Paediatric dose: W.bancrofti, L.loa and B.malayi: Day 1, 25-50 mg; Day 2,
25-50 mg 3 times; Day 3, 50-100 mg 3 times; from Day 4 through to Day
21, 2 mg/kg 3 times daily.
Visceral larva migrans: Day 1, 1 mg/kg; Day 2, 1 mg/kg 3 times daily;
Day 3, 2 mg/kg 3 times daily; then 3 mg/kg 3 times daily for 21 days.
Preparations include:
- 359 -

Hetrazan-tablets, 50 mg
Tetrahydropyrimidine derivatives
Pyrantel
It may be used in the treatment of round-, thread- and hookworm
infestations; it is not effective against whipworm. Pyrantel produces
depolarising neuromuscular blockade in the helminths that leads to spastic
paralysis. The paralysed worms are dislodged and expelled by peristaltic
activity.
Indications: Roundworm, pinworm (threadworm) and hookworm
infestations.
Contraindications: Relative - impaired liver function, severe anaemia or
malnutrition.
Pregnancy: Teratogenicity has not been shown in animals, but safety to the
human fetus has not been established; use not recommended unless
essential.
Lactation: Poor absorption and low maternal serum concentrations mean
that significant amounts are unlikely to appear in breast milk; use with
caution.
Paediatrics: No adequate, well-controlled studies done in children under 2
years old; however some authorities indicate that paediatric doses are for
children over 6 months.
Adverse effects: Usually mild and transient - nausea and vomiting,
anorexia, abdominal pain, diarrhoea, headache, dizziness and skin rash.
Occasionally - a transient elevation of serum transaminases.
Special Prescriber's Points
* Use of a purgative is not necessary.
* May be taken with milk or other fluid.
- 360 -

Adult dose: Oral, 10 mg/kg as a single dose (maximum 1 g).
Hookworm: 10 mg/kg once daily for 3 days for more severe infestations of
N.americanus.
Paediatric dose: 10 mg/kg as a single dose.
Preparations include:
Combantrin -suspension, 50 mg/mL (as pamoate) and ablets, 125 mg
Anticestode
Agents used: Niclosamide and praziquantel are effective against T.solium
and T.saginata (affecting the adult worms in the intestine). Albendazole
and mebendazole are alternatives. The theoretical risk of developing
cysticercosis from treating T.solium worms with niclosamide should not
be a clinical problem, provided dosage instructions are followed.
Niclosamide and praziquantel are effective against D.latum (fish
tapeworm) and H.nana (dwarf tapeworm). Praziquantel is used in the
treatment of cerebral cysticercosis, but is not recommended in ocular
cysticercosis. In parenchymal brain cysticercosis, albendazole is as
effective as (and in some recent studies reported to be more effective than)
praziquantel. In hydatid disease, while surgery remains standard
management, albendazole is the most effective chemotherapeutic agent
available for inoperable cases, and pre- and post-operatively to reduce the
risk of metastatic spread. It has greater systemic bioavailability and has
superseded mebendazole in this area.
Niclosamide
Niclosamide inhibits metabolic processes in helminths, resulting in the
death of scolices and proximal proglottids (but not of the ova). Scolices
are detached from the intestinal wall and the worms may be partly
digested before they are excreted.
Indications: Eradication of beef (T.saginata), pork (T.solium), dwarf
(H.nana), and fish (D.latum) tapeworm.
Contraindications: No absolute contraindications.
- 361 -

Pregnancy: Poorly absorbed; adverse effects on the fetus are unlikely but
it is recommended that treatment be deferred until after delivery, or until
the second or third trimester, if therapy is essential. Category B.
Lactation: Since little is absorbed, significant amounts are unlikely to
appear in breast milk.
Paediatrics: No adequate, well-controlled studies done in children under 2
years of age; has been used for all ages.
Adverse effects: Occasional - gastrointestinal disturbances,
lightheadedness, pruritus ani.
Rare - urticaria and skin rashes, possibly due to absorption of disintegrated
parasite material.
Special Prescriber's Points
* Patients with chronic constipation should receive a purgative the night
before treatment.
* An antiemetic may be given on wakening as a precaution against the
possible development of cysticercosis.
* Given as a single dose, after a light breakfast.
* Tablets must be chewed thoroughly or crushed finely and swallowed
with a small amount of water.
* For T.solium, an effective purge (e.g. magnesium sulphate) should be
given 2 hours afterwards to eliminate all mature segments before the
viable ova can be released into the gut.
* It is recommended that no alcohol be taken during treatment.
Adult dose: Beef, pork and fish tapeworm: 2 g as a single dose.
H.nana: 2 g on the first day followed by 1 g for the following 6 days.
Paediatric dose: Children over 6 years, as adult dose; 2-6 years, half the
adult dose; under 2 years, one-quarter the adult dose.
- 362 -

Preparations include: Yomesan-tablets, 500 mg
Antimalariae drugs
Chloroquine and Hydroxychloroquine sulfate
An antimalarial drug that was first used in the 1940s, until the first
evidence of quinine resistance appeared in the 1960s. It is now ineffective
against falciparum malaria almost everywhere. However, because it is
inexpensive, it is still the antimalarial drug most widely used in Africa.
Native individuals with partial immunity may have better results with
chloroquine than a traveler with no previous exposure.Reported side
effects include gastrointestinal disturbance, headache, dizziness, blurred
vision, insomnia, and pruritus, but generally these effects do not require
that the drug be discontinued. High doses of chloroquine, such as those
used to treat rheumatoid arthritis, have been associated with retinopathy;
this serious side effect appears to be extremely unlikely when chloroquine
is used for routine weekly malaria prophylaxis. Chloroquine and related
compounds have been reported to exacerbate psoriasis.

