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

VANESSA YARDLEY Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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SIMON L. CROFT Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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SIMONNE DE DONCKER Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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JEAN-CLAUDE DUJARDIN Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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SIDDHARTHA KOIRALA Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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SUMAN RIJAL Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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CESAR MIRANDA Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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ALEJANDRO LLANOS-CUENTAS Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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FRANCOIS CHAPPUIS Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; B P Koirala Institute of Health Sciences, Dharan, Nepal; Instituto Tropical “Alexander von Humbolt,” Lima, Peru; Hôpitaux Universitaires de Genève, Switzerland

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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 μg/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 μg/mL, L.(V.) guyanensis (N = 2) > 30 to 1.9 μg/mL, L.(L.) mexicana (N = 1) > 30 μg/mL, and L. (V.) lainsoni (N = 4) was 3.4 to 1.9 μg/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.

Author Notes

Reprint requests: Vanessa Yardley, ITD, LSHTM, Keppel Street, London WC1E 7HT, UK. Fax: +44 (0)20 7927 2807, E-mail: vanessa.yardley@lshtm.ac.uk.
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