Transcript Trypanosomiasis Jane Ngai – Simon Zappia

Trypanosomiasis
Jane Ngai – Simon Zappia
Protista  Kinetoplastida  Trypanosoma
• African Trypanosomiasis – 400,000
affected causing 50,000 to 70,000
deaths/year.
• American Trypanosomiasis – 11
million people affected causing 50,000
deaths/year.
Trypomastigote
FORM
Epimastigote
Promastigote
Amastigote
• African Trypanosomiasis
– Sleeping Sickness
– Trypanosoma brucei brucei (cattle)
– Trypanosoma brucei gambiense
– Trypanosoma brucei rhodesiense
• American Trypanosomiasis
– Chagas Disease
–  Trypanosoma cruzi
AFRICAN TRYPANOSOMIASIS
Fly belt distribution
Transmission
• Via vector – bite from
the tse tse fly
• Mother to child
infection (perinatal
death)
• Blood transfusion
• Sexual contact
Lifecycle
Fly injects metacyclic
trypomastigotes when
it feeds on blood.
Trypomastigotes
reproduce asexually in
the bloodstream
Parasite reproduces asexually in
the fly’s gut (epimastigotes),
migrates to the fly’s salivary glands
(metacyclic trypomastigote)
Fly ingests
trypomastigotes when
it feeds on blood of
infected individual.
Pathogenesis (2 stages)
• Stage 1: Haemolymphatic
stage (ACUTE)
– Most patients do not notice this
stage of infection.
– Small papule from bite may
develop exciting local
inflammation.
– When trypomastigotes enter
the haemo-lymphatic system to
multiply,clinical symptoms
include:
– Fever, headache and joint pain
– Winterbottom’s sign: swelling
of lymph nodes at the posterior
neck region.
• Stage 2: Meningoencephaltic
stage (CHRONIC)
– Sleeping sickness stage because
trypanosomes have crossed the
blood-brain barrier
– Personality changes, headaches
and withdrawal from the
environment.
– Simple tasks become harder to
accomplish as individual
experience nocturnal insomnia
and daytime lethargy, apathy and
ultimately succumb to secondary
infections such as pneumonia.
Treatment
• Stage I
– Pentamidine: 7-10 injections for T. b.
gambiense infection. Side effects
include: Painful injections with risk of
hypotension and shock, pancreatic,
renal or hepatic dysfunction; bone
marrow suppression and
polyneuropathy
– Suramin – multiple doses on varying
days for T.b. rhodesiense infection.
Side effect include: renal impairment,
peripheral neuropathy and bone
marrow suppression.
Treatment
• Stage II
– Melarsoprol (arsenical compound) –
slow IV injection. Side effects
include: encephalopathy
– Eflornithine – infusion for 2 weeks
every 6 hours. Drug is expensive and
more effective against T. b.
gambiense.
Cyclical waves of infection
Prevention
• Control in the reservoirs
like livestock and
wildebeest
• Remove scrub (where tse
tse flies reproduce)
• DDT
• Education
• Public awareness
•Only specific species of genus Glossina transmit the
parasite resulting in a spotty distribution through the fly belt.
T. b. gambiense
(Chronic)
T. b. rhodesiense
(Acute)
AMERICAN TRYPANOSOMIASIS
Transmission
• Mediated via vector of
genus Triatoma, Rhodnius
and Panstrongylus also
known as “kissing bugs”
• Ingestion of food
contaminated with
parasites
• Blood transfusion
• Fetal transmission (13%
stillborn deaths/year in
Brazil)
Lifecycle
Pathogenesis (Acute)
• Acute phase
– Starts 1 week after
infection
– Fever, lymph node
enlargement, unilateral
swelling of the eyelids
(Romana’s sign),
acute myocarditis,
damaged muscle cells
and edema.
Pathogenesis (Chronic)
• Chronic Phases:
– Starts 2 months after initial
infection.
– Indeterminate form: 60-70% of
people with Chagas. Completely
free of cardiac, gastrointestinal
and neurological symptoms but 25% of patients convert to cardiac
or digestive forms each year
(reason not clear).
Cardiac manifestation
• Cardiac form:
– 30-40% of people with
Chagas. Induces
arrhythmia, cardiac failure,
thromboembolism,
atrioventricular fibrillation,
ventricular hypertrophy
Gastrointestinal manifestation
• Digestive form:
– 10% of people. Megaoesophagus 3%,
megacolon and may be associated with
cardiac form. Difficulty in swallowing,
regurgitation, aspiration may cause
pneumonia and death. Chronic
constipation, fecal compacting causes
perforation of the colon.
Treatment
• Treatment exists for symptoms but there are
no cures for the disease.
• All available pharmaceuticals are expensive
and are of inefficient efficacy. No medications
are given to patients with the chronic phase.
Prevention
• Elimination of “kissing bug” environment with
building structures that discourage the bug’s
habitation.
• Avoid pets in the home environment to limit
attraction.
• Avoid building homes with palm roofs and cracks.
• Use of insecticides.
• Mechanical elimination of the vector (ie. squish it).
• Education.
New developments
• Clinical manifestations of the cardiac and
gastrointestinal forms are unknown.
• Heart problems may be linked to
autoimmune responses triggered by
parasites being engulfed in the
macrophage and not completely
destroyed.
• Others think heart problems may be linked
to the parasites themselves.
• Inconclusive data.
Questions
• Consider the nature of both diseases; their
vector, distribution and impact on local
populations. Which disease, in your opinion,
deserves more attention and funding? Why? How
would you invest the money?