1. Vector-Borne Diseases: Trypanosomiasis April 1 st, 2010

2. The Pathogen Genus Trypanosoma Two species of human health importance: –Trypanosoma brucei –Trypanosoma cruzi The T. brucei complex (2 subspecies): –Trypanosoma brucei rhodesiense –Trypanosoma brucei gambiense –Cannot tell them apart by morphology –Cause distinct disease entities

3. The Pathogen Protozoan hemoflagellates –Single celled –flagella Complex life cycle –Vector –Human –animals Reservoirs: –Humans –Cattle

4. The Pathogen Trypanosoma brucei ssp. in thin blood smears stained with Giemsa.

5. Overview Three types of trypanosomiasis –West African (sleeping sickness) –East African (sleeping sickness) –American (Chaga’s disease) Differences –Geographic distribution –Vectors –Disease process

6. West African Trypanosomiasis Sleeping sickness Trypanosoma brucei gambiense Geographic distribution –Western and Central Africa –Vector distribution Always fatal without treatment Disease course over years –acute and chronic phases

7. West African Trypanosomiasis This form is ~95% of reported cases 12,000-15,000 reported cases/year, WHO estimates 50-60,000 are really infected Humans are the reservoir Disease of rural areas; urban transmission is rare

8. East African Trypanosomes Trypanosoma brucei rhodesiense Geographic distribution –East and Southeast Africa Always fatal without treatment Acute course compared to gambiense form Cattle are additional reservoir

9. Cases of African trypanosomiasis

10. Geographic distribution

12. The vector Tsetse fly Glossina species Takes a blood meal trypomastigotes are the form transmitted to the host Daytime feeder Savannah and riverine flies

13. Life Cycle: Trypanosomes

14. Disease Length of disease process differs between two Sore may develop at site of initial inoculation –hemolymphatic stage –fever, lymphadenopathy, and pruritus. meningoencephalitic stage –Parasite crosses blood-brain barrier –invasion of the central nervous system –headaches, somnolence, abnormal behavior –loss of consciousness and coma more acute disease with T. b. rhodesiense than T. b. gambiense.

15. Immunity Humans do mount immune response No residual immunity cyclic fluctuation in the number of parasites in blood Each new wave of parasite represents a different antigenic variant

16. Diagnosis Microscopic examination –chancre fluid –lymph node aspirates –Blood –bone marrow –cerebrospinal fluid (late stages of infection) smear stained with Giemsa

17. Treatment Pentamidine isethionate –hemolymphatic stage of West African suramin –hemolymphatic stage of East African Melarsoprol –arsenical –late disease with central nervous system involvement –T.b. gambiense or T. b. rhodiense Eflornithine –Expensive –not widely available –effective only for West African

18. Control Bite prevention –Difficult with daytime biters Control vector habitats Treat infected people –Screening methods are available Bednets not useful

19. Vector control Control with insecticides –sequential aerosol spraying technique (SAT) –ground spraying –insecticide-treated targets or insecticide- treated animals Traps sterile insect technique (SIT).

20. American trypanosomiasis Chaga’s Disease Trypanosoma cruzi Geographic distribution –southern United States to southern Argentina A disease of poor, rural areas of Mexico, Central America, and South America Humans and animals are reservoir

21. Geographic distribution

22. Vector triatomine bugs (kissing bugs) Triatoma, Rhodinius, and Panstrongylus Takes a blood meal Releases trypomastigotes in its feces near the site of the bite Enter host through the wound

23. Life Cycle: Chaga’s disease

24. Disease Acute phase –usually asymptomatic –fever, anorexia, lymphadenopathy, myocarditis –Lesion (chagoma) at site of inoculation Resolve over a period of a few weeks or months into an asymptomatic chronic form –20-30% of cases Years or decades after initial infection: –cardiomyopathy –GI complications –can be fatal

25. Diagnosis Microscopic examination –fresh anticoagulated blood –thin and thick blood smears stained with Giemsa Isolation of the agent: –inoculation in culture with specialized media –inoculation into mice –xenodiagnosis

26. Treatment Benznidazole nifurtimox Treatment is most effective during the acute phase Drugs are fairly toxic IND protocol from the CDC

27. Control Vector control Poorly constructed houses and houses with thatched roofs are at risk Treatment of houses with insecticides Get rid of places in dwellings where vector and reservoir animals can live and breed Bednets