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Leslie T, Mayan MI, Hasan MA, et al. Sulfadoxine-Pyrimethamine, Chlorproguanil-Dapsone, or Chloroquine for the Treatment of Plasmodium vivax Malaria in Afghanistan and Pakistan: A Randomized Controlled Trial. JAMA. 2007;297(20):2201–2209. doi:10.1001/jama.297.20.2201
Author Affiliations: HealthNet TPO Malaria and Leishmaniasis Control Programme, Peshawar, Northwest Frontier Province, Pakistan (Drs Mayan, Hasan, and Klinkenberg, and Messrs Leslie and Safi); Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, England (Drs Whitty and Rowland, and Mr Leslie).
Context In areas where Plasmodium falciparum and Plasmodium vivax coexist and treatments for the 2 species differ, misdiagnosis can lead to poor outcomes in either disease. A unified therapy effective against both species would reduce reliance on species-specific diagnosis, which in many areas is difficult to maintain. The antifolates are an important and affordable antimalarial class to which it is often assumed P vivax malaria is intrinsically resistant.
Objective To test the relative efficacy and safety of 2 antifolate drugs against P vivax malaria and compare each with chloroquine.
Design, Setting, and Patients An open-label randomized controlled trial comparing chloroquine, sulfadoxine-pyrimethamine, and chlorproguanil-dapsone for the treatment of P vivax malaria was conducted in eastern Afghanistan and northwestern Pakistan, areas in which P vivax malaria predominates. A total of 20 410 patients older than 3 years were screened; 767 patients (315 in Pakistan and 452 in Afghanistan) with confirmed P vivax malaria were enrolled and followed up daily for 4 days, then weekly for 28 days, between March 2004 and June 2006.
Main Outcome Measures Complete clearance of parasites with no recrudescence by day 14. Secondary outcomes included being parasite-free by day 28, clinical failure, and anemia.
Results By day 14, only 1 patient in the sulfadoxine-pyrimethamine group had parasites. By day 28, failure rates were found in 2 of 153 patients (1.3%) in the chloroquine group, 5 of 290 patients (1.7%) in the sulfadoxine-pyrimethamine group, and 27 of 272 patients (9.9%) in the chlorproguanil-dapsone group. Chlorproguanil-dapsone was less effective than sulfadoxine-pyrimethamine (adjusted odds ratio [OR], 6.4; 95% confidence interval [CI], 2.4-17.0; P<.001) and chloroquine (adjusted OR, 8.4; 95% CI, 2.0-36.5; P = .004). Chloroquine and sulfadoxine-pyrimethamine were equivalent in efficacy at day 28 (adjusted OR, 1.3; 95% CI, 0.3-7.0; P = .73). Chloroquine cleared gametocytes and asexual parasites more rapidly than sulfadoxine-pyrimethamine or chlorproguanil-dapsone did. All drugs were well tolerated.
Conclusions Although chloroquine remains the drug of choice, antifolates are effective against P vivax malaria in South Asia. These drugs may be appropriate for unified treatment where species-specific diagnosis is unavailable, most likely in combination with other drugs.
Trial Registration clinicaltrials.gov Identifier: NCT00158561
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