What proportion of children and young people with bacterial meningitis develop physical and psychological morbidity?Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Bedfordet al., 2001 162
Cohort study
EL 2+
Aim: To describe seqelae at 5 years of meningitis in first year of life compared to matched controls.
Setting: England and Wales
Cases: N=1717 eligibleN=1485 recruited
Population: Survivors of acute meningitis in infancy (between 1985 and 1987 in England and Wales)
Study sample: Cases: Parents and GPs of survivors of acute meningitis in infancy between 1985 and 1987N=1584
Pathogens:H. influenzae= 413 (26%)Neisseria meningitidis= 402 (25%)S. pneumoniae= 143 (9%)E. coli= 70 (4%)Echovirus= 31 (2%)Other virus= 19 (1%)Other Gram +ve bacteria= 29 (2%) Other Gram –ve bacteria= 32 (2%)L. monocytogenes= 16 (1%)Other microorganism= 7 (0.5%)No organism grown= 320 (20%)Not known= 4 (0.2%)
Controls: Parents and GPs
GPs asked to complete specially designed questionnaire including info on:developmental problems in:neuromotor development, learning, vision, hearing, speech and language, behaviour;seizure disorderParents asked to complete questionnaire on child’s health, development and learning.Info from GPs and parents combined. Where severity of a condition differed between GP and parent, most severe cited category chosen.
Disability at age 5 classified as:severe if child unable to attend mainstream school; moderate if disability impaired functioning but not associated with severe intellectual or developmental impairment; mild disorder if child has condition prevalent among children of same age but not typically associated with meningitis; no disability if no evidence of developmental problem.
Cases vs controls:Learning difficulties:RR (95% CI) = 7.0 (4.1 – 11.8)Neuromotor disabilitiesRR (95% CI) = 8.6 (4.9 to 15.2)Seizure disordersRR (95% CI) = 2.7 (1.9 to 3.9)Hearing problemsRR (95% CI) = 1.9 (1.6 to 2.2)Sensorineural hearing lossRR (95%CI) 22.8 (7.22 to 72.1)Ocular or visual disordersRR (95% CI) = 3.4 (2.6 to 4.6)Speech or language problems, or both RR (95% CI) = 3.5 (2.8 to 4.6)Behavioural problemsRR (95% CI) = 3.6 (2.6 to 4.9)
Cerebral palsy:Cases= 79 (5.3%), Controls= 2 (0.1%)
Hemophilus influenzae:Severe disability= 14
Pre Hib vaccine; a quarter of cases had meningitis due to Hib.
Subjects of this study were the survivors from a national incidence study of infantile meningitis in England and Wales between 1985 and 1987. The same subjects were used in Halket et al., (2003) 182 and de Louvois et al., (2007) 183.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
of age and sex matched children from same GP lists.N=1391
(3.4%)Moderate disability= 30 (7.3%)Mild disorder= 134 (32.5%)No disability= 235 (57.0%)
Neisseria meningitidis:Severe disability= 12 (2.9%)Moderate disability= 26 (6.5%)Mild disorder= 120 (29.8%)No disability= 244 (60.7%)
Streptococcus pneuomniae:Severe disability= 14 (9.7%)Moderate disability= 20 (13.9%)Mild disorder= 37 (25.8%)No disability= 72 (50.3%)
Escherichia coli:Severe disability= 4 (5.7%)Moderate disability= 13 (18.6%)Mild disorder= 18 (25.7%)No disability= 35 (50.0%)
Group B Streptococcus:
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Severe disability= 13 (13.3%)Moderate disability= 17 (17.3%)Mild disorder= 18 (18.4%)No disability= 50 (51.0%)
Other gram positive bacteria:Severe disability= 6 (20.6%)Moderate disability= 8 (27.6%)Mild disorder= 5 (17.2%)No disability= 10 (34.5%)
Halket et al., 2003 182
Cohort study
EL 2+
Aim: To assess how meningitis in first year of life affects teenage behaviour.
Setting: England and Wales
739 cases, 480 controls
Cases: Survivors from a national incidence study of infantile meningitis (between 1985 and 1987 in England and Wales) aged 4 to 16.
Controls: age and sex matched from same GP lists.
Mean age: 13.3 years (SD 0.4)
The incidence of each strain of meningitis was not
A postal questionnaire (the Strengths and Difficulties Questionnaire) was sent to parents and school teachers.
25 questions divided into categories on emotional symptoms, conduct problems, hyperactivity, peer problems and prosocial behaviour.
Also questions on the
A total deviance score of 0-13 is considered ‘normal’. A total prosocial behaviour score of 10-6 is considered ‘normal’.
Impact score from 0 (not at all) to 2 (a great deal). Maximum burden scores are 10 for parents and 6 for teachers.
Complicated meningitis vs. controls:Parent’s response: Not normal total deviance:RR (95% CI) = 2.18 (1.77-2.68)Not normal impact score:RR (95% CI) = 3.48 (2.56-4.73)
Teacher’s response:Not normal total deviance:RR (95% CI) = 1.62 (1.27-2.08)Not normal impact score:
Missing information:Total deviance scores:Complicated meningitis – 3 parents and83 teachersUncomplicated meningitis - 85 teachers Control – 129 teachers
Impact score:Complicated meningitis – 15 parents and 92 teachers
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
specified. Although the subjects of this study were from the same cohort as Bedford et al., (2001) 162 (who did report the incidences) and de Louvois et al., (2007) 183, not all of the cohort was used.
impact of the child’s behaviour on the family or classroom.
Complicated meningitis group: one or more of the following – meningitis diagnosed at <28 days, birth weight <2,000g, coma, convulsions, hydrocephalus, a temperature >40oC, ventriculitis, relapse.
RR (95% CI) = 1.59 (1.25-2.03)
Uncomplicated meningitis vs. controls:Parent’s responses:Not normal total deviance:RR (95% CI) = 1.79 (1.44-2.22)Not normal impact score:RR (95% CI) = 2.46 (1.78-3.39)
Teacher’s responses:Not normal total deviance:RR (95% CI) = 1.45 (1.13-1.86)Not normal impact score:RR (95% CI) = 1.44 (1.13-1.84)
All meningitis cases vs. control; total deviance ratings:Parent and teacher rate as normal:RR (95% CI) = 0.73 (0.64-0.83)
Parents and teacher rate as not normal:RR (95% CI) = 2.18 (1.56-3.04)
Uncomplicated meningitis – 8 parents and 93 teachersControl – 19 parents and 139 teachers
Subjects of this study were the survivors from a national incidence study of infantile meningitis in England and Wales between 1985 and 1987. The same subjects were used in Bedford et al., (2001) 162 and de Louvois et al., (2007) 183.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Parent rates as normal, teacher as not normal:RR (95% CI) = 0.99 (0.68-1.45)
Parent rates as not normal, teacher rates as normal:RR (95% CI) = 2.09 (1.43-3.06)
All meningitis cases vs. control; normal social skills score:Parents:RR (95% CI) = 0.82 (0.73-0.91)
Teachers:RR (95% CI) = 0.88 (0.80 to 0.98)
de Louvois et al., 2007 183
Cohort study
EL 2+
Aim: To assess whether meningitis in first year of life adversely affects academic achievement at age 16.
460 cases, 288 controls
Cases: 16 year olds who had had meningitis in infancy (between 1985 and 1987)Controls: age and sex matched from same GP lists.
