Neurological complications of sickle cell anaemia and malarial anaemia in low- and middle-income countries: a narrative review

Sickle cell anaemia and Plasmodium falciparum malaria are the two dominant causes of severe anaemia in children of sub-Saharan Africa and other low- and middle-income countries (LMICs), and both injure the developing brain. Sickle cell disease affects close to eight million people worldwide, most of them in Africa, where the majority of affected children still die before the age of five. Malaria caused an estimated 282 million cases and 610,000 deaths in 2024. In sickle cell anaemia, chronic haemolysis, large-artery vasculopathy and reduced oxygen delivery lead to overt stroke, silent cerebral infarcts and progressive cognitive impairment. In malaria, cerebral malaria and severe malarial anaemia cause coma, seizures and brain swelling, and survivors carry long-term epilepsy, motor deficits and measurable losses in cognition and school achievement into adolescence. The two conditions interact: sickle trait protects against severe malaria, but in children with sickle cell anaemia even low-density infection can precipitate fatal anaemic crises. This review summarises current evidence on mechanisms, epidemiology and outcomes, and examines interventions adapted to resource-limited settings. Trials conducted in Africa have shown that hydroxyurea is safe in malaria-endemic regions, reduces malaria and other complications, prevents stroke in children with abnormal transcranial Doppler velocities, and may protect cognition. Malaria chemoprevention, vaccines and post-discharge chemoprevention reduce the burden of severe anaemia. We argue that integrated, tiered care that links newborn screening, hydroxyurea, malaria prevention and neurodevelopmental follow-up offers the greatest neurological return for LMIC health systems.