http://bmj.com/cgi/content/full/323/7312/523
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Editorials
Legacy of bacterial meningitis in infancy
Many children continue to suffer
functionally important deficits
After the introduction of conjugate H influenzae b vaccines the
United States has seen a 73% reduction in the incidence of paediatric
bacterial meningitis, with fewer than 3000 cases each year.4 A
meta-analysis of 1602 prospectively enrolled children with
bacterial meningitis from 19 studies in Europe and North America
found that 4.5% died, but at least one major adverse outcome was
present (severe intellectual disability, spasticity, paresis, seizures,
deafness) in 16.4% of survivors.5 The
assessments were, however, limited to neurological examinations and
tests of general intellectual function or hearing acuity, with
review restricted to less than two years' follow up. The long term
effects may thus have been underestimated, as many cognitive skills
are undeveloped at the time of meningitis, and functionally
important deficits may not emerge until after the child starts school.
There are few reports of the long term complications of bacterial
meningitis. A Canadian study of 97 survivors of H influenzae b
meningitis identified by chart review found that those suffering acute
neurological complications (seizures, coma, focal neurological deficits,
hearing loss) had poorer school performance and more behaviour
difficulties than their siblings.6 These
findings were extended by a prospective cohort study from Melbourne,
where 130 school aged children were assessed seven and
12 years after meningitis. 7 8 Though
they achieved average scores on measures of intelligence, learning,
and high level neuropsychological skills, after adjusting for
sociodemographic variables these scores were consistently below
those of age and grade matched controls. Only 53% of children
experiencing acute neurological complications were judged as normal,
while those presenting during infancy performed especially poorly on
language and reading measures and complex learning tasks.9 There were
also increased behaviour problems over time, possibly from academic
difficulties and low self esteem.8 Twelve
years after meningitis, 38% of patients had either major neurological,
auditory, or intellectual impairments or functionally important
behaviour or learning disorders impeding their academic performance.
In comparison, 11% of controls had minor functional disabilities.
Similar findings of cognitive and behaviour impairment have recently
been observed in another prospective cohort study in which
115 survivors of meningococcal disease from Liverpool were
compared 10 years after their illness with age and sex matched controls.10
In this week's issue Bedford et al (p 533)
report the results from a questionnaire survey of parents and general
practitioners about 1717 children aged 5 years who had had
meningitis during infancy, together with matched controls. The
children were originally identified by a prospective national study
of infantile meningitis in England and Wales in 1985-7. Those
who had had meningitis were at significantly greater risk of
disability across all health, developmental, and behavioural
categories tested, but especially in the domains of learning and
neuromotor function. At greatest risk were neonates and those
infected by S pneumoniae and Gram negative bacilli. Of
concern, 2% who survived their original illness had died by the age
of 5 and at least half of these deaths seemed attributable to
complications of meningitis.
The strengths of this study include its prospective design, recruitment
restricted to infants within a national population base, large
numbers affected by different pathogens, and high retention rates.
This provides future opportunities for comprehensive neuropsychometric
assessments during school years and into adolescence and adulthood.
Outcomes that may be clarified include the long term complications
of neonatal meningitis, effects of pathogens other than H
influenzae b, and whether higher cognitive functions, like some
lower order skills, improve with maturation.8 This should
also help in understanding critical phases of postnatal brain development.
Bacterial meningitis exacts a large physical, social, and economic toll on
the world's children. This is especially true in developing countries,
where greater rates of adverse outcomes are superimposed on poverty,
other severe illness, and illiteracy.11 Furthermore,
despite advances in antibiotic treatment, the morbidity from
meningitis has not improved and a role for routine steroid administration
is unproved. Strategies required to reduce neonatal meningitis
include improved antenatal care, aseptic techniques during labour
and delivery, and promotion of breast feeding and domestic hygiene.
