1. A SYSTEMIC PROTOZOAL DISEASE Visceral Leishmaniasis Annie Kleve April 6, 2010

2. Leishmaniasis is caused by various species of Trypanosome in one genus Promastigote being engulfed by macrophage Genus: Leishmania Characterized by William Boog Leishman Two lifecycle forms: a small, round amastigote AND a larger, flagellated promastigote Image taken from biologyreference.com

3. Leishmaniasis is caused by various species of Trypanosome in one genus: Leishmania CDC Dr. Francis Chandler WHO/TDR El-Hassan Leishmania donovani amastigotes in a PBL in bone marrow Macrophages in the spleen infected with many amastigotes

4. Visceral Leishmaniasis aka Kala-azar* is Endemic World-wide Chappuis et al. Nature Rev Micro 5, 2007 *Hindi for “Black fever” WRAMC

5. Visceral Leishmaniasis aka Kala-azar* results from infection by different species of Leishmania with different reservoirs Chappuis et al. Nature Rev Micro 5, 2007 *Hindi for “Black fever” L. chagasi L. donovani L. chagasi L. infantum

6. But 90% of cases occur in just 5 countries: Brazil, India, Bangladesh, Nepal, & Sudan Chappuis et al. Nature Rev Micro 5, 2007

7. More than 500,000 people are infected 10% of those infected die every year Left untreated, 95% of people with active, presenting symptoms will die Peter Martell/ IRIN newsMédecins Sans Frontières (MSF)

8. More than 50,000 deaths per year Images taken from WHO/TDR Kuzoe Symptoms: Fever Anemia Weight Loss and Muscle Atrophy Enlarged Spleen and Liver 200,000 million people live in at-risk areas

9. VL Appears in Very Different Environments Nature Revs Micro 5, (2007) Vector/Host systems are united by the close proximity of animal reservoirs

10. VL Has aTwo Stage Life Cycle

11. Parasite detection requires serological tests or invasive tissue analysis DAT test Diagnosis: Finding a Gold Standard OR WHO/TDR Chappuis et al. Nature Rev Micro 5, 2007

12. Treatment: Few Options Until Recently SSG = Sodium Stibogluconate (Pentavalent Antimonials) Amphotericin B intravenous

13. Paromomycin Developed by OneWorld Health Aminoglycoside from Streptomyces Given by intramuscular injection

14. Miltefosine: The first oral treatment Mass produced in India beginning in 2004 Major Restriction: Teratogenic

15. VL and the “War on Terror” Images taken from USACHPPM

16. Elimination through Vaccine and Vector Control? MSF Station in Umkara, SudanOngoing Vaccine Trials in Bihar, India WHO/TDR/Crump WHO/TDR

17. A Disease of the “Poorest of the Poor” Treatment averages $20-50 U.S Risk factors for visceral leishmaniasis have increased in the last 20 years

18. References and Further Reading Chappuis F., Sundar S., Hailu A., Ghalib H., Rijal S., Peeling R.W., Alvar J., Boelaert M. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol, 5:873-882 (2007). Desjeux P. The increase in risk factors for leishmaniasis worldwide. Trans R Soc Trop Med Hyg, 95: 239-243 (2001). Murray H.W., Berman J.D., Davies C.R., Saravia N.G. Advances in leishmaniasis. Lancet, 366(9496): 1561–1577 (2005). Van Griensven J., Balasegaram M., Meheus F., Alvar J., Lynen L., Boelaert M. Combination therapy for visceral leishmaniasis. Lancet Infect Dis, 10: 184-194 (2010). Rodriguez-Cortes A., Ojeda A., Francino O., Lopez-Fuertes L., Timon M., Alberola J. Leishmania Infection: Laboratory Diagnosing in the Absence of a "Gold Standard" Am J Trop Med Hyg, 82: 251-256 (2010). Sundar S., and Olliaro P.L. Miltefosine in the treatment of leishmaniasis: clinical evidence for informed clinical risk management. Ther Clin Risk Manag, 3:733-740 (2007). Sundar S., Rai M., Chakravarty J., et al. New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine. Clin Infect Dis, 47: 1000- 1006 (2008).

19. References and Further Reading The Institute for OneWorld Health The United States first Non-profit pharmaceutical company http://www.oneworldhealth.org/ U.S. Army Center for Health Promotion and Preventative Medicine http://phc.amedd.army.mil/default2.asp UNDP/World Bank/WHO/TDR Special Programme for Research and Training in Tropical Diseases http://apps.who.int/tdr/.