African and American trypanosomiasis

1. Jarmila Kliescikova, MD, 1st Faculty of Medicine, Charles University in Prague African and American trypanosomiasis

2. Sleeping sickness

3. Sleeping sickness • Kinetoplastida: Salivaria Trypanosoma brucei gambiense Western and central Africa (chronic disease) Trypanosoma brucei rhodensiense East and SE Africa (acute disease) • Extracellular parasite • Vector: tse-tse fly (Glossina) DRC, Angola, CAR, South Sudan - prevalence up to 50%. 1. or 2. most common cause of death in these countries

4. In Africa, patients with sleeping sickness • are poor • live in remote / poor / unstable / neglected areas • Patient prognosis is dependent on accurate and early diagnosisand staging • The incidence of sleeping sickness has decreased in the most affected countries since 2000 ( elimination ?) • The maintenance of vertical programmes are more difficult to justify and fund  integration into existing health structures is the trend  practical and cheap diagnostic tools must be used

5. Epidemiology Distribution: tropical Africa (Chad, Congo, Cote de Ivoire, Guinea, Malawi, Uganda, Tanzania, CAR) Botswana, Swaziland and Namibia – trasmission seems interruped Connected to the vector distribution Prevalence approximately - 50 mil. 20 – 50 thousand new cases per year Approximately 55 thousand deaths/year Belongs to so called neglected diseases East African form rarely imported to Europe – infection usually during safari

6. Simarro et al., 2010

7. The vector = Glossina spp. – both genders able to transmit the disease T. b. gambiensae Gl.palpalis/tachinoides – River glossina The maximum is the end of dry season Antroponoosis – human is the main reservoir, rarely dog, swine, sheep, cattle,.. T. b. rhodesiensae Gl. morsitans/fuscipesSavannah glossina Zoonosis – reservoir antelope, lions, cattle, sheeps, dogs

9. Life cycle

10. Pathogenity Site of inoculation Local inflammation Lymph, blood Chronic inflammation of the lymph system CSF Leptomeningitis

11. Variable Surface Antigens change = The main mechanism of pathogenicity • Variabile surface coat VSG (variabile glycoproteins) • Trypanosomas posses several different genes coding the surface antigens • VSG protects from phagocytosis and lysis by alternative complement pathway • Exhaustion of the immune system • Toxic and end metabolic products of trypanosomas released in the organism

12. The surface antigen changes

13. Alteration of the human immune response Malvy and Chappuis, 2011

14. Clinical infection: I.Local reaction • IP 6-14 days • Local reaction at inoculation site: oedema, erythema „chancre“ formation (Grafs chancre) (trypanozomas found in the secret) Hyperpigmentation of skin Intermitent fever Loal lymphadenopathy

15. Graafs chancre

16. Malvy and Chappuis, 2011

17. 2. Heamolytical stage: Lymfadenitis Cervical nodes Generalisation • Intermittent fever generalized weakness, headache

18. 2. Haemolymphatic stage: Posterior cervical lymphadenopathy Nodes are soft, non dolorous, elastic Winterbotts sign

19. 2. heamolymphatic stage Hepatosplenomegy Subcutaneous oedemas (face, lids) Exantema – tripanid

20. 2. Heamolymphatic stage: Myocarditis tachycardia (100-140/min); heart failure Anaemia Polyneuropathy sensitive, motoric Weakness kachexia

21. 3. Meningoencefalic stage Periferal polyneuropathy (late hypersteasia after pressure on limbs and muscles, pruritus) Headache Inverse sleep Personality, character changes Chorea, atetosis, dyskinesis, tremor, ataxia, tonic-clonic seizures Sexual behaviour dysfunctions, endocrinne dysregulation Wasting syndrome

23. CT, NMR: Atrophic changes, hydrocephalus, thickening of meninges

25. Laboratory • ESR (> 100 mm/h) • Blood count • Anaemia: severe, normochromatic • Lymphocytosis and monocytosis with relative neutropenia • Trombocythopenia • Serum protein • Total increase • Hypergamaglobulineamia and macroglobulinaemia (↑ IgM) • Elevation of α2-globulins • CSF (v II. stage) • Proteinrhachia (up to 10% IgM) • Mononuclear cells

26. Diagnostics – direct methods • Biopsy of ulcus, local lymph nodes • Blood film, thick film • Concentration techniques • CSF examination

