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

Debashish, Das, Price, Ric N., Bethell, Delia, Guerin, Philippe J. and Stepniewska, Kasia (2013). Early parasitological response following artemisinin-containing regimens: a critical review of the literature. Malaria Journal,12:125-1-125-11.

Document type: Journal Article
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Title Early parasitological response following artemisinin-containing regimens: a critical review of the literature
Author Debashish, Das
Price, Ric N.
Bethell, Delia
Guerin, Philippe J.
Stepniewska, Kasia
Journal Name Malaria Journal
Publication Date 2013
Volume Number 12
ISSN 1475-2875   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84876285225
Start Page 125-1
End Page 125-11
Total Pages 11
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DIISR)
Abstract Background
Parasitaemia 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.

Methods
The 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.

Results
In 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.

Conclusions
These 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.
Keywords Artemisinins
Malaria
Plasmodium falciparum
Restistance
DOI http://dx.doi.org/10.1186/1475-2875-12-125   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Open access True
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 4.0 License
URL http://creativecommons.org/licenses/by/4.0/au/legalcode


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