Trypanosoma

spp.

Polymorphic spindle-shaped
Kinetoplast
Flagella & undulating membrane
 Protozoa
General characteristic of the Protozoa are :

1- Unicellular ( consist of one cell ) this cell performs all phsiological

function ( activities ) of life such as locomation , reproduction ,
respiration , ingestion , digestion and excretion .

2- They vary in size and shape some are visible while others require
high magnification ( by microscope ) .

3- The majority of protozoa are free living but some are parasitic .

4- Both sexual and asexual reproduction occur in protozoa ( the majority

of protozoa reproduce by asexual reproduction ) .
Class : Mastigophora .

Order:kinetoplastida

Family: trypanosomatidae

Genus:trypanosoma

Disease:typansomiasis.

1- T.gambiense :cause African sleeping sickness in human.

2- T .crusi :cause chagas disease (American trypanosomiasis)
in human and dog.
3- T .evansi : cause surra disease of all domestic animals.
4- T. equiperdum : cause Dourine disease in horse & donky .
 Trypanosoma
• require more than one host to complete their
life cycle
• transmitted through blood feeding
invertebrates (insects)
• mostly live in blood tissue but can be found in
different locations in the host
• uses antigen variation, or variation of the
protein coat, in order to avoid detection by the
body
• It cause sleeping sickness or
Trypanosomiasis
Trypanosomes
• T .evansi
Salivarian • T .rhodesiense ,T.theileri,
Trypanosome T.equiperdum,
• T .gambiense

Stercorian • T.cruzi
Trypanosomes
• T.lewzi
 Human Trypanosomiasis
African Trypanosomiasis
West-Africa: Trypanosoma brucei gambiense
“sleeping sickness”.
East-Africa: Trypanosoma brucei rhodiesiense

American Trypanosomiasis
Trypanosoma cruzi
Transmission or intermediet hosts (vector):-

T .brucei
T .gambiense tse tse fly
(glossina).
T .rhodesiense

T .evansi tabanus (horse fly).

T .cruzi kissing bug
(panstrongylus).
T. equiperdum transmition by coitus .

Trypanosoma are present in blood , lymph ,

lymphnodes and cerebrospinal fluid
.trypanosoma is multiply by longitudinal
Morphology :-
1-trypanosmes is an elongated , spindle-shape
cell with a single nucleus near the middle of
parasite.
2-it has kinetoplast.
3-it has undulating membrane.
4-possess a slender-single flagella at the anterior
end.
5-flagellum serve as organ of attachment and
locomotion.
Diagnosis:-
1.blood smear , trypanosomes found in
blood.
2.Lymph smear .
3.Serological test
6-there are four stages in life cycle :-
A –trypomastigote:- postnuclear kinetoplast
, flagellum start from anterior end with
undulating membrane , found in vertebrate
and insects .
B –epimastigote:- kinetoplast anterior to
nucleus flagellum emerging from the body and
continuing to the anterior end with short
undulating membrane.
C –promastigote:- kinetoplast at the anterior end.
Flagellum emerging from anterior end of the
body . there is no undulating membrane.
D–amastigote:- spherical or oval in shape without
undulating membrane . flagellum not extend
from outside the membrane , start from the
kinetoplast .
 Trypomastigote Epimastigote Promastigote Amastigote

