• Abel Kakuru, Prasanna Jagannathan, Mary K Muhindo, Paul Natureeba, Patricia Awori, Miriam Nakalembe, Bishop Opira, Peter Olwoch, John Ategeka, Patience Nayebare, Tamara D Clark, Margaret E Feeney, Edwin D Charlebois, Gabrielle Rizzuto, Atis Muehlenbachs, Diane V Havlir, Moses R Kamya, and Grant Dorsey.
• From the Infectious Diseases Research Collaboration (A.K., M.K.M., P. Natureeba, P.A., B.O., P.O., J.A., P. Nayebare), the Department of Obstetrics and Gynecology, Makerere University College of Health Sciences (M.N.), and the School of Medicine, Makerere University College of Health Sciences (M.R.K.) - all in Kampala, Uganda; the Departments of Medicine (P.J., T.D.C., M.E.F., D.V.H., G.D.), Pediatrics (M.E.F.), and Pathology (G.R.) and the Center for AIDS Prevention Studies (E.D.C.), University of California, San Francisco, San Francisco; and the Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta (A.M.).
• N. Engl. J. Med. 2016 Mar 10; 374 (10): 928-39.

BackgroundIntermittent treatment with sulfadoxine-pyrimethamine is widely recommended for the prevention of malaria in pregnant women in Africa. However, with the spread of resistance to sulfadoxine-pyrimethamine, new interventions are needed.MethodsWe conducted a double-blind, randomized, controlled trial involving 300 human immunodeficiency virus (HIV)-uninfected pregnant adolescents or women in Uganda, where sulfadoxine-pyrimethamine resistance is widespread. We randomly assigned participants to a sulfadoxine-pyrimethamine regimen (106 participants), a three-dose dihydroartemisinin-piperaquine regimen (94 participants), or a monthly dihydroartemisinin-piperaquine regimen (100 participants). The primary outcome was the prevalence of histopathologically confirmed placental malaria.ResultsThe prevalence of histopathologically confirmed placental malaria was significantly higher in the sulfadoxine-pyrimethamine group (50.0%) than in the three-dose dihydroartemisinin-piperaquine group (34.1%, P=0.03) or the monthly dihydroartemisinin-piperaquine group (27.1%, P=0.001). The prevalence of a composite adverse birth outcome was lower in the monthly dihydroartemisinin-piperaquine group (9.2%) than in the sulfadoxine-pyrimethamine group (18.6%, P=0.05) or the three-dose dihydroartemisinin-piperaquine group (21.3%, P=0.02). During pregnancy, the incidence of symptomatic malaria was significantly higher in the sulfadoxine-pyrimethamine group (41 episodes over 43.0 person-years at risk) than in the three-dose dihydroartemisinin-piperaquine group (12 episodes over 38.2 person-years at risk, P=0.001) or the monthly dihydroartemisinin-piperaquine group (0 episodes over 42.3 person-years at risk, P<0.001), as was the prevalence of parasitemia (40.5% in the sulfadoxine-pyrimethamine group vs. 16.6% in the three-dose dihydroartemisinin-piperaquine group [P<0.001] and 5.2% in the monthly dihydroartemisinin-piperaquine group [P<0.001]). In each treatment group, the risk of vomiting after administration of any dose of the study agents was less than 0.4%, and there were no significant differences among the groups in the risk of adverse events.ConclusionsThe burden of malaria in pregnancy was significantly lower among adolescent girls or women who received intermittent preventive treatment with dihydroartemisinin-piperaquine than among those who received sulfadoxine-pyrimethamine, and monthly treatment with dihydroartemisinin-piperaquine was superior to three-dose dihydroartemisinin-piperaquine with regard to several outcomes. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT02163447.).

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