Combining Antibiotics And Antimalarials Could Significantly Lower Child Malarial Deaths: Research 

Researchers recommend PCR testing and administering antibiotics alongside antimalarials to improve the diagnosis and outcomes of malarial coma in children

Two parallel studies published today in The Lancet Global Health reveal new insights and approaches that could significantly lower the number of febrile coma deaths in children, often caused by malaria.

Febrile coma – the simultaneous presence of fever and coma – is a common reason for hospital admission among African children, with malarial infection of the brain being the most frequent cause, followed by bacterial meningitis. Accurately differentiating between the two conditions and administering the right treatment is often challenging, as they present with similar clinical features and diagnostic tools are frequently limited.

Led by researchers at the University of Sydney, the studies present findings from the largest analysis to date of febrile coma in children on the African continent.

The first study found the death rate from febrile coma among African children has remained unchanged for nearly 50 years, with nearly one death per every five children. This is despite decades of research and health interventions to reduce overall malarial illness, such as bed-nets, rapid diagnostics for malaria and improved antimalarial drugs.

According to the World Health Organization, there were almost 600,000 malaria deaths globally in 2023. Africa carries a disproportionately high share of the global malaria burden, with 95 percent of all deaths. Of the region, children under five accounted for about 76 percent of all malaria deaths.

The second study found that among children with malarial coma, co-infection with bacterial meningitis is a key cause of death. It also showed that by treating co-infected children with a combination of antibiotics and antimalarial drugs significantly reduced child mortality by fivefold – from 57.3 percent to 10 percent.

The studies were led by Professor Michael John Griffiths, Director of the Centre for Child and Adolescent Health Research and Professor of Paediatric Neuroscience in the University of Sydney’s Faculty of Medicine and Health, whose team gathered evidence for the research while working at the Queen Elizabeth II Hospital in Blantyre, Malawi.

“Administering antibiotics to children with malarial coma offers to significantly reduce mortality compared to those who do not receive them,” said Professor Griffiths.

“Children presenting to health centres with febrile coma usually have no specific clinical signs or symptoms to determine the underlying cause. As a result, detection of malaria often leads to the child being treated solely with antimalarials.

“Our study, however, shows that bacterial infections frequently occur alongside malaria. These findings highlight the need for immediate antibiotics combined with antimalarials for children presenting with febrile coma. We hope that our results will support an update to national and WHO guidelines on severe malaria and coma, as well as stimulate changes in clinical practice.”

Among the Malawian children studied, the researchers found that using tools like pathogen-specific PCR tests dramatically improve the detection of pathogens among children with febrile coma by fifteen-fold compared with standard microbiology.

“Pathogen-specific PCR tests are increasingly cheap, easy-to-use and provide almost instant results, making them the ideal diagnostic tool in underserved areas. On the frontline, there often aren’t the local resources for culture samples to be processed in a microbiology laboratory, which are often limited to central hospitals,” Professor Griffiths said.

The most common bacterial co-infection types were streptococcus pneumonia and non-typhoid salmonella, which typically respond to commonly available antibiotics, such as ceftriaxone.

“The use of antibiotics always raises the concern of antimicrobial resistance. However, a child presenting with deep coma or fever and a high risk of death justifies their use,” he said.

Through magnetic resonance imaging (MRI) of the brain in children with malarial febrile coma, the researchers also found a high prevalence of brain abnormality, suggesting significant brain damage.

“Compared to brain imaging of children presenting with meningitis in higher resource countries, the children in our study appear to have more frequent and extensive acute brain abnormalities, potentially suggesting severe and/or protracted illness prior to hospital presentation,” he said.

The researchers recommend the practice of administering antibiotics with antimalarials be promoted in both local and global World Health Organisation guidelines. They also recommend greater uptake of molecular tools like PCR tests to improve diagnosis and treatment.

“Improving access to healthcare for children with severe coma, through better education and infrastructure, could lead to earlier treatment and save even more lives. Ensuring that health units are equipped and accessible is also key to reducing preventable deaths,” he said.

“It’s true that many underserved areas lack in resources, but with this comes a great resourcefulness. Tapping into this trait, taking a pragmatic approach and making use of what’s readily available – in this case antibiotics and rapid testing – could drastically improve health outcomes. After so many years, this might be just what begins to shift the dial on malaria.”

Key findings

• Despite large numbers of clinical studies and multiple interventions to reduce malaria illness (bed-nets, rapid diagnostics for malaria and improved antimalarial drugs) the fatality rate for malarial febrile coma among sub-Saharan African children remains unchanged at 18 percent from studies over nearly five decades.
• Malaria is the leading cause of coma, but over a quarter of cases involve co-infections with bacteria or viruses, with molecular tools like pathogen-specific PCR tests significantly improving their detection.
• Children with malaria co-infections have a higher death rate compared to those with malaria alone.
• Administering antibiotics to children with malarial coma co-infection significantly reduces risk of death.
• MRI brain imaging in children with malarial febrile coma revealed a high frequency of brain abnormalities, suggesting significant brain damage.