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Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis

Abdulla, Salim, Ashley, Elizabeth, Bassat, Quique, Bethell, Delia, Björkman, Anders, Borrmann, Steffen, D'Alessandro, Umberto, Dahal, Prabin, Day, Nicholas P. J., Diakite, Mahamadou, Djimde, Abdoulaye, Dondorp, Arjen M., Duong, Socheat, Edstein, Michael D., Fairhurst, Rick M., Faiz, M. Abdul, Falade, Catherine, Flegg, Jennifer A. and Price, Ric N. (2015). Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis. Malaria Journal,14(Article No. 359).

Document type: Journal Article
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IRMA ID 11381xPUB170
Title Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis
Author Abdulla, Salim
Ashley, Elizabeth
Bassat, Quique
Bethell, Delia
Björkman, Anders
Borrmann, Steffen
D'Alessandro, Umberto
Dahal, Prabin
Day, Nicholas P. J.
Diakite, Mahamadou
Djimde, Abdoulaye
Dondorp, Arjen M.
Duong, Socheat
Edstein, Michael D.
Fairhurst, Rick M.
Faiz, M. Abdul
Falade, Catherine
Flegg, Jennifer A.
Price, Ric N.
Journal Name Malaria Journal
Publication Date 2015
Volume Number 14
Issue Number Article No. 359
ISSN 1475-2875   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84942511604
Total Pages 12
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DIISR)
Abstract Background
Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up.

Methods
Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive.

Results
PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28–63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 >5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2–12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95–4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44–3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007.

Conclusions
Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
Keywords Malaria
Parasite clearance
Artemisinin resistance
Drug resistance
Plasmodium falciparum
DOI http://dx.doi.org/10.1186/s12936-015-0874-1   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
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 https://creativecommons.org/licenses/by/4.0/au


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