01820nas a2200277   4500000000100000008004100001653003900042653001800081653002000099653002200119100001800141700001400159700001500173700001400188700002000202700002500222700001500247700001800262700001900280245008600299856009800385300001300483490000700496520102500503022001401528       2017                            d10aNeglected tropical diseases (NTDs)10aLeishmaniasis10aDrug Resistance10aTreatment Failure1 aPonte-Sucre A1 aGamarro F1 aDujardin J1 aBarrett M1 aLópez-Vélez R1 aGarcía-Hernández R1 aPountain A1 aMwenechanya R1 aPapadopoulou B00aDrug resistance and treatment failure in leishmaniasis: A 21st century challenge.  uhttp://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0006052&type=printable  ae00060520 v113 a<p>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.</p>
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