Intermittent Treatment for the Prevention of Malaria during Pregnancy in Benin: A Randomized, Open-Label Equivalence Trial Comparing Sulfadoxine-Pyrimethamine with Mefloquine

Background. In the context of the increasing resistance to sulfadoxine-pyrimethamine (SP), we evaluated the efficacy of mefloquine (MQ) for intermittent preventive treatment during pregnancy (IPTp). Methods. A multicenter, open-label equivalence trial was conducted in Benin from July 2005 through April 2008. Women of all gravidities were randomized to receive SP (1500 mg of sulfadoxine and 75 mg of pyrimethamine) or 15 mg/kg MQ in a single intake twice during pregnancy. The primary end point was the proportion of low birth-weight (LBW) infants (body weight, <2500 g; equivalence margin, 5%). Results. A total of 1601 women were randomized to receive MQ (n = 802) or SP (n = 799). In the modified intention-to-treat analysis, which assessed only live singleton births, 59 (8%) of 735 women who were given MQ and 72 (9.8%) of 730 women who were given SP gave birth to LBW infants (difference between low birth weights in treatment groups, -1.8%; 95% confidence interval [CI], -4.8% to 1.1%]), establishing equivalence between the drugs. The per-protocol analysis showed consistent results. MQ was more efficacious than SP in preventing placental malaria (prevalence, 1.7% vs 4.4% of women; P = .005), clinical malaria (incidence rate, 26 cases/10,000 person-months vs. 68 cases/10,000 person-months; P = .007), and maternal anemia at delivery (as defined by a hemoglobin level <10 g/dL) (prevalence, 16% vs 20%; marginally significant at P = .09). Adverse events (mainly vomiting, dizziness, tiredness, and nausea) were more commonly associated with the use of MQ (prevalence, 78% vs 32%; P < 10(-3)). One woman in the MQ group had severe neuropsychiatric symptoms. Conclusions. MQ proved to be highly efficacious-both clinically and parasitologically-for use as IPTp. However, its low tolerability might impair its effectiveness and requires further investigations. Clinical Trials Registration. NCT00274235.