For older children vaccination remains the only realistic hope for
improvement. As disease is greatest in the young, conjugate vaccines
are necessary, first with H influenzae b and eventually for
pneumococcal and meningococcal infections. Cost is the greatest
obstacle. It is sobering to consider that although conjugate H
influenzae b immunisation leads to a 90% reduction of invasive
disease, this has resulted in only a 6% decrease in cases of H
influenzae b meningitis globally.3 Bulk purchasing
and decreased numbers of vaccine doses may help to address this
disparity. 3
12
Meanwhile, even in countries able to afford conjugate vaccines there are
many survivors of meningitis, most of whom are considered by their
parents and peers to be normal. Nevertheless, they are at moderate
risk of developmental problems associated with learning and
behaviour difficulties. Doctors need not only to check vision and
hearing after bacterial meningitis but also to ensure that caregivers
and schoolteachers are aware of possible language deficits and
problems understanding language based material. Simple educational interventions
may help compensate for these deficits, improving academic
performance, behaviour, and self esteem.
Keith Grimwood
Wellington School of Medicine and Health Sciences,
Wellington, New Zealand (grimwood@wnmeds.ac.nz)
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1. |
Stoll BJ. The global impact of neonatal infection. Clin
Perinatol 1997; 24: 1-21 |
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2. |
Peltola H. Burden of meningitis and other severe bacterial
infections of children in Africa: implications for prevention. Clin Infect
Dis 2001; 31: 64-75 |
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3. |
Peltola H. Worldwide Haemophilus influenzae type B
disease at the beginning of the 21st century: global analysis of the disease
burden 25 years after the use of the polysaccharide vaccine and a decade
after the advent of conjugates. Clin Microbiol Rev 2000; 13: 302-317 |
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4. |
Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M,
Reingold AL, et al. Bacterial meningitis in the United States in 1995. N
Engl J Med 1997; 337: 970-976 |
|
5. |
Baraff LJ, Lee SI, Schriger DL. Outcome of bacterial
meningitis in children: a meta-analysis. Pediatr Infect Dis J 1993;
12: 389-394 |
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6. |
Taylor HG, Mills EL, Ciampi A, du Berger R, Watters GV,
Gold R, et al. The sequelae of Haemophilus influenzae meningitis in
school-age children. N Engl J Med 1990; 323: 1657-1663 |
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7. |
Grimwood K, Anderson VA, Bond L, Catroppa C, Hore R, Keir
EH, et al. Adverse outcomes of bacterial meningitis in school-age survivors. Pediatrics
1995; 95: 646-656 |
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8. |
Grimwood K, Anderson P, Anderson V, Tan L, Nolan T. Twelve
year outcomes following bacterial meningitis: further evidence for persisting
effects. Arch Dis Child 2000; 83: 111-116 |
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9. |
Anderson V, Bond L, Catroppa C, Grimwood K, Keir E, Nolan
T. Childhood bacterial meningitis: impact of age at illness and acute medical
complications on long term outcome. JINS 1997; 3: 147-158 |
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10. |
Fellick JM, Sills JA, Marzouk O, Hart CA, Cooke RWI,
Thomson APJ. Neurodevelopmental outcome in meningococcal disease: a
case-control study. Arch Dis Child 2001; 85: 6-11 |
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11. |
D'Angio CT, Froehlke RG, Plank GA, Meehan DJ, Aguilar CM,
Lande MB, et al. Long-term outcome of Haemophilus influenzae
meningitis in Navajo Indian children. Arch Pediatr Adolesc Med 1995;
149: 1001-1008 |
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12. |
Heath PT, Booy R, Azzopardi HJ, Slack MPE, Bowen-Morris J,
Griffiths H, et al. Antibody concentration and clinical protection after Hib
conjugate vaccination in the United Kingdom. JAMA 2000; 284: 2334-2340 |
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Other related articles in
BMJ:
PAPERS
Meningitis in infancy in England and Wales: follow up at age 5 years.
Helen Bedford, John de Louvois,
Susan Halket, Catherine Peckham, Rosalinde Hurley, and David Harvey
BMJ 2001 323: 533.
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