TOXOPLAS

MA
MOHD FARIS BIN MOHD
PUADI (M132001834)

MEDICAL
PARASITOL
OGY

i.

INTRODUCTION

Toxoplasma gondii (tk's-plz'm gn'd-') is an obligate, intracellular,

parasitic protozoan that causes the disease toxoplasmosis. Found worldwide, T.
gondii is capable of infecting virtually all warm-blooded animals, although felids
such as domestic cats are the only known definitive hosts in which the parasite
can undergo sexual reproduction.
In humans, T. gondii is one of the most common parasites; serological studies
estimate that 3050% of the global population has been exposed to and may be
chronically infected with T. gondii, although infection rates differ significantly
from country to country. For example, previous estimates have shown the
highest prevalence of persons infected with T. gondii to be in France, at 84%.
Although mild, flu-like symptoms occasionally occur during the first few weeks
following exposure, infection with T. gondii produces no readily observable
symptoms in healthy human adults. This asymptomatic state of infection is
referred to as a latent infection and has recently been associated with numerous
subtle adverse or pathological behavioral alterations in humans. In infants,
HIV/AIDS patients, and others with weakened immunity, infection can cause
serious and occasionally fatal illness (toxoplasmosis).

T. gondii tachyzoites under 100x magnification with oil

ii.

LIFE CYCLE:

The only known definitive hosts for Toxoplasma gondii are members of family
Felidae (domestic cats and their relatives). Unsporulated oocysts are shed in the
cats feces

. Although oocysts are usually only shed for 1-2 weeks, large

numbers may be shed. Oocysts take 1-5 days to sporulate in the environment
and become infective. Intermediate hosts in nature (including birds and rodents)
become infected after ingesting soil, water or plant material contaminated with
oocysts

. Oocysts transform into tachyzoites shortly after ingestion. These

tachyzoites localize in neural and muscle tissue and develop into tissue cyst
bradyzoites

. Cats become infected after consuming intermediate hosts

harboring tissue cysts

. Cats may also become infected directly by ingestion of

sporulated oocysts. Animals bred for human consumption and wild game may
also become infected with tissue cysts after ingestion of sporulated oocysts in
the environment

. Humans can become infected by any of several routes:

eating undercooked meat of animals harboring tissue cysts

consuming food or water contaminated with cat feces or by contaminated

environmental samples (such as fecal-contaminated soil or changing the
litter box of a pet cat)

blood transfusion or organ transplantation

transplacentally from mother to fetus

In the human host, the parasites form tissue cysts, most commonly in skeletal
muscle, myocardium, brain, and eyes; these cysts may remain throughout the
life of the host. Diagnosis is usually achieved by serology, although tissue cysts
may be observed in stained biopsy specimens

. Diagnosis of congenital

infections can be achieved by detecting T. gondii DNA in amniotic fluid using

molecular methods such as PCR

iii. MORPHOLOGY
Cellular stages
During different periods of its life cycle, individual parasites convert into various
cellular stages, with each stage characterized by a distinct cellular morphology,
biochemistry, and behavior. These stages include the tachyzoites, merozoites,
bradyzoites (found in tissue cysts), and sporozoites (found in oocysts).
Tachyzoites

Two tachyzoites, transmission electron microscopy[46]

Motile, and quickly multiplying, tachyzoites are responsible for expanding the
population of the parasite in the host. [46][47] When a host consumes a tissue cyst
(containing bradyzoites) or an oocyst (containing sporozoites), the bradyzoites or
sporozoites stage-convert into tachyzoites upon infecting the intestinal
epithelium of the host.[48] During the initial, acute period of infection, tachyzoites
spread throughout the body via the blood stream. [32] During the later, latent
(chronic) stages of infection, tachyzoites stage-convert to bradyzoites to form
tissue cysts.
Merozoites

An unstained T. gondii tissue cyst, bradyzoites can be seen within

Like tachyzoites, merozoites divide quickly, and are responsible for expanding
the population of the parasite inside the cat intestine prior to sexual
reproduction.[47] When a feline definitive host consumes a tissue cyst (containing
bradyzoites), bradyzoites convert into merozoites inside intestinal epithelial cells.
Following a brief period of rapid population growth in the intestinal epithelium,
merozoites convert into the noninfectious sexual stages of the parasite to
undergo sexual reproduction, eventually resulting in the formation of zygotecontaining oocysts.[49]

Bradyzoites
Bradyzoites are the slowly dividing stage of the parasite that make up tissue
cysts. When an uninfected host consumes a tissue cyst, bradyzoites released
from the cyst infect intestinal epithelial cells before converting to the
proliferative tachyzoite stage.[48] Following the initial period of proliferation
throughout the host body, tachyzoites then convert back to bradyzoites, which
reproduce inside host cells to form tissue cysts in the new host.
Sporozoites
Sporozoites are the stage of the parasite residing within oocysts. When a human
or other warm-blooded host consumes an oocyst, sporozoites are released from
it, infecting epithelial cells before converting to the proliferative tachyzoite stage

iv. SYMPTOMS/PATHOLOGY

Infection with Toxoplasma gondii is usually asymptomatic in healthy individuals.