FORM
Trypanosoma cruzi. A, B, C: Trypomastigotes in blood; D, E:
epimastigote (with short anterior undulating membrane); F:
amastigote colony in heart muscle.
American Trypanosomiasis
( Chagas Disease)
 Chagas disease, or American •
trypanosomiasis, is caused by the parasite
Trypanosoma cruzi. Infection is most
commonly acquired through contact with
the feces of an infected triatomine bug (or
"kissing bug"), a blood-sucking insect that
feeds on humans and animals.
Infection can also occur from:
mother-to-baby (congenital), •
contaminated blood products •
(transfusions),
an organ transplanted from an infected •
 Epidemiology
Chagas disease is endemic throughout •
much of Mexico, Central America, and
South America where an estimated 8 to 11
million people are infected. The triatomine
bug thrives under poor housing conditions
(for example, mud walls, thatched roofs),
so in endemic countries, people living in
rural areas are at greatest risk for
acquiring infection
 Life Cycle
The protozoan parasite, Trypanosoma •
cruzi, causes Chagas disease, a zoonotic
disease that can be transmitted to humans
by blood-sucking triatomine bugs.
 Disease
Chagas disease has an acute and a chronic •
phase. If untreated, infection is lifelong.
Acute Chagas disease occurs immediately •
after infection, may last up to a few weeks or
months, and parasites may be found in the
circulating blood. Infection may be mild or
asymptomatic. There may be fever or
swelling around the site of inoculation (where
the parasite entered into the skin or mucous
membrane). Rarely, acute infection may
result in severe inflammation of the heart
muscle or the brain and lining around the
brain.
 Following the acute phase, most infected •
people enter into a prolonged
asymptomatic form of disease (called
"chronic indeterminate") during which few
or no parasites are found in the blood.
During this time, most people are unaware
of their infection. Many people may remain
asymptomatic for life and never develop
Chagas-related symptoms. However, an
estimated 20 - 30% of infected people will
develop debilitating and sometimes life-
threatening medical problems over the
course of their lives.
 Complications of chronic Chagas disease
may include:
heart rhythm abnormalities that can cause •
sudden death; a dilated heart that doesn’t
pump blood well; a dilated esophagus or
colon, leading to difficulties with eating or
passing stool.
In people who have suppressed immune •
systems (for example, due to AIDS or
chemotherapy), Chagas disease can
reactivate with parasites found in the
circulating blood. This occurrence can
potentially cause severe disease.
 Laboratory Diagnosis
Demonstration of the causal agent is the diagnostic
procedure in acute Chagas disease. It almost always
yields positive results, and can be achieved by:
Microscopic examination: a) of fresh anticoagulated •
blood, or its buffy coat, for motile parasites; and b) of
thin and thick blood smears stained with Giemsa, for
visualization of parasites.
Isolation of the agent: a) inoculation in culture with •
specialized media (e.g. NNN, LIT); b) inoculation into
mice; and c) xenodiagnosis, where uninfected
triatomine bugs are fed on the patient's blood, and
their gut contents examined for parasites 4 weeks
later.
 Antibody Detection
During the chronic phase of infection, •
parasitemia is low; immunodiagnosis is a
useful technique for determining whether
the patient is infected.
 Antiparasitic Treatment
Antiparasitic treatment is indicated for all cases of •
acute or reactivated Chagas disease and for chronic
Trypanosoma cruzi infection in children up to age 18.
Congenital infections are considered acute disease.
Treatment is strongly recommended for adults up to
50 years old with chronic infection who do not already
have advanced Chagas cardiomyopathy. For adults
older than 50 years with chronic T. cruzi infection, the
decision to treat with antiparasitic drugs should be
individualized, weighing the potential benefits and
risks for the patient. Physicians should consider
factors such as the patient's age, clinical status,
preference, and overall health.
The two drugs used to treat infection with
Trypanosoma cruzi are nifurtimox and
benznidazole.
Common side effects of benznidazole
treatment include:
allergic dermatitis •
peripheral neuropathy •
anorexia and weight loss •
insomnia •
The most common side effects of nifurtimox
are:
anorexia and weight loss •
polyneuropathy •
nausea •
vomiting •
headache •
dizziness or vertigo •

Contraindications for treatment include

severe hepatic and/or renal disease.
Drug Age group Dosage and duration

Benznidazole < 12 years 10 mg/kg per day orally in 2

divided doses for 60 days.