Quinine
One of the first treatments for malaria, quinine is a natural product made
from the bark of the Cinchona tree. It was popular until being superseded
by the development of chloroquine in the 1940s. In the wake of
widespread chloroquine resistance, however, it has become popular again.
Quinine, or its close relative quinidine, can be given intravenously to treat
severe malaria.
Doxycycline
Doxycycline can cause photosensitivity, usually manifested as an
exaggerated sunburn reaction. The risk of such a reaction can be
minimized by avoiding prolonged, direct exposure to the sun and by using
sunscreens that absorb long-wave UVA radiation. In addition, doxycycline
use is associated with an increased frequency of Candida vaginitis.
Gastrointestinal side effects (nausea or vomiting) may be minimized by
taking the drug with a meal. To reduce the risk of esophagitis, travelers
should be advised not to take doxycycline before going to bed.
Doxycycline is contraindicated in persons with an allergy to tetracyclines,
during pregnancy, and in infants and children <8 years of age. Vaccination
- 363 -

with the oral typhoid vaccine Ty21a should be delayed for >24 hours after
taking a dose of doxycycline.
Mefloquine
An antimalarial drug that was developed by the United States Army in the
early 1980s. Today, malaria resistance to this drug has become a problem
in some parts of Asia (especially Thailand and Cambodia).
Mefloquine (Lariam) has been associated with rare serious adverse
reactions (e.g., psychoses or seizures) at prophylactic doses; these
reactions are more frequent with the higher doses used for treatment.
Other side effects that have occurred in chemoprophylaxis studies include
gastrointestinal disturbance, headache, insomnia, abnormal dreams, visual
disturbances, depression, anxiety disorder, and dizziness. Other more
severe neuropsychiatric disorders occasionally reported during post-
marketing surveillance include sensory and motor neuropathies (including
paresthesia, tremor, and ataxia), agitation or restlessness, mood changes,
panic attacks, forgetfulness, confusion, hallucinations, aggression,
paranoia, and encephalopathy. On occasions, psychiatric symptoms have
been reported to continue long after mefloquine has been stopped. During
prophylactic use, if psychiatric symptoms such as acute anxiety,
depression, restlessness, or confusion occur, these may be considered
prodromal to a more serious event. In these cases, the drug must be
discontinued and an alternative drug substituted. Mefloquine is
contraindicated for use by travelers with a known hypersensitivity to
mefloquine or related compounds (e.g., quinine and quinidine) and in
persons with active depression, a recent history of depression, generalized
anxiety disorder, psychosis, schizophrenia, other major psychiatric
disorders, or seizures. It should be used with caution in persons with
psychiatric disturbances or a previous history of depression. A review of
available data suggests that mefloquine may be used in persons
concurrently on beta blockers, if they have no underlying arrhythmia.
However, mefloquine is not recommended for persons with cardiac
conduction abnormalities.


- 364 -

Primaquine
The most common adverse event in G6PD-normal persons is
gastrointestinal upset if primaquine is taken on an empty stomachthis
problem is minimized or eliminated if primaquine is taken with food.
Primaquine can cause hemolysis that can be fatal, in G6PD-deficient
persons.
Sulfadoxone/pyrimethamine (Fansidar)
An antimalarial drug developed in the 1960s. It is the first drug tried in
some parts of the world where chloroquine resistance is widespread. It has
been associated with severe allergic reactions due to its sulfa component
Arteminisinins
A family of antimalarial products derived from an ancient Chinese herbal
remedy. Two of the most popular varieties are artemether and artesunate,
used mainly in southeast Asia in combination with mefloquine.











- 365 -

CHAPTER SEVENTEEN (17)
Summary of the common symptoms and signs of the commonest
human parasitic disease
Abdominal pain:
-Amebic colitis
-Giardiasis
-Ascariasis
-Strongyloidiasis
-Anisakiasis
-Angiostronyliasis
Note: pain is seldom present in intestinal worms except in ascaris
infection accompanied with intestinal or biliary obstruction.
Anemia
-Malaria
-hookworm
-Diphyllobothriasis
-Babesiosis
-Kala-azar
-Trypanosomiasis
-Schistosomiasis
-Fasciolopiasis
-Trichuriasis
- 366 -

Appendicitis
-Amebic ulceration (cecal area)
-Ascariasis
-Trichuriasis
-Angiostronyliasis
Ascites
-Schistosomiasis (mansoni/japonicum)
-Kala azar (may occur in late stage due to malnutrition)
Asthmatic attacks
-Ascariasis and most worms have a stage of pulmonary migration
-Toxocariasis (visceral larva migrans infection)
-House dust mite (Dermatophagoides)
Calabar swelling
-Loiasis
Cerebral calcification
-Toxoplasmosis (congenital)
-Cysticercosis
Chagoma
-Trypanosoma cruzi (chagas disease)
Chyluria
-Filariasis (lymphatic)
- 367 -

Coma
-Malaria (cerebral malaria)
-African trypanosomiasis
-Primary amebic meningoencephalitis
-Cysticercosis (cerebral)
Conjunctivitis
-Onchocerciasis
-Oestrus ovis (sheep botfly may lay its eggs and develop into larvae in
conjunctiva)
-Thelazia (larvae deposited in conjunctival sac by flies)
Convulsions
- Any parasite infect central nervous system
-Malaria paroxysm (common in children)
-Congenital toxoplasmosis
-Ascariasis (in children)
Cutaneous ulcers
-Leishmaniasis
-African trypanosomiasis
- Amebiasis
- Dracunculiasis
Dermatitis
- 368 -

-Leishmania donovani
-Schistosomiasis
-Strogyloidiasis
-Cutaneous lavae migrans
-Loiasis
-Dracunculiasis
-Onchocerciasis
Diarrhea
- Kala azar
- Malaria (falciparum)
-Amebiasis
-Balantidiasis
-Isosporiasis
-Cryptosporidiasis
-Microsporidiasis (Enterocytozoon bieneusi)
-Giardiasis
-Hymenolepiasis (H.nana)
-Trichinellosis
-Strongyloidiasis
-Capillariasis (C. philippinensis)
-Schistosomiasis (mansoni/ japonicum)
- 369 -

-Hookworms (heavy infection)
-Fasciolopiasis
-Taenia (sometimes)
Dysentry( passage six to eigth of blood flecked stools a day)
-Amebiasis
- Balantidiasis
-Kala azar
-Malaria (falciparum)
-Stronyloidiasis
-Schistosomiasis
Edema
-Trichinosis (circumorbital/hands)
-Loaiasis (circumorbital)
- Sparganosis (ocular)
-A.trypanosomiasis (chagas disease)
-A. sleeping sickness
-Hookworm (sever infection)
-Fasciolopsiasis
-Diphylolobothriasis
Elephantiasis
-Filariasis
- 370 -

-Onchocerciasis
-Schistosomiasis (haematobium)
Eosinophilia
It must be realized that eosinphilia is an index of host reaction to the
parasite, and it varies considerably from one patient to another.
Eosinophilia is a consistent finding in helminth infections, though it may
be quite variable in degree. In general , tissue parasites provoke more
pronounced eosinophilia than those that live only in the lumen of the
bowel. Eosinophilia is not characteristic of any of the protozoan infection.
Marked eosinophilia (20 to 70 %) frequently seen in
-Trichinosis
-Strongyloidiasis
-Hookworm
-Visceral .L. Migrans (VLM)
-Cutaneous .L. Migrans
-Schistosomiasis
- Fasciolopiasis
Moderate eosinophilia (6 to 20 %)
- Trichuriasis
- Ascariasis
- Paragonmiasis
- Taeniasis
- Eosinophilic meningitis
- 371 -

