Nearly one-third of adults in a Swedish cohort who contracted bacterial meningitis as children have permanent neurologic disabilities as a result, according to a team of scientists.
Their findings, they said, underscore the need to educate parents on the benefits of pneumococcal vaccination and to promote the importance of clinical vigilance in detecting disabilities – particularly behavioural and emotional disorders, hearing loss, and visual problems – among paediatric bacterial meningitis survivors.
Led by teams from Merck and the Karolinska Institutet in Stockholm, the analysis of nationwide registry data included 3 623 adults who had bacterial meningitis before they were 18-years-old, from 1987 to 2021, and 32 607 matched uninfected controls.
The median age at meningitis diagnosis was 1.5 years, 44.2% were women, and 55.8% were men; median follow-up was 23.7 years.
Bacterial meningitis, inflammation of the membranes covering the brain and spinal cord, is a rare but life-threatening infection most common among children and older adults, reports CIDRAP.
Often caused by Streptococcus pneumoniae, it can be cured with antibiotics, but because the medication may need a few days to cross the blood-brain barrier, by the time it reaches the brain, neurons can already have been damaged.
“Further, there is the constant threat of antibiotic-resistance to face in the clinics,” the researchers wrote in JAMA Network Open.
Higher risk of structural head injuries
Participants who had bacterial meningitis as children had a higher rate of all seven studied neurologic disabilities, and nearly one-third (29.0%) had at least one such disability, compared with one-tenth of controls. The highest absolute risk of disabilities was for behavioural and emotional disorders, hearing loss, and impaired vision.
The greatest adjusted hazard ratios (aHRs) were for structural head injuries (aHR, 26.0), hearing loss (aHR, 7.90), and motor function disorders (aHR, 4.65). The aHRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for people infected with S pneumoniae (eg, aHR, 7.89 for seizures), compared with Haemophilus influenzae (aHR, 2.46) and Neisseria meningitidis (aHR, 1.38).
The aHRs for cognitive disabilities, seizures, behavioural and emotional disorders, and intracranial structural injuries were significantly higher for children who developed bacterial meningitis at a younger age. For example, the aHR for seizures was 5.43 for those diagnosed when they were younger than the median age, compared with 2.87 for those diagnosed when older.
“Our interpretation is that the damage to the brain and nervous system that can follow an episode of bacterial meningitis is more detrimental for young children who are at a sensitive stage in their physical and mental development,” the researchers wrote.
Importance of pneumococcal vaccine, clinical vigilance
The relative risk of disabilities was highest in the first three years after diagnosis but remained elevated at five years post-diagnosis.
“The young age at diagnosis in this study (median, 1.5 years) imposes clinical difficulties on detection of disabilities after an episode of bacterial meningitis, which could explain why there was no significantly elevated risk of behavioural and emotional disorders during the first one to three years of follow-up (these disabilities are difficult to detect at an early age),” said the authors.
Co-author Federico Iovino, PhD, of the institute’s neuroscience department, said childhood illness affected the entire family.
“If a three-year-old child has impaired cognition, a motor disability, impaired or lost vision or hearing, it has a major impact,” he said.
“These are lifelong disabilities that become a major burden for both the individual and society, as those affected need healthcare support for the rest of their lives.”
Iovino said he and his colleagues are researching how to protect neurons during the time it takes for antibiotics to cross the blood-brain barrier. “We have very promising data from human neurons and are just entering a pre-clinical phase with animal models,” he said. “We hope to present this in the clinic within the next few years.”
Study details
Increased risk of long-term disabilities following childhood bacterial meningitis in Sweden
Salini Mohanty, Urban Johansson Kostenniemi, Sven Arne Silfverdal, et al.
Published in JAMA Network Open on 19 January 2024
Abstract
Importance
Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort.
Objective
To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden.
Design, Setting, and Participants
This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analysed from July 13, 2022, to November 30, 2023.
Exposure
A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021.
Main Outcomes and Measures
Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioural and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood.
Results
The cohort included 3 623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioural and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all seven disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]).
The adjusted HRs for cognitive disabilities, seizures, behavioural and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median.
Conclusions and Relevance
The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.
CIDRAP ARTICLE – Researchers detail long-term burden of pediatric bacterial meningitis (Open access)
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