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.


RESULTS
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
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.
Department of Medical Microbiology, Section of Parasitology, Academic Medical Center, Amsterdam, The Netherlands.
Caspar J
CJ
Hodiamont
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Piet A
PA
Kager
Department of Medical Microbiology, Section of Parasitology, Academic Medical Center, Amsterdam, The Netherlands.
Aldert
A
Bart
Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
Henry J C
HJ
de Vries
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands; Ministry of Defence, The Hague, The Netherlands.
Pieter P A M
PP
van Thiel
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands; Ministry of Defence, The Hague, The Netherlands.
Tjalling
T
Leenstra
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, Tergooi Hospitals, Hilversum, The Netherlands.
Peter J
PJ
de Vries
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Michèle
M
van Vugt
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Martin P
MP
Grobusch
Department of Medical Microbiology, Section of Parasitology, Academic Medical Center, Amsterdam, The Netherlands.
Tom
T
van Gool
D000666:Amphotericin B / Q000008:administration & dosage; D006801:Humans; D007891:Leishmania / Q000145:classification*; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology*; D017410:Practice Guidelines as Topic; D013045:Species Specificity; D057236:Travel Medicine; D014344:Trypanocidal Agents / Q000008:administration & dosage*
D014344:Trypanocidal Agents; D000666:Amphotericin B