Study shows urgent change needed to reduce deaths from malaria and meningitis in comatose African children

The research, published today in The Lancet Global Health, are together the largest analysis of febrile non-traumatic coma in children on the African continent to date.

Fever and coma is a common hospital presentation in African children, most often caused by malaria of the brain (cerebral malaria), followed by bacterial meningitis. However, these diseases have very similar symptoms and the limited diagnostic testing available makes them difficult to diagnose and treat.

The first study: The aetiology, mortality and disability of non-traumatic coma in African children: A systematic review and meta-analysis, reviewed all previous studies for non-traumatic coma in African children, and found that the death rate due to malaria infection has remained unchanged for nearly fifty years, with nearly one in every five children dying. This is despite decades of research and health interventions like bed-nets, rapid diagnostics for malaria and improved antimalarial drugs.

The second study, Aetiology, neuroradiological features, long-term neurosequelae and risk factors for mortality of febrile coma in Malawian children: A prospective cohort study, was undertaken in Malawi, and found that cerebral malaria is the leading cause of febrile coma and that over a quarter of cases were complicated by co-infections. These infections were mostly bacterial, and detected through the use of molecular tools like pathogen-specific PCR tests on blood and spinal fluid, which are significantly more accurate than routine laboratory methods. Children with malaria and a bacterial meningitis co-infection were more likely to die, compared to those with malaria alone, and the risk of death was even greater if co-infected children did not receive antibiotics. 

Crucially, the findings confirm a need to urgently re-consider frontline management for children who present with fever and coma, and indicate the critical need for immediate antibiotics (alongside antimalarials), irrespective of malaria diagnosis.

Dr. Stephen Ray, Principal Investigator at the Oxford Vaccine Group led the study alongside Dr Charlotte Fuller, from the Brain Infection and Inflammation Group at the University of Liverpool.

Dr Ray said: “Too often malaria parasites found in the blood of a sick African child stop medical staff from looking for and treating additional bacterial infections. A positive malaria test commonly leads to only treating the child with antimalarials, and therefore it becomes a risk factor for children to die from untreated bacterial infections. Our study found there were frequent bacterial infections, often alongside malaria, and these results emphasise the need for immediate antibiotics to be given to all children presenting with fever and coma, even if they have a positive malaria test. Our hope is that these findings cause a change in practice and save lives”.

By scanning children’s brain (MRI) at admission, the researchers identified that 90% of children had brain injury and half had brain swelling when hospitalised. They also found most children with meningitis had severe complications, such as intracranial pus, that could have been treated earlier with neurosurgery.

The researchers also performed face to face neurological follow-up assessments of survivors and identified a disability over half of these children. These data have been made available to support an update of national and WHO guidelines on severe malaria and coma, and changes to clinical practice.

University of Liverpool’s Dr Charlotte Fuller said: “Our cohort study highlights the value of molecular and radiological diagnostics in the management of life-threatening brain infections. The frequent complications found on admission brain scans illustrate that earlier escalation to specialist care, with neurosurgical capacity, may be most critical.  Further work is needed to facilitate widescale deployment of affordable molecular and radiological diagnostics across the African continent”.

The meta-analysis, covering studies across five decades and 30 African countries, showed that non-traumatic coma (NTC) in sub-Saharan Africa is associated with much higher disability and death rates, compared to high-income settings.

Senior author, Professor Michael Griffiths, Director of the Centre for Child & Adolescent Health Research at the University of Sydney, and a member of the University of Liverpool, said: “It is unacceptable to find that poor outcomes for children with non-traumatic coma across Africa have remained unchanged in over 50 years. There is an urgent need for co-ordinated political strategy, investment, education, health service and diagnostic technology provision to widen access to specialist care for these children.”

This work was funded by the Wellcome Trust.

ENDS

Further information:

The full articles can be found here:

Aetiology, neuroradiological features, long-term neurosequelae and risk factors for mortality of febrile coma in Malawian children: A prospective cohort study: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4771349 

The aetiology, mortality and disability of non-traumatic coma in African children: A systematic review and meta-analysis: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4771360 

Contact:

For more information and interviews please contact:

Oxford: Laura Borg, Communications Lead: laura.borg@paediatrics.ox.ac.uk or 07773226017

Liverpool: Jenny Morgan (Media Relations Manager) on J.L.Morgan@liverpool.ac.uk or 07775547589

Notes to Editors:

About The Oxford Vaccine Group

The Oxford Vaccine Group is part of the Department of Paediatrics at the University of Oxford. It led the rapid clinical development of vaccinations against COVID-19 in the pandemic and has made significant contributions to knowledge, supporting national and global policy on immunisation over three decades.

OVG was founded in 1994 by Professor E. Richard Moxon.  It is one of the world’s leading academic vaccine research teams, and has been led by Professor Sir Andrew Pollard since 2001. The OVG undertakes vaccine research spanning basic science and preclinical studies through to epidemiological studies, human challenge models and phase I-III clinical trials. Current research includes the study of vaccines for outbreak pathogens and pandemics, enteric pathogens, bacterial and viral respiratory infections, and use of human challenge models to accelerate vaccine development.

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The Department of Paediatrics at the University of Oxford is a global leader in the research, delivery and advancement of the health and care of children and adolescents. It hosts internationally renowned programmes in drug development, gastroenterology, haematology, HIV, immunology, neuroimaging, neuromuscular diseases and vaccinology to name a few, and its work spans from early proof-of-concept and fundamental science to its application in clinical settings.

The Department of Paediatrics’ pioneering research, policy development and clinical excellence is led by world-class experts in their field and it has a long track record of success in the development and delivery of effective treatments and interventions. Its work is supported by the clinical and educational resources of one of the world’s foremost academic institutions.

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Founded in 1881 as the original ‘red brick’, the University of Liverpool is one of the UK’s leading research-intensive higher education institutions with an annual turnover of £675.1 million, including an annual research income of £160.6 million.

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