Advances in VL and PKDL Case Detection, Management and Prevention

1. Advances in VL and PKDL Case Detection, Management and Prevention Dr. Dinesh Mondal, MD, PhD Senior Scientist, icddr,b and Project Director, KalaCORE

2. Plan for today’s discussion Overview of Leishmaniasis and visceral leishmanisis (VL) Recapitulation of life cycle of Leishmaniadonovani (LD) Historical milestone Corner stone for intervention and prevention Research activities in Bangladesh Epidemiology and risk factor VL and PKDL case detection and referral VL and PKDL diagnosis VL and PKDL treatment and follow up Prevention: Early case detection Vector control Vaccine

3. Source: www.stanford.edu/class/humbio153/ImmuneEvasion/Analysis.html

5. 34 countries reporting Leishmaniasis/ HIV co-infection worldwide

6. Visceral leishmaniasis in Bangladesh • Epidemic peaks 1820s, 1860s, 1920s, 1940s • 1860s-1870s: Dhaka District, Garo Hills • 1920s: Tangail, Jessore, Mymensingh, Noakhali • 1940s: Rajshahi, Dinajpur, Jessore, Noakhali, Chittagong • Kala-azar below detection level 1950s-60s • Malaria eradication programme, indoor DDT spraying • Resurgence 1980s • Sirajganj, Pabna, Mymensingh, Rajshahi, Tangail • Role of PKDL as interepidemic reservoir Source: Caryn Bern etal

7. Causative agents

8. Amastigote and Promastigote

9. Cause of VL • The causative agent of VL in Bangladesh is the parasite Leishmania donovani.

10. Sandfly

11. Leishmania: Parasite Life Cycle

12. VL Clinical Features • Persistent Fevers – greater than 2 weeks, and often for months • Enlarged spleen and liver – abdominal swelling • Wasting/Weight Loss/Decrease in body size • Darkening of skin • Bleeding – nose, mouth, other

13. Post Kala-azar Dermal Leishmaniasis

15. Cutaneous Leishmaniasis

16. Historical Milestones • 1824 – First Disease Description • 1903 – Discovery of causative agent by W.B. Leishman and C. Donovan • 1904 – The parasite was cultured in vitro by Rogers and morphology, cultural characteristics and protozological features of the parasite was described. • 1921 – Naiper developed serological test (Aldehyde test) for diagnosis of VL • 1940 – Swaminath proved that P. argentipes was the vector of VL • 1915 – 1939 Development of Anti-leishmanial Drugs

17. Corner stones for prevention - backbone of research activities

18. Epidemiology

19. Clinical Trial

20. VL vector control

21. Operational and other research

22. Demographic characteristics of the Kala-azar cases, Muktagacha (2000-14)

23. Study one: distribution of case Legend Asymptomatic Cases (131) PKDL Cases (75) Symptomatic/VL Cases (12) River

24. Trend in disease burden Predicted VL cases for 2010 to 2014 based on observed cases of 2000-09 Muktagacha Upazila, Mymensingh Program impact could be from 2010 onward considering following: Program launch-2007; Improve treatment -2008/09 Vector control activities-2010

25. Observed Vs Predicted VL cases with llinearization at predictive point onward Benefit of VL elimination program Average 63.8% monthly VL case reduction explored by the predictive model (P<0.0001)

26. Yearly seasonal pattern of Kala-azar

27. Breeding Places of Sandfly

28. Socio-economic • Poverty, Lack of awareness about VL • Lack / slackness of program activity Risk factors Host factor Exposed to VL endemic areas Proximity to VL, PKDL and asymptomatic cases Malnutrition Co-Infection with HIV, TB Inadequate health seeking behavior Not using bed-net • Environmental • Mud house • Crack and crevices in household wall • Unclean peri-domestic areas including cattle shed • Rain / Precipitation / Humidity • Parasite factor • Development of drug resistance • Development of insecticide resistance • Activation of more virulent gene

29. Early VL and PKDL case detection

30. Does ACD matter?

31. How to do ACD? So far different types of ACD are proposed and investigated:1. Blanket approach / House to House search (Gold Standard) 2. Camp approach (all HHs in a village are invited)3. Focal approach / index case based approach (60 HHs around an index case)4. Incentive based approach (private / NGO health worker based)5. Accelerated ACD (all HHs in a village from where recent / current case is reported)6. No Transmission Strategy / activity (index case-based approach plus deploying IRS and larvicide in 60 HHs)7. Combined camp approach (camp approach for VL, PKDL, leprosy, filaria, TB, malaria etc plus vector control)

32. Referral Centre (Close to you is in red)

33. Diagnostic tools • Microscopy : Tissue aspirate; peripheral blood buffy coat • Serological methods: rK39, rK28, rKRP42 by RDT / ELISA using serum, saliva, urine • Molecular methods: Ln-PCR, qPCR, LAMP, RPA

38. LAMP

40. Suitcase Lab

41. Mobile Suitcase Lab automatic pipettes automatic pipettes Gloves Gloves Scissors Waste Vortex Waste Vortex Magnet Disinfectant Tubescanner Disinfectant Heatblock Tips 100 µl Tips 100 µl microtube rack Tips 1000 µl microtube rack Tips 10 µl Centrifuge Centrifuge extraction using the SpeedXtract amplification and detection using the RPA assay 15-20 minutes 15 minutes

42. TREATMENT

43. Current treatment options

44. Treatment options for CL and PKDL

48. Thanks to all