Chemotherapy and Experimental Models of Visceral Leishmaniasis

Abstract

Visceral leishmaniasis (VL) is a neglected tropical parasitic disease in humans caused by protozoan parasite Leishmania donovani and transmitted to humans by the bite of an infected female sand fly, a haemoflagellate vector. According to WHO, every year 0.7–1 million leishmaniasis cases are reported globally, and over 20,000–30,000 deaths occur. Current anti-leishmanial drug (pentavalent antimonials, miltefosine, amphotericin B, pentamidine and paromomycin) therapy is fraught with several problems and causes serious adverse effects, which limit their clinical application. The emergence of drug resistance and non-availability of an effective vaccine(s) against leishmaniasis poses a serious challenge to leishmaniasis treatment and control. Environmental and socio-economic status of people like deforestation, global warming and poverty exacerbates both parasite survival and disease progression. Pentavalent antimonial-resistant strains of L. donovani are rampant in Bihar, a highly endemic zone of VL in India. Development of co-infections (HIV-VL and Malaria-VL) often leads to poor diagnosis and treatment. There are no proper prognostic and diagnostic markers for VL. Therefore, there is an urgent need for the development of new anti-leishmanial drugs for the treatment and control of devastating VL. Effective immunotherapy/immuno-chemotherapy is considered as a viable alternative to chemotherapy. Cytokines (granulocyte-macrophage colony-stimulating factor, interferon-γ and interleukin-12) both stand-alone and in combination with current anti-leishmanial drugs are being thought to reduce the drug resistance and useful in VL treatment. The development and availability of the reliable models for anti-leishmanial drug screening is very much warranted.