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Visceral Leishmaniasis

Visceral Leishmaniasis

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Visceral Leishmaniasis

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  1. Visceral Leishmaniasis A Systemic Protozoal Disease Annie Kleve April 6, 2010

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

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

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

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

  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 news Médecins Sans Frontières (MSF)

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

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

  10. VL Has aTwoStage Life Cycle

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

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

  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? WHO/TDR MSF Station in Umkara, Sudan Ongoing Vaccine Trials in Bihar, India WHO/TDR WHO/TDR/Crump

  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 GriensvenJ., BalasegaramM., 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. LeishmaniaInfection: Laboratory Diagnosing in the Absence of a "Gold Standard" Am J TropMed Hyg , 82: 251-256 (2010). Sundar S., and Olliaro P.L. Miltefosine in the treatment of leishmaniasis: clinical evidence for informed clinical risk management. TherClin 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/ .