Superiority of 3 over 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine for the prevention of malaria during pregnancy in mali: a randomized controlled trial

Clin Infect Dis. 2011 Aug 1;53(3):215-23. doi: 10.1093/cid/cir374.

Abstract

Background: In 2003, Mali introduced intermittent preventive therapy in pregnancy (ITPp) with sulfadoxine-pyrimethamine (SP) for the control of malaria in pregnancy, consisting of 2 doses of SP given in the 2nd and 3rd trimester. This widely used regimen, although very effective, leaves many women unprotected from malaria during the last 4-to-8 weeks of gestation, which is a pivotal period for fetal weight gain. The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight (LBW).

Methods: We conducted a parallel-group, open-label, individually randomized controlled superiority trial involving 814 women of all gravidity, enrolled from April 2006 through March 2008. All women were seen at least 3 times and received either 2 (n = 401) or 3 (n = 413) doses of IPTp-SP. The primary endpoint measured was placental malaria, LBW, preterm births, and maternal anemia were secondary endpoints, and severe maternal skin reactions and neonatal jaundice were safety endpoints.

Results: Among the 96% of study subjects who were followed up until delivery, the prevalence of placental malaria was 2-fold lower in the 3-dose group (8.0%) than in the 2-dose group (16.7%); the adjusted prevalence ratio (APR) was 0.48 (95% confidence interval [CI], 0.32-0.71). LBW and preterm births were also reduced; the prevalence of LBW was 6.6% in the 3-dose group versus 13.3% in the 2-dose group (APR, 0.50; 95% CI, 0.32-0.79), and the prevalence of preterm births was 3.2% versus 8.9% (APR, 0.37; 95% CI, 0.19-0.71). No significant reductions in maternal anemia or differences in safety endpoints were observed.

Conclusions: Adding a third dose of ITPp-SP halved the risk of placental malaria, LBW, and preterm births in all gravidae, compared with the standard 2-dose regimen, in this area of highly seasonal transmission with low levels of SP resistance.

Clinical trials registration: ISRCTN 74189211.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia / prevention & control
  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects
  • Chemoprevention / adverse effects
  • Chemoprevention / methods*
  • Drug Combinations
  • Female
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Jaundice, Neonatal / prevention & control
  • Malaria / prevention & control*
  • Mali
  • Middle Aged
  • Pregnancy
  • Pregnancy Complications, Infectious / prevention & control*
  • Premature Birth / prevention & control
  • Pyrimethamine / administration & dosage*
  • Pyrimethamine / adverse effects
  • Skin Diseases / chemically induced
  • Sulfadoxine / administration & dosage*
  • Sulfadoxine / adverse effects
  • Treatment Outcome
  • Young Adult

Substances

  • Antimalarials
  • Drug Combinations
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • Pyrimethamine

Associated data

  • ISRCTN/ISRCTN74189211