Three-month postdischarge malaria chemoprevention among children who had severe anemia reduced deaths in areas with intense malaria transmission. These findings, from a multicenter, randomized, placebo-controlled trial, were published in The New England Journal of Medicine.
Children (N=1049) younger than 5 years of age who had severe anemia were recruited at 9 hospitals in Kenya and Uganda between 2016 and 2018. Children were randomly assigned in a 1:1 ratio to receive malaria chemoprevention with 3-day dihydroartemisinin-piperaquine at 2, 6, and 10 weeks (n=524) or placebo (n=525). All children in the treatment arm received 3-day artemether-lumefantrine and 2 mg/kg iron supplementation and some also received 130 to 520 mg folic acid for 28 days. Caregivers were contacted daily by telephone to ensure compliance. Children were assessed through 26 weeks for hospital readmission and mortality.
In total, 7.6% of children withdrew or were lost to follow-up.
A total of 500 hospital readmissions or deaths were observed among 315 of 1049 (30.0%) of the children. Fewer events were observed among the chemoprevention group (n=184) than the placebo group (n=316). At study conclusion, the risk for readmission or death was 35% lower among the chemoprevention group (hazard ratio [HR], 0.65; 95% CI, 0.54-0.78; P <.001).
During the intervention period, the decreased risk among the chemoprevention group was 70% lower (HR, 0.30; 95% CI, 0.22-0.42; P <.001). Postintervention, the risk was reduced by 13% (HR, 1.13; 95% CI, 0.87-1.47; P =.35) among the placebo group. Chemoprevention delayed the time to readmission or death (HR, 0.58; 95% CI, 0.47-0.73), in which the time to first instance was 135 days (95% CI, 123-149) among the chemoprevention group and 55 days (95% CI, 43-66) among the placebo cohort.
Children who had severe malarial anemia at baseline had increased incidence of readmission or death (41% vs 9%) compared with children with nonmalarial anemia.
Fewer adverse events were observed among the chemoprevention group (284 vs 534; P <.001). None of the adverse events were determined to be as a result of the interventions. Of deaths that occurred during the study, 9 were due to severe anemia, 8 to severe malarial anemia, and 11 to other causes.
This study was limited by not having access to nonmalarial causes for hospital readmissions.
These data indicated children with severe anemia living in areas with intense malaria transmission benefited from a 3-month postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine therapy.
Kwambai TK, Dhabangi A, Idro R, et al. Malaria chemoprevention in the postdischarge management of severe anemia. N Engl J Med. 2020;383(23):2242-2254. doi:10.1056/NEJMoa2002820