The incidence of each strain
Pupils were asked to list all the GCSE examinations they had taken, the number passed and the grades obtained through use of a standard questionnaire.
Passes in five key subjects (English language, English literature, mathematics, science and a modern foreign language) were scored (grade A*=
GCSE point score in five key subjects:0:Index= 67 (14.6%)Control= 10 (3.5%)
1-14:Index= 190 (41.3%)Control= 75 (26.0%)
The study reports 461 cases and 289 controls, but the analyses does not include 1 case and 1 control as they did not attend a comprehensive, independent,
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
of meningitis was not specified. Although the subjects of this study were from the same cohort as Bedford et al., (2001) 162 (who did report the incidences) and Halket et al., (2003) 182, not the entire cohort was used.
6 points, grade A= 5 points… grade E pass= 1 point). Five passes (C or above) at GCSE equated to fifteen points.
15-24:Index= 130 (28.3%)Control= 123 (42.7%)
>24:Index= 73 (15.9%)Control= 80 (27.8%)
Number of GCSE passes:0:Index= 117 (25.4%)Control= 19 (4.13%)
1-4:Index= 105 (22.8%)Control= 41 (14.2%)
5-10:Index= 198 (43.0%)Control= 189 (65.6%)
>10:Index= 40 (8.7%)Control= 39 (13.5%)
There was a significant difference in mean number of GCSE passes between index and control in comprehensive schools (5.05 SD 4.1 vs. 6.88 SD 3.5, p<0.0001).
grammar or special school (coded as ‘other’).
Study done prior to Hib vaccine – almost a third of the 16 year olds who attended special schools (total n= 36) had had meningitis due to H influenzae
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
There was no significant difference in mean number of GCSE passes between index and control in grammar or independent schools.
Legood et al., 2008 166
Cohort study
EL 2+
Aim: to estimate the overall long-term health related quality of life implications of an episode of pneumococcal meningitis in childhood.
70 cases66 controls
Cases: Children aged 5 and over who had S. pneumoniae disease in Oxford and North East Thames regions of the UK.
Controls: 61 controls were siblings of cases, 5 were neighbourhood controls of similar age and same sex.
Mean age: Cases= 9.9 years (5.4-20.4)Controls= 11.3 years (5.3-28.8)
Pathogens: S. pneumoniae= 70 (100%)
HUI-3 :Health utility index that measures health related quality of life.
Measures health related quality of life.
Parent completed questionnaire if child was under 11.
HUI score for vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain.
Mean HUI in cases vs. controls:
Vision:0.981 (0.952-1.009) vs. 0.992 (0.988-0.997)p= 0.434
Hearing:0.930 (0.886-0.974) vs. 0.996 (0.987-1.004)p= 0.005
Speech:0.976 (0.945-1.006) vs. 0.995 (0.985-1.005)p= 0.248
Ambulation:0.986 (0.957-1.014) vs. 1.000 (1.000-1.000)p= 0.333
Dexterity:1.000 (1.000-1.000) vs. 1.000 (1.000-1.000)P= 1.000
*= data is missing for one case
Univariate analyses were conducted for each attribute with no correction for multiple comparisons (e.g. Bonferroni correction), and so the significance levels reported may over estimate the true effects. Also, the significance of the overall score probably reflects the effect of hearing.
This study was done in the UK. Funding was received from the Meningitis Research Foundation.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Emotion:0.915 (0.877-0.954) vs. 0.942 (0.911-0.972)p= 0.297
Cognitive:0.871 (0.822-0.921) vs. 0.916 (0.877-0.955) p= 0.167
Pain*: 0.952 (0.927-0.978) vs. 0.972 (0.956-0.987)p= 0.203
Overall score*:0.774 (0.711-0.837) vs. 0.866 (0.824-0.907)p= 0.019
Anderson et al., 2004 167
Prospective cohort study
EL 2+
Aim: to investigate long-term neurobehavioural outcome from childhood bacterial meningitis.
7 year followup: 130 cases, 130 controls
12 year followup:109 cases,96 controls
Cases: children aged 3 months to 14 years admitted to Royal Children’s Hospital, Melbourne, with bacterial meningitis from October 1983 to October 1986.
Median age at illness was 18 months.
Children with documented
Wechsler Intelligence Scale for Children-III for children 16 years and younger, Wechsler Adult Intelligence Scale-III for children aged 17 and 18.
Full Scale Intellectual Quotient
Wide Range
Outcomes: verbal comprehension, perceptual organisation and freedom from distractibility, reading (word decoding), spelling and arithmetic ability.
Full scale IQ, mean (SE):Case= 97.2 (1.1)Control= 101.6 (1.2)Difference: 4.3 (95% CI; 1.1-7.6) p=0.10
Verbal comprehension, mean (SE):Case= 95.0 (1.1)Control= 99.4 (1.2)Difference: 4.3 (95% CI; 1.1-7.6) p=0.009
*= n= 107 as 2 cases were unable to complete the tests
This study was done in Australia and was funded by the Government Employee’s Medical Research Fund and the Murdoch Childrens Research Institute.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
pre-existing neurologic and developmental deficits, immunodeficiency states, previous CNS surgery or meningitis secondary to cranial trauma or shunt infections were excluded.
Controls: Grade and sex matched controls recruited from the classroom of each case child (one control was from neighbouring school). Controls for cases at special schools were taken from another school in the same region.
Pathogens:Haemophilus influenzae type B= 85 (78%)Staphylococcus pneumoniae= 12 (11%)Neisseria meningitidis= 6 (5.5%)Other= 6 (5.5%)
Achievement Test-3 Perceptual organisation, mean (SE):Case= 99.4 (1.3)Control= 103.6 (1.4)Difference: 4.1 (95% CI; 0.4-7.9) p= 0.029
Freedom from distractibility, mean (SE):Case= 97.7 (1.4)Control= 99.7 (1.5)Difference: 2.0 (95% CI; -2.0 to 6.0) p=0.323
Reading ability, mean (SE):Case= 99.0 (1.3)Control= 104.3 (1.4)Difference: 5.2 (95% CI; 1.4-9.1)P= 0.007
Spelling, mean (SE):Case= 95.4 (1.3)Control= 101.3 (1.3)Difference: 5.9 (95% CI; 2.2-9.5) p= 0.002
Arithmetic, mean (SE):Case= 95.0 (1.2)Control= 97.4 (1.2)Difference: 2.5 (95% CI; -0.9 to 5.8) p=0.146
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
The age at which children developed meningitis was not a significant predictor of long-term health related quality of life, although meningitis before 12 months of age was significantly related to poorer performance on tasks requiring language and executive skills.
Oostenbrink et al., 2002 168
Retrospective cohort study
2+
Aim: to evaluate the neurological outcome of bacterial meningitis in children
Setting: One hospital in Rotterdam, The Netherlands, between 1988 and 1998.
103 children with bacterial meningitis
1 month to 15 years old.
51 male (50%)
Pathogens:N. Meningitidis = 51 (50%)Steptococcus pneumoniae (SP) = 10 (10%)H. influenzae type B= 34 (33%)No pathogen identified= 8 (8%)
Clinical records Follow-up:Median= 6.7 months
Outcomes:Neurological and audiological sequelae
Death= 2 children (2%)
Number of children whose persistent neurological sequelae were assessed during follow-up= 13
Number of children whose hearing function was assessed= 83
Hearing loss= 7Neurological sequelae= 7Total sequelae= 13
Deafness= 1
Mild hearing loss= 6
Mental retardation= 5
This study was done in the Netherlands; no source of funding is reported.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Persistant palsy of the abducens nerve= 3 Locomotion deficits= 3 Epilepsy= 1
Ritchi et al., 2008 169
Cohort study
2+
Aim: To examine behaviour problems, personality, self-perceived competence and academic deficits in children who had recovered from non-Haemophilus influenzae type b bacterial meningitis without obvious medical sequelae.
