Drug resistance and treatment failure in leishmaniasis: A XXI century challenge

Abstract

Re-evaluation of treatment guidelines for Old and New World leishmaniasis are urgently needed on a global basis since treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the XX century, but the last 10-20 years have witnessed an increase in clinical resistance, for example in North Bihar in India. In this review, we discuss the meaning of resistance related to leishmaniasis, and its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B and miltefosine are also outlined.