-Loiasis
-Mansonllosis (M. perstans)
-Trichuriasis
-Onchocerciasis
Eosinophilic meningitis
- Angiostrongylus cantonensis (main cause; synonym Parastrongylus
cantonensis)
- Gnatostoma spinigerum
- Toxocara canis and T. catis : visceral larva migrans
- Baylisascaris procyonis (normal host is the raccoon, Procyon lotor) and
Baylisascaris transfuga (round-worm of the bear)
- Taenia solium, though in the majority of neurocysticercoses the
cerebrospinal fluid is normal F
- Fasciola hepatica and Paragonimus sp. (ectopic localisations)
- Filaria: Loa loa (specially severe reactions after DEC treatment),
Meningonema peruzzi (monkey parasite)
-Strongyloides stercoralis in hyperinfection syndrome (beware steroids)
-Trichinella spiralis (massive infection)
- Non-infectious origins (lymphoma, medications, ventriculoperitoneal
shunts)
-Schistosomiasis
Epididymitis
-Bancroftian filariasis
- 372 -

Fever
-Malaria
-Kala -azar
-Amebic hepatitis
-Fascioliasis
-Clonorchiasis (acute)
-Schistosomiasis
-African trypanosomiasis.
-American trypanosomiasis.
-Filariasis
Funiculitis
-Bancroftian filariasis
Hematuria
-Schistosomiasis (haematobium)
Hemoglobinuria
-Malaria (P. falciparum)
Hepatitis
-Amebiasis
Hepatomegaly
-Amebic liver abscess
-Visceral larvae migrans
- 373 -

-Liver fluke infection
-Schistosomiasis (mansoni/japonicum -early)
-Malaria (in early -P.falciparum )
-Toxoplasmosis (congenital)
-Hydatid infection
Hives
-Ascariasis
-Schistosomiasis
Hydatid thrill
-Large unilocular echinococcus
Hydrocele
-Filariasis
Hydrocephalus
-Toxoplasmosis (congenital)
-Intraventricular cysticerci
Hyperpigmentation
-Kala-azar
-Onchocerciasis
-Pediculosis (vagabonds disease)
Jaundice
-Sever liver fluke infections (obstructive)
- 374 -

-Malaria (P. falciparum)
Kerandels sign
-African trypanosomiasis
Keratitis
-Onchocerciasis
-Acanthamoebiasis
Leukocytosis
-Amebic liver abscess
-Visceral larvae migrans
-Trichinosis
-Strogyloidiasis
-Malaria
Note: leukocytosis early in the course of infection, followed by leucopenia
with a relative monocytosis, is common to many protozoan and helminth
infections.
Leukopenia (WBC < 4000 per mm
3
)
-Kala-azar
-Malaria
Lymphadenitis
-Filariasis
-Toxoplasmosis
-African trypanosomiasis
- 375 -

-American trypanosomiasis
Lymphangitis
-Filariasis (lymphatic)
Lymphocytosis
-American trypanosomiasis (chagas disease)
Lymph varices
-Filariasis
Melena
-Strogylodiasis
Meningoencephalitis
-African trypanosomiasis
-Malaria
-Primary amebic meningoencephalitis (Naegleria)
-Chronic granulomatous meningoencephalitis (Acanthamoeba)
-Eosinophilic meningoencephalitis (Angiostrongylus cantonesis)
Myocarditis
-American trypanosomiasis (chagas disease)
-African trypanosomiasis (sleeping sickness)
-Toxoplasmosis (acute)
-Trichinosis
Myositis (see Tropical myositis below)
- 376 -

-Trichinosis
- Sarcocystis
Tropical pyomyositis (tropical myositis):
Definition
The term tropical pyomyositis should be restricted to primary muscle
abscesses arising within skeletal muscles. This condition must be
distinguished from abscesses extending into muscle either from
subcutaneous sites following infection through the skin, or from
osteomyelitis or suppuration originating in tissues other than muscle.
Epidemiology
Tropical myositis has been reported from most parts of tropical Africa,
Malaysia, Thailand, Indonesia, Oceania, Central and South America, and
the Caribbean. It is common in many tropical countries, accounting for 4
per cent of admissions to a hospital in Uganda and for 2.2 per cent of all
surgical admissions to a hospital in eastern Ecuador. In temperate
climates, pyomyositis is extremely rare, but a few cases have been
described, including some with immunosuppression resulting from HIV
infection, asplenia, and Felty's syndrome.
Etiology
Staphylococcus aureus is the organism most commonly cultured from the
abscesses. Streptococcus pyogenes (usually group A) is responsible for a
few cases, but tropical pyomyositis must be distinguished from
streptococcal necrotizing myositis (also known as peracute streptococcal
pyomyositis or spontaneous streptococcal gangrenous myositis) which is
more fulminant and diffuse and has a very high mortality . Other isolates
have included S. pneumoniae, Haemophilus influenzae, E. coli, and
Pseudomonas species. The strikingly different incidence of pyomyositis in
tropical and temperate countries has not been explained. In Africa and
South America, the condition appears to be relatively more common in
indigenous peoples. A history of preceding trauma to the affected muscle
is obtained from more than 20 per cent of patients in most series. It has
been suggested that, by analogy with osteomyelitis, a muscle haematoma
provides a nidus for blood-borne infection. A number of predisposing
- 377 -

causes has been suggested: preceding viral infection (for example an
arbovirus), general debilitation, and nematode infectionsparticularly
toxocariasis, Lagochilascaris minor, and filariasis. None has been
supported by convincing evidence, but sickle-cell disease may be a
genuine predisposing cause in a minority of cases. Most of the abscesses
associated with helminth infections should not be termed pyomyositis as
they are inter- rather than intramuscular. For example, Dracunculus
medinensis can give rise to deep intermuscular abscesses secondarily
infected with Staphylococcus aureus.
Pathology

