Anti-Leishmania activity of artesunate and combination effects with amphotericin B against Leishmania (Mundinia) martiniquensis in vitro.

The figure shows anti- Leishmania activity of artesunate against promastigotes and amastigotes of L. martiniquensis and its combination with amphotericin B against amastigotes of L. martiniquensis. [Display omitted] • Promastigote and intracellular amastigote stages of Leishmania martiniquensis are susceptible to artesunate. • Artesunate in combination with amphotericin B provides a strong synergism against L. martiniquensis without toxicity to host cells. • The strong synergistic combination had the highest dose reduction index (DRI), approximately a 9.7-fold reduction in amphotericin B used. • Combination of artesunate and amphotericin B might lead to application in leishmaniasis treatment to improve the therapeutic outcome for the Leishmania species. Leishmaniasis is an emerging disease in several countries over the world, especially in tropical regions. In Thailand, Leishmania (Mundinia) martiniquensis is the most frequent cause of visceral leishmaniasis and disseminated cutaneous leishmaniasis among HIV/AIDs patients. Amphotericin B (AmB) is the only drug currently available for the treatment of leishmaniasis in Thailand, but has some limitations like high renal toxicity and the prolonged hospitalization required for the treatment. Moreover, recurrence of the disease has been reported in several cases, indicating that new drugs or treatment strategies should be improved. In this study, Artesunate (ARS) was determined for anti- Leishmania activity against L. martiniquensis in promastigotes and amastigotes. In addition, the combination effects of ARS and AmB against intracellular amastigotes on THP-1 derived macrophages were also investigated for the first time. The result showed that L. martiniquensis was susceptible to ARS in both stages of the parasite. ARS was effective against intracellular amastigotes and safe to macrophage host cells, showing a SI value of 1,065. Furthermore, combination effects of ARS and AmB showed five synergistic combinations with a combination index (CI) value less than 1.0 (0.28–0.92) for intracellular amastigotes ranging from slight synergism to strong synergism. The strong synergistic combination had the highest dose reduction index (DRI), approximately a 9.7-fold reduction in AmB used. None of the treatments in combination had noticeable toxicity to THP-1 derived macrophages in the concentration range examined. The data provided in this study lead to further study in vivo and to develop a novel formulation of drug combinations to improve the outcome of leishmaniasis treatment. [ABSTRACT FROM AUTHOR]