Sulfadoxine-pyrimethamine resistance undermines the only approved drug for malaria in pregnancy

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is the WHO-recommended strategy to protect pregnant women from malaria, but SP resistance driven by mutations in the dhfr and dhps genes is now widespread across East and Southern Africa. SP has already been abandoned as a treatment drug in children because of inadequate efficacy, yet it remains the only approved drug for IPTp. This matters because malaria in pregnancy causes placental malaria, which restricts fetal growth, causes severe maternal anemia, and leads to low birth weight, the single largest risk factor for neonatal mortality in sub-Saharan Africa. In areas of high SP resistance, IPTp-SP's ability to clear placental parasites is greatly reduced, but programs continue using it because there is literally no alternative approved at scale. Pregnant women are receiving a drug known to be failing, creating a false sense of security. The problem persists because clinical trials for alternative IPTp regimens (dihydroartemisinin-piperaquine, mefloquine, azithromycin combinations) have been slow, underfunded, and complicated by safety concerns unique to pregnancy. The regulatory bar for approving drugs for use in pregnant women is exceptionally high, and pharmaceutical companies see no commercial return in developing drugs for this population. WHO has not updated its IPTp recommendation since 2012 despite mounting resistance evidence.