In sub-Saharan Africa, many children are hospitalised with serious illnesses that cause both fever and coma, and which can often lead to brain damage, disability, or death. A study of Malawian children from 2018 to 2022 found that about one in three children with this condition died, and of those who survived, half were left with long-term disabilities. One major reason for this is the lack of medical tools to find out exactly what is causing the illness, how it damages the brain, or which children are most at risk.
In this project, Dr Ray and his international collaborators will examine high-quality samples from these children to explore the causes of their brain injury, to improve our understanding of these conditions and to enhance outcomes for critically ill children with brain infections and severe brain injury in sub-Saharan Africa.
In sub-Saharan Africa, children are often hospitalised with a serious illness that causes both fever and coma. This condition often leads to brain damage, disability, or death – especially in lower-income countries where outcomes are worse than in wealthier ones.
The most common known cause is cerebral malaria, a severe brain infection from malaria parasites. However, another frequent cause is brain infection from bacteria, like meningitis. It is very hard for doctors to tell the difference between these illnesses just by looking and examining, and sometimes both are present at the same time. Hospitals also often do not have the equipment needed for proper diagnosis, meaning that many children are treated based on guesswork, and treatments may therefore not be effective.
In richer countries, doctors have recently discovered that in such circumstances the body’s immune system can sometimes mistakenly attack the brain, causing coma. These immune-related causes have not yet been studied in African children with coma.
Dr Ray and his colleagues are using a uniquely well-defined group of 352 Malawian children who fell into a coma due to fever between 2018 and 2022 – the largest and most detailed studied group like this in Africa – to better understand this kind of brain injury. By working with leading brain research labs in the UK and the US, using advanced tools that analyse brain chemistry and infections, the team will examine high-quality samples from these children to explore the causes of brain injury in this under-researched group.
The main goal of the project is to discover known and new causes, biological warning signs, and the processes that lead to brain injury in children with fever and coma. By combining powerful global research tools with this unique group of Malawian children, the team intend to: better understand how brain injury happens in children with fever-related coma in high-infection, low-resource settings; predict outcomes, including long-term brain problems, whether the infection is in the brain or elsewhere in the body, and what caused the coma; and use advanced lab techniques to find out whether the coma was caused by infection or by an autoimmune disease.
This research aims to enhance understanding, diagnosis, and outcomes for critically ill children with brain infections and severe brain injury in sub-Saharan Africa. The project seeks to uncover how various infections lead to devastating neurological damage. Data generated by this project will be used to apply for more substantial funding to advance prediction, diagnosis, and treatment further, ultimately aiming to reduce brain injury and improve outcomes for affected children in high-burden settings.
Dr Stephen Ray is a clinical lecturer at University of Oxford, working in both The Paediatric Infectious Diseases Department at Oxford University Hospital and The Oxford Vaccine Group at University of Oxford.
This project also brings together two world-leading research teams: The Brain Infection and Inflammation Group in at University of Liverpool, led by Professor Benedict Michael, which has developed new tools to measure brain injury more accurately and which works closely with patients
and global organisations to improve brain health around the world; and the Wilson Lab at the University of California, San Francisco, led by Professor Michael Wilson, MD, which has created powerful tests that can detect infections or immune problems in the brain using just one sample.
Acquired brain and spinal cord injury (including stroke) is one of our current research priorities, reflecting the large unmet need in this area. Our aim is to fund research to advance understanding of how to promote repair of the brain and spinal cord following injury.
Read about our other research projects under this theme:
Find out about our other research in this area:
