Chemotherapy of Leishmaniasis: Past, Present and Future
Pp. 97-130 (34)
Jyotsna Mishra, Anubha Saxena and Sarman Singh
Leishmaniasis is a parasitic disease caused by hemoflagellate,
Leishmania spp. The parasite is transmitted through the bites of an infected female
phlebotomine sandfly. Leishmaniasis is prevalent throughout the world and in at
least 88 countries. For its treatment, nearly 25 compounds are reported to have
anti-leishmanial effects but not all are in use. Pentavalent antimony compounds
had remained mainstay for nearly 75 years. However, emergence of resistance to
this drug, led to the use of other compounds such as -Amphotericin B, Pentamidine,
Paromomycin, Allopurinol etc. Amphotericin B, an antifungal macrolide polyene
is characterized by the hydrophilic polyhydroxyl and hydrophobic polyene faces
on it long axis which acts on membrane sterols resulting in parasite cell lysis.
Presently, it is the only drug with highest cure rate. Other anti-fungals like
ketoconazole, fluconazole and terbinafine are found less effective. Recently,
anticancer alkylphosphocholines have been found to be the most effective oral
compounds. These act as membrane synthetic ether-lipid analogues, and consist of
alkyl chains in the lipid portions. Most promising of these are miltefosine
(hexadecylphosphocholine), Edelfosine (ET-18-OCH3) and Ilmofosine (BM 41.440).
However, the recent focus has been on identifying newer therapeutic targets in the
parasite such as DNA topoisomerases. The present review describes the current
understanding of different drugs against leishmaniasis, their chemistry, mode of
action and the mechanism of resistance in the parasite. Future perspectives in the
area of new anti-leishmanial drug targets are also enumerated. However, due to the
vastness of the topic main emphasis is given on visceral leishmaniasis.
Leishmaniasis, kala-azar, Antileishmanial drugs, chemotherapy, drug resistance,
antimonials, miltefosine and natural products.
Division of Clinical Microbiology, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India