Global Research Endeavors to Advance Treatment/Prevention of Neurological Disorders in Africa (GREAT Neurology in Africa)

Global Research Endeavors to Advance Treatment of Neurological Disorders in Africa (GREAT Neurology) is a multidisciplinary research program funded by the National Institutes of Health and led through work running from 2021 to 2029 under grant number 1R35NS122265-01, the program addresses the disproportionate burden of neurological disorders in resource-limited tropical settings by combining clinical characterization, mechanistic investigation and capacity-building efforts in Zambia and Malawi. The program aims both to inform locally relevant prevention and treatment strategies and to elucidate pathophysiological processes broadly relevant to global neurology. A principal focus is cerebral malaria in children: a prospective cohort study embedded in a randomized controlled trial of aggressive antipyretics, supplemented by a non-RCT, more representative cohort. Investigators will assess the role of neuroinflammation in structural brain injury and subsequent neurologic morbidity through laboratory measures of acute inflammation, serial neuroimaging, and long-term neurological outcome assessments.

The study design permits examination of ischemia, hemorrhage, thrombosis, and other structural injuries, and uniquely positions the research to evaluate the effects of co-infection with SARS-CoV-2 on parasite clearance, inflammatory mediators associated with malarial mortality, and neurologic sequelae. Another major axis of inquiry is neuro-HIV. With widespread availability of antiretroviral therapy, the program pivots to studying noncommunicable disorders associated with chronic, low-grade inflammation and possible HIV-associated accelerated aging of the nervous system. Using a network of rural and urban HIV clinics, the team will pursue imaging studies and cohort investigations among adults and children. Prior findings of high rates of subclinical cerebrovascular disease among children with long-standing, effectively treated HIV motivate further imaging work, including enrollment of HIV-uninfected but exposed children and community controls to identify risk factors for cerebrovascular disease, to assess metabolic effects of antiretroviral therapies, and to probe relationships between premature cerebrovascular disease and prior or concurrent SARS-CoV-2 infection. Among adults with HIV, GREAT Neurology implements a five-year prospective cohort study to monitor for cognitive impairment, psychiatric symptoms, strokes, neuropathies, and seizures, and to evaluate whether SARS-CoV-2 infection contributes to accelerated neurologic aging.

Beyond clinical and mechanistic studies, the award supports infrastructure, mentorship, and trainee engagement, creating a scholarly environment for both U.S. and African investigators and prioritizing development of young clinician-scientists across a broad range of research endeavors. Classified under clinical characterization and management and involving randomized controlled trial elements, the program enrolls both adult (18 and older) and pediatric (1 to 12 years) populations. Known financial commitments reported for the project total $447,800. By linking detailed pathophysiologic investigation with rigorous clinical study designs and capacity-building, GREAT Neurology seeks to generate insights that improve prevention and treatment of neurologic disease in African settings while contributing to global understanding of neurologic disorders.