Trypanosomiasis.

Sleeping sickness and Chagas diesese.

African trypanosomiasis
(Sleeping sickness)
• – protozoan disease transmitted to human beings by
the bite of infected tsetse flies.
 Classification:
• Eukaryota (organisms with
nucleated cells),Kingdom
Protista, Phylum Protozoa.
• East African
trypanosomiasis is caused
by the parasite
Trypanosoma brucei
rhodesiense.
• West African
trypanosomiasis is caused
by Trypanosoma brucei
gambiense. The parasites
are spread by tsetse flies,
found only in Africa.
 Morphology
• Trypanosomes have a single
central nucleus and a single
flagellum originating at the
kinetoplast and joined to the
body by an undulating
membrane.
• The outer surface of the
organism is densely coated
with a layer of glycoprotein,
the variable surface
glycoprotein (VSG).
 Morphological Forms

TRYPOMASTIGOTE
• The kinetoplast (kt) is located on the
posterior end of the parasite. The
flagellum emerges from the posterior
end and folds back along the parasite's
body. This attachment of the flagellum
to the body forms an undulating
membrane (um) that spans the entire
length of the parasite and the free
flagellum emerges from the anterior
end.
• The undulating membrane functions
like a fin and increases the motility of
the organism.
 Morphological Forms

EPIMASTIGOTE
• The kinetoplast (kt) is more
centrally located, usually just
anterior to nucleus (Nu). The
flagellum (fg) emerges from the
middle of the parasite and forms
a shorter undulating membrane
(um) than observed in
trypomastigotes.
• Epimastigotes are noticeably
less motile than
trypomastigotes.
 Morphological Forms

PROMASTIGOTE
• The kinetoplast (kt) is towards
the anterior end and a free
flagellum (fg) with no
undulating membrane
emerges.
• The end that the free
flagellum emerges from in all
three motile forms is
designated as the anterior end
because they swim in that
direction. In other words, the
flagellum pulls the organism.
 Morphological Forms

AMASTIGOTE
• The parasite is more spherical in
shape and has no free flagellum.
A basal body (bb) and the base
of the flagellum is still present.
The kinetoplast (kt) is usually
detectable as a darkly staining
body near the nucleus (Nu).
This form is a non-motile
intracellular stage.
 Etiology.
There are two clinical
forms of African
trypanosomiasis:
• 1) a slowly developing
disease caused by
Trypanosome brucei
gambiense (92% of
reported cases) and
• 2) a rapidly progressing
disease caused by T.
brucei rhodesiense.(8%)
• The Rhodesian type of sleeping sickness evolves
more acutely to death and its neurologic effects are
less characteristic.
• The Gambian form tends to be more chronic and
sometimes takes several years to develop central
nervous system (CNS) involvement.
 Major Differences Between African
Trypanosome Species
Attribute T. rhodesiense T. gambiense
tsetse vector G. morsitans group G. palpalis group

ecology dry bush, woodland rainforest, riverine, lakes

transmission cycle ungulate-fly-human human-fly-human

non-human reservoir wild animals domestic animals

epidemiology sporadic, safaris endemic, some epidemics

disease progression rapid, often fatal slow (~1 yr) acute ⇒

chronic
parasitemia high low
asymptomatic carriers rare common
Life cycle of Trypanosoma brucei parasites
 Epidemiology
• Human trypanosomiasis has caused
massive epidemics in the past. At
the turn of the century, in Zaire and
around Lake Victoria, large
epidemics caused at least
three-quarters of a million deaths.
Although only approximately 20000
cases are reported each year to the
World Health Organization, gross
under-reporting, reduced
surveillance, and recent epidemics
in Zaire, Uganda, Tanzania,
Mozambique, and Sudan underline
the continuing importance of
human trypanosomiasis in public
health.
 Epidemiology
• Trypanosomiasis of domestic
animals and man remains an
important deterrent to
development in endemic areas
and shows increased prevalence
associated with war, civil
disturbance, and refugee groups as
well as deteriorating health
services and disease-specific
control programmes.
Pathogenesis

• Inflammatory changes (possibly autoimmune) cause

CNS demyelination. Immunosuppression by the
parasite facilitates secondary infections.
 Clinical Symptoms

