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American Tegumentary Leishmaniasis: Is Antimonial Treatment Outcome Related to Parasite Drug Susceptibility?

Yardley, Vanessa ; Ortuño, Nimer ; Llanos-Cuentas, Alejandro ; Chappuis, François ; De Doncker, Simonne ; Ramirez, Luis ; Croft, Simon ; Arevalo, Jorge ; Adui, Vanessa ; Bermudez, Hernan ; Decuypere, Saskia ; Dujardin, Jean-Claude

In: The Journal of Infectious Diseases, 2006, vol. 194, no. 8, p. 1168-1175

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    Titel
    • American Tegumentary Leishmaniasis: Is Antimonial Treatment Outcome Related to Parasite Drug Susceptibility?
    Autor
    • Yardley, Vanessa. London School of Hygiene and Tropical Medicine, Department of Infectious and Tropical Diseases, London, United Kingdom
    • Ortuño, Nimer. London School of Hygiene and Tropical Medicine, Department of Infectious and Tropical Diseases, London, United Kingdom
    • Llanos-Cuentas, Alejandro. Instituto de Medicina Tropical "Alexander von Humboldt,” Laboratory of Molecular Parasitology, Lima, Peru
    • Chappuis, François. Hopitaux Universitaires de Geneve, Department of Community Medicine, Geneva, Switzerland
    • De Doncker, Simonne. Hopitaux Universitaires de Geneve, Department of Community Medicine, Geneva, Switzerland
    • Ramirez, Luis. Instituto de Medicina Tropical "Alexander von Humboldt,” Laboratory of Molecular Parasitology, Lima, Peru
    • Croft, Simon. London School of Hygiene and Tropical Medicine, Department of Infectious and Tropical Diseases, London, United Kingdom
    • Arevalo, Jorge. Instituto de Medicina Tropical "Alexander von Humboldt,” Laboratory of Molecular Parasitology, Lima, Peru
    • Adui, Vanessa. Instituto de Medicina Tropical "Alexander von Humboldt,” Laboratory of Molecular Parasitology, Lima, Peru
    • Bermudez, Hernan. Centro Universitario de Medicina Tropical, Cochabamba, Bolivia
    • Decuypere, Saskia. Institute of Tropical Medicine, Molecular Parasitology, and
    • Dujardin, Jean-Claude. Institute of Tropical Medicine, Molecular Parasitology, and
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • The Journal of Infectious Diseases, 2006, vol. 194, no. 8, p. 1168-1175. The University of Chicago Press
    Andere elektronische Ausgabe
    Klassifikation
    • Gesundheit
    OAI-PMH-ID
    • oai:doc.rero.ch:300280
    Summary
    BackgroundAntimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes MethodsThirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined ResultsWe observed 29 SbV-resistant isolates among 4 species of subgenus Viannia most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy ConclusionAntimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factors