674 children with certified diagnoses of bacterial meningitis
Cohort was divided by whether parents were concerned about school achievement and health status. From both groups, samples of children with (n= 100) and without (n= 101) were drawn for further assessment.
After checking exclusion criteria, final cohort of children with
57% male
Average age at onset of meningitis= 2.4 years (1 mo to 9.4 years)
Mean age: 10 years (5-14yrs)
Pathogens:Streptococcus pneumoniae= 26 (14%)Neisseria meningitidis= 146 (80%)Other= 10 (5%)
Part II of the Child Behaviour Checklist (completed by parents)
Personality Questionnaire for children (completed by parents)
Dutch adaptation of the Self-Perception Profile for children (completed by children)
Academic Achievement Test (completed by children, involves writing to dictation, copying sentences, reading aloud and solving written arithmetic problems)
Follow-up:4-10 yrs after surviving meningitis
Outcomes:Ratings for behaviour, personality and self-perceived confidence.
Academic deficits.
Total behavioural problem score (n= 61, 9%): d=0.52* (95% CI: 0.30-0.74, p<0.001)
Estimated percentage of children with behaviour problems after surviving bacterial meningitis= 9%
Deviation on at least 2 of 4 academic deficit tasks: n= 184 (27%)
Deficit in writing to dictation: n= 258 (38%)
Deficit in reading aloud: n= 159 (24%)
Deficit in copying sentences: n= 116 (17%)
Deficit in written arithmetic: n= 222 (33%)
*= effect size of 0.2 is considered to be a small deviation, 0.5 a moderate deviation, and 0.8 a large deviation from the norm.
Mean effect sizes in the total cohort (n= 674) were estimated from effect sizes and percentages in a cohort with (n= 84) and without (n= 98) academic or behavioural problems.
This study was done in the Netherlands. Funding was provided by the Health Research and Development Council of the Netherlands and from Fonds Bevordering Neuropsychologisch Onderzoek bij
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
(n= 84) and without (n= 98) academic or behavioural problems (total n= 182).
Kinderen (Fund for the advancement of neuropsychological research in children).
Douglas et al., 2008 170
Retrospective cohort study
2+
Aim: to demonstrate whether one causative agent of meningitis is more likely to cause profound hearing loss and labyrinthitis ossificans
Setting: One territory of Australia between 1984-2005
35 of 59 patients who received cochlear implants after meningitis and for whom a causative agents could be confirmed from medical records.
70 ears (11 bilateral cochlear implantations)
22 females, 37 males
Mean age at time of deafness: 2yrs 9mos (4mos – 30 yrs 9 mos)
51 of 59 patients were under 3 yrs old.
Pathogens: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae.
Notifiable Diseases Database System of the New South Wales health department
Australian National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases
Sydney Cochlear Implant Centre
Outcome:Incidence of cochlear implant by causative agent of meningitis.
Total cases of meningitis= 1568
Total number of cochlear implant patients= 80
Cause of meningitis (total n= 1568):Streptococcus pneumoniae= 645 (41.1%)
Neisseria meningitidis= 892 (56.9%)
Haemophilus influenzae= 31 (1.9%)
Cochlear implant by causative agent (total n= 59, n from Streptococcus pnuemoniae, Neisseria meningitidis or Hib= 35):Streptococcus pneumoniae= 30 (85.7%)
Neisseria meningitidis= 4 (11.4%)
This study was done in Australia. Funding was provided by the Graham Fraser foundation (UK).
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Haemophilus influenzae= 1 (2.9%)
Incidence of cochlear implant for each causative agent (total n= 1568):Streptococcus pneumoniae= 30 (4.7%)
Neisseria meningitidis= 4 (0.4%)
Haemophilus influenzae= 1 (3.2%)
Bibliographic information
Study type & evidence level
Study details Number of patients
Patient Characteristics Intervention & Comparison
Follow up & outcome
Results & Effect size Reviewer comment
Wellman et al., 2003 177
Retrospective case series
EL= 3
Aim: to establish the proportion of children who develop sensorineural hearing loss after bacterial meningitis and to correlate such loss with patient factors
N= 79, of which 68 had an audiological assessment and were included in the final analysis
Age:<2 years= 58/79 (73.4%)2-5 years= 13/79 (16.4%)>5 years= 8/79 (10.2%)
Male= 57/79 (72%)
Cases were identified by searching medical records
Children from 1 day to 18 years old with a confirmed diagnosis of bacterial
Audiological assessment
Levels of hearing:Normal: < 30 dBMild: 30 to 55 dBModerate: 55 to 70 dBSevere: 70 to 90 dBProfound: > 90 dB
Mean number of days between admission and assessment (inpatients, n= 42)= 13.2 days (±7.25)
Mean number of days between discharge and assessment (outpatients, n=
Some degree of loss= 22/68 children (32.3%)
Permanent sensorineual hearing loss= 11/17 of the children who were followed up (64.7% of those followed up, 16.1% of the total number of children undergoing audiological assessment)
A statistically significant
Bacterial meningitis: presence of a positive CSF culture, an accompanying positive CSF gram stain or a consistent CSF profile defined as CSF glucose level less than 2.12 mmol/L, CSF protein level > 1490 mg/L, and polymorphonuclear cell count > 2500
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
meningitis who underwent hearing assessment either as inpatients (n= 42, 61.7%) or as outpatients (n= 26, 38.3%)
Causative agent:S. pneumoniae= 29/79 (36.7%)N. meningitidis= 13/79 (16.5%)Group B Strep.= 12/79 (15.2%)H. influenzae= 11/79 (13.9%)E. coli= 7/79 (8.87%)
Excluded if a bacterial etiology could not be confirmed (203 cases), death (9 cases) or had a pre-existing neurologic or sensorineual hearing loss (14 cases).
26)= 74.3 days (±13.8)
association between Streptococcus pneumoniae meningitis and sensorineural hearing loss was found (p<0.001)
No statistically significant differences between sensorineural hearing loss and patients’ age, sex, duration of illness before admission, and pathogens other than S. pneumoniae were found.
cells/ μL
This study was done in Canada. No source of funding is cited.
Grimwood Et ol 1995 171
Prospective cohort study
EL= 2+
Aim: to determine the outcomes of bacterial meningitis in school-age survivors
158 survivors of bacterial meningitis, with 130 completing followup (131 cases as one child had meningitis twice)
Male= 83 (53%)
3 months to 14 years old
Median age at admission= 17 months
Bacterial meningitis: clinical presentation and
Medical examination, neuropsychological evaluation, audiologic assessment, behaviour and social adjustment assessment, socio-demographic assessment.
A questionnaire for demographic data, presenting history and examination findings, laboratory and treatment details, and clinical course was completed
Full scale IQ <70:Survivors= 11/130 (8.5%)Controls= 0/130 (0%)P < 0.001
Spasticity:Survivors= 3/127 (2%)Controls= 0/129 (0%)P not reported
All patients were initially treated with intravenous benzylpenicillin G (180 mg/kg per day) and chloramphenicol (100 mg/kg per day).
