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15 April 2007

Volume 44, Number 8
Clinical Infectious Diseases 2007;44:1067–1074
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4408-0009$15.00
DOI: 10.1086/512677
MAJOR ARTICLE

Dihydroartemisinin‐Piperaquine versus Artesunate‐Amodiaquine: Superior Efficacy and Posttreatment Prophylaxis against Multidrug‐Resistant Plasmodium falciparum and Plasmodium vivax Malaria

A. R. Hasugian,1

H. L. E. Purba,1

E. Kenangalem,2,3

R. M. Wuwung,4

E. P. Ebsworth,4,5

R. Maristela,4,5

P. M. P. Penttinen,4,5

F. Laihad,6

N. M. Anstey,7

E. Tjitra,1 and

R. N. Price7,8

1National Institute of Health Research and Development and 2Directorate General of Communicable Disease Control and Environmental Health, Ministry of Health, Jakarta, 3Menzies School of Health Research–National Institute of Health Research and Development Malaria Research Program and 4District Ministry of Health, Timika, and 5Public Health and Malaria Control Department, PT Freeport, and 6International SOS, Tembagapura, Papua, Indonesia; 7International Health Program, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia; and 8Centre for Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom

Background.Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax. In southern Papua, Indonesia, where both strains of plasmodia coexist, we have been conducting a series of studies to optimize treatment strategies.

Methods.We conducted a randomized trial that compared the efficacy and safety of dihydroartemisinin‐piperaquine (DHP) with artesunate‐amodiaquine (AAQ). The primary end point was the overall cumulative parasitological failure rate at day 42.

Results.Of the 334 patients in the evaluable patient population, 185 were infected with P. falciparum, 80 were infected with P. vivax, and 69 were infected with both species. The overall parasitological failure rate at day 42 was 45% (95% confidence interval [CI], 36%–53%) for AAQ and 13% (95% CI, 7.2%–19%) for DHP (hazard ratio [HR], 4.3; 95% CI, 2.5–7.2; ). Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP (HR, 3.4 [95% CI, 1.2–9.4] and 4.3 [95% CI, 2.2–8.2], respectively; ). By the end of the study, AAQ recipients were 2.95‐fold (95% CI, 1.2‐ to 4.9‐fold) more likely to be anemic and 14.5‐fold (95% CI, 3.4‐ to 61‐fold) more likely to have carried P. vivax gametocytes.

Conclusions.DHP was more effective and better tolerated than AAQ against multidrug‐resistant P. falciparum and P. vivax infections. The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection, decreased the rate of recurrence of P. vivax infection, and reduced the risk of P. vivax gametocyte carriage and anemia.

Received 21 September 2006; accepted 12 December 2006; electronically published 5 March 2007.

  • (See the editorial commentary by Plowe on pages 1075–7)

Reprints or correspondence: Dr. Ric Price Menzies School of Health Research, PO Box 41096, Casuarina, Darwin, NT 0811 Australia ().

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