Abstract

Malaria continues to be one of the most significant global health challenges, particularly among children under 
five years of age in sub-Saharan Africa, where it remains a major cause of morbidity and mortality. Despite 
considerable progress in prevention and treatment, comorbidities such as anemia, malnutrition, respiratory 
infections, diarrheal diseases, HIV/AIDS, sickle cell disease, and tuberculosis complicate clinical management, 
exacerbate disease severity, and increase fatality rates. This narrative review examines the management of malaria 
with comorbidities, emphasizing the need for high-quality diagnostics, integrated care approaches, and context
specific preventive strategies. It highlights the persistence of poor case management in pediatric malaria and the 
clinical overlap that often results in misdiagnosis and overtreatment. Artemisinin-based combination therapies 
remain the standard for uncomplicated malaria, while integrated models of care that address HIV, malnutrition, 
and other concurrent infections have shown promising results in improving outcomes. Preventive strategies such 
as insecticide-treated nets (ITNs), indoor residual spraying (IRS), and the introduction of the RTS,S/AS01 malaria 
vaccine have reduced transmission rates, yet inequities in access and socioeconomic determinants continue to 
undermine progress. Furthermore, emerging research emphasizes the role of proteomics and epidemiologic 
mapping in understanding malaria pathophysiology and comorbidity interactions. Persistent gaps in diagnosis, 
treatment adherence, and surveillance systems call for policy reforms and increased investments in research, 
innovation, and healthcare infrastructure. Achieving malaria elimination will require coordinated multi-sectoral 
collaboration, sustained funding, and community engagement to integrate malaria control within broader child 
health and development agendas.