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Randomized comparison of the efficacies and tolerabilities of three artemisinin-based combination treatments for children with acute Plasmodium falciparum malaria in the Democratic Republic of the Congo.

Abstract:
An open-label, randomized controlled trial was carried out in 2011-2012 in the Democratic Republic of the Congo to test the efficacy, safety, and tolerability of the artemisinin-based combination treatments dihydroartemisinin-piperaquine, amodiaquine-artesunate, and artemether-lumefantrine. Six hundred eighty-four children aged 3 to 59 months with uncomplicated Plasmodium falciparum malaria were randomly allocated to each study arm. Children were hospitalized for 3 days, given supervised treatment, and followed up weekly for 42 days. All regimens were well tolerated and rapidly effective. The median parasitemia clearance half-life was 2.2 h, and half-lives were similar between arms (P=0.19). The PCR-uncorrected cure rates by day 42 were 73.0% for amodiaquine-artesunate, 70.2% for artemether-lumefantrine, and 86.3% for dihydroartemisinin-piperaquine (P=0.001). Early treatment failure occurred in three patients (0.5%), one in each arm. The PCR-corrected cure rates were 93.4% for amodiaquine-artesunate, 92.7% for artemether-lumefantrine, and 94.3% for dihydroartemisinin-piperaquine (P=0.78). The last provided a longer posttreatment prophylactic effect than did the other two treatments. The day 7 plasma concentration of piperaquine was below 30 ng/ml in 47% of the children treated with dihydroartemisinin-piperaquine, and the day 7 lumefantrine concentration was below 280 ng/ml in 37.0% of children who received artemether-lumefantrine. Thus, although cure rates were all satisfactory, they could be improved by increasing the dose. (This study has been registered with the International Standard Randomized Controlled Trial Number Register [www.isrctn.org] under registration no. ISRCTN20984426.).
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1128/aac.02682-14

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author


Publisher:
American Society for Microbiology
Journal:
Antimicrobial agents and chemotherapy More from this journal
Volume:
58
Issue:
9
Pages:
5528-5536
Publication date:
2014-09-01
DOI:
EISSN:
1098-6596
ISSN:
0066-4804


Language:
English
UUID:
uuid:785224d6-872b-450f-81bd-dedd1271c743
Local pid:
pubs:475820
Source identifiers:
475820
Deposit date:
2014-07-21

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