Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure

Malaria Journal

Research

Dennis E Kyle¹  Andrea Codd²  Michelle L Gatton²  Franka Teuscher³  Qin Cheng³ 

[1] Department of Global Health, College of Public Health, University of South Florida, USA;Malaria Drug Resistance and Chemotherapy Laboratory, Queensland Institute of Medical Research, Brisbane, Australia;Malaria Drug Resistance and Chemotherapy Laboratory, Queensland Institute of Medical Research, Brisbane, Australia;Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia;

关键词: Artesunate;    Atovaquone;    Treatment Failure Rate;    Single Dose Treatment;    Parasite Clearance Time;   

DOI  :  10.1186/1475-2875-10-56

 received in 2010-12-20, accepted in 2011-03-08,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundArtemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance.MethodsIn this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment.ResultsThe model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials.ConclusionsAlthough further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.

【 授权许可】

Unknown   
© Codd et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.