Updated review on modern context of drug resistance in visceral leishmaniasis

Visceral leishmaniasis, a multifactorial disease, is life-threatening infectious neglected tropical disease caused by Leishmania donovani in the Indian subcontinent causing immune suppression to the host. There are annually 50 thousand to 90 thousand new cases of VL occur worldwide, while, only 25-45% reported to WHO and unfortunately 95% cases of these are still left untreated. In addition, higher cytotoxicity, severe side effects, and lower therapeutic indexes of the current anti-leishmanial drugs have created a necessity to develop new therapeutics. Furthermore, in poor endemic countries their extensive use was condensed immensely due to the emergence of their resistance. Several resistance cases were reported from the different regions of the world leading to treatment failure with the non-responsiveness of drugs. So, it is an intense issue to combat the arrival of resistance to new drugs. To overcome this condition, new treatment options or combination therapy, monitoring of therapy and enhanced diagnostics could play a vital role. The list of standard drugs presently available are the pentavalent antimonial, amphotericin B, and miltefosine (oral) which are most effective, while, paromomycin and very few compounds proposed by DNDi are still under clinical trial. There are some accepted mechanisms of drug resistance of leishmaniasis in field isolates. In this review, we have described the mechanism of drug resistance, the possible treatment options, and strategies to overcome the challenges of present treatments.