Malaria Chemoprevention in the Postdischarge Management of Severe Anemia

Background

Children hospitalized with severe anemia in malaria-endemic areas of Africa are at high risk of readmission or death within six months post-discharge. No strategy specifically addresses this period. We conducted a multi-center, two-arm, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine if three months of malaria chemoprevention could reduce morbidity and mortality post-discharge.

Methods

Children aged <5 years with admission hemoglobin of <5g/dL were eligible. They received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks post-discharge, they were randomized to receive 3-day dihydroartemisinin-piperaquine treatment courses or placebo at two, six, and ten weeks post-discharge and followed until week-26 inclusive using passive case-detection. The primary outcome was the time to one or more hospital readmissions or death by six months post-discharge. Conditional risk set modeling for recurrent events (Prentice-Williams-Peterson total-time) was used to calculate hazard ratios (HR).

Results

Between May-2016 and November-2018, 1049 participants were randomized (dihydroartemisinin-piperaquine=524, placebo=525). There were 184 and 316 primary outcome events in the dihydroartemisinin-piperaquine and placebo arms, respectively, between 3-26 weeks post-discharge (HR=0.65, 95% CI 0.54-0.78, p<0.001). The reduction was restricted to the intervention period (3-14 weeks post-discharge) (HR=0.30, 0.22-0.42) and not sustained afterward (15-26 weeks) (HR=1.13, 0.87-1.47). No serious adverse events were attributable to dihydroartemisinin-piperaquine.

Conclusion

In areas with intense malaria transmission, three months of post-discharge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children recently transfused for severe anemia results in substantial reductions in deaths or all-cause readmissions post-discharge. (ClinicalTrials.gov number, NCT02671175).