Meningitis Has a Much Greater Impact on Child Mortality than Previously Thought

Meningitis contributes to higher child mortality rates than estimated by the WHO, according to a new study by the CHAMPS network and led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by “la Caixa” Foundation. The study, published in Journal of Infection, reveals a high prevalence of drug-resistant bacteria in hospital cases, highlighting the need for earlier suspicion and faster diagnosis and appropriate treatment to reduce mortality.

Meningitis remains a serious condition, especially for young children, with high death rates and lasting neurological effects in survivors. Vaccines can protect against the most common types of meningitis-causing bacteria, such as Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, and Neisseria meningitidis. Yet, reaching the World Health Organization’s (WHO) goal to eliminate meningitis by 2030 requires a clearer understanding of the global impact of this disease and the specific pathogens involved.

“Meningitis poses a diagnostic challenge due to its non-specific symptoms, which often resemble those of other serious illnesses,” explains senior author Quique Bassat, ICREA researcher and General Director at ISGlobal. “Identifying the specific pathogens behind meningitis cases would allow us to make a better use of resources and guide the development of new highly-awaited vaccines,” he adds.

The study draws on data from the CHAMPS network, which is conducting an in-depth investigation into causes of childhood deaths in seven countries: Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa. Using a technique called MITS (minimally invasive tissue sampling), researchers perform biopsies to obtain samples of key organs or fluids, including cerebrospinal fluid, followed by histopathological examination, molecular testing for 126 pathogens, and microbiological cultures.

A significant contributor to death

The study found that meningitis was a contributing factor in 7% of the 3,857 deaths analysed. The highest proportions of child deaths due to meningitis were observed in South Africa (16.6%) and Ethiopia (15.6%), followed by Mali and Sierra Leone. Most of these deaths (66%) occurred in newborns, with the remaining cases diagnosed in older infants and young children. “The higher incidence among newborns may be due to the vertical transmission of pathogens infecting their mothers, and the lack of specific strategies to protect them during delivery. Additionally, their underdeveloped immune systems also confer a higher vulnerability,” says Sara Ajanovic, ISGlobal researcher and co-author of the study.

A shift towards antibiotic-resistant bacteria

The prevalence of pathogens associated with meningitis deaths in the hospital and in the community varied between regions. However, the most common pathogens were Acinetobacter baumannii and Klebsiella pneumoniae, particularly in deaths occurring in healthcare settings. These multi-drug resistant bacteria are often acquired in the hospital, which means that improving infection prevention practices in hospitals is essential for reducing meningitis cases. Worryingly, it also means that without the appropriate antibiotics, the risk of dying from meningitis remains high. 

Almost half of meningitis deaths occurred at the community, likely due to limited access to healthcare. While vaccines have significantly reduced cases of Streptococcus pneumoniae, this bacterium still caused many of the community-acquired cases of meningitis.

These findings indicate a shift in the landscape of pathogens associated with meningitis, with an increase of pathogens like K. pneumoniae and A. baumannii, alongside a decline in S. pneumoniae and Hib due to vaccination efforts. This shift, the authors point out, “challenges the foundations of current empirical antibiotic guidelines.”

Implications for public health

CHAMPS' findings suggest that meningitis contributes to higher child mortality rates (7%) than the WHO’s estimate of 5.1%. Critically, many of these cases had not been recognized as meningitis before death, highlighting the need for faster diagnosis and treatment to prevent fatalities. “Less than a quarter of all confirmed meningitis cases had undergone a lumbar puncture -the gold standard technique for diagnosing meningitis - prior to death, highlighting the urgent need to deploy more actively this diagnostic approach to avoid missing cases of this life-threatening infection,” says Bassat.

"The changing landscape of the pathogens causing lethal meningitis in children in these settings underscores the positive effect of vaccine campaigns conducted in the last decades, which must be continued,” adds Ajanovic. However, the findings highlight an urgent need for developing new vaccines against emerging pathogens such as K. pneumoniae, and for updating clinical guidelines. This includes testing for these pathogens and their resistance patterns, as well as adjusting antibiotic regimens to ensure an effective treatment.

CHAMPS work recognised in Catalonia

On 26 October, the Catalan Society of Clinical Microbiology and Infectious Diseases awarded the Josep Barrio Infectious Diseases Prize to Quique Bassat for the best scientific paper published in 2023 by a member of the society. The paper was a study by the CHAMPS network showing that infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition.

Reference

Mahtab S, Madewell ZJ, Baillie V et al. Etiologies and Comorbidities of Meningitis Deaths in Chilren Under 5 Years in High-Mortality Settings: Insights from the CHAMPS Network in the Post-Pneumococcal Vaccine Era. J Infection. 10.1016/j.jinf.2024.106341