Chapter 18: Molecular Basis of Drug Resistance in Leishmania
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Published:26 Oct 2017
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Special Collection: 2017 ebook collectionSeries: Drug Discovery
A. Mondelaers, S. Hendrickx, G. Caljon, and L. Maes, in Drug Discovery for Leishmaniasis, ed. L. Rivas and C. Gil, The Royal Society of Chemistry, 2017, ch. 18, pp. 371-386.
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Leishmaniasis has been treated for decades with pentavalent antimony preparations until the emergence of antimony resistance has forced a switch in hyperendemic areas towards alternative therapeutics, such as miltefosine, amphotericin B and paromomycin. The use of miltefosine and amphotericin B has particularly been encouraged as first-line therapy for visceral leishmaniasis, however, all are increasingly confronted with treatment failures and/or the emergence of drug resistance. This chapter provides a concise overview of the mode-of-action of the current anti-leishmanial drugs and links this to the different resistance mechanisms that have been proposed over the past years. The pivotal importance of proactive drug-resistance research is highlighted with reference to the most commonly used laboratory methods.