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

Author(s): 
Ratcliff, A.
Siswantoro, H.
Kenangalem, E.
Maristela, R.
Wuwung, R. M.
Laihad, F.
Ebsworth, E. P.
Anstey, N. M.
Tjitra, E.
Price, R. N.
Item Type: 
Journal Article
Publication Title: 
Lancet (London, England)
Journal Abbreviation: 
Lancet
Publication Date: 
3/3/2007
Publication Year: 
2007
Pages: 
757-765
Volume: 
369
Issue: 
9563
ISSN: 
1474-547X
DOI: 
10.1016/S0140-6736(07)60160-3
Library Catalog: 
PubMed
Extra: 
PMID: 17336652 PMCID: PMC2532500

Turabian/Chicago Citation

A. Ratcliff, H. Siswantoro, E. Kenangalem, R. Maristela, R. M. Wuwung, F. Laihad, E. P. Ebsworth, N. M. Anstey, E. Tjitra and R. N. Price. 3/3/2007. "Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison." Lancet (London, England) 369: 9563: 757-765. 10.1016/S0140-6736(07)60160-3.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/S0140-6736(07)60160-3 | issn = 1474-547X | volume = 369 | pages = 757-765 | last = Ratcliff | first = A. | coauthors = Siswantoro, H., Kenangalem, E., Maristela, R., Wuwung, R. M., Laihad, F., Ebsworth, E. P., Anstey, N. M., Tjitra, E., Price, R. N. | title = Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison | journal = Lancet (London, England) | date = 3/3/2007 | pmid = | pmc = }} </ref>