Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy

N Engl J Med. 2016 Mar 10;374(10):928-39. doi: 10.1056/NEJMoa1509150.

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.).

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / adverse effects
  • Antimalarials / therapeutic use*
  • Artemisinins / administration & dosage*
  • Artemisinins / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Resistance
  • Female
  • Humans
  • Incidence
  • Malaria / epidemiology
  • Malaria / prevention & control*
  • Parasitemia / epidemiology
  • Pregnancy
  • Pregnancy Complications, Parasitic / prevention & control*
  • Pregnancy Outcome
  • Pyrimethamine / adverse effects
  • Pyrimethamine / therapeutic use*
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Sulfadoxine / adverse effects
  • Sulfadoxine / therapeutic use*
  • Uganda
  • Vomiting / chemically induced
  • Young Adult

Substances

  • Antimalarials
  • Artemisinins
  • Drug Combinations
  • Quinolines
  • fanasil, pyrimethamine drug combination
  • dihydroartemisinin
  • Sulfadoxine
  • piperaquine
  • Pyrimethamine

Associated data

  • ClinicalTrials.gov/NCT02163447