Effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaqunine against malaria in pregnancy in Tanzania: A Randomized Controlled Trial.

Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to prevent malaria and adverse birth outcomes is threatened by Plasmodium falciparum resistance to sulfadoxine-pyrimethamine. We investigated the effectiveness of intermittent preventive treatment in pregnancy with monthly Dihydroartemisinin-piperaquine (IPTp-DHP) as an alternative option to IPTp-SP. A total of 956 malaria-free (mRDT negative) pregnant women from moderate malaria transmission areas in Tanzania were enrolled and randomized to receive monthly IPTp-DHP (n=478) or IPTp-SP (n=478) and followed for maternal and birth outcomes. The primary outcome was the prevalence of histopathologically confirmed placental malaria (active or past infection). Secondary outcomes were overall malaria at delivery, symptomatic-malaria, parasitemia during pregnancy, and adverse birth outcomes as a composite of spontaneous-abortion, premature birth, stillbirth, low birth weight (LBW) fetal anemia. Outcome differences between treatment groups were expressed as the protective efficacy (PE), defined as 1-prevalence ratios or 1-incidence rate ratio. The prevalence of histopathologically confirmed placental malaria was significantly lower in IPTp-DHP (2.5%, 12/478) than IPTp-SP (8.2%, 39/478); PE=69% (95% CI: 42 to 84) p<0.001. The prevalence of maternal malaria at delivery was significantly lower in IPTp-DHP (8.2%) than IPTp-SP (18.2%) p<0.001. The incidence of symptomatic-malaria (0.02 versus 0.12, p=0.002) and parasitemia during pregnancy (0.28 versus 0.67, p<0.001) were significantly lower in IPTp-DHP than IPTp-SP group. The prevalence of any adverse birth outcomes (composite) was not significantly (p=0.06) different between IPTp-DHP (17.9%) and IPTp-SP (23.8%). However, the prevalence of LBW (4.6% versus 9.6%, p=0.003) was significantly lower in IPTp-DHP compared to IPTp-SP. We report superior protective efficacy of monthly IPTp-DHP against malaria in pregnancy and LBW than IPTp-SP.