Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial

Abstract

Clara Menéndez and colleagues conducted an open-label randomized controlled trial in HIV-negative pregnant women in Benin, Gabon, Mozambique, and Tanzania to evaluate the safety and efficacy of mefloquine compared to sulfadoxine-pyrimethamine for intermittent preventative therapy for malaria. Please see later in the article for the Editors' Summary

Mefloquine Versus Sulfadoxine–Pyrimethamine for Intermittent Preventive Treatment in Pregnancy: A Joint Analysis on Efficacy and Tolerability

“…Recently, a larger clinical trial conducted in five African countries confirmed that MQ at the dose of 15 mg/kg was not associated with an increased risk of severe neuropsychiatric effects. 7 Another strength of this study is the way in which missing data were handled. Missing data on LBW, placental malaria, and maternal anemia were likely to be random since most deliveries, which occurred outside the maternity clinics and for which outcomes could not be measured, were associated with traveling from outside the study area or transportation difficulties.…”

“…Although concerns have been raised about a possible increase in stillbirths in women treated with curative doses of MQ, 19 this finding was confirmed neither in larger datasets nor in two recent multicenter trials on MQ for IPTp conducted in around 6,000 pregnant women. 6,7,9,20,21 As guidelines, we would recommend not including overcoming AE criteria such as stillbirths, congenital malformations, or mother-to-child transmission (MTCT) of HIV-when relevant-in the multiple outcome analysis since these outcomes have to be evaluated separately, prior to other criteria. In such cases where the drug "under test" has been associated with a significant increased risk for one of these major outcomes, we consider that the multiple outcome approach is not appropriate because the drug should not be given in this indication.…”

“…In two recent clinical trials, MQ-IPTp has proven to be equivalent to SP-IPTp in preventing LBW. 6,7 It was also found to be more efficacious than SP-IPTp in preventing maternal anemia, symptomatic malaria, and placental, and peripheral malaria infections at delivery both in human immunodeficiency virus (HIV)-negative and HIV-positive women. [6][7][8][9] However, owing to its moderate tolerability, the Malaria Policy Advisory Committee to the WHO, which met in September 2013, proposed that MQ at the 15 mg/kg dose regimen should not be recommended for IPTp.…”

“…6,7 It was also found to be more efficacious than SP-IPTp in preventing maternal anemia, symptomatic malaria, and placental, and peripheral malaria infections at delivery both in human immunodeficiency virus (HIV)-negative and HIV-positive women. [6][7][8][9] However, owing to its moderate tolerability, the Malaria Policy Advisory Committee to the WHO, which met in September 2013, proposed that MQ at the 15 mg/kg dose regimen should not be recommended for IPTp. 10 In the current debate regarding the relevance of MQ for IPTp, we reanalyzed data from the first Beninese trial with an original statistical approach already used to assess treatments in rheumatology, 6 which made it possible to perform a global comparison of SP and MQ for IPTp taking into account both the preventive and adverse effects of the treatments simultaneously.…”

Maternal HIV infection is an important health determinant in non-HIV-infected infants

“…Results from the trial showed no differences in mortality, morbidity and nutritional status between infants born to women allocated to either study group [23,24]. As part of clinical trial procedures, at delivery, newborns were given a study number to be uniquely identified.…”