12 years or older 5-7 mg/kg per day orally in

2 divided doses for 60 days

Nifurtimox ≤ 10 years 15-20 mg/kg per day orally

in 3 or 4 divided doses for
90 days

11-16 years 12.5-15 mg/kg per day

orally in 3 or 4 divided
doses for 90 days

17 years or older 8-10 mg/kg per day orally in

3 or 4 divided doses for 90
days
 Trypanosomiasis in Africa
Vector - Tse Tse fly
Trypanosoma brucei gambiense , causes chronic
infection lasting years, and affects countries of western
and central Africa Glossina palpalis (Western Africa)
Trypanosoma brucei rhodesiense , causes acute
illness (much worse) lasting several weeks in southern
and eastern Africa.
Glossina mortisans (Eastern Africa)
Millions of square kilometers of
Africa are home to the tsetse fly,
vector of trypanosomiasis:
•

Uganda
Kenya
Tanzania
Malawi
Ethiopia
Zaire
Zimbabwe
Botswana
• After the fly bites the protist enters the bloodstream
and begins to avoid the bodies immune system by
antigenic variation.
• While this is ocuring it gives the protist a chance to
replicate and inhabit other parts of the body. The
replicated protists move throughout the body and
begin affecting the bodies organs.
• In advanced cases of this disease the parasite invades
the central nervous system and can change the
patients behavior and cause other neurological
problems
 Signs & Symptoms

First Stage
• In the first stage the parasite is found in the peripheral
circulation, but has not yet invaded the central nervous
system. hemolymphatic stage
• Symptoms include:
– Headaches
– aching muscles and joints
– Fever
– Swollen lymph nodes all over the body
– Swollen, red, painful nodule at site of fly bite (Primary
chancre) - resolves 2-3 weeks

* The symptoms of both West and East African Sleeping Sickness are
essentially the same
 Winterbottom's sign - Swollen
lymph nodes along back of neck in
child with early trypanosomiasis
Chronic Disease Phase
• In the second stage, the parasite crosses the blood-
brain barrier and infects the central nervous system.
Neurological phase
• Symptoms include:
– Confusion
– Personality or mood changes
– Difficulty walking and talking
– Seizures
– Night insomnia
– loss of consciousness and coma
 Diagnosis
• Microscopic examination
– chancre fluid
– lymph node aspirates
– Blood
– bone marrow
– cerebrospinal fluid (late stages of infection)
• Serology
• Animal inoculation
 How is it Transmitted?
• African sleeping sickness is
transmitted by the tsetse fly, found
only in rural Africa. There are over 22
types of this fly and all scrictly feed on
Blood
• Breed by Rivers and streams
•
• A pregnant woman could pass the
infection to her child and, in theory,
the infection could also be transmitted
by blood transfusion or sexual contact
 Pathophysiology

The parasites escape the initial host defense •

mechanisms by extensive antigenic variation of
parasite surface glycoproteins known as major
variant surface glycoprotein (VSG). This evasion
of the humoral immune responses contributes to
parasite virulence. During the parasitemia, most
pathologic changes occur in the hematologic,
lymphatic, cardiac, and central nervous systems.
This may be the result of immune-mediated
reactions against antigens on red blood cells,
cardiac tissue, and brain tissue, resulting in
hemolysis, anemia, pancarditis, and
meningoencephalitis
 A hypersensitivity reaction causes skin
problems, including persistent urticaria,
pruritus, and facial edema. Increased
lymphocyte levels in the spleen and lymph
nodes infested with the parasite leads to
fibrosis but rarely hepatosplenomegaly.
Monocytes, macrophages, and plasma
cells infiltrate blood vessels, causing
endarteritis and increased vascular
permeability
The gastrointestinal system is also affected. •
Kupffer cell hyperplasia occurs in the liver,
along with portal infiltration and fatty
degeneration. Hepatomegaly is rare. More
commonly in East African trypanosomiasis, a
pancarditis affecting all heart tissue layers
develops secondary to extensive cellular
infiltration and fibrosis. Arrhythmia or cardiac
failure can cause death prior to the
development of CNS manifestations. CNS
problems include perivascular infiltration into
the interstitium in the brain and spinal cord,
leading to meningoencephalitis with edema,
bleeding, and granulomatous lesions.
 Epidemiology
Sleeping sickness threatens millions of •
people in 36 countries.In 1986, it was
estimated that some 70 million people
lived in areas where disease transmission
could take place.
In 1998, almost 40 000 cases were •
reported, but estimates were that 300 000
cases were undiagnosed and therefore
untreated.
In 2009, after continued control efforts, the •
number of cases reported has dropped
below
10 000 (9878) for first time in 50 years.
The estimated number of actual cases is
currently
30 000.
 Mortality/Morbidity

