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.
