title: Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy.
abstract: BACKGROUND
  Intermittent 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The 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.).
authors.affiliation: 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.).
authors.forename: Abel
authors.initials: A
authors.lastname: Kakuru
authors.affiliation: 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.).
authors.forename: Prasanna
authors.initials: P
authors.lastname: Jagannathan
authors.affiliation: 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.).
authors.forename: Mary K
authors.initials: MK
authors.lastname: Muhindo
authors.affiliation: 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.).
authors.forename: Paul
authors.initials: P
authors.lastname: Natureeba
authors.affiliation: 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.).
authors.forename: Patricia
authors.initials: P
authors.lastname: Awori
authors.affiliation: 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.).
authors.forename: Miriam
authors.initials: M
authors.lastname: Nakalembe
authors.affiliation: 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.).
authors.forename: Bishop
authors.initials: B
authors.lastname: Opira
authors.affiliation: 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.).
authors.forename: Peter
authors.initials: P
authors.lastname: Olwoch
authors.affiliation: 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.).
authors.forename: John
authors.initials: J
authors.lastname: Ategeka
authors.affiliation: 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.).
authors.forename: Patience
authors.initials: P
authors.lastname: Nayebare
authors.affiliation: 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.).
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Clark
authors.affiliation: 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.).
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
authors.affiliation: 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.).
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Charlebois
authors.affiliation: 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.).
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rizzuto
authors.affiliation: 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.).
authors.forename: Atis
authors.initials: A
authors.lastname: Muehlenbachs
authors.affiliation: 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.).
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.affiliation: 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.).
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.affiliation: 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.).
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006801:Humans; D015994:Incidence; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control*; D018512:Parasitemia / Q000453:epidemiology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control*; D011256:Pregnancy Outcome; D011739:Pyrimethamine / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects; D013413:Sulfadoxine / Q000009:adverse effects / Q000627:therapeutic use*; D014454:Uganda; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011739:Pyrimethamine; D011804:Quinolines; D013413:Sulfadoxine; C001205:fanasil, pyrimethamine drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines