Project Summary Most morbidity and mortality worldwide due to sickle cell disease, bacterial meningitis, and cerebral malaria occurs in children in sub-Saharan Africa (SSA). An estimated 225,000 children are born with sickle cell disease (SCD) annually on the continent, with upwards of 60,000 suffering ischemic strokes due to progressive vasculopathy each year. Bacterial meningitis (BM) affects over 1 million individuals annually and carries a 30-50% mortality rate, primarily due to intracranial complications including ischemic stroke. Malaria results in 405,000 deaths annually. Cerebral malaria (CM) is a severe manifestation of the disease with case fatality rates that range from 15% to 40%. In more than 50% of survivors, CM results in deficits in gross motor or sensory function, cognition, and behavior. Evaluation of the neurovasculature in each of these conditions has important diagnostic and therapeutic implications that have a proven or likely impact on morbidity and mortality reduction. However, advanced neuroimaging approaches commonly used to diagnose pathophysiological changes to the neurovasculature in developed countries are not widely available in the regions of the world that are most heavily impacted by these diseases. Transcranial Doppler ultrasound (TCD) is a portable, relatively inexpensive, non-invasive tool that evaluates, in real time, the cerebral blood flow velocities (CBFV) and cerebral hemodynamics in all the major cerebral vessels. Our group has, over the last six years, performed several pilot studies confirming TCD use is feasible in SSA and provides valuable insight into the diagnosis and prognosis of children at risk of neurologic complications from SCD, BM, and CM. Access to TCD in SSA, however, remains very limited. Our objective is to form TCD Centers of Excellence (COE) at five sites in SSA. Aim 1 will establish the human resource and material infrastructure required to launch the COE. Aim 2 will address the skills gaps of local practitioners by designing and implementing training courses to teach standardized approaches to scanning, interpretation, and documentation of TCD examinations in children in SSA. Aim 3 will define TCD parameters in the populations of interest. Namely, we will establish normative TCD values in healthy African children, a necessary step to advance the field. Furthermore, it will form a collective database of CBFVs in children with SCD, BM, and CM to improve our understanding of examination findings and their associations with outcomes in these population. This proposal is significant in that COE will fill an unmet need of improving diagnostic capabilities for neurologic disease in African children. The COE are innovative in that they will be the first of their kind in SSA, accommodating a severely affected population of children. In the long-term, this network of comprehensive centers will be positioned to provide TCD-based care and research aimed to reduce the burden of neurodisability from SCD, BM, and CM in African children.

Project Narrative Brain injury due to stroke from sickle cell disease or neuroinfection significantly contributes to childhood death and disability in sub-Saharan Africa. Improving access to and expertise in the use of important diagnostic and monitoring tools is necessary to improve outcomes. Transcranial doppler ultrasound (TCD) is one such technology that, through the formation of the proposed Centers of Excellence, will become more widely available to battle sickle cell disease, meningitis, and cerebral malaria in children in Africa.