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Kwambai, Titus, Dhabangi, Aggrey, Idro, Richard, Opoka, Robert, Watson, Victoria, Kariuki, Simon, Nickline, Kuya, Onyango, Eric D, Otieno, Kephas, Samuels, Aaron, Desai, Meghna, Boele van Hensbroek, Michael, Wang, Duolao 
ORCID: https://orcid.org/0000-0003-2788-2464, John, Chandy C, Robberstad, Bjarne, Phiri, Kamija S and terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617
(2020)
'Malaria Chemoprevention in the Postdischarge Management of Severe Anemia'. The New England Journal of Medicine, Vol 383, pp. 2242-2254.
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Abstract
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).
| Item Type: | Article |
|---|---|
| Subjects: | WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 155 Anemia WS Pediatrics > WS 100 General works WS Pediatrics > By Age Groups > WS 430 Infancy |
| Faculty: Department: | Biological Sciences > Vector Biology Department Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1056/NEJMoa2002820 |
| Depositing User: | Helen Wong |
| Date Deposited: | 09 Dec 2020 15:44 |
| Last Modified: | 03 Jun 2021 01:02 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/15360 |
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