The abscesses may be large, are usually loculated, and are situated within
skeletal muscles beneath the deep fascia. Histologically, there is focal
muscle necrosis with an infiltration of mononuclear cells and
inflammatory oedema.
Clinical features
Tropical pyomyositis can occur at any age but its highest incidence is in
the second decade. It is more common in males. The earliest symptom is
pain and tenderness of the affected muscle. Any of the skeletal muscles
may be involved, but those of the trunk and lower limbs are the most
commonly affected. Usually there is a single localized abscess, but
multiple abscesses in distantly separated muscles can occur. At an early
stage, an ill-defined tender and thickened area may be palpable in the
muscle. Later, a localized, very tender, and hot swelling is palpable. There
may be redness and oedema of the overlying skin, but the skin is not
primarily involved. The swelling is usually non-fluctuant and there is no
local lymphadenopathy. Symptoms and signs usually develop over a few
days. Peripheral leucocytosis is not invariable. Eosinophilia is frequently
described but is usually common in the populations most affected by
tropical pyomyositis. In spite of considerable muscle destruction at the site
of the abscess, serum concentrations of muscle enzymes may not be
elevated, but in some cases there is myoglobinaemia, myoglobinuria, and
acute renal failure. Complications are uncommon and consist of spread of
infection from the affected muscle to other structures such as joints,
resulting in septic arthritis; to the pleural cavity, resulting in empyema; or
by haematogenous spread to the heart valves. Mortality of hospitalized
cases is said to be less than 1.5 per cent.
- 378 -

Laboratory diagnosis
The differential diagnosis is from pus tracking from abscesses in other
organs and tissues, muscle haematomas, torn muscles, certain highly
vascular or necrotic tumours of connective tissue or muscle (such as
rhabdomyosarcoma), and the inflammatory and allergic swellings
resulting from the migration of helminths such as Loa loa, Gnathostoma,
Paragonimus, and sparganum. Staphylococcus aureus is usually cultured
from the pus, but blood cultures are positive in less than 5 per cent of
cases. Ultrasound and CT scans are useful for localizing abscesses and
guiding needles for diagnostic and therapeutic aspiration.
Treatment
Full surgical exploration, debridement, and drainage is essential. Because
the abscesses are usually loculated, needle aspiration is inadequate.
Parenteral treatment with a &bgr;-lactamase resistant penicillin
(flucloxacillin) should be started immediately, but if group A
Streptococcus is cultured, benzyl penicillin is the drug of choice.


Neurologic Symptoms
-A. trypanosomiasis
-Malaria
-Schistosomiasis
-Trichinosis
-Hydatid cyst
- 379 -

-Coenurus cyst
-Cysticercus cyst
-Sparganum proliferum
-Paragonimus westermani
-Amebiasis
Subcutaneous nodules
-Onchocerciasis (onchocercoma)
- Cysticercus
- Coenurus
-Spargana
- Dermatobia hominis
Intestinal obstruction
-Ascaris
-Angiostrongylus costaricensis
Orchitis
-Filariasis
Pain
Abdominal Pain
- Giardiasis
- Cryptosporidiosis
-Trchinosis
- 380 -

-Strongyloidiasis
-Amebiasis
-Ascariasis
B-Muscle pain
- Trichinosis
- A.trypanosomiasis
Peritonitis
-Ascariasis
Pica
-Hookworm disease
-Ascariasis
Pneumonitis
-Ascariasis
- Strongyloidosis
-Schistosomiasis
-Pneumocystis carinii
-Amebic abscess
-Toxoplasmosis
Proteinuria
-Malaria
Pruritic Ani
- 381 -

-Enterobiasis
-Taeniasis (saginata)
Pulmonary chronic symptoms
-Schistosomiasis
-Paragonmiasis
-Pulmonary echinococcosis
Pulmonary eosinophilic syndrome
-Stronyloidiasis
-Ascariasis
-Hookworm
-Tropical eosinophilia
Tropical lung diseases;Each year, millions of travelers visit tropical
countries and many spend time in the areas where they are at risk for
infectious diseases. Today it is essential for the practicing physician to be
aware of the common tropical lung diseases. In particular, when
evaluating pulmonary infections in a returned traveler, a thorough
understanding of common organisms, their epidemiology, and their modes
of presentation is required. Although tuberculosis and malaria are the most
common infectious diseases prevalent in tropics, this review of the
common tropical pulmonary disorders is necessarily selective, primarily
focusing on parasitic diseases (including protozoa; worms such as
nematodes, cestodes, trematodes, and pentastomes) affecting the lung
(Table-1-).

Parasites Causing Lung Diseases in Humans
Nematodes (roundworms)
- 382 -

Lffler's syndrome Ascaris lumbricoides
Ancylostoma braziliense (cutaneous larva
migrans)
Ancylostoma duodenale (hookworm)
Necator americanus (hookworm)
Strongyloides stercoralis
Trichinella spiralis
Toxocara canis, Toxocara cati (visceral
larva migrans)
Chronic cough Capillaria spp
Gnathostoma spinigerum
Tropical eosinophilia Wuchereria bancrofti (lymphatic filariasis)
Brugia malayi
Solitary nodule on radiograph Dirofilaria immitis (dog heartworm)
Cestodes (tapeworms)
Tapeworm Echinococcus granulosus (hydatid
disease)
Lung mass Echinococcus multilocularis
Calcification of intercostal
muscle
Cysticercus cellulosae
Trematodes (flatworm)
Pleural effusion Paragonimus westermani
Pulmonary infiltrates Schistosoma mansoni
Pulmonary hypertension Schistosoma haematobium
Clonorchis sinensis Lffler-like syndrome
Fasciola hepatica
Arthropod
Linguatula serrata Pentastomiasis
Armillifer armillatus
Protozoa
Pleural effusion Entamoeba histolytica
- 383 -

Respiratory failure Plasmodium falciparum
Pulmonary infiltrate Toxoplasma gondii
Note: The term "tropics" refers to the region of the earth lying between
the Tropic of Cancer and the Tropic of Capricorn. The warm climate and
general socioeconomic status in tropical countries provide an ideal
environment for pathogenic organisms, their vectors, and intermediate
hosts to flourish.
Rash
-Schistosomiasis
-Ascariasis
-Toxoplasmosis
- African trypanosomiasis
Retinochoroiditis
-Toxoplasmosis
-Amebiasis (E.histolytica)
-Onchocerciasis
-Toxocariasis
-Angiostrongyliasis
Romana
,
s sign
-American trypanosomiasis
Shock
-Malaria
- 384 -

- Echinococcus cyst
Splenomegaly
-African trypanosomiasis
- American trypanosomiasis
- Visceral leishmaniais (Kala azar)
- Malaria
- Schistosomiasis
Splinter hemorrhages
-Trichinosis
Steatorrhea
- Giardiasis
- Strongyloidiasis
-Capillariasis
- Cryptosporidiosis
- Isosporiasis
Tachycardia
-American trypanosoimiasis
Urethritis
-Trichomoniasis
Vaginitis
-Trichomoniasis
- 385 -

