Abstract:
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 (malaria rapid diagnostic test (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, and 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% confidence interval (CI): 42–84, 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
per person-years at risk for symptomatic-malaria (0.02 vs. 0.12, P = 0.002) and parasitemia during pregnancy (0.28 vs.
0.67, P < 0.001) were significantly lower in the IPTp-DHP group than in the 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% vs. 9.6%, P = 0.003) was significantly lower in IPTp-DHP compared with IPTp-SP.
We report superior protective efficacy of monthly IPTp-DHP against malaria in pregnancy and LBW than IPTp-SP
