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Open Access Research

Dihydroartemisinin-piperaquine versus chloroquine to treat vivax malaria in Afghanistan: an open randomized, non-inferiority, trial

Ghulam Rahim Awab12, Sasithon Pukrittayakamee1, Mallika Imwong1, Arjen M Dondorp134, Charles J Woodrow35, Sue Jean Lee34, Nicholas PJ Day134, Pratap Singhasivanon1, Nicholas J White134* and Faizullah Kaker2

Author Affiliations

1 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

2 Ministry of Public Health, Islamic Republic of Afghanistan, Kabul, Afghanistan

3 Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand

4 Centre for Tropical Medicine, Churchill Hospital, Oxford, UK

5 Division of Clinical Sciences, St. George's, University of London, UK

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Malaria Journal 2010, 9:105  doi:10.1186/1475-2875-9-105

Published: 21 April 2010

Abstract

Background

Afghanistan's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection, the parasite responsible for the majority of its malaria burden. Chloroquine resistance in P. vivax is emerging in Asia. Therapeutic responses across Afghanistan have not been evaluated in detail.

Methods

Between July 2007 and February 2009, an open-label, randomized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted. Consistent with current national guidelines, primaquine was not administered. Subjects were followed up daily during the acute phase of illness (days 0-3) and weekly until day 56. The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment, with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine (Δ = 5% difference in proportion of failures).

Results

Of 2,182 individuals with positive blood films for P. vivax, 536 were enrolled in the trial. The day 28 cure rate was 100% in both treatment groups. Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine. At day 56, there were more recurrent infections in the chloroquine arm (8.9%, 95% CI 6.0-13.1%) than the dihydroartemisinin-piperaquine arm (2.8%, 95% CI 1.4-5.8%), a difference in cumulative recurrence rate of 6.1% (2-sided 90%CI +2.6 to +9.7%). The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine (p = 0.003). Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence. Both regimens were well tolerated and no serious adverse events were reported.

Conclusions

Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan. In a setting where radical therapy cannot be administered, dihydroartemisinin-piperaquine provides additional benefit in terms of post-treatment prophylaxis, reducing the incidence of recurrence from 4-8 weeks after treatment.

Trial Registration

The trial was registered at ClinicalTrials.gov under identifier NCT00682578.