Visceral leishmaniasis: an endemic disease with global impact

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1 Visceral leishmaniasis: an endemic disease with global impact Professor Olivier Lortholary, MD, PhD Department of Infectious and Tropical diseases Hôpital Necker-Enfants Malades Université Paris Descartes and IHU Imagine Paris

2 Geographical distribution of visceral leishmaniasis (VL) / kala-azar 1 1. Manual on visceral leishmaniasis control. PAHO/WHO/ODA, Accessed at March accessed March 2011.

3 Geographical distribution of visceral leishmaniasis (VL) / kala-azar 1 1. Manual on visceral leishmaniasis control. PAHO/WHO/ODA, Accessed at March accessed March 2011.

4 Leishmania donovani 1 The VL parasites Occurs in East Africa and the Indian subcontinent Anthroponotic transmission from human to vector to human Infects all age groups. Leishmania infantum 1 Occurs in Europe, North Africa and Latin America Zoonotic transmission from animal to vector to human Humans are occasional hosts and animals, mainly dogs, are the reservoir hosts of the parasite. Infects mostly children and immunosuppressed individuals Vector: ~30 species of the phlebotomine sandfly 1 1. Chappuis F et al. Nature Reviews Microbiology 2007;5:

5 Leishmania amastigotes (immunocompetent) Leishmania amastigotes BM Leishmania amastigote typical splenic aspirate Images supplied by R. Davidson

6 Leishmania amastigotes (HIV+) Leishmania amastigotes huge burden in BM Leishmania amastigote in neutrophil Images supplied by R. Davidson

7 Clinical manifestations of VL in immunocompetent children and adults Images supplied by R. Davidson

8 Clinical manifestations of VL in patients with HIV Images supplied by R. Davidson

9 WHO DNDi MSF NGO key VL management strategies Facilitate early diagnosis and prompt treatment 1 Support control of sandfly populations 1 Provide healtheducation/training materials 1 Detect and contain epidemics in early stages 1 Diagnose early, and effectively manage HIV/VL co-infections 1 Improve use of existing treatments through geographical extension and new combinations 2 Register new drugs through new formulations of existing treatments and therapeutic switching 2 Invest in new compounds and improved research capacity 2 Lower the price of existing drugs 3 Register drugs 3 Develop new and simplified diagnostic tools 3 Improve use of existing drugs 3 Invest in research and development 3 Improve funding of national control programmes Accessed March Accessed March MSF Fact sheet: Kala azar (visceral leishmaniasis). Accessed at in March 2011.

10 Anti-TNF agents and VL Anti-TNF therapy is associated with an increased risk for opportunistic infections 1,2,3,4 Reactivation of latent VL and new cases of VL have been observed in patients receiving anti-tnf agents including adalimumab, 5,6 infliximab 7,6 and etanercept 8,6 Be aware of the possibility of VL in patients who have received anti-tnf agents 6 1. Infliximab, Summary of Product Characteristics, Feb Adalimumab, Summary of Product Characteristics, Feb Etanercept, Summary of Product Characterisics, Feb Golimumab, Summary of Product Characteristics, Feb Bassetti M et al. Rheumatology 2006;45: Xynos ID et al. Emerg Infect Dis 2009;15: Tektonidou MG & Skopouli FN. Clin Rheumatol 2008;27: Bagalas V et al. Clin Rheumatol. 2007;26:

11 VL in solid organ transplant recipients Use of immunosuppressive therapy: mainly cyclosporine and azathioprine 1 Majority of cases reported in kidney transplant recipients 1,2 Pre-transplant Infected sandfly Immunosuppressive drugs Post-transplant Transplant of leishmania infected organ Asymptomatic leishmania infection Reactivation Interleukin 2, interleukin 12 Interferon γ Inhibition of T-cell and B-cell proliferation (mycophenolate mofetil) Depletion of T-cells (OKT3 monoclonal antibody; antithymocyte globulin) Inhibition of pan- T-cell and macrophages (corticosteriods) Visceral leishmaniasis Transfusion of leishmania-infected blood Acute infection Infected sandfly Image adapted from Antinori et al Basset D et al. Microbes and Infection. 2005;7: Antinori C et al. Lancet Infect Dis 2008;8:

12 Current issues regarding VL Relapse in HIV/VL co-infected individuals despite initiation of HAART to restore immune function 1,2 Need for easy-to-use, non-invasive tests for the diagnosis of primary VL and relapse, and to assess treatment efficacy 3 No satisfactory strategy for control of canine reservoir hosts 4 No available vaccine for VL in humans 3 Current treatment options have drawbacks, investment in drug development is needed 3 Areas affected often poor and remote with limited access to appropriate healthcare resources 5 Need for increased awareness of VL in the Mediterranean 6 1. Mira JA et al. Am J Trop Med Hyg 2004;70(3): Fernández Cotarelo MJ et al. Clin Infect Dis 2003;37: Chappuis F et al. Nature Reviews Microbiology 2007;5: Guerin PJ et al. Lancet 2002;2: Bhattacharya SK et al. Clin Infect Dis 2004;38: Gabutti G et al. Lancet 1998;351:1136.