28 children were lost
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Grade and sex matched controls – next same sex student on the class roll or from equivalent school in same area.
either 1) the isolation of bacteria from the CSF by culture, 2) CSF leukocytosis (>100x106/L) and abnormal CSF biochemistry (glucose <45mg/dL [<2.5 mmol/L] and protein>50 mg/dL [>0.5g/L]) with isolation of bacteria from blood culture or CSF antigen detection by latex agglutination or 3) CSF leukocytosis (>1500 x 106/L with >75% neutrophils) and abnormal CSF biochemistry.
Excluded: children with known pre-existing neurologic or developmental abnormalities, immunodeficiency states, previous central nervous system surgery, or meningitis secondary to cranial trauma or CSF shunt infections. Also excluded at follow up those who died during the illness.
Hib= 100/131 (76%)S. pneumoniae= 18/131 (14%)
during hospitalisation and at the discharge neurologic examination.
If a change in auditory responsiveness was suspected during recovery, an initial audiological assessment was made in the hospital. All other patients received their first audiologic assessments within 4 to 6 weeks from discharge.
Blind:Survivors= 1/127 (1%)Controls= 0/129 (0%)P not reported
Deaf (severe to profound):Survivors= 3/126 (3%)Controls= 0/129 (0%)P not reported
Epilepsy:Survivors= 5/127 (5%)Controls= 0/129 (0%)P not reported
VP shunt:Survivors= 2 (2%)Controls= 0 (0%)P not reported
No problems:Survivors= 95 (73%)Controls= 116 (89%)P not reported
One minor problem (e.g. IQ 70-80, mild to moderate deafness):Survivors= 16 (12%)Controls= 14 (11%)P not reportedMore than one minor problem or at least one
to followup (26 were unable to be found, 1 refused to participate and 1 had died from unrelated causes)
This study was done in Australia and was supported by an Australian National Health and Medical Research Council Project Grant.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
N. meningitidis= 6/131 (5%)
major problem (e.g. IQ<70, blind, severe to profound deafness):Survivors= 20 (15%)Controls= 0 (0%)P not reported
Pikis et al., 1996 178
Case series
EL= 3
Aim: to assess the long-term effects of pneumococcal meningitis in children
63 children with pneumococcal meningitis, 47 children completed follow up
1 month to 14 years (mean age 2.6±3.6 years)
55% were less than 1 year old
33 (70%) male
Diagnosis made by CSF culture of S. pneumoniae.
Excluded if died before follow up (n= 16), mental retardation (n= 2), neurological deficits before meningitis (n=2), death subsequent to hospitalisation (n= 2) or if meningitis occurred more than once in the same child (n= 7).
Interval history; social history; complete physical examination, including neurologic, ophthalmologic, and hearing evaluations; psychometric and psychological assessment.
Unable to contact 16 survivors, so their medical records were used for follow-up.
Follow up: 4-23 years (mean 12.3 ±5.8 years) after discharge from hospital
No complication= 33 (70%)
At least one defect= 14 (30%)
Combinations of complications= 8 (17%)
Mental retardation= 9 (19%)
Sensorineural hearing loss= 8 (17%)
Profound or severe hearing loss= 4 (9%)
Moderate or mild hearing loss= 4 (9%)
Seizure disorder= 7 (15%)
Motor defect= 5 (11%)
Behavioural problems with marginal IQ= 1 (2%)Visual impairment= 1 (2%)
This study was done in Greece and the US, looking at children presenting to a Greek hospital.
No funding sources are cited.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Koomen et al., 2003 163
Cohort study
EL= 2+
Aim: to determine the occurrence of educational, behavioural and general health problems in Dutch school age survivors of bacterial meningitis.
680 children who survived bacterial meningitis
304 controls (235 (77%) siblings, 64 (21%) close friends, 5 (2%) unknown relationship)
Median age:Survivors= 8.5 years (4.3 - 13.6)Controls= 9.1 years (3.2 - 14.9)P<0.01
Males:Survivors= 387/680 (57%)Controls= 147/304 (48%)P<0.02
Excluded: Hib, rare pathogens and incomplete pathogen data, death, meningitis with complex onset (ie secondary to immunodeficiency state, central nervous system surgery, etc), missing hospital charts, no response from parents or paediatrician, too old to participate
Scales:Educational problems: The School Achievement Rating Scale (SAR)
Behavioural problems: The Functional Status II R 14-item version (FS-II)
General health status: The Health Utilities Index mark 2 (HUI-2)
Hearing impairment: information obtained from parents. No data was available on the type of hearing impairment.
Illness variables: information on age at infection, gender and causative pathogen was gathered from the Reference Laboratory.
Repeated/ing kindergarten year:Survivors= 55/111Controls= 9/25P<0.001
Parents’ report of children with perfect health:Survivors= 47%Controls= 70%P<0.001
Mean multiattribute functional utility score:Survivors= 0.92 (SD 0.11)Controls= 0.97 (SD 0.06)P*<0.001
Hearing problems:Survivors= 48 (7%)Controls= 3 (1%)P<0.001
Mean FS-II score (behavioural problems):Survivors= 84.6 (SD 12.6)Controls= 89.9 (SD 8.9)P*<0.001
S. pneumoniae survivors= 85.3 (SD 12.5)N. meningitidis survivors= 84.7 (SD 12.3)
*= adjusted for gender and age at evaluation
This study was done in The Netherlands and was supported by the Health Research and Development Council of the Netherlands.
