1. Acknowledge for Dr. Wiser
KINETOPLASTIDS
widespread parasites
animals (fishhumans)
insects
plants
kinetoplast near the base of the flagellum
unifying feature = kinetoplast
Giemsa staining structure
Kinetoplast
Nucleus
Acknowledge for Dr. Wiser

2. flagellum
undulating membrane
flagellar pocket
nucleus
mitochondrion
subpellicular microtubules
basal body
kinetoplast

3. = trypanosomal
= crithedial
= leptomonad
= Leishmanial

4. Disease Causing Kinetoplastids
Trypanosoma brucei complex
African trypanosomiasis
Trypanosoma cruzi
Chagas’ disease
Leishmania species
leishmaniasis
African trypanosomiasis
60 million at risk
25-45,000 reported cases
3-500,000 estimated cases

5. Species Distribution

6. tsetse = Glossina

9. Endemic T. gambiense transmission

10. T. rhodesiense transmission
wild animal reservoir
Zoonosis:
infection naturally transferable between animals and humans
bush buck

11. Metacyclic trypomasitgotes transferred with saliva during tse-tse feeding.2 1
Trypomastigotes replicate in blood stream and tissues of mammal.
Preadaptation for tse-tse. 3 4
Ingestion by tse-tse.

12. Blood Stage blood-stream forms preadaptation for tsetse long slender
rapid replication
binary fission
preadaptation for tsetse
morphological (short stumpy)
slower replication
metabolic (mitochondria)

13. 7 6 5 Maturation to metacyclic trypomastigotes.
long-slender 7
Migration to salivary glands and transformation to epimastigotes. 6
intermediate
Procyclic trypomastigotes replicate in tse-tse midgut.
loss of surface coat
metabolic changes (mitochondria)
short-stumpy 5

14. Migration to Salivary Glands: Two Possible Routes

15. Maturation to Metacyclic Trypomastigotes in Salivary Glands

17. Infection Tsetse Bite pain hypersensitivity tsetse are pool feeders
metacyclic trypomastigotes in saliva and enter bite wound
Tsetse Bite
pain
hypersensitivity

18. Acute Symptoms and Blood Stage
1-3 week asymptomatic incubation period
sometimes a local inflammation
'trypanosomal chancre'
parasite replication at bite site
invasion of blood characterized by irregular fever and headache
T. rhodesiense can develop into fulminating infection
T. gambiense can be self-limiting or slowly progressing to more serious disease

19. Lymphatic Stage cachexia
disease progression often involves invasion of lymphatics
Winterbottom’s sign
rash
itching
edema
continued febrile attacks
weight loss
weakness
cachexia

20. CNS Disease Course and Symptoms
parasites crossing blood-brain barrier result in CNS involvement and nervous impairment
described as meningoencephalitis
increased apathy and fatigue
confusion and somnolence
motor changes including tics, slurred speech, incoordination
convulsions, coma
progression to CNS involvement is rapid (weeks) in Tr and slow (6-12 months) in Tg
death results from disease (eg., convulsions, hyperpyrexia) or other infections

22. Diagnosis Clinical Features Laboratory Diagnosis
travel or residence in endemic area
history or scar of 'trypanosomal chancre'
irregular fever and enlarged lymph nodes
particularly posterior cervical
behavioral changes/mental symptoms
Laboratory Diagnosis
serological tests
IFA, ELISA, CATT (card agglutination trypanosomiasis test)
demonstration of trypanosomes
especially during fever
definitive diagnosis

23. Detection of African Trypanosomes
Blood
examine on several days
stained thin or thick smears
fresh (characteristic movement)
buffy coat (microhematocrit)
mini-anion exchange chromato-graphy technique (m-AECT)
inoculate rats or mice

24. Detection of African Trypanosomes
Lymph Node Aspirates
fresh or stained
Cerebrospinal Fluid
examine sediment
 cells and protein (presumptive)

25. Treatment Early Stage--no CNS involvement suramin pentamidine
excellent prognosis
Late Stage--CNS involvement
melarsoprol
arsenical based drug
high toxicity (4-12% mortality)
eflornithine (resurrection drug)
expensive
14 consecutive daily injections
oral formulation in phase 3 trials

26. Acknowledge for Dr. Wiser
Prophylaxis and Control
drugs contraindicated
mask infections
toxicity
insect repellants
protective clothing
community activities
surveillance and treatment
traps, insecticides
habitat alteration
Acknowledge for Dr. Wiser