- Enterobiasis
Visual difficulties
-Toxocariasis
-Ascariasis
- Angylostronyliasis
- Onchocerciasis
- Cysticercosis
- Coenurus
- Ophtalmomyiasis
Winterbottom
,
s sign
-African trypanosomiasis
Parasitic disease with X-ray evidences
-Amebiasis
- Giardiasis
- Pneumocystosis
- Dracunculiasis
- Filariasis
- Loiasis
- Ascariasis: Pneumonitis
- Stronyloidiasis Pneumonitis
- Hookworm Pneumonitis
- 386 -

- Cysticercosis
- Echinococcosis
- Paragonimiasis
- Schistosomiasis
- Pentastomiasis
















- 387 -

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- 395 -

Index

Acanthamebiasis
Etiology , 50
Morphology, 50
Epidemiology, 51
Transmission/Life cycle, 51
Clinical features/Pathology, 52
Granulomatous amoebic encephalitis
(GAE), 52
Lab diagnosis, 52
Treatment, 53
African trypanosomiasis (Sleeping
sickness), 67
Nagana, 67
Etiology, 67
Morphology, 67
Epidemiology, 68
Transmission, 68
Life cycle, 69
Clinical features, 70
Chancre, 71
Haemolymphatic stage, 71
Winterbottom sign, 71
CNS stage, 72
Kerandle sign, 72
Pathology/immunology, 72
Variant surface antigens, 68-73
Lab diagnosis, 73
Lymph gland puncture, 73
Treatment, 75
Prevention/control, 76
American trypanosomiasis (Chagas
disease), 75
Etiology, 76
Morphology, 76
Epidemiology, 76
Transmission, 77
Life cycle, 77
Clinical features, 78
Chagoma, 79
Romanas sign, 79
Acute stage, 79
Chronic stage, 80
Organomegaly, 80
Pathology/immunology, 81
Lab diagnosis, 81
Xenodiagnosis, 82
Treatment, 82
Prevention/control, 82
Amoeba, 21
Pathogenic amoeba, 21
Intestinal non- pathogenic amoeba
(commensals), 38
Amoebiasis (Entamoeba histolytica),
21
Etiolog, 21
Morphology, 22
Epidemiology, 23
Transmission/Life cycle, 24
Clinical feature, 26
Symptoms, 26
Signs, 28
Amoebic colitis, 26-28
Ameboma, 26-31
Amoebic liver abscess (ALA), 26-28
Amoebic peritonitis, 27
Amoebic pericarditis, 28
Cerebral amoebiasis, 28
Pleuropulmonary amoebiasis, 28
Genital ulcer, 29
Amoebic ulceration, 29
Bacillary dysentery :Differential
diagnosis, 29
Pathology, 30
Flask shaped ulcer, 30
Mechanism of pathogenesis, 32
Amebic complications, 33
Lab diagnosis, 34
Imaging studies, 35
Procedures, 36
Treatment, 37
Prevention/Control, 37
Prognosis, 38
Amoeba (Free living), 47
Anasakiasis, 336
Etiology, 336
Morphology, 335
Epidemiology, 336
Transmission/Life cycle, 336
Clinical features/Pathology, 338
Lab diagnosis, 338
Treatment, 338
Ancylostomiasis/Necatoriasis, 312
Etiology, 312
Morphology, 312
- 396 -

Epidemiology, 313
Transmission/Life cycle, 313
Clinical features/Pathology, 315
Lab diagnosis, 316
Treatment / Control, 317
Angiostrongyliasis, 284
Etiology, 284
Morphology, 285
Epidemiology, 285
Transmission and Life cycle, 285
Clinical features / Pathology, 286
Lab diagnosis, 287
Treatment, 288
Prevetion / Control, 288
Annelides(segmented worms), 341
Leeches, 341
Aquatic leeches, 342
Terrestial leeches, 342
Antiparasites, 346
Antitrematode, 346
Praziquantel, 346
Oxamniquine347
Metrofonate, 349
Antinematodes, 349
Albendazole, 350
Mebendazole, 352
Thiabendazole, 354
Piperazine, 355
Diethylcarbamazine, 357
Pyrantel, 358
Anticestode, 360
Niclosamide, 360
Antimalaria drugs, 362
Chloroquine, 362
Quinine, 362
Doxycycline, 362
Mefloquine, 363
Primaquine, 364
Sulfadoxone&Pyrimimethamine, 364
Arteminisinins, 364
Apseudoparasite, 44
Ascariasis, 306
Etiology, 306
Morphology, 306
Epidemiology, 306
Transmission /Life cycle, 307
Clinical features/Pathology, 308
Pica, 309-316
Lab diagnosis, 309
Fertilized egg, 309
Decorticated egg, 310
Unfertilized egg, 310
Treatment / Prevention, 310
Autoinfection, 11
Babesiosis, 133
Etiology, 133
Morphology, 133
Epidemiology, 134
Transmission, 134
Life cycle, 134
Clinical features/pathology, 135
Lab diagnosis, 136
Treatment/control, 136
Balamuthia, 50-51
Balantidiasis, 96
Etiology, 97
Morphology, 97
Epidemiology, 97
Transmission/Life cycle, 97
Clinical feature/Pathology, 98
Lab diagnosis, 99
Treatment, 99
Blastocystis hominis, 44
Etiology, 44
Morphology, 44
Epidemiology, 45
Transmission/ Life cycle, 45
Clinical features, 46
Lab diagnosis, 46
Treatment, 47
Blood Protozoa, 67
Brugia malayi, 251
Morphology, 251
Epidemiology, 251
Transmission /Life cycle, 252
Clinical features, 253
Pathology, 253
Lab diagnosis, 254
Treatment, 254
Brugia timori, 254
Morphology, 254
Epidemiology, 255
Transmission /Life cycle, 255
Clinical features/Pathology, 255
Lab diagnosis, 255
Treatment, 255
Capillariasis, 325
Etiology, 325
Morphology, 326
Epidemiology, 326
- 397 -