This study uses the same cohort of children as Koomen et al., (2003) 164
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
≤ 1 month old at onset= 84.1 (SD 14.6)>1 month old at onset= 84.6 (SD= 12.5)P*>0.5
Deficient school achievement:Survivors= 136 (20%)Controls= 14 (5%)OR*= 5.6 (3.0-10.7)
S. pneumoniae survivors= 25 (22%)N. meningitidis survivors= 98 (19%)OR*= 1.3 (0.8-2.2)
≤ 1 month old at onset= 12 (30%)>1 month old at onset= 124 (19%)OR*= 2.2 (1.0-4.8)
Concentration problems:Survivors= 147(22%)Controls= 16 (5%)OR*=5/7 (3.1-10.5)
S. pneumoniae survivors= 26 (23%)N. meningitidis survivors= 107 (21%)OR*= 1.3 (0.8-2.2)
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
≤ 1 month old at onset= 11 (28%)>1 month old at onset= 136 (21%)OR*= 1.6 (0.7-3.5)
Hyperactive behaviour:Survivors= 200 (29%)Controls= 53 (17%)OR*=1.8 (1.3-2.6)
S. pneumoniae survivors= 35 (31%)N. meningitidis survivors= 151 (29%)OR*= 1.1 (0.7-1.8)
≤ 1 month old at onset= 15 (38%)>1 month old at onset= 185 (29%)OR*=1.3 (0.7-2.8)
Slowness:Survivors= 131 (19%)Controls= 19 (6%)OR*=3.7 (2.2-6.4)
S pneumoniae surviors= 28 (25%)N. meningitidis survivors= 87 (17%)OR*=1.7 (1.0-2.9)
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
≤ 1 month old at onset= 11 (28%)>1 month old at onset= 120 (19%)OR*= 1.9 (0.8-4.0)
Poor school motivation:Survivors= 104 (16%)Controls= 25 (8%)OR*= 2.2 (1.3-3.6)
S. pneumoniae survivors= 14 (12%)N. meningitidis survivors= 80 (15%)OR*= 0.9 (0.5-1.7)
≤ 1 month old at onset= 8 (20%)>1 month at onset= 96 (15%)OR*=1.7 (0.7-4.0)
Depressed mood:Survivors= 49 (7%)Controls= 4 (1%)OR*= 5.0 (1.8-14.3)
S. pneumoniae survivors= 6 (5%)N. meningitidis survivors= 38 (7%)OR*= 0.7 (0.3-1.8)
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
≤ 1 month old at onset= 2 (5%)>1 month old at onset= 47 (7%)OR*= 0.9 (0.2-3.8)
Repeating a year:Survivors= 111 (16%)Controls= 25 (8%)OR*= 2.5 (1.5-4.2)
S. pneumoniae survivors= 13 (12%)N. meningitidis survivors= 92 (18%)OR*= 0.7 (0.4-1.4)
≤ 1 month old at onset= 4 (10%)>1 month at onset= 107 (17%)OR*= 1.1 (0.4-3.3)
Special needs school:Survivors= 52 (8%)Controls= 5 (2%)OR*=5.5 (2.0-15.4)
S. pneumoniae survivors= 14 (12%)N. meningitidis survivors= 35 (7%)OR*= 1.9 (0.9-3.7)
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
≤ 1 month old at onset= 3 (8%)>1 month old at onset= 49 (8%)OR*= 1.1 (0.3-3.7)
Functional Limitation:Sensation:Survivors= 166 (25%)Controls= 49 (16%)OR*= 1.6 (1.1-2.3)
Mobility:Survivors= 6 (1%)Controls= 1 (0.3%)OR*= 2.4 (0.3-20.5)
Cognition:Survivors= 182 (27%)Controls= 18 (6%)OR*= 5.9 (3.4-10.1)
Self-care:Survivors= 13 (3%)Controls= 0 (0%)OR*= could not be calculated
Emotion:Survivors= 179 (26%)Controls= 20 (7%)OR*= 4.9 (3.0-8.1)
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Pain:Survivors= 93 (14%)Controls= 15 (5%)OR*= 3.9 (2.1-7.2)
Ispahani et al., 2003 179
Prospective case series
EL= 3
Aim: to evaluate the incidence, spectrum of clinical manifestations, and outcome of invasive pneumococcal disease in children. To determine the main serogroups of S. pneumoniae responsible for invasive disease and the potential coverage by the new pneumococcal conjugate vaccines.
61 children with pneumococcal meningitis
Age: 1 month to 16 years old, majority 2-11 months old.
Looked at all children in a 20 year period presenting at two hospitals in Nottingham with invasive pneumococcal disease.
Excluded if died (n=17), transient neurological deficits or pre-existing neurological deficits (n=5).
At least one neurological sequela= 16 (26%)
Cerebral palsy= 6 (10%)
Global development delay= 8 (13%)
Epilepsy= 7 (11%)
Sensorineural hearing impairment= 7/51 (14%) who had auditory assessment
Multiple neurological deficits= 8 (13%)
This study was done in the UK. No source of funding is cited.
Klinger et al., 2000 172
Retrospective cohort study
EL= 2+
Aim: to build predictive models of severe adverse outcome at various times in the course of neonatal bacterial meningitis.
101 cases of bacterial meningitis
M:F= 1.3:1
Mean age at diagnosis= 10.8 days
Included: 1) diagnosis of bacteria confirmed by CSF culture 2) GA greater than or equal to 35 weeks 3) age at diagnosis equal to or
Outcome information was available for all survivors to 1 year of age, mean age for latest outcome information was 4 years (range 1-19 years)
Group B streptococcus= 50 (49.5%)
Escherichia coli= 25 (24.8%)
Streptococcus pneumoniae= 5 (5%)
Hemophilus influenze= 3
This study was done in Canada. No sources of funding are cited.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
less than 28 days.
Excluded: coexisting intrapartum asphyxia, major congenital anomalies, any congenital CNS anomaly, known syndrome, genetic condition, or chromosomal anomaly.
Premature infants born GA<35 weeks were excluded due to risk of neurologic disability.
(3%)
Development delay= 10 (9.9%)
Cerebral palsy= 1 (1%)
Microencephaly= 3 (3%)
Hemiparesis= 3 (3%)
Hearing loss= 1 (1%)
Blindness= 2 (2%)
Seizure disorder= 3 (3%)
Age at diagnosis (days):Good outcome= 11.2 (9)Adverse outcome= 9.1 (7.8)P=0.314
Grimwood et al., 2000 173
Cohort study
EL= 2+
Aim: to determine whether intellectual and cognitive impairments observed seven years following early childhood bacterial meningitis persist into adolescence.
N=166 in original cohort (1983-86), 130 (82%) in cohort at first follow up (1991-3), 109 (66%) in cohort at second follow up (1996-7).
130 grade and
Age: 3 months to 14 years.
Mean age at first follow up= 8.4 years (SD 1.6)
Males:Survivors= 60 (55%)Controls= 51 (53%)
Mean time since meningitis: At first follow up= 6.7 years (SD 0.8, range 5.3-9.3)At second follow up= 11.5 years (SD 0.9, range 9.9 – 13.9)
Major impairment (IQ<70, spasticity, blind, severe-profound sensorineural deafness >70dB, epilepsy, VP shunt):Survivors= 9 (8%)Controls= 0 (0%)
IQ<70:Survivors= 4 (4%)Controls= 0 (0%)
This study was done in Australia and was financed by grants from the Government Employee’s Medical Research Fund and the Royal Chidlren’s Hospital Research Institute.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
sex matched controls were found at first follow up, and 96 (74%) were re-evaluated at second follow up.
109 survivors and 96 controls were used in the final analyses.
Spasticity:Survivors= 2 (2%)Controls= 0 (0%)
Blind:Survivors= 1 (1%)Controls= 0 (0%)Deaf (>70 dB):Survivors= 3 (3%)Controls= 0 (0%)
Epilepsy:Survivors= 4 (4%)Controls= 0 (0%)
VP Shunt:Survivors= 2 (2%)Controls= 0 (0%)
Minor impairment (IQ 70-80, educational deficit, mild-moderate sensorineural deafness 25-69 dB, behaviour problem):Survivors= 32 (29%)Controls= 11 (11%)OR= 3.2 (CI 95% 1.5 to 6.7)
IQ 70-80:Survivors= 5 (5%)Controls= 3 (3%)OR= 1.5 (CI 95% 0.4 to 5.8)
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Educational deficits:Survivors= 11 (10%)Controls= 3 (3%)OR= 3.5 (CI 95% 1.0 to 15.9)
Deaf (25-69 dB):Survivors= 7 (7%)Controls= 0 (0%)
Behaviour problems:Survivors= 25 (23%)Controls= 7 (7%)OR= 3.8 (CI 95% 1.6 to 9.8)
No problems:Survivors= 68 (62%)Controls= 85 (89%)OR= 0.2 (CI 95% 0.1 to 0.4)
One minor impairment:Survivors= 16 (15%)Controls= 6 (6%)OR= 2.6 (1.0 to 7.4)
One major and/or more than one minor impairment:Survivors= 25 (23%)Controls= 5 (5%)OR= 5.4 (CI 95% 2.0 to 14.3)
Overall, meningitis subjects
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
were at substantially greater risk of an adverse outcome: OR= 4.7 (CI 9%) 2.2 to 10.0
Stevens et al., 2002 174
Cohort study
EL= 2+
Aim: to quantify long term impairment after neonatal meningitis.
