Risk factors for malaria-related mortality among children under five at Mbale Regional Referral Hospital, Uganda, 2020–2024: a case-control study

Background Malaria remains a major global health burden, with 264 million cases and 569,000 deaths reported in 2023. Uganda ranks third globally in malaria cases and tenth in malaria-related deaths. As of 2022, approximately 95% of the country was endemic for malaria, and children < 5 years old were most vulnerable to severe illness and mortality. Despite existing control measures, Mbale Regional Referral Hospital (MRRH) in Eastern Uganda, reported a paediatric malaria case fatality rate of 2.7% between 2020 and 2024. This study aimed to identify factors associated with malaria-related deaths among children under five admitted to the hospital during this period. Methods We conducted an unmatched 1:2 case–control study using retrospective surveillance data from MRRH for 2020–2024. Cases were children aged ≤ 59 months admitted with World Health Organization (WHO)-defined severe Plasmodium falciparum malaria who died during hospitalization (n = 100). Controls were similar children who recovered (n = 200), systematically sampled from approximately 32,400 eligible admissions. Data were abstracted from patient records. Multivariable logistic regression was performed to identify factors associated with mortality. Results Among the 100 cases, 73% were aged < 24 months, and 61% were male. Multivariable analysis showed that convulsions on admission significantly increased odds of death (adjusted odds ratio [aOR] = 17; 95% CI: 4.2–71). Loss of consciousness (aOR = 14; 95% CI: 1.4–113), severe anaemia (aOR = 3.4; 95% CI: 1.4–8.2), vomiting (aOR = 3.1; 95% CI: 1.4–6.9), and delays in seeking care over 24 hours after symptom onset (aOR = 8.8; 95% CI: 2.3–34) were also associated with increased mortality. Conclusion Malaria-related mortality among under-five children was strongly associated with neurological complications, severe anaemia, vomiting, and delayed care-seeking, while older age reduced risk. Early recognition of danger signs, timely referral, and prompt treatment especially for neurological symptoms and anaemia could reduce paediatric malaria deaths in high-burden settings like Mbale.