Leishmaniasis chemotherapy—challenges and opportunities

Abstract

Although there have been significant advances in the treatment of visceral leishmaniasis (VL), there remain challenges to ensure that treatments effective in India are also effective in other regions of the world and to identify treatment for post kala-azar dermal leishmaniasis as well as the opportunity to develop a safe oral short-course treatment. At the same time, there have been few advances for the treatment of simple or complex forms of cutaneous leishmaniasis (CL), other than topical paromomycin formulations. The main challenge for CL is to ensure that this disease is on the research and development agenda, so that new drugs are evaluated or compounds are screened in appropriate models, and that the standardization of quality of clinical trials is guaranteed. Problems also remain in the treatment of HIV/leishmaniasis co-infected patients. We are some way from having the ideal treatments for VL and CL and drug research and development for these diseases must remain focused.

An Essential Type I Nitroreductase from Leishmania major Can Be Used to Activate Leishmanicidal Prodrugs

“…Recent progress has been made in developing new leishmanicidal agents with several compounds such as amphotericin B, paromomycin, and miltefosine coming to market (1). However, there are issues associated with the use of these as they are expensive and require medical administration with some having teratogenic and other unwanted toxicity problems (6). Against this backdrop, the development of new cost-effective treatments is a priority, but given that leishmaniasis mainly affects people living in developing countries, these infections are not deemed commercially attractive by pharmaceutical companies.…”

Oleanonic acid from Lippia lupulina (Verbenaceae) shows strong in vitro antileishmanial and antitrypanosomal activity

“…The leishmaniasis treatment includes pentavalent antimonials (Pentostam® and Glucantime®), the polyene antibiotic amphotericin B (including the lipid preparation Ambisome®) and pentamidine. However, such drugs are costly, show undesirable side effects and resistant strains have emerged (Croft and Olliaro 2011;Tempone et al 2011) which reinforces the need for novel therapeutic agents.…”

Antileishmanial activity of some Brazilian plants, with particular reference to Casearia sylvestris

“…Current chemotherapeutic agents for the treatment of all clinical manifestations of leishmaniasis are pentavalent antimonials compounds (e.g., sodium stibogluconate and meglumine antimoniate) and amphotericin B, which unfortunately are considerably toxic (Croft and Olliaro 2011, Tempone et al 2011, Singh and Sundar 2012. Furthermore, these drugs exhibit several limitations, including high cost and the need for daily parenteral administration (Singh and Sundar 2012).…”