Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial

Abstract

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 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