Trypanosoma spp.

Hemoflagellates

Family Trypanosomidae
3 species known to be pathogenic
in human are:
1. Trypanosoma gambiense
2. Trypanosoma rhodesiense
3. Trypanosoma cruzi

Causes human sleeping sickness

Trypanosoma gambiense
General

Causes Mid African trypanosomiasis

Vector: Tse Tse fly (Glossina palpalis)
Final host: humans
Reservoir host: pig, goat, and cattle
The parasite lives in blood plasma, lymph
nodes, spleen and brain
Trypanosoma can also be transmitted
through blood transfusions, organ
transplantation, transplacentally, and in
laboratory accidents

Different stages of Haemoflagellates

Morphology

Trypanosoma gambiense
Morphology

Bugs, Assassin bugs (or kissing bugs)

The
Vector

Glossina
(Tsetse fly)

African
Trypanosomiasis
Trypanosoma
gambiense
Life Cycle

Gambian Trypanosomiasis
General

West African sleeping sickness

Infection occurs through the bite of tsetse fly
of Glossina palpalis and Glossina tachinoides,
injecting pleomorphic trypanosomes into
human blood stream by anterior inoculation
Infection is characterized by three
progressive stages: subcutaneous,
hemolymphatic, and meningoencephalitic
(chronic) stage

Gambian Trypanosomiasis
Clinical manifestations

Subcutaneous
stage: local
inflammation in
the biting site
(raises after
about 3 wks),
leads to primary
chancre

Gambian Trypanosomiasis
Clinical manifestations
Hematogeneous
stage: fever,
malaise, anorexia,
headache, and
postcervical
lymphadenopathy
(Winterbottoms
sign)

Gambian Trypanosomiasis
Clinical manifestations
Chronic stage: expresses 612 months after the first
onset: increased fatigue,
mental dullness to
somnolence.
Sleepiness progresses to
coma and eventually death.

Gambian Trypanosomiasis
Treatment
Successful treatment depends on
early patient management
Drugs commonly used:
pentamidine, suramin, melarsoprol
Pentamidine is used for early stage,
admministerde by im injection
Suramin is for early stage by iv
Melarsoprol is for chronic stage by
iv administration

Trypanosoma rhodesiense
General

Causes East African trypanosomiasis

Vector: Tse Tse fly (Glossina morsitans)
Final host: humans
Reservoir host: antelopes (wild animal)
Morphologically similar to the
proceeding species

Rhodesian Trypanosomiasis
Clinical manifestations
East African sleeping sickness
Vectored by Glossina pallidipes, G.
morsitans, and G. swynnertoni
The stages of diseases and symptomatology
parallel those of prior trypanosomiasis; only
the disease progresses rapidly and has
shorter clinical course
The entire course may take only 9-12
months

Rhodesian Trypanosomiasis
Diagnosis and Treatment
The diagnosis is made in the
same manner as the prior one
The drugs used in rhodesian
trypanosomiasis are also the
same
Prognosis is poor since the
clinical course is shorter

Immunoregulation:
Trypanosome Elimination
Antibody mediated
Destruction by Kupffer cells
Splenic macrophages minor role (cf malaria)
Uptake - C3b - C3bi - direct?
C mediated lysis not important
Trypanosome destroyed within minutes

Immunoregulation
No secondary response to VSGs unless cured by
chemotherapy
Failure of 1ry or 2ndry response prior to death
Non specific polyclonal activation
Suppresser Macrophages
Failure of Ag presentation
Anti idiotype responses

Immunoregulation:
Variable Surface Glycoprotein
60kd (450aa) glycoprotein (CHO 7-17%)
C-terminal anchored in membrane
Often as a dimer (alpha helix)
Densely clustered 107molecules/parasite
Only epitopes in end third of N-terminal exposed
Presented as topographical array
T-independent antigen

Immunoregulation:
VSG
Constant & Variable regions
Random rearrangement of N terminal end (2/3)
Almost no homology between V VSGs
Except cystein residues S-S bonds
Switching not initiated by IR
But selected

VSG Specific IR
3-4 days post infection strong IgM response
Trypanosome disappear within hours
VSG specific IgG appears - not relevant
IgM response often >IgG
After several cycles VSG abs vanish
But abs to invariant ags remain elevated

Are you suffering from sleeping sickness?

Trypanosoma cruzi
General

Causes South American trypanosomiasis

or Chagas disease
Vector: Triatomine bug
Final host: humans
Reservoir host: pets, rodents, monkeys,
armadillos
Living in two forms in human body:
1. trypanosoma form (trypomastigote)
found in peripheral blood vessels
2. leishmania form (amastygote) found in
muscles, brain, reticuloendothelial
system, and lymph nodes

Trypanosoma cruzi
Life Cycle

Chagas Disease
Clinical manisfestations

Most victim is child under 5 yrs old

In 1-2 wks, the itchy bite wound
leads to a local inflammatory
reaction
The inflammation blocks lymphatic
flow and produces an erythematous
primary lession called chagoma

Chagas Disease
Clinical manisfestations
It develops to
conjunctivitis
and unilateral
edema o/t
face and
eyelids called
Romanas sign

Chagas Disease
Clinical manisfestations
Acute stage appears 4-14 dys
later, characterized by fever
and chill, malaise, myalgia,
and fatigue
Abdominal rash may also occur
The most severe symptoms are
seen if CNS is involved

