A child surrounded by DNA strands, representing the genetic basis of meningitis.

Decoding Childhood Meningitis: How Gene Expression Holds the Key to Better Outcomes

Samir D’Costa in Health & Wellness December 2025 • 4 min read.

"New research unveils how gene activity in children with pneumococcal meningitis could lead to improved treatments and survival rates."

Pneumococcal meningitis remains a significant threat to children worldwide. This severe infection, caused by the bacterium Streptococcus pneumoniae, leads to inflammation of the membranes surrounding the brain and spinal cord. Despite medical advances, it continues to cause substantial morbidity and mortality, especially in young children and those with HIV.

While antibiotics target the bacteria, the body's own inflammatory response also plays a critical role in determining the severity and outcome of the disease. Understanding this complex interplay between infection and immune response is essential for developing more effective treatments.

A new study published in BMJ Paediatrics Open delves into the intricacies of this host response by examining gene expression patterns in the blood of children with pneumococcal meningitis. By comparing these patterns in children with and without HIV, as well as in survivors and non-survivors, the researchers hope to identify key factors that contribute to poorer outcomes and pave the way for targeted therapies.

Unlocking the Genetic Secrets of Meningitis: What the Study Revealed

A child surrounded by DNA strands, representing the genetic basis of meningitis.

The study, a prospective case-control observational study conducted at a tertiary hospital in Malawi, enrolled children aged 2 months to 16 years diagnosed with pneumococcal meningitis or pneumonia. Researchers used advanced techniques like Affymetrix arrays and real-time quantitative PCR (RT-qPCR) to analyze RNA gene expression in blood samples. They compared gene expression profiles between cases and controls, HIV-infected and uninfected cases, and survivors and non-survivors.

The findings revealed significant differences in gene expression between children with pneumococcal meningitis and healthy controls. Cases showed increased expression of genes involved in several critical processes:

Immune Activation: Genes regulating the body's defense mechanisms were highly active.
Oxidative Stress: Genes related to cellular damage from reactive oxygen species were upregulated.
Leukocyte Adhesion and Migration: Genes controlling the movement of white blood cells to the site of infection were more expressed.
Arginine Metabolism: Genes involved in the breakdown of arginine, an important amino acid, were altered.
Glucocorticoid Receptor Signaling: Genes related to the body's response to stress hormones were affected.

Interestingly, the study found no significant differences in gene expression between HIV-infected and uninfected children with meningitis. However, in survivors compared to non-survivors, there was increased expression of folate receptor 3 (FOLR3) and S100A12, suggesting these genes may play a protective role.

The Future of Meningitis Treatment: Personalized Approaches

This study provides valuable insights into the complex host response to pneumococcal meningitis in children. By identifying key genes and pathways involved in the disease process, it opens the door for developing targeted therapies that can improve outcomes. Further research is needed to validate these findings in larger cohorts and to explore the potential of personalized medicine approaches based on individual gene expression profiles.

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This article is based on research published under:

DOI-LINK: 10.1136/bmjpo-2017-000092, Alternate LINK

Title: Peripheral Blood Rna Gene Expression In Children With Pneumococcal Meningitis: A Prospective Case–Control Study

Subject: Pediatrics, Perinatology and Child Health

Journal: BMJ Paediatrics Open

Publisher: BMJ

Authors: Benard W Kulohoma, Fiona Marriage, Olga Vasieva, Limangeni Mankhambo, Kha Nguyen, Malcolm E Molyneux, Elizabeth M Molyneux, Philip J R Day, Enitan D Carrol

Published: 2017-08-01

Everything You Need To Know

What is pneumococcal meningitis and why is it a significant health concern for children?

Pneumococcal meningitis is a severe infection caused by the bacterium Streptococcus pneumoniae. It leads to inflammation of the membranes surrounding the brain and spinal cord. It remains a significant threat to children worldwide due to substantial morbidity and mortality, especially in young children and those with HIV, despite medical advances.

How does the body's inflammatory response affect the outcome of pneumococcal meningitis, and why is it important to study it?

While antibiotics target the bacteria causing pneumococcal meningitis, the body's own inflammatory response plays a critical role in determining the severity and outcome of the disease. Understanding the complex interplay between infection and immune response is essential for developing more effective treatments that can modulate this response to improve patient outcomes. The study of gene expression helps understand the precise mechanisms of inflammation.

What were the key findings regarding gene expression in children with pneumococcal meningitis compared to healthy controls?

The study revealed significant differences in gene expression between children with pneumococcal meningitis and healthy controls. Cases showed increased expression of genes involved in immune activation, oxidative stress, leukocyte adhesion and migration, arginine metabolism, and glucocorticoid receptor signaling. These changes indicate a complex immune and metabolic response to the infection.

Were there any differences in gene expression observed between HIV-infected and uninfected children with pneumococcal meningitis in the study?

Interestingly, the study found no significant differences in gene expression between HIV-infected and uninfected children with pneumococcal meningitis. This suggests that the host response to the infection, as measured by gene expression, is similar in both groups. Further research might explore the impact of HIV on other aspects of the disease.

What potential role do FOLR3 and S100A12 play in pneumococcal meningitis, and what implications does this have for future treatments?

In survivors of pneumococcal meningitis, there was increased expression of folate receptor 3 (FOLR3) and S100A12 compared to non-survivors. This suggests that these genes may play a protective role in combating the infection. Further investigation into the mechanisms and functions of FOLR3 and S100A12 could lead to the development of targeted therapies that enhance their protective effects, potentially improving survival rates. Personalized medicine approaches based on individual gene expression profiles is key to that.