Chapter 18: Molecular Basis of Drug Resistance in Leishmania

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.