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Lancet. 2007 Mar 3;369(9563):757-765. doi: 10.1016/S0140-6736(07)60160-3.

Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison.

Author information

1
International Health Programme, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
2
National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia.
3
MSHR-NIHRD Malaria Research Programme, Timika, Indonesia; District Ministry of Health, Timika, Papua, Indonesia.
4
Public Health and Malaria Control Department, PT Freeport, Indonesia, Tembagapura, Papua, Indonesia; International SOS, Tembagapura, Papua, Indonesia.
5
Public Health and Malaria Control Department, PT Freeport, Indonesia, Tembagapura, Papua, Indonesia.
6
Directorate General of Centre for Disease Control and Environmental Health, Ministry of Health, Jakarta, Indonesia.
7
International Health Programme, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia; Centre for Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK. Electronic address: rnp@menzies.edu.au.

Abstract

BACKGROUND:

The burden of Plasmodium vivax infections has been underappreciated, especially in southeast Asia where chloroquine resistant strains have emerged. Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax.

METHODS:

774 patients in southern Papua, Indonesia, with slide-confirmed malaria were randomly assigned to receive either artemether-lumefantrine or dihydroartemisinin-piperaquine and followed up for at least 42 days. The primary endpoint was the overall cumulative risk of parasitological failure at day 42 with a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, trial number 00157833.

FINDINGS:

Of the 754 evaluable patients enrolled, 466 had infections with P falciparum, 175 with P vivax, and 113 with a mixture of both species. The overall risk of failure at day 42 was 43% (95% CI 38-48) for artemether-lumefantrine and 19% (14-23) for dihydroartemisinin-piperaquine (hazard ratio=3.0, 95% CI 2.2-4.1, p<0.0001). After correcting for reinfections, the risk of recrudescence of P falciparum was 4.4% (2.6-6.2) with no difference between regimens. Recurrence of vivax occurred in 38% (33-44) of patients given artemether-lumefantrine compared with 10% (6.9-14.0) given dihydroartemisinin-piperaquine (p<0.0001). At the end of the study, patients receiving dihydroartemisinin-piperaquine were 2.0 times (1.2-3.6) less likely to be anaemic and 6.6 times (2.8-16) less likely to carry vivax gametocytes than were those given artemether-lumefantrine.

INTERPRETATION:

Both dihydroartemisinin-piperaquine and artemether-lumefantrine were safe and effective for the treatment of multidrug-resistant uncomplicated malaria. However, dihydroartemisinin-piperaquine provided greater post-treatment prophylaxis than did artemether-lumefantrine, reducing P falciparum reinfections and P vivax recurrences, the clinical public-health importance of which should not be ignored.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00157833.

PMID:
17336652
PMCID:
PMC2532500
DOI:
10.1016/S0140-6736(07)60160-3
[Indexed for MEDLINE]
Free PMC Article

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