Early parasitological response following artemisinin-containing regimens: a critical review of the literature

Malaria Journal

Research

Delia Bethell¹  Philippe J Guerin¹  Debashish Das¹  Kasia Stepniewska¹  Ric N Price² 

[1] WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, OX3 7LE, Oxford, UK;WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, OX3 7LE, Oxford, UK;Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia;

关键词: Artemisinins;    Malaria;    Plasmodium falciparum;    Resistance;   

DOI  :  10.1186/1475-2875-12-125

 received in 2012-11-06, accepted in 2013-02-08,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundParasitaemia on Day 3 has been proposed as a useful alert of potential artemisinin resistance, however, the normal variation of parasite clearance observed in artemisinin-based combination therapy clinical trials is poorly documented.MethodsThe trends in early parasitological response following treatment with an artemisinin anti-malarial regimen were reviewed. A PubMed literature search identified all studies using an artemisinin regimen for uncomplicated falciparum malaria published between January 2000 and December 2011. Data from clinical studies were extracted for analysis using a standardized questionnaire.ResultsIn total 65,078 patients were enrolled into 213 clinical trials with 413 treatment arms containing either an artemisinin derivative alone (n=26) or in combination with a partner drug (n=387). The proportion of patients remaining parasitaemic at 24, 48 and 72 hours was documented in 115 (28%), 167 (40%) and 153 (37%) treatment arms, respectively. Excluding resistance studies in Cambodia, the median proportion of patients still parasitaemic was 53.8% [range 3–95, IQR=30.5-69.2] on Day 1, 6% [range 0–65.9, IQR=2-11.5] on Day 2 and 0 [range 0–12.6, IQR=0-2] on Day 3. Comparing studies from 2000 to 2005 and 2006 to 2011, the median proportion of patients reported to remain parasitaemic at 72 hours decreased in Africa (1.2% vs 0%, p=0.007), but increased in Asia (0.4% vs 3.9%, p=0.076). In 95% of studies the proportion of patients with peripheral parasitaemia was less than 6% at 72 hours.ConclusionsThese results highlight the normal distribution of early parasitological responses following ACT, and the influence that heterogeneity in study design, host and parasite factors have in confounding a surveillance system based on Day 3 parasite positivity. Greater understanding of factors influencing parasite clearance is crucial, but will require analysis of pooled data from individual patient records.

【 授权许可】

Unknown   
© Das et al.; licensee BioMed Central Ltd. 2013. 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.