THE SENSITIVITY OF CLINICAL ISOLATES OF LEISHMANIA FROM PERU AND NEPAL TO MILTEFOSINE.


Yardley, V; Croft, SL; DE Doncker, S; Dujardin, JC; Koirala, S; Rijal, S; Miranda, C; Llanos-Cuentas, A; Chappuis, F; (2005) THE SENSITIVITY OF CLINICAL ISOLATES OF LEISHMANIA FROM PERU AND NEPAL TO MILTEFOSINE. The American journal of tropical medicine and hygiene, 73 (2). pp. 272-5. ISSN 0002-9637

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Abstract

Clinical isolates of Leishmania, from visceral leishmaniasis (VL) cases in Nepal and from cutaneous leishmaniasis (CL) cases in Peru, were cultured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to type species and strain. Promastigotes from 38 isolates, within eight passages from isolation, were used to infect mouse peritoneal macrophage cultures in vitro, and the amastigote sensitivity to miltefosine was determined. The concentration required to kill 50% of intracellular amastigotes from Nepalese VL isolates, all typed as Leishmania (L.) donovani (N = 24) from both Sbv responders and nonresponders, ranged from 8.7 to 0.04 microg/mL. In contrast, the concentration required to kill 50% intracellular amastigotes from isolates from Peru, typed as L.(V.) braziliensis (N = 8), was > 30 to 8.4 microg/mL, L.(V.) guyanensis (N = 2) > 30 to 1.9 microg/mL, L.(L.) mexicana (N = 1) > 30 microg/mL, and L. (V.) lainsoni (N = 4) was 3.4 to 1.9 microg/mL. This demonstrates a notable difference in the intrinsic sensitivity of Leishmania species to miltefosine in vitro. If this model can be correlated to therapeutic outcome, it may have implications for the interpretation of clinical trials.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
PubMed ID: 16103588
Web of Science ID: 231272700010
URI: http://researchonline.lshtm.ac.uk/id/eprint/13280

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