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

The burden of neurological disorders disproportionately impacts resource-limited tropical settings resulting in grossly insufficient capacity for care provision or research. This global research program aims to advance our understanding of common neurological disorders in the African context to inform the local prevention and treatment of these conditions while also elucidating pathophysiological processes more broadly relevant. This will be accomplished through the continuation of Dr. Birbeck's neuro-HIV and cerebral malaria investigations plus support and mentorship for young clinician scientists engaged in a broad range of research endeavors. Research activities include-- • Cerebral malaria: In a prospective cohort study of children with CNS malaria, we will examine the role of neuroinflammation in structural injury and neurologic morbidity with laboratory assessments of acute inflammation, serial neuroimaging, and long term neurological outcomes. The novel study population will include children in a randomized controlled trial (RCT) of aggressive antipyretics as well as a more representative non-RCT population. The effects of co-infection with SARS-CoV-2 on parasite clearance, inflammatory factors associated with malarial death and neurologic sequelae and structural injuries including ischemia, bleeding, and thromboses will be ascertained. • Neuro-HIV: Given the widespread availability of HIV therapies, the next challenge in neuro-HIV care in Africa includes noncommunicable disorders associated with chronic low grade inflammation. Utilizing our network of rural and urban HIV clinics, we will study HIV-associated accelerated aging of the nervous system. Given its highly inflammatory state, SARS-CoV-2 could potentially contribute to this burden. Among children, we have recently reported high rates of subclinical cerebrovascular disease (CVD) despite long-standing, effectively treated HIV. We will pursue further imaging studies including in HIV uninfected but exposed children and community controls to identify risk factors for CVD, examine the metabolic impact of antiretroviral therapies and assess the relationship between premature CVD and infection with SARS-Co-V2. Among adults with HIV, SARS-Co-V2 infection will be evaluated for its possible role in accelerated aging in a 5-year prospective cohort study monitoring for cognitive impairment, psychiatric symptoms, strokes, neuropathies and seizures. This research will be undertaken in Zambia and Malawi where Dr. Birbeck has worked for over 25 years. This research program award will also provide infrastructure, mentorship and a vibrant environment for scholarship and trainee engagement with both US and African academics.