Dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy

1. No overall significant difference was found in infant malaria incidence between mothers taking intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine.

2. Dihydroartemisinin-piperaquine (DP) was associated with lower incidence of malaria infant males compared to traditional sulfadoxine-pyrimethamine (SP) use in the first year of life.

Evidence Rating Level: 2 (Good)

To prevent maternal malarial infection, the World Health Organization currently recommends intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) to pregnant women living in regions with moderate to high malaria transmission intensity. However, with growing antifolate resistance reducing the efficacy of SP, recent studies show a promising alternative, dihydroartemisinin-piperaquine (DP), that is much more effective at reducing malaria parsitemia prevalence, incidence of clinical malaria during pregnancy, and risk of placental malaria at delivery, though trials have yet to show it as a superior agent for preventing adverse birth outcomes or providing chemoprevention during infancy. In this double-blind, randomized controlled trial, 687 pregnant, HIV-uninfected women were followed at one dedicated study clinic in the Busia district, SE Uganda (high malaria transmission intensity) from December 2016 to December 2017. Each participant was randomly assigned in a 1:1 ratio to receive either IPTp-DP (dihydroartemisinin 40mg/piperaquine 320mg 3 tabs PO once daily x 3 days) or IPTp-SP (sulfadoxine 500mg/pyrimethamine 25mg 3 tabs PO x single dose) every 4 weeks from 16 or 20 weeks of gestation along with placebo tablets of the other drug to maintain blinding. In the first phase, pregnant women attended routine visits every 4 weeks to receive their medication, get laboratory testing, and get treated for symptomatic, not asymptomatic malaria. Then, all 678 live births were followed for up to 12 months, where infants with history of 24h fever and tympanic temperature of >=38^oC were tested and positive thick blood smears were treated. The primary outcome was the incidence of malaria during the first 12 months of life. Although the incidence rate was lower in infants with mothers who received IPTp-DP over those who received IPTp-SP, this difference was not statistically significant (1.71 vs 1.98 episoders per person-year, incident rate ratio (IRR) 0.87, CI 0.73-1.03, p=0.11). However, among male infants, the incidence of malaria was significantly lower among those with mothers in the DP group vs the SP group (IRR 0.75, 95% CI 0.58-0.98, p=0.03). This difference was not found among female infants and only remained significant in male infants between >3-12 months of age. Moreover, the incidence of complicated malaria was lower among infants with mothers given DP (IRR=0.54, 95% CI 0.32-0.92, p=0.02), an effect also observed in the male infants specifically (IRR 0.36, 95% CI, 0.17-0.89, p=0.01). In terms of secondary outcomes, the effect of lower incidence of all-cause hospitalizations among infants with mothers who received DP was only significant in male infants (IRR 0.20, 95% CI 0.05-0.82, p=0.03), with no significant different in infant mortality rate between the groups. Ultimately, as some benefit has been seen in male infants of mothers receiving DP over SP, these results may add support for IPTp-DP replacing IPTp-SP in areas with widespread antifolate resistance. Further research should follow up infants beyond the neonatal age, as well as conduct trials in settings with different malaria transmission intensities, to see if trends of decreasing IRR associated with IPTP-DP can be extrapolated.

Click to read the study in BMC Medicine

Image: PD

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