• A tsetse fly bite is often painful and

can develop into a red sore, called a
chancre.
 Clinical Symptoms
• fever,
• severe headache,
• irritability,
• extreme tiredness,
• swollen lymph glands,
• aching muscles and
joints.
 Clinical Symptoms
• Weight loss and a body rash
are also common.
• Infection of the central
nervous system causes
confusion, personality
changes, slurred speech,
seizures, and difficulty in
walking and talking. If left
untreated, the illness
becomes worse, and death
occurs within several weeks
to months
 Laboratory Diagnostics:
• In the early stages of the disease,
the parasites can be
demonstrated in lymph nodes
and blood; later, they appear in
the cerebrospinal fluid. In the
Rhodesian type, lumbar puncture
is indicated because of early CNS
invasion. Culture or laboratory
animal inoculations can be useful.
Serologic tests, such as indirect
immunofluorescence, direct card
agglutination, and indirect
hemagglutination, are used
successfully for diagnosis.
 Treatment

• Medicine for the treatment of African trypanosomiasis

is available. Treatment should be started as soon as
possible and is based on the infected person's
symptoms and laboratory tests results.
• Patients need to be hospitalized for treatment and
require periodic follow-up exams for 2 years.
• The current standard treatment for first stage disease
is: Intravenous pentamidine (for T.b. gambiense); or
suramin (for T.b. rhodesiense).
• The current standard treatment for second stage
disease is: Intravenous melarsoprol.
• In areas with melarsoprol resistance or in patients who
have relapsed after melarsoprol monotherapy, the
treatment should be: melarsopsol and nifurtimox, or
eflornithine.
Prevention

• There is no vaccine or drug to prevent African

trypanosomiasis.
• When traveling in areas where the disease occurs,
take these precautions against bites from tsetse flies
and other insects.
Prevention

• Cover Up
• Apply Repellent
• Light Clothing
• Avoid Scents
• Use Bed Nets
• Screened Accommodations
• Avoid Peak Times
• Avoid Wildlife Areas
• Trypanosoma cruzi belongs to the subkingdom
Protozoa. They are flagellar organisms that have one
nucleus and an organelle, the kinetoplast, that gives
rise to one mitochondrion and mitochondrial DNA.

• Chagas disease, named for Carlos Chagas, the

Brazilian doctor who first described the disease in
1909, is caused by Trypanosoma cruzi,a flagellate
protozoan parasite.
 Classification

• Eukaryota (organisms with nucleated

cells),Kingdom Protista, Phylum Protozoa.
• Trypanosoma cruzi.
• T. cruzi reproduce asexually by binary fission.
• Like all other trypanosomes, T. cruzi live one
stage of their lives in the blood and/or
tissues of vertebrate hosts and during other
stages they live in the digestive tracts of
invertebrate vectors (temporary hosts).
Case of human
trypanosomiasis have been
reported in almost all countries of the
Americas, including the southern United
States, but the main foci are in poor rural
areas of Latin America.
 Life cycle of Trypanosoma cruzi.

• An infected triatomine
insect vector (or “kissing”
bug) takes a blood meal
and releases
trypomastigotes in its
feces near the site of the
bite wound.
• Inside the host, the
trypomastigotes invade
cells, where they
differentiate into
intracellular amastigotes .
 Life cycle of Trypanosoma cruzi.

• The amastigotes
multiply by binary
fission and
differentiate into
trypomastigotes, and
then are released into
the circulation as
bloodstream
trypomastigotes
• Trypomastigotes infect cells from a variety of tissues and
transform into intracellular amastigotes in new infection
sites.
• The bloodstream trypomastigotes do not replicate.
• Replication resumes only when the parasites enter another
cell or are ingested by another vector.
• The “kissing” bug becomes infected by feeding on human
or animal blood that contains circulating parasites.
• The ingested trypomastigotes transform into epimastigotes
in the vector’s midgut .
• The parasites multiply and differentiate in the midgut.
 Epidemiology
• Chagas disease is transmitted by
cone-nosed triatomine bugs of several
genera (Triatoma, Rhodnius,
Panstrongylus).

• Trypanosoma cruzi can also be

transmitted through blood transfusions,
organ transplantation,
transplacentally,breast milk and in
laboratory accidents.
 Transmission Methods of T. cruzi

• Contamination
Contamination through the
insect's feces is the
primary mechanism by
which vinchucas pass T.
cruzi to humans.
 Transmission Methods of T. cruzi

• Blood Transfusions and

Organ Transplants
Blood transfusions are
the second most common
mechanism of
transmission of Chagas'
disease to people in Latin
America, Europe,and the
United States.
 Transmission Methods of T. cruzi

• Transmission Through Birth

Mothers pass T. cruzi on
to their children as T.
cruzi travels through the
placenta, birth canal, and
possibly maternal milk.
This type of transmission
occurs less frequently
than other methods.

