Leishmaniases are parasitic diseases that spread in many countries with a prevalence of 12 million cases. There are few available treatments and antimonials are still of major importance in the therapeutic strategies used in most endemic regions. However, resistance toward these compounds has recently emerged in areas where the replacement of these drugs is mainly limited by the cost of alternative molecules. In this paper, we reviewed the studies carried out on antimonial resistance in Leishmania. Several common limitations of these works are presented before prevalent approaches to evidence antimonial resistance are related. Afterwards, phenotypic determination of resistance is described, then confronted to clinical outcome. Finally, we detail molecular mechanisms and targets involved in resistance and already identified in vitro within selected mutant strains or in clinical isolates. 1. Introduction Leishmaniases are a set of vector-borne diseases caused by a flagellate protozoan transmitted by the bite of an insect vector, the phlebotomine sandfly. This group of diseases affects 98 countries with three distinct entities: cutaneous, mucocutaneous, and visceral leishmaniasis [1]. Various clinical outcomes are described from a simple skin lesion that may heal spontaneously to a multi-organ failure, fatal if untreated. There is still no human vaccine against this disease [2] and therapy takes a major place in the control strategies. Moreover, there are few drugs available and their effectiveness is variable. The use of the liposomal form of amphotericin B, a highly active molecule with reduced side effects, is still restricted to the treatment of visceral leishmaniasis in countries that can afford its cost, such as European countries. However Europe accounts for less than 1% of the approximately 500,000 cases per year which occur mainly in the Indian subcontinent, Sudan, and Brazil [3]. Other molecules such as pentamidine, miltefosine, or fluconazole are available but their use is restricted owing to side effects, cost, or effectiveness [4]. This accounts for the still predominant place of antimony derivatives, sodium stibiogluconate (Pentostam), and meglumine antimoniate (Glucantime) which have been used in the treatment of the majority of cases of leishmaniases for more than 60 years worldwide. Currently, these molecules have two major limitations: first, side effects are frequent and can be serious; second, parasite resistance is emerging in some endemic areas, causing an increase in treatment failure [5, 6]. Resistance to antimonials has emerged
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