27. Sleeping sickness Current diagnostic approach and tools • Screening: • Serology (CATT, IFI, ELISA) • Cervical lymph node palpation • Diagnostic confirmation (parasitology): • Cervical lymph node puncture • Detection of trypanosomes in blood • Stage determination: CSF examination (LP): • Search for trypanosomes (centrifugation) • WBC/mm3 > 5 • Raised IgM

28. Blood film

29. Brun at al., 2010

30. Serology • Agglutination tests: Paper stripes Only for T.b.gambiense

31. THERAPY

32. THERAPY • Acute trypanosomiasis • Suramin (BAYER 205, ANTRYPOL) • 5 mg/kg v 5-10 ml H2O slow i.v. 1. day • 10 mg/kg v 10 ml H2O slow i.v. 3. day • 20 mg/kg v 10 ml H2O i.v. 5.,11.,17.,23.and 30. d • Pentamidin isethionate (PENTACARINATE) • 3-4 mg/kg (150-300 mg)/day i.m. or i.v Every other day, together 7-10 doses • Chronic trypanosomiasis • Melarsoprol (MEL B, ARSOBAL) Strictly i.v. slow injection with increasing dosage, max. 3,6 mg/kg/day in several (3-4) 3-4 day cycles • Before malarsoprol use suraminem or pentaminidine (Jarisch-Herxheimer reaction) • High toxicity (5-10% fatal) arsenic encephalopathy • Mannitol i.v. in isotonic glucose á 6 hours. • Prednisolon 50 mg/day, dexametason 6-8 mg/day i.v. EFLORITHINE -2 weeks 4 infusions per day

33. Vector control http://influentialpoints.com/Gallery/Tsetse-flies_Louse-flies_and_Lice.htm

34. American trypanosomiasis Trypanosoma cruzi – Kinetoplastida: Stercoraria • Vector: Triatoma; Rhodnius • Chagas disease • Rezervoir: human, live stock • Transmission: by vector transfusion/transplantation transplacentary

35. Where are we now: 2012 • Transmission by Triatoma infestans halted in 1999 in Uruguay, 1999 in Chile, 2006 in Brazil and 2009 in Guatemala • Triatoma eliminated also from some parts of Argentina and Paraguay • Disease now „common“ in non-endemic areas: Europe and USA • WHO launched an initiative for controlling of disease in non-endemic areas • USA Food and Drug Administration approved the first serological screening for blood donors

36. Emergence of secondary domestic and peridomestic vectors • 8-11 mil people infected predominantly in Mexico, Central and South America • Incidence has dropped from 700 000 new cases per year to 40 000 • The number of deaths has dropped from approximately 45 thousand to 12 500 (chronic kardiomyopathy)

37. Europe and Chagas disease 3 periods: Description of Chagas disease and in 1980 first case description in Europe Description of non-endemic transmission via transfusion or congenital transmission (southern Europe, Spain) Chagas disease recognized as global problem – transmission reported in 28 countries worldwide

38. Estimates of migrant residents from Chagas disease endemic areas in nine studied European countries Basile et al, Eurosurveillance, 2009

39. Source: Basile at al, Eurosurvaillence, 2009

40. Estimated number of migrants infected with Chagas disease Basile et al., Eurosurveillance 2009

41. Underdiagnosis of Chagas disease in Europe Basile et al., Eurosurveillance 2009

42. Estimated congenital transmission in Europe Basile et al., Eurosurveillance 2009

43. Endemic Chagas disease distribution 2011

44. Triatoma/Rhodnius Blood sucking bed bugs The parasite is found within feaces Actively penetrates the skin Transmitted by adults and progeny Biting at night

45. Typical sites of vector multiplication

46. Typical sites of vector multiplication The vector can live in the crevices that are common in the mud and wood used to build walls and floor

47. Chagas Disease in a Domestic Transmission Cycle in Southern Texas, USAreal and predicted distribution of Triatoma gerstaeckeri Beard et al, 2003 from CDC

48. Life cycle

49. Trypanosoma cruzi • Intracellular parasite • Spread by blood to different organs • Preference: RES heart cells muscle cells neuroglia • In blood the flagellated forms are found • Intracellulary amastigotes are found

50. Chagas disease has two phases Acute phase: Local or diffuse inflammation of myocardium Chronic phase Inflammatory fibrotic reaction damaging the cardiac muscle and conduction network and the enteric nervous system