N= 111 children who survived neonatal meningitis
113 hospital controls matched for sex and close as possible birth date, birth weight and hospital of birth where possible.
49 GP controls born at term and matched for birth date and sex
Mean age:Survivors= 9.39 (0.24) yearsHospital controls= 9.42 (0.26) yearsGP controls= 9.42 (0.22)
Excluded: any less common cases of meningitis caused by organisms other than Group B Streptococcus, Gram negative bacteria or Listeria monocytogenes.
Wechsler intelligence scale for children (WISC-III)
Movement assessment battery for children (mABC)
Sweep screening of hearing*
Sonksen-Silver acuity system for visual acuity
Social and medical data was obtained from a questionnaire.
Severe outcome= severe disability or a significant functional impairment such as cerebral palsy, significant learning problems (IQ<55), global delay and/or special education.
Listeria:Number of children= 13Outcome:Severe= 1 (7.7%)Moderate= 0Mild= 2 (15.4%)Normal= 10 (76.9%)
Gram negative:Number of children= 7Outcome:Severe= 2 (28.0%)Moderate= 2 (28.0%)Mild= 1 (14.0%)Normal= 2 (30%)
E coli:Number of children= 42Outcome:Severe= 2 (4.8%)Moderate= 4 (9.6%)Mild= 9 (21.4%)Normal= 27 (64.2%)
Group B Streptococcus:Number of children= 49Outcome:Severe= 7 (14.3%)
*= mild hearing loss 20-40 dB, moderate 41-60 dB and severe as >60dB. This differs from other studies.
This study was done in the UK and received grants from the regional health authority, Portland Hospital, London.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Moderate outcome= moderate to mild disability or an abnormality that impairs function without significant intellectual or developmental impairment e.g. mild cerebral palsy, mild learning problems (IQ 55-69), sensorineural hearing loss.
Mild outcome: an impairment without disability, e.g. neuromotor signs without overt functional loss, isolated hydrocephalus, isolated epilepsy, borderline learning problems (IQ 70-80), isolated occurrence of all mABC component scores being below the 5th centile.
Moderate= 4 (8.1%)Mild= 7 (14.3%)Normal= 31 (63.3%)
IQ:Survivors= 88.8 (85 to 92)Hospital controls= 99.4 (97 to 102)GP controls= 99.6 (95 to 103)Survivors vs. hospital controls: p<0.001Survivors vs. GP controls: p<0.002
There was no significant difference between GP and hospital controls. (Children were grouped as either moderate/severe or mild/normal for analysis)
E coli= 87.9 (CI 95% 82.3 to 93.5)Group B Streptococcus= 88.7 (CI 95% 83 to 74.4)P=0.106
102 survivors were fully tested (6 were too impaired to complete the test, 3 children had incomplete results), 110 hospital controls were fully tested
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
(3 had incomplete results). All GP controls were fully tested.
mABC:Survivors= 7.1 (5.9 to 8.5)Hospital controls= 5.0 (4.3 to 5.8)GP controls= 4.0 (2.9 to 5.4)Survivors vs. hospital controls: p=0.001Survivors vs. GP controls: p=0.003
There were no significant differences for mABC between ages at onset or type of infecting microbe.
Seizures:Survivors= 5.4%Hospital controls= 1.8%GP controls= 0%
Severe overall outcome:Survivors= 10.8%Hospital controls= 0GP controls= 0
Moderate overall outcome:Survivors= 9%Hospital controls= 1.8%GP controls= 0
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Mild overall outcome:Survivors= 17.1%Hospital controls= 11.5%GP controls= 16%
Normal overall outcome:Survivors= 63.1%Hospital controls= 86.7%GP controls= 84%
Koomenet al., 2003 164
Cohort study
EL= 2+
Aim: to establish the incidence of sensorineural hearing loss in children who survived non-Hib bacterial meningitis to highlight the actual percentage whose hearing was evaluated, and to develop a prediction rule to identify those who are at risk of hearing loss.
N= 628 Male= 57%
Mean age at infection= 2.4 years (range 0-9.5 years)
Mean age at follow-up= 11.7 years (range 7.5-16.3 years)
Excluded: Hib (n= 117), rare pathogens (n=4) and incomplete pathogen data, death, meningitis with complex onset (n= 84) (ie secondary to immunodeficiency state, central nervous system surgery, etc), missing hospital charts, no response from parents or paediatrician, too old to participate, cognitive or behavioural problems
Parents were sent questionnaires on long-term outcomes and on exclusion criteria.
Medical records were used to obtain detailed data on admission and follow-up.
395 of 578 (68%) of children had hearing evaluated as part of the routine follow up after meningitis.
Hearing loss was detected within 6 months of meningitis in all but two children.
Survivors with hearing loss= 43/395 (11%)
Survivors with unilateral hearing loss= 20 (5%)Survivors with bilateral hearing loss= 23 (6%)Survivors with severe (71-90dB) hearing loss= 11 (3%)Survivors with profound (>90dB) hearing loss= 21
This study was done in the Netherlands and was supported by the Health Research and Development Council of the Netherlands.
This study uses the same cohort of children as Koomen et al., (2003) 211
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
before meningitis (n=23), diseases after meningitis that could have caused cognitive or behavioural problems (n= 5).
(5%)Survivors with cochlear implants= 5 (1%, all with profound hearing loss)
Mean age at infection (n= 628):Hearing loss= 1.6 (SD 1.5)No hearing loss= 2.5 (SD 2.1)P=0.006
Causative pathogen (n=628): p<0.001
Neisseria meningitidis:Hearing loss (n= 43)= 20 (46%)No hearing loss (n= 585)= 475 (81%)
S. pneumoniae:Hearing loss (n= 43)= 21 (49%)No hearing loss (n= 585)= 82 (14%)
Escherichia coli:Hearing loss (n=43)= 2 (5%)No hearing loss (n= 585)= 8 (1%)
S. agalactiae:
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Hearing loss (n= 43)= 0 (0%)No hearing loss (n= 585)= 18 (3%)
Listeria monocytogenes:Hearing loss (n= 43)= 0No hearing loss (n= 585)= 2 (1%)
King et al., 2004 180
Case series
EL= 3
Aim: to gain information on epidemiology, outcome and microbiology of pneumococcal meningitis to target vaccination strategies.
N= 94 (93 children, one child had two episodes of meningitis)
Age: 1 day-16.5 years
Neonates: 3
Median age: 12.4 months
67 (71.3%) < 2 years old
55 (58.5%) male.
All children had microbiologicall confirmed pneumococcal meningitis.
Demographic and outcome data was gathered from medical notes.
Severe deficit: cerebral palsy of any degree, severe or profound bilateral hearing loss, intellectual deficit, blindness or hydrocephalus.
Less severe deficits: learning problems, unilateral or mild to moderate bilateral hearing loss, isolated cranial nerve palsy or isolated seizure disorder.
Hearing loss:Profound: >85dB
Medical records were obtained 12-140 months post diagnosis
8 deaths due to conditions related to meningitis:5 died within 3 days of diagnosis3 died 4-24 months after discharge
1 additional death due to unrelated causes.
All deaths occurred in children diagnosed with meningitis at 12 months or less of age.
85 survivors:61 children with no apparent sequelae.