About 10-20% of those with an acute infection will have enlarged lymph nodes in
the cervical and inguinal region as well as flu-like symptoms (fever, headache,
muscle pain). The infection is generally self-limited and the symptoms usually
resolve in a few months.
Immunocomprimised persons often show involvement of the central nervous
system but may also have heart and lung complications. In persons with AIDS,
toxoplasmic encephalitis and brain lesions may occur.
Congenital infection occurs if the mother is infected during pregnancy.
Toxoxplasma gondii tachyzoites are thought to cross the placenta to the fetus
which may lead to stillbirths or severe birth defects. Early diagnosis and
treatment of the mother may reduce the probability of congenital infection.
Chronic infections may also lead to blindness over time as sarcocysts in the eye
develop and rupture the infected cells.

PREVALANCE IN MALAYSIA AND SOUTHEAST

ASIA
Table 1 shows that the seroprevalence of toxoplasmosis seems to increase with
the time duration as particularly seen in Indonesia; 2 to 63% in 1964 to 1980 (De
Roever-Bonnet et al., 1964; Yamamoto et al., 1970; Clarke et al., 1973a-b, 1975;
Cross et al., 1975a-d, 1976; Partono and Cross, 1975; Durfee et al., 1976; Srisari,
1978; Srisari and Endardjo, 1980), 3.1 to 60% from 1981 to 1994 (Chomel et al.,
1993) and 58 to 70% during 1995 till 2003 (Uga et al., 1996; Konishi et al., 2000;
Terazawa et al., 2003). This largest country clearly showed the highest
Toxoplasma prevalence in this region. Furthermore, only one study was reported
in Laos PDR, where 15.3% of Toxoplasma seroprevalence was shown in a group
of inhabitants with a prevalence increasing with age (Catar et al., 1992).
However, in Malaysia, the seroprevalence of toxoplasmosis varied from 13.9 to
30.2% in healthy persons. The Malays showed the highest prevalence when
compared to other ethnic groups, signifying that Toxoplasma seropositivity tends
to increase with age. Moreover, a higher prevalence was found in males and
unemployed individuals, whereas a lower rate was observed in people with

higher incomes. The risk behaviors such as contact with cat and consumption of
uncooked meat were found to be the main sources of Toxoplasma infection (Tan
and Zaman, 1973; Dissanaike et al., 1977; Thomas et al., 1980; Sinniah et al.,
1984; Zahedi et al., 1985; Hakim et al, 1994; Nissapatorn et al., 2002). Two cases
of human acquired toxoplasmosis were reported in the early period (Leong et al.,
1976) and thereby toxoplasmosis was also suggested to be given priority in the
investigation of pyrexia of unknown origin (PUO) cases (Tan et al., 1978).
Similarly, from 1975 to 2000, studies in the Philippines showed varying results of
Toxoplasma seroprevalence from < 2 to 61.2% in different settings. The
prevalence tended to increase with age and a significantly higher rate was found
in rural than urban areas (Cross et al., 1997; Eduardo, 1991; Kawashima et al.,
2000). Subsequently in Singapore, the first report on Toxoplasma seroprevalence
was 41.3% in the sera of clinically suspected cases and 17.2% in healthy
individuals (Singh et al., 1968). Taking into account the comparison between
different regions, the highest Toxoplasma seropositivity was found among the
Malays, with their living habits and sanitary conditions greatly attributing to this
finding (Zaman and Goh, 1969).
During the period of 80s, Toxoplasma seroprevalence was 42.5% in clinically
suspected cases (Lim et al., 1982). From 1991 to date, 18.8% of Toxoplasma
seroprevalence was shown in healthy individuals and the epidemiology and
clinical profiles of patients presenting with acute toxoplasmosis were indicative of
asymptomatic cervical lymphadenopathy (Mohan et al., 1991a, b). The first study
in Thailand showed that 4 out of 265 slaughter workers were Toxoplasma
seropositivities (Sungkasuwan, 1967), while, a report of three fatal cases on
human toxoplasmosis was found in the late 70s (Bunyaratvej et al., 1978).

Ta The prevalence of
ble Toxoplasma infection
1: and clinical evidence of
toxoplsmosis in different
groups of the Southeast
Asian population

Ta The prevalence of
ble Toxoplasma infection
2: and clinical evidence of
toxoplsmosis in patients
with ocular diseases and
other
immunosuppressed

v.

EPIDEMIOLOGY & RISK FACTORS

In various places throughout the world, it has been shown that up to 95% of
some populations have been infected with Toxoplasma. Infection is often highest
in areas of the world that have hot, humid climates and lower altitudes.
Toxoplasmosis is not passed from person-to-person, except in instances of
mother-to-child (congenital) transmission and blood transfusion or organ
transplantation. People typically become infected by three principal routes of
transmission.

