Post-discharge Malaria Chemoprevention in Children Admitted with Severe Anaemia in Malaria-Endemic Settings in Africa: A systematic review and Individual Patient Data meta-analysis of randomised controlled trials

Phiri, Kamija, Khairallah, Carole, Kwambai, Titus, Bojang, Kalifa, Dhabangi, Aggrey, Opoka, Robert, Idro, Richard, Stepniewska, Kasia, Boele van Hensbroek, Michael, John, Chandy C, Robberstad, Bjarne, Greenwood, Brian and terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 (2024) 'Post-discharge Malaria Chemoprevention in Children Admitted with Severe Anaemia in Malaria-Endemic Settings in Africa: A systematic review and Individual Patient Data meta-analysis of randomised controlled trials'. Lancet Global Health, Vol 12, Issue 1, E33-E44.

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Abstract

Background: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted an individual patient data (IPD) meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention (PDMC) in children recovering from severe anaemia.

Methods: Following PRISMA-IPD guidelines, we searched multiple databases, without time or language restrictions, for randomised controlled trials comparing monthly PDMC with placebo or standard-of-care among children admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. Fixed-effects two-stage meta-analysis of risk ratios (RR) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data were analysed using one-stage mixed-effects Prentice-Williams-Peterson Total-Time models to obtain hazard ratios (HRs). This study is registered with PROSPERO-CRD42022308791.

Findings: Three double-blind placebo-controlled trials involving 3,663 children with severe anaemia fulfilled the eligibility criteria; 3,507 (95.7%) contributed to the modified intention-to-treat analysis. They received either monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (average 3.1 courses/child) (N=1,085, the Gambia), monthly artemether-lumefantrine given at the end of the 4th and 8th week post-discharge (N=1,373, Malawi), or monthly dihydroartemisinin-piperaquine given at the end of the 2nd, 6th, and 10th week post-discharge (N=1,049, Uganda and Kenya). During the period of chemoprevention, PDMC was associated with a 77% reduction in mortality (RR=0.23 [95% CI 0.08-0.70], p=0.0094, I2=0%) and a 55% reduction in all-cause readmissions (HR=0.45 [0.36-0.56], p<0.0001). The reductions were not sustained after protective drug levels had waned. The small number of trials limited our ability to assess heterogeneity, its sources and publication bias.
Interpretation: In malaria-endemic Africa, PDMC reduces mortality and readmissions in recently discharged children recovering from severe anaemia. PDMC can be a valuable strategy for the post-discharge management of this high-risk group. Future research should focus on methods of PDMC delivery, options to prolong the protection duration, other hospitalised special risk groups, and interventions targeting non-malarial causes of post-discharge morbidity.

Item Type:	Article
Subjects:	WC Communicable Diseases > WC 20 Research (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WS Pediatrics > WS 20 Research (General) WS Pediatrics > Diseases of Children and Adolescents > By System > WS 300 Hemic and lymphatic system
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/S2214-109X(23)00492-8
Depositing User:	Tracy Seddon
Date Deposited:	19 Dec 2023 15:15
Last Modified:	19 Dec 2023 15:15
URI:	https://archive.lstmed.ac.uk/id/eprint/23462

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