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Malaria Chemoprevention in the Postdischarge Management of Severe Anemia
Titus K Kwambai1, Aggrey Dhabangi1, Richard Idro1
1From the Centre for Global Health Research, Kenya Medical Research Institute (T.K.K., S.K., N.A.K., E.D.O., K.O., F.O.K.), and the Kisumu County Department of Health, Kenya Ministry of Health (T.K.K.) and the Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention (CDC) (A.M.S., M.R.D.) - all in Kisumu; the Department of Clinical Sciences, Liverpool School of Tropical Medicine (T.K.K., V.W., D.W., F.O.K.), and the Department of Biostatistics, University of Liverpool (V.W.), Liverpool, United Kingdom; Makerere University College of Health Sciences, Kampala, Uganda (A.D., R.I., R.O.); the Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, CDC, Atlanta (A.M.S., M.R.D.); Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam (M.B.H.); the Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, Indianapolis (C.C.J.); the Section for Ethics and Health Economics and the Center for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway (B.R.); and the School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre (K.S.P.).
Insights
Post-discharge malaria chemoprevention with dihydroartemisinin-piperaquine significantly reduced readmissions and deaths in anemic children in Africa. The protective effect was concentrated during the initial treatment period.
Area of Science:
- Global Health
- Infectious Diseases
- Pediatrics
Background:
- Children hospitalized with severe anemia in malaria-endemic regions face high post-discharge mortality.
- Existing prevention strategies do not adequately address this critical post-discharge period.
Purpose of the Study:
- To evaluate the efficacy of 3-month malaria chemoprevention in reducing morbidity and mortality in young children after hospitalization for severe anemia.
Main Methods:
- A multicenter, randomized, placebo-controlled trial involving 1049 children under 5 years in Kenya and Uganda.
- Children received standard care and a discharge course of artemether-lumefantrine, followed by monthly dihydroartemisinin-piperaquine or placebo for 3 months post-discharge.
- Primary outcome: hospital readmission or death within 6 months, analyzed using recurrent event modeling.
Main Results:
- The chemoprevention group experienced significantly fewer readmissions or deaths (184 events) compared to the placebo group (316 events) (HR, 0.65; P<0.001).
- This benefit was primarily observed during the intervention period (weeks 3-14), with no sustained effect thereafter.
- No serious adverse events were linked to dihydroartemisinin-piperaquine.
Conclusions:
- Three months of postdischarge malaria chemoprevention with dihydroartemisinin-piperaquine effectively reduced deaths and readmissions in severely anemic children in high malaria transmission areas.
- The findings highlight the importance of targeted interventions during the immediate post-discharge period.
Background:
Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period.
Methods:
We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin-piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice-Williams-Peterson total-time approach.
Results:
From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin-piperaquine.
Conclusions:
In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo. (Funded by the Research Council of Norway and the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT02671175.).
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