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Monitoring drug resistance in leishmaniasis
1Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. simon.croft@lshtm.ac.uk
Abstract:
There are many factors that can influence the efficacy of drugs in the treatment of leishmaniasis. These include both an intrinsic variation in the sensitivity of Leishmania species, described for pentavalent antimonials, paromomycin, azoles and other drugs that have reached clinical trials, as well as acquired drug resistance to antimonials. Acquired resistance has been studied in the laboratory for several decades but it is only recently that clinical resistance in L. donovani field isolates has been demonstrated. The monitoring of resistance is problematic due to a reliance on the amastigote-macrophage culture assay to adequately correlate clinical and in vitro resistance and a lack of knowledge about the molecular and biochemical mechanisms of resistance to antileishmanial drugs.
Insights
Drug resistance in leishmaniasis treatment is a growing concern. Understanding intrinsic and acquired resistance mechanisms is crucial for developing effective therapies against Leishmania parasites.
Area of Science:
- Parasitology
- Infectious Diseases
- Pharmacology
Background:
- Leishmaniasis treatment efficacy is influenced by Leishmania parasite sensitivity and acquired drug resistance.
- Intrinsic drug sensitivity varies among Leishmania species for antimonials, paromomycin, and azoles.
- Acquired resistance to antimonials has been observed clinically in Leishmania donovani field isolates.
Purpose of the Study:
- To highlight the factors influencing drug efficacy in leishmaniasis.
- To discuss the challenges in monitoring drug resistance.
- To emphasize the need for understanding resistance mechanisms.
Main Methods:
- Review of existing literature on drug resistance in leishmaniasis.
- Analysis of factors affecting drug efficacy.
- Discussion of current methods for resistance monitoring.
Main Results:
- Intrinsic variations in Leishmania sensitivity to various drugs are documented.
- Clinical resistance to antimonials in Leishmania donovani has been recently demonstrated.
- Current methods for monitoring drug resistance are problematic and lack mechanistic understanding.
Conclusions:
- Drug resistance poses a significant challenge to leishmaniasis treatment.
- Further research into the molecular mechanisms of drug resistance is essential.
- Improved monitoring strategies are needed to guide clinical practice and drug development.