Abstract
Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because 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 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of “resistance” related to leishmaniasis and discuss 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.
Highlights
The leishmaniases are complex diseases oftropical regions of the world caused by Leishmania spp. (Protozoa, Kinetoplastida, Trypanosomatidae) and spread by sand flies
The World Health Organization (WHO) considers the leishmaniases to be prominent among the global causes of death by infectious diseases [1]
SSG treatment failure (TF) offers a challenge to our efforts to control the leishmaniases
Summary
Chemotherapy is central to the control and management of leishmaniasis. Antimonials remain the primary drugs against different forms of leishmaniasis in several regions. December 14, 2017 patients treated with MIL, which has replaced antimonials within the kala-azar elimination program in the ISC. The rise of drug resistance impacts treatment outcome, and understanding its causes, spread, and impact will help us manage the risks it imposes. Molecular mechanisms causing resistance to anti-leishmanials are discussed along with the appropriate use of additional available drugs, as well as the urgent need to consolidate strategies to monitor drug efficacy, epidemiological surveillance, and local policies. Coordination of these activities in national and international programs against leishmaniasis might represent a successful guide to further research and prevention activities
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