The symptoms of East African •

trypanosomiasis develop more quickly
(starting 1 mo after bite) than the
symptoms of West African
trypanosomiasis, which can begin months
to a year after the first bite
 Clinical Presentation
History •

Stage 1 (early, or hemolymphatic, stage) •

Painless skin chancre that appears about 5-15 days after the •
bite, resolving spontaneously after several weeks (seen less
commonly in T brucei gambiense infection)
Intermittent fever (refractory to antimalarials), general •
malaise, myalgia, arthralgias, and headache, usually 3 weeks
after bite
Generalized or regional lymphadenopathy (Posterior cervical •
lymphadenopathy [Winterbottom sign] is characteristic of T
brucei gambiense African trypanosomiasis [sleeping
sickness].)
 Facial edema (minority of patients). •
Transient urticarial, erythematous, or •
macular rashes 6-8 weeks after onset
Trypanids (ill-defined, centrally pale, •
evanescent, annular or blotchy edematous
erythematous macules on trunk)
 Stage 2 (late, or CNS, stage) Persistent •

headaches (refractory to analgesics) •

Daytime somnolence followed by nighttime •
insomnia
Behavioral changes, mood swings, and, in •
some patients, depression
Loss of appetite, wasting syndrome, and •
weight loss
Seizures in children (rarely in adults) •
Fevers, tachycardia, irregular rash, edema •
 Physical •
Stage 1 (early, or hemolymphatic, stage) •
Indurated chancre at bite site •
Skin lesions (trypanids) in light-skinned patients •
Lymphadenopathy: Axillary and inguinal •
lymphadenopathy are more common in patients
with East African trypanosomiasis. Cervical
lymphadenopathy is more common in patients with
West African trypanosomiasis. The classic
Winterbottom sign is clearly visible (ie, enlarged,
nontender, mobile posterior cervical lymph node).
Fevers, tachycardia, irregular rash, edema, and •
weight loss
Organomegaly, particularly splenomegaly (T •
brucei gambiense African trypanosomiasis)
 Stage 2 (late, or CNS, stage) •

CNS symptoms: The CNS symptoms of •

West African trypanosomiasis have a slower
onset of, ie, months to a year. Symptoms
include irritability, tremors, increased muscle
rigidity and tonicity, occasional ataxia, and
hemiparesis, but rarely overt meningeal
signs. East African trypanosomiasis usually
has a faster onset, ie, weeks to a month, and
does not exhibit a clear distinction between
the two stages.
Kerandel sign, including delayed pain on •
compression of patient's soft tissue
Behavioral changes consistent with mania •
or psychosis, speech disorders, and
seizures
Stupor and coma (giving rise to the name •
sleeping sickness)
Psychosis •
Sensory disorders, tremor, and ataxia •
 Laboratory Studies

