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Drug resistance in leishmaniasis
Simon L Croft1, Shyam Sundar, Alan H Fairlamb
1Drugs for Neglected Diseases Initiative, 1 Place Saint-Gervais, CH-1201 Geneva, Switzerland. scroft@dndi.org
Clinical Microbiology Reviews
|January 19, 2006
Summary
Visceral leishmaniasis treatment resistance is rising, particularly to pentavalent antimonials in India. Understanding drug resistance mechanisms is crucial for developing new strategies against Leishmania parasites.
Area of Science:
- Parasitology
- Infectious Diseases
- Pharmacology
Background:
- Leishmaniasis presents as visceral and cutaneous forms, caused by diverse Leishmania species.
- Drug sensitivity varies significantly among Leishmania species, impacting treatment efficacy.
- High rates of treatment failure, exceeding 60%, are observed in visceral leishmaniasis patients in Bihar, India, attributed to acquired drug resistance.
Purpose of the Study:
- To investigate the mechanisms of drug action and resistance in Leishmania parasites.
- To inform strategies for preventing drug resistance in leishmaniasis treatment.
- To highlight the importance of new therapies and monitoring for combating leishmaniasis.
Main Methods:
- Analysis of drug metabolism pathways in Leishmania.
- Investigation of thiol metabolism and drug efflux mechanisms.
- Review of treatment outcomes with pentavalent antimonials, miltefosine, and paromomycin.
Main Results:
- Mechanisms of action and resistance for pentavalent antimonials have been recently elucidated.
- Resistance is linked to alterations in drug metabolism, thiol metabolism, and drug efflux.
- Emergence of resistance necessitates proactive management strategies.
Conclusions:
- Understanding drug resistance mechanisms is vital for effective leishmaniasis treatment.
- Combination therapy, treatment monitoring, and improved diagnostics are essential for preventing resistance to new drugs.
- Strategic approaches are required to maintain the efficacy of existing and emerging antileishmanial therapies.