Chagas Disease
Clinical manisfestations
The symptoms of chronic stage
are dependent on the organ
system affected and the extend
of cellular damage
Cardiomegaly, dyspnea, and
aphasia may occur due to the
involvement of heart, lung, and
CNS

Chagas Disease
Treatment and Prevention
Drugs of choice:
Nifurtimox
Nifrofurazone
Preventive action is the
combination of disease and
vector control

Trypanosoma
Laboratory diagnosis :
Microscopic examination : blood,
lymphnode fluid, CNS fluid, biopsy of
chancre
Concentration techniques and serial
examinations are frequently needed.
Serologic testing , normally is used for
screening purposes only

Leishmania spp.
General

Class Zoomastigophorea
Order Kinetoplastida
Family Trypanosomidae
3 species known to be pathogenic
in humans are:
1.
2.
3.

Leishmania donovani
Leishmania tropica
Leishmania braziliensis

Leishmania donovani
General

Causes leishmaniasis visceral,

Kala-azar disease, black water
fever
Final host: humans
Habitat is humans
reticuloendothelial cells
Vector: Phlebotomus fly (sandfly)
Reservoir host: canine

The Vector

Sand fly

Leishmania donovani
Morphology

During the life cycle, Leishmania

has two stages:
1. Leishmania stage (amastigote) found
in humans and canines RE cells
2. Leptomonas (promastigote) stage
found in vectors intestine

Amstigote is rounded or ovoid,

measured 2-4 microns, contains
kinetoplast, blepharoplast, and
rizoplast

Leishmania donovani
Morphology

Promastigotes

Leishmania donovani
Life Cycle

Leishmaniasis
Cutaneous Leishmaniasis
Mucocutaneous Leishmaniasis
Visceral Leishmaniasis

Leishmaniasis

Etiologic agents
Cutaneous leishmaniasis:
Oriental sore :
is caused by Leishmania tropica complex
Distributed in India and Middle East countries
Vectored by Phlebotomus sandfly

Bay sore
is caused by Leishmania mexicana complex
Extends from southern Texas, Mexico, Central and South America
Vectored by Lutzomyia sandfly

Mucocutaneous leishmaniasis
Caused by Leishmania braziliensis complex

Visceral leishmaniasis
Caused by Leishmania donovani complex

Cutaneous Leishmaniasis
Clinical manifestations

The clinical manifestations of both

cutaneous leishmaniasis are similar
Incubation period vary from several
wks to three yrs

Cutaneous Leishmaniasis
Clinical manifestations

The first sign is small red

papule at the initial site of the
insect bite
Formation of crateriform
lession
Generally heal spontaneously,
but may leave serious scars
Contact spread of infection is
possible

Cutaneous Leishmaniasis
Diagnosis

Specimen of choice is taken

by aspiration or biopsy from
the active lession
Finding amastigote form in
microscopic examination
Montenegro (leishmanin)
skin test
Serologic test

Cutaneous Leishmaniasis
Treatment and Prevention

Drug of choice: sodium stibogluconate

(antimony sodium gluconate: Pentostam), im
for 10 days
Alternate choice: meglumine antimonate
(Glucantime), amphotericin B, and
ketoconazole
Prevention lies in vector and reservoir
control, as well as the other vector
transmitted infections

Mucoutaneous Leishmaniasis
General

Etiologic agents: Leishmania

braziliensis complex
Vectored by Lutzomyia and
Psychodopygus sandflies

Mucoutaneous Leishmaniasis
Clinical manifestations

Primary lession develop in the same

manner as oriental sore
It tends to invade the
mucous membrane of
the mouth and
nasopharynx by
hematogenous or
lymphatic
transmission

Mucoutaneous Leishmaniasis
Clinical manifestations

Clinical
progression may
take years, results
in ulcers that erode
soft tissue o/t face
and palate

Mucoutaneous Leishmaniasis
Clinical manifestations

Leishmanioma

Mucoutaneous Leishmaniasis
Diagnosis and Treatment

Diagnosis, treatment and

preventive action is similar
to cutaneous leishmaniasis

Visceral Leishmaniasis
General

Also known as kala azar or dum-dum fever

The most severe leishmania infection
Causative agents: Leishmannia donovani
complex, parasitized the
reticuloendothelial cells
Distributed troughout India, Pakistan,
Thailand, parts of Africa, and China
Vectored by Phlebotomus and Lutzomyia
sandfly

Visceral Leishmaniasis
Clinical manifestations

Variable incubation period, 3 wks to 2

yrs
Infected macrophages migrate by
lymphatic and hematogenous spread to
distant lymphoid tissue
Prodromal symptoms include headache,
malaise, fever, and weight loss
The fever may occurs periodically,
mimicking malaria

Visceral Leishmaniasis
Clinical manifestations

Physical examination:
hepatosplenomegaly
and lymphadenopathy
Hyperpigmentation o/t
forehead and hands
(kala azar) may be
observed
Prognosis of untreated
cases is poor

Visceral Leishmaniasis
Diagnosis

Tissue biopsy from spleen and

liver demonstrating
amastigote with Giemsa
staining
Serologic examination
Montenegro skin test

Visceral Leishmaniasis
Treatment and Prevention

Drugs of choice: Pentostam and

pentamidine isothionate (Lomidine)
Alternate choice: amphotericin B
Combination of allupurinol and
Pentostam is effective
Preventive actions include managing
the vector and reservoir host

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