General •
In African trypanosomiasis (sleeping sickness), the most significant •
laboratory abnormalities include anemia, hypergammaglobulinemia,
low complement levels, elevated erythrocyte sedimentation rate
(ESR), thrombocytopenia, and hypoalbuminemia, but not
eosinophilia or abnormal liver function.
In West African trypanosomiasis, the total immunoglobulin M (IgM) •
level is notably higher in blood and CSF (along with high CSF
protein).
A definitive diagnosis of infection requires actual detection of •
trypanosomes in blood, lymph nodes, CSF, skin chancre aspirates,
or bone marrow. However, symptomatic improvement after empiric
treatment is the usual confirmatory test in areas where diagnostic
studies are not readily available.
 Lymph node aspiration at a high dry •
magnification (X400) is commonly used as
a rapid test for trypanosomes. It requires
immediate search for parasites because
they are mobile for only 15-20 minutes.
This test has more utility in T brucei
gambiense trypanosomiasis.
 Blood smear
A wet smear of unstained blood or Giemsa-stained •
thick smear (more sensitive) is used to evaluate for
mobile trypanosomes, again for 15-20 minutes. Wright
and Leishman stains are inadequate. This technique is
most sensitive in early stages of disease, when the
number of circulating parasites is highest (≥5000/mL),
particularly in T brucei rhodesiense trypanosomiasis.
Better assays are now available, including the •
hematocrit centrifugation technique for buffy coat
examination and the miniature anion-exchange
centrifugation technique (mAECT), which filters out the
red cells but not the trypanosomes. This test can be
used to detect parasitemia levels as low as 5
parasites/mL; the test can be repeated on subsequent
days to increase the yield when results are negative.
 Chancre aspirate can be used as a wet •
preparation, especially in East African
trypanosomiasis, but a blood smear is more
sensitive.
Bone marrow aspiration results may be •
positive in some patients.
CSF assay
Lumbar puncture should be performed •
whenever trypanosomiasis is suspected. CSF
examination helps to diagnose and stage the
disease. However, a negative result does not
necessarily rule out the diagnosis.
The double centrifugation technique is the •
most sensitive method to detect the
trypanosomes.
 Imaging Studies
CT scanning and MRI of the head: Both •
head CT scanning and MRI reveal
cerebral edema and white matter
enhancement, respectively, in patients
with late-stage African trypanosomiasis.
EEG in neurologic involvement usually •
shows slow wave oscillations (delta
waves), a nonspecific finding
 Treatment & Management
Prehospital care of African trypanosomiasis •
(sleeping sickness) centers on management
of the acute symptoms of fever and malaise
while closely monitoring the patient’s
neurologic status.
In the emergency department, if CNS •
symptoms are severe, then airway
management to prevent aspiration becomes
important, along with an immediate blood
smear, CBC count, and lumbar puncture for
trypanosome detection.
Type of Trypanosomiasis Stage 1 Stage 2

(Hemolymphatic Stage) (Neurologic [CNS] Stage)

East African Suramin 100-200 mg IV test Melarsoprol 2-3.6 mg/kg/d

trypanosomiasis (caused by dose, then 1 g(20mg/kg) IV IV for 3 d; after 1 wk, 3.6
T brucei rhodesiense) on days 1, 3, 7, 14, 21 mg/kg/d for 3 d; after 10-21
d, repeat the cycle
West African Pentamidine isethionate 4 Melarsoprol 2-3.6 mg/kg/d
trypanosomiasis (caused by mg/kg/d IM for 10 d IV for 3 d; after 1 wk, 3.6
T brucei gambiense) mg/kg/d for 3 days; after 10-
21 d, repeat the cycle

or or

Suramin 100-200 mg IV test Eflornithine 400 mg/kg/d IV

dose, then 1 g(20mg/kg) IV in 4 divided doses for 14 d
on days 1, 3, 7, 14, 21
 Suramin (Metaret)

