Burden and Predictors of Neurocognitive Impairment Among HIV-Infected Patients with Meningitis in Rural, Northern Uganda

About This Grant

This IRSDA K-award will provide me with mentored research and career development training to build expertise in translating global health findings to benefit U.S. populations and underserved healthcare systems. I will learn to validate neurocognitive impairment (NI) screening tools and analyze inflammatory biomarkers that predict NI in meningitis patients with or without HIV in rural, northern Uganda, an area of high meningitis burden within Africa’s meningitis belt. Meningitis affects over 2.5 million people globally each year, and causes significant disability, with 20-32% of survivors experiencing long-term morbidity and 14-38% developing prolonged NI, yet data on NI burden in meningitis patients remain scarce. Despite evidence that inflammation in central nervous system infections is associated with NI, limited information is available about the biomarkers involved in NI development. This study seeks to fill the gaps in our understanding of the burden and pathogenesis of NI by identifying which brain injury biomarkers are expressed in patients with NI and can be used to predict NI development among meningitis patients with and without HIV. This study will be embedded within my primary mentor’s existing Meningitis Diagnosis and Treatment Program (MEN-DTP) at Lira Regional Referral Hospital in northern Uganda, which focuses on understanding mortality due to various meningitis etiologies in an area with high meningitis and HIV burden. Aim 1 is to validate neurocognitive assessment tools to determine the burden of NI among meningitis patients living with and without HIV, including follow-up for two years to assess long- and short-term NI burden. Aim 2 is to identify clinical parameters and immune/inflammatory biomarkers predictive of NI. Serum and CSF samples will be collected from meningitis patients who do or do not develop NI to identify biomarkers specifically associated with NI. Investigating immunologic and brain injury biomarkers will provide insights into inflammatory pathways activated by meningitis that lead to NI in those with or without HIV. Our neurocognitive assessments will help determine the true burden of NI and enable timely diagnoses and interventions. Our findings from this high-burden setting will inform neurocognitive assessment and early intervention strategies to improve care for meningitis patients that could be implemented in underserved U.S. populations and globally.