1. Trypanosomiasis Lecture with Dr. Balsam Mahdi Nasir MBBS/YEAR1/SEM2/2012

2. African trypanosomiasis (sleeping sickness) 3/14/2016Dr. Balsam2  Definition:  It is a vector-borne disease.  Endemic to sub-Saharan Africa.  It is caused by the single cell flagellate protozoan Trypanosoma brucei.  Geographic distribution: Trypanasoma brucei gambiense (West African sleeping sickness or Gambian trypanasomiasis). Trypanasoma brucei rhodesiense (East African sleeping sickness or Rhodesian trypanosomiasis).

3. Geographic distribution 3/14/2016Dr. Balsam3

4. 3/14/2016Dr. Balsam4  Mode of transmission Via the bite of an infected tsetse fly.

5. Morphology 3/14/2016Dr. Balsam5  In the vertebrate it exists as a TRYPOMASTIGOTE.  Elongated rather flattened.  Spindle shaped organism.  Blunted posterior end.  Finely pointed anterior end.  Central large oval nucleus.  Kinetoplast is small and is situated at the posterior end.  Undulating membrane.  Flagellum.

6. Blood forms 3/14/2016Dr. Balsam6 1. Trypomastigote (long slender)→ dividing form. 2.Trypomastigotes (short broad stumpy form with or without attenuated flagellum)→ non dividing form → infective to tsetse fly. 3. Intermediate form.

7. 3/14/20167 procyclic trypomastigote Epimastigote Metacyclic trypomastigote Trypomastigotes Intermediate form Long slender form Short stumpy form Tsetse fly Human Infective stage to tsetse fly Infective stage to human

8. Life cycle 3/14/2016Dr. Balsam8

9. Life cycle 3/14/2016Dr. Balsam9  Definitive host Man, game and domestic animals.  Intermediate host Tsetse fly (both male & female flies) Reservoir of infection Man (Trypanosoma brucei gambiense) → West African trypanosomiasis. Animals (Trypanosoma brucei rhodesience) → East African trypanosomiasis.  Infective stage to man Metacyclic trypomastigotes

10. Pathogenesis and symptomatology Gambian disease 3/14/2016Dr. Balsam10 Inoculation of trypomastigotes. Subcutaneous nodules→ 5-15 days → painless chancre→ resolve in 2-3 weeks. Bite of infected tsetse fly Asymptomatic several weeks to months up to a year. Incubation period Intermittent fever pattern, chills, headache, myalgia, arthralgia..etc Stage 1Blood dissemination Stage 1Lymphatics Lymphadenopathy, especially in the posterior cervical nodes (on the back of the neck) →Winterbottom’s sign. Stage 2 CNS invasion Occur at the end of 1 st year or the beginning of the 2 nd year Daytime sleeping, mental dullness, apathy, tremors, convulsions and coma followed by death from asthenia during the 2 nd or 3 rd year.

11. Winterbottoms sign CDC DPDx Parasite Image Library 3/14/2016Dr. Balsam11

12. RHODESIAN SLEEPING SICKNESS clinical features 3/14/2016Dr. Balsam12 It is more acute than the Gambian form Incubation period 2-3 weeks Fever, weakness, rapid loss of weight and myocarditis are the usual manifestation. Fatal within a year of onset before involvement of the CNS. Mania and delusion may occur but the typical sleeping sickness picture is seldom seen.

13. 3/14/2016Dr. Balsam13

14. 3/14/2016Dr. Balsam14 A woman caring for her comatose husband who is dying of African trypanosomiasis, Uganda, 1990

15. Diagnosis 3/14/2016Dr. Balsam15  Clinical  Patient from endemic area, irregular fever, palpable lymph nodes (post. cervical).  Chronic disease with somnolence, personality changes and neurological symptoms.  Laboratory  Direct microscopy of a wet smear of unstained blood or Geimsa- stained thick smear → trypmastigote.  Chancre, lymph node, bone marrow and CSF aspirate → wet preparation.  Culture methods  The standard serologic assay to diagnose West African trypanosomiasis is the card agglutination test for trypanosomiasis (CATT).  Serological tests ELISA.

16. 3/14/2016Dr. Balsam16 Trypanosoma brucei

17. 3/14/2016Dr. Balsam17

18. TREATMENT 3/14/2016Dr. Balsam18 Haemo-lymphatic stage Suramine sodium→ Rhodesian disease. Suramine sodium or Pentamidine isethionate→ Gambian disease CNS involvement Melarsoprol → Rhodesian disease. Melarsoprol or DEMO (eflornithine) → Gambian disease.