Foodborne

Animal-to-human (zoonotic)

Mother-to-child (congenital)

Rare instances

Foodborne transmission
The tissue form of the parasite (a microscopic cyst consisting of bradyzoites) can
be transmitted to humans by food. People become infected by:

Eating undercooked, contaminated meat (especially pork, lamb, and

venison)

Accidental ingestion of undercooked, contaminated meat after handling it

and not washing hands thoroughly (Toxoplasma cannot be absorbed
through intact skin)

Eating food that was contaminated by knives, utensils, cutting boards, or

other foods that had contact with raw, contaminated meat

Animal-to-human (zoonotic) transmission

Cats play an important role in the spread of toxoplasmosis. They become
infected by eating infected rodents, birds, or other small animals. The parasite is
then passed in the cat's feces in an oocyst form, which is microscopic.
Kittens and cats can shed millions of oocysts in their feces for as long as 3 weeks
after infection. Mature cats are less likely to shed Toxoplasma if they have been
previously infected. A Toxoplasma-infected cat that is shedding the parasite in its
feces contaminates the litter box. If the cat is allowed outside, it can
contaminate the soil or water in the environment as well.
People can accidentally swallow the oocyst form of the parasite. People can be
infected by:

Accidental ingestion of oocysts after cleaning a cat's litter box when the
cat has shed Toxoplasma in its feces

Accidental ingestion of oocysts after touching or ingesting anything that

has come into contact with a cat's feces that contain Toxoplasma

Accidental ingestion of oocysts in contaminated soil (e.g., not washing

hands after gardening or eating unwashed fruits or vegetables from a
garden)

Drinking water contaminated with the Toxoplasma parasite

Mother-to-child (congenital) transmission

A woman who is newly infected with Toxoplasma during pregnancy can pass the
infection to her unborn child (congenital infection). The woman may not have
symptoms, but there can be severe consequences for the unborn child, such as
diseases of the nervous system and eyes.

vi. DIAGNOSIS
The diagnosis of toxoplasmosis is typically made by serologic testing. A test that
measures immunoglobulin G (IgG) is used to determine if a person has been
infected. If it is necessary to try to estimate the time of infection, which is of
particular importance for pregnant women, a test which measures
immunoglobulin M (IgM) is also used along with other tests such as an avidity
test.
Diagnosis can be made by direct observation of the parasite in stained tissue
sections, cerebrospinal fluid (CSF), or other biopsy material. These techniques
are used less frequently because of the difficulty of obtaining these specimens.
Parasites can also be isolated from blood or other body fluids (for example, CSF)
but this process can be difficult and requires considerable time.

Molecular techniques that can detect the parasite's DNA in the amniotic fluid can
be useful in cases of possible mother-to-child (congenital) transmission.
Ocular disease is diagnosed based on the appearance of the lesions in the eye,
symptoms, course of disease, and often serologic testing.

A Toxoplasma-positive reaction, stained by immunofluroescence (IFA). (CDC

Photo)

vii. TREATMENT
Healthy people (nonpregnant)
Most healthy people recover from toxoplasmosis without treatment. Persons who
are ill can be treated with a combination of drugs such as pyrimethamine and
sulfadiazine, plus folinic acid.
Pregnant women, newborns, and infants
Pregnant women, newborns, and infants can be treated, although the parasite is
not eliminated completely. The parasites can remain within tissue cells in a less
active phase; their location makes it difficult for the medication to completely
eliminate them.

Persons with ocular disease

Persons with ocular toxoplasmosis are sometimes prescribed medicine to treat
active disease by their ophthalmologist. Whether or not medication is
recommended depends on the size of the eye lesion, the location, and the
characteristics of the lesion (acute active, versus chronic not progressing).
Persons with compromised immune systems
Persons with compromised immune systems need to be treated until they have
improvement in their condition. For AIDS patients, continuation of medication for
the rest of their lives may be necessary, or for as long as they are
immunosuppressed.

viii. PREVENTION

Certain precautions can help prevent toxoplasmosis:

Wear gloves when gardening or handling soil.

Don't eat raw or undercooked meat.

Wash kitchen utensils thoroughly.

Wash all fruits and vegetables.

Don't drink unpasteurized milk.

Cover children's sandboxes.

For cat lovers

If pet owner is pregnant or otherwise at risk of toxoplasmosis or its
complications:

Help the to cat stay healthy. Keep cat indoors and feed it dry or canned
cat food, not raw meat. Cats can become infected after eating infected
prey or undercooked meat that contains the parasite.

Avoid stray cats or kittens. Although all stray animals need good
homes, it's best to let someone else adopt them. Most cats don't show
signs of T. gondii infection, and although they can be tested for
toxoplasmosis, it may take up to a month to get the results.

Have someone else clean the cat's litter box. If that's not possible,
wear gloves and a face mask to change the litter. Then wash the hands
well. Change the litter daily so that excreted cysts don't have time to
become infectious

ix. REFERENCE
1. https://en.wikipedia.org/wiki/Toxoplasma_gondii
2. http://www.mayoclinic.org/diseasesconditions/toxoplasmosis/basics/definition/con-20025859
3. http://www.cdc.gov/parasites/toxoplasmosis/
4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC106833/
5. https://www.msu.edu/course/zol/316/tgontissue.htm