Clinical presentation of severe malaria in children who received the RTS,S/AS01E malaria vaccine, seasonal malaria chemoprevention or the combination of both interventions in Burkina Faso and Mali

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• Picked for Pediatrics and Child Health (paper of the day, 3 November 2026): Childhood malaria vaccine and chemoprevention clinical outcomes

Abstract

BACKGROUND: Severe Plasmodium falciparum malaria is a leading cause of death in sub-Saharan Africa, with most deaths occurring in children younger than five years of age. The RTS,S/AS01E (RTS,S) malaria vaccine delivered seasonally with Seasonal Malaria Chemoprevention (SMC) led to a two-third reduction in severe malaria and malaria deaths compared with either intervention given alone. The aim of this study was to assess and compare the clinical phenotype distribution among severe malaria admissions by intervention groups and country. METHODS: We conducted a secondary ad-hoc analysis of hospital admissions in children aged 5 to 17 months of age when enrolled in the RTS,S + SMC trial in April 2017 in Houndé, Burkina Faso, and Bougouni, Mali, and who were followed until they reached five years of age. RESULTS: Among the 5,920 children enrolled in Burkina Faso and Mali, 337 serious adverse events were reported during the trial with 222 (65.9%) in Burkina Faso and 115 (34.1%) in Mali, and 48.1% (162/337) due to severe malaria. The mean age of children with severe malaria was 2.9 years; 79.0% (128/162) of the cases occurred in children aged 3 years or less and 21.0% (34/162) in those aged 4 to 5 years. The most common presentation was severe anemia reported in 50% (81/162) of children, followed by repeated convulsions 25.3%, (41/162), prostration 11.1%, (18/162), hyperparasitaemia 8.0%, (13/162) and cerebral malaria 6.2%, (10/162). The proportion of children with the severe malaria anemia phenotype was higher among severe malaria cases in the SMC alone arm 62.1%, (36/58) compared to those in the SMC + RTS,S arm 37.1%, (13/35), p = 0.048. There was no significant difference in the proportion of other clinical presentations between the study arms. Most severe malaria cases, 85.8% (139/162) occurred during the transmission season (July to December). CONCLUSIONS: Severe anemia was the most common presentation of severe malaria in study children and its proportion among severe malaria cases was highest in the SMC alone arm. Children aged 3 years or less were the most affected and almost all the severe malaria cases occurred between July and December. Trial registration ClinicalTrials.gov, NCT04319380.

Abstract as published, via PubMed.