Transmission /Life cycle, 326
C.hepatica, 327
C. aerophila, 327
Clinical features/Pathology, 227
Lab diagnosis, 327
Treatment, 328
Cerebral malaria, 111
Cercarial dermatitis, 182
Etiology, 182
Morphology, 183
Epidemiology, 183
Life cycle, 183
Clinical features /Pathology, 184
Lab diagnosis, 184
Treatment, 185
Cestods(Tapeworms), 205
Introduction, 205
General life cycle, 206
Cestodes summary, 242
Ciliates, 96
Clonorchiasis, 185
Etiology, 185
Morphology, 185
Epidemiology, 185
Transmission/Life cycle, 185
Clinical features/Pathology, 187
Lab diagnosis, 187
Treatment, 187
Coenuriasis, 225
Etiology, 225
Coenurus cyst, 225
Morphology, 225
Epidemiology, 225
Mode of infection, 226
Clinical features/Pathology, 226
Coenurus disease, 226
Gid, 227
Lab diagnosis, 227
Treatment/Prevention, 227
Covert toxocariasis, 296
Commensalism, 9
Cryptsporidiosis, 137
Etiology, 137
Morphology, 137
Epidemiology, 137
Transmission/Life cycle, 138
Clinical features/pathology, 139
Lab diagnosis, 140
Treatment, 140
Cutaneous larva migrans(Creeping
eruption), 299
Etiology, 299
Epidemiology, 299
Life cycle, 299
Clinical features, 300
Pathophysiology, 300
Lab diagnosis, 300
Procedures, 301
Treatment, 301
Cyclosporiasis, 143
Etiology, 143
Morphology, 143
Epidemiology, 143
Transmission/Life cycle, 144
Clinical features/pathology, 145
Lab diagnosis, 145
Treatment, 145
Cysticercosis, 212
Etiology, 212
Morphology, 212
Epidemiology, 213
Transmission /Life cycle, 213
Autoinfection, 213
Clinical features/Pathology, 214
Racemose cyst, 214
Lab diagnosis, 215
Treatment, 216
Dientamebiasis , 60
Etiology, 60
Morphology, 60
Epidemiology, 61
Transmission/Life cycle, 61
Clinical features, 62
Lab diagnosis, 62
Treatment, 62
Diphyllobothriasis , 216
Etiology, 216
Morphology, 216
Adult, 216
Proglottid (Gravid segment), 216
Larvae(plerocercoid), 217
Egg, 217
Epidemiology, 217
Transmission/Life cycle, 217
Clinical features/Pathology, 218
Pernicious anaemia, 218
Lab diagnosis, 219
Treatment, 220
Dipylidiasis, 222
- 398 -

