Mechanism of Drug Resistance in Visceral Leishmaniasis
Shyam Sundar and Jaya Chakravarty
from: Leishmania: Current Biology and Control (Edited by: Subrata Adak and Rupak Datta). Caister Academic Press, U.K. (2015) Pages: 215-230.
The treatment of visceral leishmaniasis is far from satisfactory. It is further complicated by the growing resistance of the parasites to antileishmanials. The exact mechanisms of resistance to various antileishmanials are not known. However, increased intracellular thiol levels, reduced uptake of the drug, sequestration and rapid drug efflux are some of the mechanism known for antimony resistance. Reduced uptake and increased efflux of pentamidine can lead to resistance. L. donovani miltefosine transporter (LdMT) and the protein LdRos3 has shown to play an important role in resistance to miltefosine. Paromomycin being an aminoglycoside is at an increased risk of developing resistance however clinical resistance to the drug has not been reported as yet. Unresponsiveness and relapses after amphotericin B (AmB) therapy is rare however with the increasing use of AmB in lipid formulations that have longer half-lives the risk for developing resistance can become a reality. Thus there is an urgent need to know the markers of drug resistance and to develop tools to determine the emergence of drug resistance in the field read more ...