Antiparasitic agent used IV in early-stage •

African trypanosomiasis and onchocerciasis.
Suramin is a polysulfonated naphthylamine
derivative of urea. Suramin is trypanocidal
and works by inhibiting parasitic enzymes
and growth factors. Highly bound to serum
proteins and, thus, crosses the blood-brain
barrier poorly. Serum levels are
approximately 100 mcg/mL. Suramin is more
effective and less toxic than pentamidine.
Excreted in the urine at a slow rate.
 Adverse Effects
Vomiting •
Urticaria •
Paresthesia •
Peripheral neuropathy •
Kidney damage •
Blood dyscrasias •
Shock •
Optic atrophy •
Melarsoprol (Melarsen Oxide-BAL,
Mel B, RP 3854)
Trivalent arsenical used in the late or CNS •
stage of African trypanosomiasis.
Trypanocidal, inhibiting parasitic glycolysis.
Water insoluble and has a half-life of 35 h.
Serum levels range from 2-5 mcg/mL, but
CSF levels are 50-fold lower. The drug is
primarily excreted by the kidneys. Clinical
improvement is usually observed within 4 d
after starting the drug. Therapy is as high as
90-95% successful in clearing the
parasitemia. However, it can be toxic and
even fatal in 4-6% of cases.
 Studies have now demonstrated the •
effectiveness of 10-day melarsoprol
treatments for late-stage African
trypanosomiasis. In addition, melarsoprol
resistance has become a concern in the
Congo and Uganda; up to 30% of cases
do not respond to the drug.
 Adverse Effects
Hypertension •
Myocardial damage •
Encephalopathy •
Peripheral neuropathy •
Colic •
Vomiting •
Albuminuria •
Herxheimer-type reaction •
 Eflornithine (Ornidyl)

Recommended for treatment of patients •

with West African trypanosomiasis,
especially late (or CNS) disease. Selective
and irreversible inhibitor of ornithine
decarboxylase, which is a critical enzyme
for DNA and RNA synthesis. Generally
tolerated better and is less toxic than
arsenic drugs. Available via World Health
Organization. Initial response time is 1-2
wk. Used for patients in whom melarsoprol
 Adverse effects
>10%
Anemia (55%) •
Leukopenia (37%) •
Thrombocytopenia (14%) •
1-10% •
Seizures (may be due to the disease) (8%) •
Dizziness •
Alopecia •
Vomiting, diarrhea •
Eosinophilia •
Hearing impairment •
<1%
Abdominal pain •
Anorexia •
Facial edema •
Headache •
Weakness •
Pentamidine isethionate (Pentam
300, Pentacarinat, NebuPent)
Antiprotozoal agent usually used for early (or •
stage 1) African trypanosomiasis as well as
Pneumocystis jervesii pneumonia and
leishmaniasis. Works by inhibiting dihydrofolate
reductase enzyme, thereby interfering with
parasite aerobic glycolysis. Because of poor GI
absorption, the drug is administered IV/IM and is
strongly bound to tissues, including spleen, liver,
and kidney. Clinical improvement usually noted
within 24 h of injection. Reported to have a >90%
cure rate. Pentamidine does not penetrate the
blood-brain barrier effectively and, therefore, does
not treat CNS infection.
 Adverse Effects
>10%
Injection •
Incr SCr (23%) •
IM site rxns (11%) •
Leukopenia (10.3%) •
Elevated LFT's •
Nebulizer •
Cough (63%) •
Wheezing •
Pharyngitis •
Bronchospasm •
Chest pain •
Rash •
 1-10%
Injection •
Anemia •
Confusion/hallucinations •
Hypoglycemia •
Hypotension •
Fever •
Anorexia/Nausea/Vomiting •
Rash •
Thrombocytopenia •
Nebulizer •
Bitter/metallic ta •
 <1%
Injection: •
ARF •
Dizziness •
Neuralgia •
Frequency Not Defined
Anemia •
Bronchitis •
Neutropenia •
Pleuritis •
Rales •
Thrombocytopenia •
 Control
Destruction of animal reservoir
Vector Control
Diagnosis & treatment
 Prevention

• Currently there is no vaccine or drug to

prevent infection of African sleeping
sickness.
• This illness is only spread by the bite of a
Tsetse fly, so if possible, the best way to
prevent this illness is to avoid travelling to
Africa.
• Preventative Measures Include:
– Wearing long-sleeved shirts and pants of
medium-weight material in neutral colors.
– Inspecting vehicles for flies before entering.
– Avoiding bushes since tsetse flies are less
active during the hottest parts of the day.