Etiology , 222
Morphology, 222
Adult, 222
Proglottid (Gravid segment), 222
Egg capsules, 223
Epidemiology, 223
Transmission/Life cycle, 223
Clinical features, 225
Lab diagnosis, 225
Treatment, 225
Dracunculiasis (Guina worm disease),
275
Etiology, 275
Morphology, 275
Epidemiology, 275
Transmission/ Life cycle, 276
Clinical features/Pathology, 277
Lab diagnosis, 278
Treatment/Prevention, 278
Dirofilariasis, 278
Etiology, 278
Morphology, 279
Epidemiology, 280
Transmission/Life cycle, 280
Clinical features/Pathology, 281
Human pulmonary dirofilariasis, 281
Coin pulmonary lesion, 281
Subcutaneous dirofilariasis, 282
Lab diagnosis, 283
Treatment, 284
Ecchinococosis, 227
Etiology, 227
Morphology, 227
Adult, 227
Larvae, 227
Unilocular hydatid cyst, 228
Alveolar hydatid cyst, 228
Polycystic hydatid cyst, 228
Osseous cyst, 234
Protoscolex, 228
Hydatid sand, 229
Epidemiology, 229
E.multilocularis, 229-233
E.alveolaris, 229
E. vogeli, 228,229-234
E. oligarthus, 230
Transmission /Life cycle, 230
Clinical features, 231
Anaphylactic shock, 232
Cyst locations, 232
Cyst rupture, 232
Hydatid thrill, 233
Pathology, 234
Lab diagnosis, 234
Preoperative diagnosis, 234
Casoni test, 235
Cyst aspiration, 235
Differential diagnosis, 235
Treatment, 236
Prevention/Control, 236
Endolimax nana, 39
Entamoeba dispar, 22
Entamoeba coli, 39
Entamoeba hartmanni, 41
Entamoeba polecki, 42
Entamoeba gingivalis, 43
Enterobiasis, 303
Etiology, 303
Morphology, 303
Epidemiology, 303
Transmission/Life cycle, 303
Clinical features and Pathology, 304
Lab diagnosis, 305
Treatment and Control, 306
Fascioliasis, 197
Etiology, 198
Morphology, 198
Epidemiology, 198
Transmission/Life cycle, 198
Clinical features/Pathology, 199
Acute fascioliasis, 199
Chronic fascioliasis, 200
Halzoun, 200-340
Black disease, 200
Lab diagnosis, 201
Pseudofascioliasis, 201
Treatment, 202
Fasciolopiasis, 201
Etiology, 201
Morphology, 202
Epidemiology, 202
Transmission/Life cycle, 202
Clinical features, 203
Lab diagnosis, 203
Treatment, 204
Filariasis, 243
Bancroftian filariasis(Wucheraria
bancrofti infection), 244
Morphology, 244
Epidemiology, 244
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Transmission /Life cycle, 245
Clinical features, 246
Elephantiaisis, 246-247-262
Common sites, 247
Epididymitis, 247
Funiculitis, 247
Hydrocele, 247
Lymph varices, 247
Chyluria, 248
Pathology, 248
Tropical Pulmonary Eosinophilia
(Eosinophilic syndrome), 249
Lab diagnosis, 249
Treatment, 250
Prevention/ Control, 251
Non-filarial Elephantiasis, 256
Sub-cutaneous filariasis, 256
Flukes (Trematodes), 169
Introduction, 169
General flukes life cycle, 170
Flagellates, 53
Intestinal flagellates, 53
Non-pathogenic intestinal flagellates,
60
Extraintestinal flagellates, 62
Giardiasis (Girdia Lamblia infection),
54
Etiology, 54
Morphology, 54
Epidemiology, 54
Transmission/Life cycle, 55
Clinical features/ pathology, 56
Malabsorptive syndrome, 57
Post-giardia lactose intolerance, 57
Steatorrhea, 57
Immunology, 57
Lab diagnosis, 58
Enterotest (string test), 58
Intestinal biopsy, 58
Tropical sprue, 58
Treatment/control, 58
Gnathostomiasis, 288
Etiology, 288
Morphology, 288
Epidemiology, 289
Transmission/Life cycle, 289
Clinical features/Pathology, 290
Lab diagnosis, 290
Treatment, 290
Prevetion /Control, 290
Haemoflagellates, 67
Haemonchus contortus, 318
Helminths, 168
Heterophyiasis, 196
Etiology, 196
Morphology, 196
Epidemiology, 196
Transmission/Life cycle, 196
Clinical features, 197
Lab diagnosis, 197
Treatment, 197
Hookworms disease, 311
Hosts, 9
Definitive host, 9
Intermediate host, 9
Reservoir host, 9
Accidental host, 10
Permissive host, 10
Non-permissive host, 10
Paratenic host, 10-293
Hymenolepiasis, 236
Etiology, 236
Morphology, 237
Adult, 237
Egg , 237
Epidemiology, 237
Transmission/ Life cycle (H.nana), 238
Transmission /Life cycle (H.diminuta),
239
Clinical features/Pathology, 240
Lab diagnosis, 241
Treatment, 241
Iodamoeba butschlii, 40
Isosporiasis, 140
Etiology, 140
Morphology, 141
Epidemiology, 141
Transmission/Life cycle, 141
Clinical features/pathology, 142
Lab diagnosis, 143
Enterotest, 143
Treatment, 143
Leishmaniasis, 84
Etiology/Epidemiology, 84
L.Donovani.Complex, 84
L.Tropica.Complex, 84
L.Mexican.Complex, 85
L.Brazilliensis.Complex, 85
Morphology, 86
Transmission/Life cycle, 86
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Clinical features, 87
Visceral Leishmaniasis(Kala
Azar/Dumdum fever), 87-93
Pancytopenia, 88
L.Infantum, 89
Black disease, 89
PostkalaAzar Dermal Leishmaniasis, 90
Cutaneous Leishmaniasis (Old world
Leishmaniasis), 90-93
L.tropica (Dry oriental sore), 90
L.recidiva, 91
L.major (Wet oriental sore), 91
L.aethiopica, 91
Diffuse cutaneous leishmaniasis, 91
Mucocutaneus leishmaniasis (New
world), 92
Espundia, 92
Uta, 92
L.brazilliensis, 92
Chicleros ulcer, 92
Pianbois, 92
Pathology, 93
Immune/blood changes, 93
Lab diagnosis, 94
NNN culture, 94
Leishman test (Montonegro test), 95
Treatment/Prevention, 95
Loaiasis/Eye worm, 267
Morphology, 267
Epidemiology, 267
Transmission/Life cycle, 267
Clinical feature, 269
Calabar swelling, 269
Pathology, 269
Lab diagnosis, 270
Treatment, 270
Loefflers syndrome (Simple
pulmonary eosinophilia), 311
Malaria, 100
Etiology, 101
Morphology, 101
Ring form, 102
Ameboid form
Accole form, 102
Maures dots, 102
Schuffners dots, 102
Band form, 102
Bird eye form, 102
James dot, 102
Epidemiology, 103
Malaria endemic countries map, 104
Transmission, 104
Life cycle, 104
Exo-erythrocytic cycle, 105
Erythrocytic cycle, 105
Sporogonic cycle, 105
Relapse, 107
Clinical features, 107
Fever/Hyperpyrexia, 107
Anemia, 108
Splenomegaly, 108
Joundice, 108
Bilious vomittent fever, 108
Nephrotic syndrome, 109
Malaria paroxysm phases, 109
Tertian/Quartan malaria, 109
Malaria in pregnancy, 110
Malaria in children, 110
P.falciparum, 110
Symptoms/differential diagnosis, 111
Complications, 111
Symptoms/ Differential diagnosis, 112
Cerebral malaria pathogenesis, 112-116
Microcirculatory arrest, 112-116
Acute renal failure, 113
Hypoglycemia, 113
Black water fever, 113
Algid syndrome, 113
Pulmonary edema, 114
Dysentry, 114
Shock, 114
Tropical splenomegaly syndrome, 114
Pathology /Immunology, 115
Cerebral malarae/Pathogenetic process,
116
Biological resistance to malaria, 117
Sickle cell anaemia, 117
Thalacemia, 117
G6PD, 117
Duffy antigen, 117
Lab diagnosis, 117
Treatment, 119
Supportive treatment, 119
Specific chemotherapy, 119
Chloroquine resistance P.falciparum,
119
Cerebral malaria treatment, 120
Prevention/Control, 121
Vaccination, 122
Prophylactic drugs, 122
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Prevention of relapse, 129
Chemoprophylaxis for
infants/children/adolescent, 130
Chemoprophylaxis during pregnancy,
131
Antimalaria drugs during breast
feeding, 132
Antimalaria adverse
reaction/contraindication, 132
Chemoprophylaxis changes, 133
Mansonelliasis(M. streptocerca
infection), 265
Morphology, 265
Epidemiology, 265
Transmission/Life cycle, 265
Clinical features/Pathology, 266
Lab diagnosis, 267
Treatment, 267
Serous cavity filariasis, 270
Mansonelliasis(M perstans infection),
270
Morphology, 270
Epidemiology, 271
Transmission/Life cycle, 271
Clinical features/Pathology, 272
Kampala eye, 272
Treatment, 273
Mansonelliasis (M ozzardi infection),
273
Morphology, 273
Epidemiology, 273
Transmission/Life cycle, 273
Clinical features/Pathology, 275
Lab diagnosis, 275
Treatment, 275
Metagonimiasis , 190
Etiology, 190
Morphology, 190
Epidemiology, 190
Transmission/Life cycle, 191
Clinical features, 192
Lab diagnosis, 192
Treatment, 192
Microsporidiosis, 163
Etiology, 163
Morphology, 163
Epidemiology, 163
Transmission and life cycle, 164
Clinical features&Pathology, 165
Lab diagnosis, 166
Treatment, 166
Mutualism, 9
Naegleriasis , 47
Etiology, 47
Morphology, 47
Epidemiology, 48
Transmission/Life cycle, 48
Clinical features, 49
Acute primary amebic
meningoencephalitis (PAM), 49
Lab diagnosis, 50
Treatment, 50
Nematodes(Round worms), 243
Introduction, 243
Blood /Tissue Nematodes, 243
Intestinal nematodes, 302
Generalized life cycle, 302
Ocular larva migrans (OLM), 296
Retinoblastoma, 296
Onchocerciasis (River blindness), 256
Etiology (O.volvulus), 256
Morphology, 257
Epidemiology, 257
Transmission, 257
Life cycle, 257
Clinical features/Pathology, 259
Eye (ocular) lesion, 260
Onchocerca pathogenesis in eye, 261
Blindness, 261
Skin lesion, 261
Gale filarienne, 261
Leopard skin, 262
Sowda, 262
Erysipelas de la costa, 262
Hanging groin, 259-262
Onchocercoma, 259-262
Onchocerca pathogenesis in skin, 262
Lab disgnosis, 263
Skin snip, 263
Slit lamp, 263
Mazzotti test, 264
Treatment, 264
Nodulectomy, 264
Prevention/ Control, 264
Opistorchiasis , 187
Etiology, 187
Morphology, 188
Epidemiology, 188
Transmission /Life cycle, 188
Clinical features, 189
- 402 -

