Visceral Leishmaniasis A SYSTEMIC PROTOZOAL DISEASE Annie Kleve April 6, 2010 Leishmaniasis is caused by various species of Trypanosome in one genus Genus: Leishmania Characterized by William Boog Leishman Two lifecycle forms: a small, round amastigote AND a larger, flagellated promastigote Promastigote being engulfed by macrophage Image taken from biologyreference.com Leishmaniasis is caused by various species of Trypanosome in one genus: Leishmania Leishmania donovani amastigotes in a PBL in bone marrow CDC Dr. Francis Chandler Macrophages in the spleen infected with many amastigotes WHO/TDR El-Hassan Visceral Leishmaniasis aka Kala-azar* is Endemic World-wide WRAMC *Hindi for “Black fever” Chappuis et al. Nature Rev Micro 5, 2007 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 But 90% of cases occur in just 5 countries: Brazil, India, Bangladesh, Nepal, & Sudan Chappuis et al. Nature Rev Micro 5, 2007 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) 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 VL Appears in Very Different Environments Vector/Host systems are united by the close proximity of animal reservoirs Nature Revs Micro 5, (2007) VL Has aTwo Stage Life Cycle Diagnosis: Finding a Gold Standard Parasite detection requires serological tests or invasive tissue analysis DAT test OR WHO/TDR Chappuis et al. Nature Rev Micro 5, 2007 Treatment: Few Options Until Recently intravenous SSG = Sodium Stibogluconate (Pentavalent Antimonials) Amphotericin B Paromomycin Developed by OneWorld Health Aminoglycoside from Streptomyces Given by intramuscular injection Miltefosine: The first oral treatment •Mass produced in India beginning in 2004 •Major Restriction: Teratogenic VL and the “War on Terror” Images taken from USACHPPM Elimination through Vaccine and Vector Control? WHO/TDR MSF Station in Umkara, Sudan WHO/TDR Ongoing Vaccine Trials in Bihar, India WHO/TDR/Crump 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 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: 10001006 (2008). 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/ .