Species-Directed Therapy for Leishmaniasis in Returning Travellers: A Comprehensive Guide

Background: Leishmaniasis is increasingly reported among travellers. Leishmania species vary in sensitivity to available therapies. Fast and reliable molecular techniques have made species-directed treatment feasible. Many treatment trials have been designed poorly, thus developing evidence-based guidelines for species-directed treatment is difficult. Published guidelines on leishmaniasis in travellers do not aim to be comprehensive or do not quantify overall treatment success for available therapies. We aimed at providing comprehensive species-directed treatment guidelines. Methodology/Principal Findings: English literature was searched using PubMed. Trials and observational studies were included if all cases were parasitologically confirmed, the Leishmania species was known, clear clinical end-points and time points for evaluation of treatment success were defined, duration of follow-up was adequate and loss to follow-up was acceptable. The proportion of successful treatment responses was pooled using mixed effects methods to estimate the efficacy of specific therapies. Final ranking of treatment options was done by an expert panel based on pooled efficacy estimates and practical considerations. 168 studies were included, with 287 treatment arms. Based on Leishmania species, symptoms and geography, 25 clinical categories were defined and therapy options ranked. In 12/25 categories, proposed treatment agreed with highest efficacy data from literature. For 5/25 categories no literature was found, and in 8/25 categories treatment advise differed from literature evidence. For uncomplicated cutaneous leishmaniasis, combination of intralesional antimony with cryotherapy is advised, except for L. guyanensis and L. braziliensis infections, for which systemic treatment is preferred. Treatment of complicated (muco)cutaneous leishmaniasis differs per species. For visceral leishmaniasis, liposomal amphotericin B is treatment of choice. Conclusions/Significance: Our study highlights current knowledge about species-directed therapy of leishmaniasis in returning travellers and also demonstrates lack of evidence for treatment of several clinical categories. New data can easily be incorporated in the presented overview. Updates will be of use for clinical decision making and for defining further research. Author Summary: Human leishmaniasis is caused by unicellular parasites that are injected into the skin by sand-flies, small, flying insects. Many different Leishmania species cause various manifestations of disease, both of the skin and internal organs. Leishmaniasis is a curable disease but clear guidelines on the best available treatment are lacking. Leishmania species differ in sensitivity to available drugs. Until recently, identification of the infecting Leishmania parasite was laborious, thus therapy could not precisely be targeted to the infecting species, in contrast to many other infectious diseases. Nowadays, Leishmania parasites can be identified relatively easily with new DNA techniques. We studied efficacy of therapies for diseases due to different Leishmania species, limited to the English literature. Efficacy was summarized and presented in an easy to read format. Because of difficulties with identification of parasite species in earlier studies, quality of evidence was often limited. Our findings are a major help for clinicians to easily find optimal treatment for specific patients. Moreover, our results demonstrate where additional research is needed to further improve treatment of leishmaniasis.