TY - JOUR
T1 - 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
AU - Phiri, Kamija S.
AU - Khairallah, Carole
AU - Kwambai, Titus K.
AU - Bojang, Kalifa
AU - Dhabangi, Aggrey
AU - Opoka, Robert
AU - Idro, Richard
AU - Stepniewska, Kasia
AU - van Hensbroek, Michael Boele
AU - John, Chandy C.
AU - Robberstad, Bjarne
AU - Greenwood, Brian
AU - ter Kuile, Feiko O.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
U2 - 10.1016/s2214-109x(23)00492-8
DO - 10.1016/s2214-109x(23)00492-8
M3 - Article
SN - 2572-116X
VL - 12
SP - E33-E44
JO - The Lancet Global Health
JF - The Lancet Global Health
IS - 1
ER -
