Malaria parasites are silently damaging the brains of infected adults who show no obvious signs of neurological illness, and the long-term consequences remain unknown. This matters because falciparum malaria killed 608,000 people in 2022, and while the brain complications of cerebral malaria are well documented in children, adults have been largely ignored. The researchers’ earlier work in India found that even patients without coma or classic cerebral malaria symptoms show brain changes on MRI scans. A small UK case series confirmed similar findings and linked them to lasting cognitive impairment. Without systematic follow-up, doctors cannot predict which patients will recover fully and which will face persistent problems with memory, attention, or decision-making. If this research succeeds, it could change how malaria patients are assessed worldwide. By combining high-resolution brain imaging with psychometric tests, the team aims to identify biomarkers—such as retinal abnormalities or EEG patterns—that flag patients at risk of neurocognitive damage on the day they are admitted. This would allow clinicians to target neurorehabilitation resources to those who need them most, rather than discharging everyone without follow-up. The work is primarily clinical and diagnostic, with direct implications for patient management in malaria-endemic regions from India to sub-Saharan Africa.
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Falciparum malaria is the leading parasitic cause of death globally, resulting in 608,000 fatalities in 2022. Cerebral malaria (CM), where the infection affects the brain and causes unrousable coma, is responsible for most malaria deaths and occurs mainly in African children. Malaria is increasing globally following climate change and breakdown in endemic country control efforts, causing malaria transmission to re-emerge or spread to new areas. At least 30% paediatric survivors of CM have neurocognitive deficits, causing significant ongoing functional impairment. The disease is under-studied in adults, where it occurs in different geographical areas with seasonal or irregular malaria transmission, such as India. Well-designed cohorts with serial follow-up assessments are currently lacking in adult CM. Our ongoing research programme in India identified a specific pattern of MRI brain changes in adult CM, and we reported that mild to severe changes also occur in malaria without clinically recognised brain involvement (severe infection without a diagnosis of CM and uncomplicated malaria). The long-term functional consequences of these changes shown for the first time in India are unknown. Our recent UCLH CM case series showed similar MRI findings and demonstrated long-lasting neurocognitive impairment post-discharge. Here, we propose to investigate the occurrence, frequency, and amplitude of focal and global brain changes in adult patients with falciparum malaria admitted at two joint hospitals in Rourkela, India, and assess their evolution over time using high-resolution MRI (3 Tesla). We will combine this approach with stringent serial and targeted psychometric tests to reveal associations between specific brain changes and neurocognitive deficits. In parallel, we will evaluate the predictive value of retinopathies, EEG, and relevant biomarkers candidates on admission to identify individuals at risk of developing neurocognitive sequelae. We anticipate that the results generated by our project will fill critical knowledge gaps on the effects of falciparum malaria in adults and inform the design of new tools for their diagnostic and prognostication, ultimately supporting management and targeted neurorehabilitation efforts globally.
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