16 (18.8%) had severe sequelae8 (9.4%) had less severe sequelae
This study was done in Australia and was supported by a financial contribution from Wyeth Lederle.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Severe: 65-80dBModerate:45-60dBMild: 25-40dB
Hearing loss:Severe to profound bilateral= 10/89 (11%)Less than severe bilateral= 1/89 (1%)Unilateral, any degree= 5/89 (6%)
No significant relationship between age and risk of severe sequelae (p>0.05)
No significant relationship between age of diagnosis and risk of sensorineural hearing loss (p=0.43)
Hemiparesis= 4/89 (4.5%)Quadriparesis= 6/89 (6.7%)Cranial nerve palsy= 6/89 (6.7%)
Seizure disorder= 12/89 (13.5%)Visual deficit= 4/89 (4.5%)
De Louvois et al., 2005 5
Cohort study
EL=2+
Aim: to determine the prevalence of serious sequelae among a national cohort of 5 years old children, born in England and
N= 166 survivors of neonatal meningitis who had complete questionnaires at follow up
All survivors had meningitis as neonates.
M:F ratio ofsurvivors= 1.2
Median age at diagnosis=
Mean age at follow up:Survivors= 63.4 (4.1) monthsGP controls= 69.3 (5.4) monthsHospital controls=
Severe disability:Survivors= 9 (5%)GP controls= 0Hospital controls= 5 (2%)
Moderate disability:Survivors= 30 (18%)
This study was done in the UK and funding was received from the Meningitis Research Foundation.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Wales in 1996-7 who had had neonatal meningitis.
109 GP controls matched for sex and age
191 hospital controls matched for gestational age, birthweight, sex and age
10.6 days 63.4 (5.3) months GP controls= 2 (2%)Hospital controls= 9 (5%)
Mild disability:Survivors= 43 (26%)GP controls= 29 (27%)Hospital controls= 57 (30%)
No disability:Survivors= 84 (51%)GP controls= 87 (71%)Hospital controls= 120 (63%)
Severe/moderate disability:Survivors= 23.5%GP controls= 0Statistically significant difference between survivors and GP controls (OR 16.4, 95% CI 4.1-142.7, p<0.0001) or survivors and hospital controls (OR 3.9, 95% CI 2.0-8.1, p<0.0001)
A Statement of Special Educational Needs was significantly more common among Index cases than either GP controls (OR 4.9, 95% CI 1.1-45.4, p<0.05)
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
or hospital controls (OR 3.4, 95% CI 1.1-12.4, p<0.05).
Cerebral palsy:Survivors= 15 (9%)Hospital controls= 5 (3%)Survivors vs. hospital controls: p<0.01 OR 3.7 (95% CI 1.2-13.3) GP controls= 0
Hydrocephalus:Survivors= 14 (8%)GP controls= 0Hospital controls= 5 (3%)p<0.002 OR 8.7, 95% CI 1.9-79.7
No children were blind.
Squint:Survivors= 19 (11%)Hospital controls= 12 (6%)GP controls= 5 (5%)p>0.05
Behaviour problems:Survivors= 63/166 (38%)Hospital controls= 56/191 (27%)GP controls= 18/109 (17%)
Epilepsy:
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Survivors= 4 (2%)GP controls= 0Hospital controls= 3 (2%)
Sensorineural hearing loss:Survivors= 5 (3%)GP controls= 0Hospital controls= 2 (1%)
Conductive hearing loss:Survivors= 22 (13%)GP controls= 9 (8%)Hospital controls= 14 (7%)
Group B Streptococcus (n= 41):No disability= 16 (39%)Mild disability= 11 (27%)Moderate disability= 12 (29%)Severe disability= 2 (5%)
E. coli and other gram negative bacilli (n= 20):No disability= 10 (50%)Mild disability= 4 (20%)Moderate disability= 5 (25%)Severe disability= 1 (5%)
Berg et al., 2002 175 Retrospective cohort study
Aim: to investigate whether children
N= 304 survivors with
Males:Survivors= 156 (51%)
Gross motor function questionnaire: ability
Median age when questionnaire
Other infections:Survivors= 33 (10%)
*although there were no significant
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
EL= 2+with bacterial meningitis without obvious neurological sequelae at discharge from hospital have sequelae several years later.
sibling controls
304 sibling controls without neurological impairment
Controls= 155 (51%)
Controls excluded if have Downs syndrome (n=1) or severe mental retardation (n= 1)
H. influenzae= 258 (85%)S.pneumoniae= 28 (9%)N. meningitidis= 18 (6%)
to run, jump, ride a bike etc in comparison with other children the same age.
Fine motor function questionnaire: ability to cut with scissors, button and handle small objects
Conners Parent Questionnaire: measures attention, activity level, impulsiveness and mood
An additional questionnaire regarding symptoms of inattention and ADHD as defined in the Diagnostic and Statistical Manual of Mental Disorders 4th Edition.
completed:Survivors= 9.6 years (6.5-14.3 years)Controls= 11.0 years (6.1-15.3 years)
Controls= 10 (3%)P<0.001
Dizziness:Survivors= 9 (3%)Controls= 4 (1%)P=0.27
Balance impairment:Survivors= 19 (6%)Controls= 2 (1%)P<0.001
Headache:Survivors= 75 (25%)Controls= 40 (13%)P<0.001
Impaired vision:Survivors= 47 (15%)Controls= 49 (16%)P=0.90
Sensitivity to light:Survivors= 33 (11%)Controls= 8 (3%)P<0.001
Speech difficulties:Survivors= 20 (7%)Controls= 16 (5%)P=0.60
Hearing impairment
differences between survivors and controls on the diagnosis of inattention or hyperactivity-impulsiveness, there were significant differences between the groups in the number of symptoms of each diagnosis.
**= score of 1 or 2 is worse than peers, score of 3 is better than peers, 4 or 5 is better than peers, as rated by parents.
This study was done in Sweden and was supported by the fund for Research and Development, Bohus County Council, the Faculty of Medicine, Goteborg, Goteborg University and the Goteborg Medical Society.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
(reported by parents):Survivors= 60 (20%)Controls= 5 (2%)P<0.001
Conners Parent Questionnaire:Survivors= 48 (16%)Controls= 18 (6%)P<0.001
Inattention according to DSM-IV:Survivors= 11 (4%)Controls= 5 (2%)P=0.21
Hyperactivity-impulsiveness according to DSM-IV:Survivors= 11 (4%)Controls= 4 (1%)P=0.092
Gross motor function**:Score 1: Survivors= 6 (2%)Controls= 1 (<1%)
Score 2:Survivors= 21 (7%)Controls= 12 (4%)
Score 3:
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Survivors= 180 (59%)Controls= 181 (60%)
Score 4:Survivors= 73 (24%)Controls= 70 (23%)
Score 5:Survivors= 24 (8%)Controls= 40 (13%)
Comparison between survivors and controls:Z= -3.15P<0.01
Fine motor function**:Score 1:Survivors= 2 (1%)Controls= 1 (<1%)
Score 2:Survivors= 20 (7%)Controls= 7 (2%)
Score 3:Survivors= 195 (64%)Controls= 210 (69%)
Score 4:Survivors= 55 (18%)Controls= 57 (19%)
Score 5:
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Survivors= 32 (11%)Controls= 29 (10%)
Comparison between survivors and controls:Z= -1.19P= 0.23
Differences between survivors and controls for number of individual symptoms*:Conners Parent Questionnaire:Z= -5.84P<0.0001
Inattention:Z= -2.23P<0.05
Hyperactivity-impulsiveness:Z= -3.23P<0.01
Koomen et al., 2005 165
Cohort study Aim: to describe health related
182 non-Hib meningitis
Mean age at infection= 2.4 years (SD 1.8, range 0.1-
Child health questionnaire (CHQ-
Physical functioning:Survivors= 97.9 (SD 14.4)
Effect size: Between 0.2 and 0.49 is small,
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
EL= 2+ quality of life of survivors of meningitis and to examine the association between academic and/or behavioural limitations and health related quality of life.
survivors
353 controls representative of the general Dutch school-age population
9.5 years)
School age children who had had meningitis 5-10 years earlier without severe sequelae.