Lab diagnosis, 189
Treatment, 189
Opportunisticparasites, 343
Protozoa, 343
Nematodes, 344
Opportunistic toxoplasmosis, 157
Paragonimiasis, 192
Etiology, 192
Morphology, 192
Epidemiology, 193
Transmission /Life cycle, 193
Clinical features/Pathology, 194
Pulmonary paragonimiasis, 194
Extrapulmonary Paragonimiasis, 194
Lab diagnosis, 194
Treatment, 195
parasitology Introduction , 6
Parasitic association, 8
Parasite, 8
Parasitism, 8
Obligatory parasite, 8
Temporary parasite, 8
Facultative parasite, 8
Endoparasite, 8
Ectoparasite, 8
Pathogenic parasites, 8
Non-pathogenic parasites, 8
Pentastomida, 340
Armillifer sp, 340
Morphology, 340
Epidemiology, 340
Transmission and Life cycle, 340
Clinical features, 341
Porocephalosis,341
Treatment, 341
Pseudoparasites, 344
Air bubbles, 345
Crystals, 345
Mites, 345
Plant hair, 345
Pollen, 345
Yeast, 345
Pneumocystosis /P pneumonia, 145
Etiology, 145
Morphology, 146
Epidemiology, 146
Transmission and Life cycle, 146
Clinical features/pathology, 146
Lab diagnosis, 147
Treatment, 148
Poikilorchis congolensis, 195
Protozoa, 12
Immune defenses/Pathology, 12
Introduction, 12
Body defence (Immunity), 12
Immune escape mechanism, 14
- Antigen masking, 14
- Intracellular location, 14
- Antigenic variation, 15
- Immunosuppresion, 16
Summary of immune escape, 17
Pathology, 17
Protozoa of human body, 20
Protozoa taxonomy, 20
Niche of protozoa, 20
Protozoa groups, 21
Recrudescence, 110
Retroinfection, 304
Rhoptries, 115
Sarcocystis spp infection, 160
Morphology, 161
Life cycle, 161
Clinical feature&Pathology, 161
Lab diagnosis, 162
Treatment, 162
Schistosomiasis , 171
Etiology, 171
Morphology, 171
Epidemiology, 171
Transmission, 172
Life cycle, 172
Clinical features, 173
Swimmers itch, 173-175-184
Katayama fever, 175
Katayama fever diagnosis/treatment,
176
Schistosoma pathological
processes/complications, 176
Symmers pip stem fibrosis, 176
Granuloma, 176
S.haematobium complications, 177
S.mansoni/japonicum complications,
178
Ascites, 178
Portal hypertention, 178
Oesophageal varices, 178
Ectopic eggs, 179
Salmonella infections, 179
Lab diagnosis, 180
Treatment, 181
- 403 -

Prevention/Control, 182
Schistosoma mekongi, 182
Schistosoma intercalatum, 182
Sparganosis(Spirometra), 220
Etiology, 220
Morphology, 220
Epidemiology, 221
Transmission and Life cycle, 221
Clinical features/Pathology, 221
Ocular sparganosis, 221
Lab diagnosis, 222
Treatment/Control, 222
Sporozoa, 100
Blood sporozoa, 100
Tissue Sporozoa, 137
Strongyloidiasis, 328
Etiology, 328
Morphology, 328
Epidemiology, 329
Transmission/Life cycle, 329
Clinical features/Pathology, 331
Larvae currens, 331
Hyperinfection syndrome, 332
Lab diagnosis, 333
Treatment/ Control, 334
Strongyloides fulleborni, 334
Swollen belly syndrome, 334
Symbiosis, 8
Taeniasis , 207
Etiology, 207
Morphology, 207
Adult, 207
Gravid segment, 207
Larvae, 208
Cysticercus bovis/C.celullosae, 208
Egg , 208
Epidemiology, 209
Transmission /Life cycle, 209
Clinical features/Pathology, 210
Lab diagnosis, 211
Treatment, 211
Prevetion/Control, 212
Symptomes&Signs of parasitic
diseases, 365
Toxocariasis, 291
Etiology, 291
Morphology, 291
Epidemiology, 291
Transmission, 292
Life cycle, 292
Clinical features, 294
Visceral larva migrans (VLM), 294
General, 294
Dermatolgic, 294
Pulmonary, 295
Hepatic/Lymphatic, 295
Rheumatologic, 295
Cardiac, 295
Central nervous system, 295
Pathophysiology, 296
Lab diagnosis, 297
Treatment, 298
Prevention, 298
Toxoplasmosis, 148
Etiology, 148
Morphology, 149
Pseudocyst, 149
Plasmlema, 149
Epidemiology, 149
Transmission, 149
Life cycle, 150
Mode of human infection, 152
Clinical features/Pathology, 152-153
Congenital toxoplasmosis, 152
Chorioretinitis, 153
Hydrocephalus, 154
Cerebral calcification, 154
Acquired toxoplasmosis, 154
Infectious mononucleosis, 154
Jaundice, 154
Encephalitis, 154
Lab diagnosis, 155
Serological test (IgG/IgM), 155,156-
157
Sabin Feldman dye test, 155
Pregnant women screening, 156
Prenatal diagnosis, 157
Treatment, 158
Prevention/Control, 159
Prognosis, 160
Mental retardation, 160
Ternidens deminutus, 318
Transmission, 319
Clinical feature/Pathology, 319
Trichinellosis, 322
Etiology, 322
Morphology, 322
Epidemiology, 322
Transmission /Life cycle, 323
Clinical features, 324
- 404 -

Splinter haemorrhage, 324
Pathology/Immunology, 324
Lab diagnosis, 325
Treatment / Control, 325
Trichomoniasis, 62
Etiology, 62
Morphology, 63
Epidemiology, 63
Transmission/Life cycle, 63
Clinical features/pathology, 64
Lab diagnosis, 65
Treatment/control, 66
Trichostrongyliasis, 317
Etiology, 317
Morphology, 317
Epidemiology, 317
Transmission and Life cycle, 317
Clinical features/Pathology, 318
Lab diagnosis, 318
Treatment, 318
Trichuriasis/Whipworm disease, 319
Etiology(T.trichuria infection), 319
Morphology, 319
Epidemiology, 320
Transmission/Life cycle, 320
Clinical features/Pathology, 321
Rectal prolapse, 321
Lab diagnosis, 321
Treatment/Control, 322
Tropical pyomyositis, 376
Trypanosomiasis, 67
Trypanosoma rangeli, 83
Vectors, 11
Biological vector, 11
Mechanical vector, 11
Zoonosis, 11