19. PREVENTION AND CONTROL 3/14/2016Dr. Balsam19  Elimination of the reservoir:  Early Diagnosis and Treatment to reduce the reservoir of infection.  Breaking the channel of transmission:  Vector control.  Protection of susceptible:  Persons visiting endemic areas should wear protective clothing and apply repellents.

20. Chagas’ disease American trypanosomiasis 3/14/2016Dr. Balsam20  Definition  It is a vector-borne disease  It is prevalent throughout South and Central America  It is caused by the flagellate protozoan Trypanosoma cruzi.

21. Geographic distribution 3/14/2016Dr. Balsam21

22. 3/14/2016Dr. Balsam22  Mode of transmission Contamination of wound site, conjunctiva, or mucosa by infected feces of insect (reduviid bugs)

23. Morphology 3/14/2016Dr. Balsam23  Trypomastigote  The same as Trypanosoma brucei. 1. Long thin form 2. Short stumpy form 3. In blood film they appear C or U or S shape.  Amastigote form  Oval bodies.  Nucleus.  Kinetoplast.  Habitat: Striated muscle in heart, skeletal, neurological cells and cells of reticuloendothelial system. Tissue Blood

24. Morphology 3/14/2016Dr. Balsam24

25. 3/14/2016Dr. Balsam25 TrypomastigoteEpimastigote Metacyclic trypomastigote TrypomastigoteAmastigote Reduviid bug Human Trypomastigote

26. 3/14/2016Dr. Balsam26

27. Life cycle 3/14/2016Dr. Balsam27  Definitive host Man, wild and domestic animals.  Intermediate host Triatomine bugs (reduviid bugs)  Reservoir of infection  Besides humans, the parasite infects a variety of wild and domestic animals.  Infective stage to man Metacyclic trypomastigotes

28. Clinical features 3/14/201628 Acute In less than 50% of people bitten by a triatomine bug, characteristic first visible signs can be a skin lesion (chagoma ) or a purplish swelling of the lids of one eye (Romana sign) After 1-2 weeks → fever, headache, malaise, muscle pain, generalized lymphadenopathy and hepatosplenomegally. Cardiac abnormalities followed by meningoencephalitis. Chronic The parasites are hidden mainly in the heart and digestive tract muscle. Up to 30% of patients suffer from cardiac disorders. Up to 10% suffer from digestive (megaesophagus or megacolon), neurological or mixed alterations. In later years the infection can lead to sudden death or heart failure caused by progressive destruction of the heart muscle.

29. 3/14/2016Dr. Balsam29 Romana sign

30. 3/14/2016Dr. Balsam30 Megacolon in patient with Chagas disease

31. Diagnosis 3/14/2016Dr. Balsam31  Clinical may be suspected when general, cardiac or GIT symptoms are present in patients lived under low SES in endemic regions.  Laboratory Demonstration of the parasitic agent is the diagnostic procedure in acute Chagas'' disease. 1.Microscopic examination a) of fresh anticoagulated blood for detecting motile trypanosomes. b) of thin and thick blood smears stained with Giemsa for identification of parasites.

32. 3/14/2016Dr. Balsam32 Trypanosoma cruzi trypomastigote in a thin blood smear stained with Giemsa Trypanosoma cruzi amastigotes in heart tissue

33. Laboratory diagnosis 2. If the parasites are scanty in blood  Culture of the blood or suspected tissue specimen.  xenodiagnosis, where clean lab-reared reduviid bugs are fed on the patient's blood, and their gut contents examined for parasites 4 weeks later.  Demonstration of antibodies to T. cruzi are required to diagnose chronic Chagas disease by serology – complement-fixation, direct agglutination and indirect haemagglutinatin and ELISA.

34. Treatment 3/14/2016Dr. Balsam34  Nitrofurans and benzidazoles have been used in acute disease.  Neither drug is expected to cure established chronic disease.  It is unsatisfactory since the organisms are within cells in established infections.

35. Prevention and control 3/14/2016Dr. Balsam35  Elimination of reservoirs:  Control and elimination of domestic and peridomestic animals.  Early diagnosis and treatment of infected cases.  Vector control:  Triatomine bugs are highly susceptible to chlorinated hydrocarbon insecticides which form the major weapon for their control.  Protection of susceptible:  Provision of better housing would prevent transmission because most human infections are transmitted by bugs living in cracks and crannies in the walls of ill kept tenement dwellings.