Causative organisms included: Neisseria meningitidis (78%), Streptococcus pneumoniae (16.2%), Streptococcus agalactiae (3.4%), Escherichia coli (1.8%) or Listeria monocytogenes (0.6%).
PF50): parent completed paediatric quality of life measure. Measures: physical functioning, role functioning emotional/behaviour, role functioning physical, bodily pain, general behaviour, mental health, self esteem, general health perceptions, parental impact emotional, parental impact time, family activities and family cohesion.Health utilities index mark 2 (HUI2):Parent questionnaire obtained for each child. Measures: sensation, mobility, emotion, cognition, pain, self-care and an overall health score made from all of these.
Controls= 99.1 (SD 4.3)Effect size= 0.13P= 0.06
Role functioning: emot/beh:Survivors= 96.7 (SD 18.5)Controls= 97.9 (SD 7.2)Effect size= 0.10P= 0.17
Role functioning: physical:Survivors= 95.9 (SD 30.6)Controls= 95.8 (SD 15.6)Effect size= 0P= 0.89
Bodily pain:Survivors= 84.3 (SD 39.5)Controls= 85.7 (SD 17.2)Effect size= 0.05P=0.47
General behaviour:Survivors= 76.3 (SD 29.4)Controls= 78.5 (SD 13.1)Effect size= 0.11P=0.09
Mental health:Survivors= 79.4 (SD 24.2)Controls= 81.4 (SD 12.1)Effect size= 0.12P=0.09
between 0.5 and 0.79 is moderate, and 0.8 or larger is a large effect size
No confidence intervals were reported by the authors of the study.
This study was done in the Netherlands. No sources of funding were cited.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Self esteem:Survivors= 75.6 (SD 22.1)Controls= 79.2 (SD 11.0)Effect size= 0.23P=0.001
General health perceptions:Survivors= 70.0 (SD 29.8)Controls= 82.9 (SD 13.4)Effect size= 0.63P<0.001
Parental impact: emot:Survivors= 82.8 (SD 32.9)Controls= 86.3 (SD 15.2)Effect size= 0.15P=0.02
Parental impact: time:Survivors= 94.0 (SD 22.6)Controls= 94.0 (SD 13.0)Effect size= 0P=0.98
Family activities:Survivors= 90.2 (SD 23.2)Controls= 91.5 (SD 11.9)Effect size= 0.08P=0.22
Family cohesion:Survivors= 70.0 (SD 34.1)Controls= 72.2 (SD 19.4)Effect size= 0.09
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
P= 0.18
Physical summary score:Survivors= 54.2 (SD 13.6)Controls= 56.4 (SD 5.7)Effect size= 0.24 P<0.001
Psychosocial summary score:Survivors= 52.1 (SD 12.5)Controls= 53.2 (SD 6.4)Effect size= 0.12P=0.05
Sensation:Survivors= 0.92 (SD 0.25)Controls= 0.96 (SD 0.10)Effect size= 0.24P= 0.001
Mobility:Survivors= 1 (SD 0.04)Controls= 1 (SD 0.02)Effect size= 0P= 0.14
Emotion:Survivors= 0.95 (SD 0.20)Controls= 0.91 (SD 0.11)Effect size= -0.27P < 0.001
Cognition:
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Survivors= 0.96 (SD 0.13)Controls= 0.97 (SD 0.06)Effect size= 0.11P=0.05
Self-care:Survivors= 1 (SD 0.04)Controls= 0.99 (SD 0.11)Effect size= -0.11P=0.09
Pain:Survivors= 0.99* (SD 0.04)Controls= 0.99* (SD 0.03)Effect size= 0*P=0.02
HU12 overall score:Survivors= 0.93 (SD 0.18)Controls= 0.92 (SD 0.08)Effect size= -0.03P=0.34
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
* Too few significant figures reported to determine the direction of effect
Richardson et al., 1997176
Cohort study
EL= 2+
Aim: to investigate whether otitis media with effusion (OME) is the mechanism of reversible hearing loss after meningitis
N= 124 children with meningitis
124 age and sex matched controls
92 children (74%) had meningococcal meningitis
Conductive hearing loss (auditory brainstem responses threshold of >30 dB HL) at discharge= 5 survivors (4%)
Acute otitis media:Survivors= 0Controls= 0
Prevalence of middle ear effusion:Survivors= 7.2%Controls= 11.3%
RR of OME in survivors= 0.64 (95% CI 0.29 to 1.42)
This study was done in the UK.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Regained hearing after 9 months:Survivors= 3Controls= NA
Zalesska-Krecicka et al., 1999 212
Case series
EL= 3
Aim: objective assessment of hearing loss with the use of brainstem evoked response audiometry (BERA) in children with the history of purulent meningitis.
N= 43 survivors of purulent meningitis
Age: 4 months to 12 years (mean age= 4.4 years)
Excluded from the final analysis if there were other factors that could have led to hypoacusia, such as congenital rubella and premature birth. (excluded n= 12)
Brainstem evoked response audiometry was performed
Mean time interval from onset of disease to assessment= 30 months
Analysis of 31 children with meningitis as the only known risk factor of hearing damage:
Normal responses= 18 (58%)Hypoacusia= 9 (29%)Prolonged latencies= 4 (13%)
This study was done in Poland. No sources of funding are cited.
Taylor et al., 1996 181
Case series
EL=3
Aim: to describe the incidence of acute-phase neurologic complications in a sample of 126 children with hib meningitis.
N= 126 Male= 63 (50%)
Mean age at testing= 9.7 years (SD 2.3, 6-14 years)
Included: single episode of culture-documented Hib, age between 6 and 14 years at the time of testing, absence of any history of other neurologic diseases, schooling primarily in English for at least 1 year prior to assessment, residence within commuting distance of the treating hospital.
Medical records and some history given by parents
Mean duration since hospitalisation: 8.2 years (SD 2.5, 1-13 years).
At least one acute phase complication= 53 (42%)
34 of these cases resolved within 6 weeks of discharge.
Unresolved cases:Seizures= 3 (2%)Hearing loss= 15 (12%)Hemiparesis= 2 (2%)Cranial nerve deficit= 1 (<1%)
Low IQ= 8/119 (6.7%)
Academic deficits:Reading= 21/118 (17.8%)
This study was done in the US and was supporte by funding from a NIH Grant and MR Training Grant.
Bibliographic information
Study type & evidence
Study details Number of patients
Characteristics of studies/patients
Data collection methods
Follow up & outcome
Results & effect size Reviewer comment
Spelling= 22/118 (18.6%)Arithmetic= 24/118 (20.3%)
Grade repetition= 18/120 (15%)
Behaviour problem at home= 27/118 (22.9%)
Behaviour problem at school= 23/105 (21.9%)