Possibilites include diffusion of the parasite across the extra-embryonic

membranes, or through the maternal blood supply.
 Geographic
• Chagas disease is found
only in Latin America
• Natural foci of Chagas disease exist among wild mammals
and their associated triatomines.
• Humans and domestic animals became involved in the
epidemiologic chain several centuries ago, when insects
living under wild conditions began adapting to households.
• Opossums, armadillos, and wild rodents are reservoirs of
the parasite, linking the wild and domestic cycles
 Pathogenesis
Inflammatory reactions at the
sites of rupturing pseudocysts can
lead to pathologic manifestations,
such as acute
myocarditis and destruction
of parasympathetic ganglia of the
heart and myenteric plexus.
An autoimmune reaction may
develop.
Clinical Symptoms.

The incubation period is 7-14 days.

The human disease occurs in 3 stages:
• the acute stage shortly after the infection;
• the indeterminate stage;
• the chronic stage that may develop over 10 years.
 Acute phase of Chagas disease

• A local skin nodule called a chagoma can appear

at the site of inoculation.
• When the inoculation site is the conjunctival
mucous membranes, the patient may develop
unilateral periorbital edema
• When the inoculation site is the conjunctival
mucous membranes, the patient may develop
unilateral periorbital edema, conjunctivitis and
preauricular lymphadenitis. (Romaña's sign).
 Acute phase of Chagas disease

• The acute phase is usually

asymptomatic, but may present
symptoms of fever, anorexia,
lymphadenopathy, mild
hepatosplenomegaly
• The acute phase is usually
asymptomatic, but may present
symptoms of fever, anorexia,
lymphadenopathy, mild
hepatosplenomegaly, and myocarditis
 Other symptoms are:
• tiredness,
• sometimes a rash,
• loss of appetite, diarrhea, and vomiting.
• Infants and very young children can get an
often-fatal swelling of the brain.
Indeterminate stage

• During the indeterminate stage, about 8 to 10 weeks

after infection, infected persons have no symptoms.
 Chronic stage of Chagas disease

The disease affects the nervous system,

digestive system and heart:
• damage to the heart muscle
(cardiomyopathy), altered heart rate or
rhythm,
• sometimes dilation of the digestive tract
(megacolon and megaesophagus),
• Weight loss.
• Swallowing difficulties may be the first
symptom of digestive disturbances and may
lead to malnutrition.
Left untreated, Chagas disease can be fatal,
in most cases due to the cardiomyopathy
component.
Gross anatomy of a heart
The risk factors for getting Chagas disease

• International travel
• Undeveloped countries
• Poorly constructed houses
• Rural areas
• Mud houses
• Adobe houses
• Thatch houses
• Assassin bugs
• Persons with weakened immune
systems are at risk of severe
infections and complications.
 Laboratory Diagnostics

• microscopic blood examination,

• Xenodiagnosis;
• by culturing the blood.
• serologic tests :
● indirect hemagglutination,
● indirect immunofluorescence,
● enzyme-linked immunosorbent
assay (ELISA)]
 Xenodiagnosis

• In this test, uninfected vinchucas

are placed in a jar and tucked
under the armpit of a patient
suspected of being infected.
• The vinchucas are allowed to
consume blood for thirty
minutes, and their feces are
examined for T. cruzi thirty and
sixty days afterward.
• This technique is rarely used on
children, and many adults have
are hesitant in being willfully
bitten by vinchucas.
ELISA testing

• People without
noticeable signs of
chagas who live in
chagasic areas should
be encouraged to
have an ELISA test.
 Culturing the blood.

Trypanosoma cruzi in cultured

Amastigotes infecting cells
HeLa cells (Giemsa)
of muscle tissue
Treatment

• No effective treatment.
• Available drugs only kill extracellular parasites.
• Benznidazole and Nifurtinox: current drugs of
choice. Required daily for up to 2 months or
more.
• Hospitalization may be needed because of
adverse effects
 Preventation

• There is no vaccine or drug to prevent

Chagas disease. When traveling to areas
where Chagas disease occurs, follow these
precautions:
• Avoid sleeping in poorly constructed
thatch, mud, or adobe houses. If that is
not possible, use a bednet.
• Use insecticides to kill insects and reduce
the risk of transmission.
• Be aware of the risk of contracting Chagas
disease through blood transfusions. In
many countries, the blood supply is not
well screened.