title: Outcomes of invasive meningococcal serogroup B disease in children and adolescents (MOSAIC): a case-control study.
abstract: BACKGROUND
  Serogroup B meningococcal disease is the commonest cause of meningitis and septicaemia in high-income countries. Assessment of new serogroup B meningococcal vaccines is hampered by a scarcity of data on the burden of disease in survivors. We aimed to estimate the disease burden in children having survived serogroup B meningococcal disease.
  
  
  METHODS
  In this case-control study, we recruited children from the UK National Meningococcal Registry between May, 2008, and September, 2010. Eligible children were survivors who had had serogroup B meningococcal disease confirmed by culture or PCR and were aged 1 month to 13 years at disease. Age-matched and sex-matched controls were recruited through the family doctor of the children who had the meningococcal disease. Physical, psychological, neurocognitive, and educational outcomes were assessed through a standardised interview with validated instruments. We did matched analyses using generalised estimating equations (GEE). Researchers were masked to the children's serogroup B meningococcal status.
  
  
  RESULTS
  Of the 537 children who had serogroup B meningococcal disease and were available for recruitment, 245 were assessed. 328 controls were also recruited; 221 controls were matched with a case and 107 were additional unmatched controls. The mean age was 6·5 (SD 2·8) years in children with serogroup B meningococcal disease and 6·9 (2·9) in controls. In the full sample, children who had serogroup B meningococcal disease were more likely than controls to have bilateral sensorineural hearing loss of 40 dB or more (unmatched 11 [5%] of 232 children with meningococcal disease vs three [<1%] of 318 controls; matched odds ratio [OR] 4·8, 95% CI 1·3 to 17·4, p=0·02), lower full-scale IQ (matched mean 99·5 for children with meningococcal disease and 107·2 for controls; matched coefficient -7·6, 95% CI -9·9 to -5·4, p<0·0001), and psychological disorders (61 [26%] of 235 children with meningococcal disease vs 33 (10%) of 322 controls; matched full sample OR 2·6, 1·6 to 4·2, p<0·0001). Disabling amputations were noted in three (1%) of 239 children who had serogroup B meningococcal disease compared with none of the 322 controls. Children with meningococcal disease were also more likely to have deficits in executive function and multiple aspects of memory. Deficits were identified in 87 (36%) of 244 children with serogroup B meningococcal disease and 49 (15%) of 328 controls (matched OR 2·7, 1·8 to 4·1, p<0·0001). Major disabling deficits were identified in 21 (9%) of 244 children with meningococcal disease compared with six (2%) of 328 controls (matched OR 5·0, 2·0 to 12·6, p=0·001). No significant differences were noted in attentional function or post-traumatic stress disorder between children with serogroup B meningococcal disease and controls.
  
  
  CONCLUSIONS
  Most children survive serogroup B meningococcal disease without major sequelae. However, about a tenth have major disabling deficits and more than a third have one or more deficits in physical, cognitive, and psychological functioning, with the additional burden of memory deficits and executive function problems. These findings should help to guide assessments of new vaccines and suggest that all survivors of serogroup B meningococcal disease should be screened for psychological disorders and cognitive deficits in addition to hearing loss.
  
  
  BACKGROUND
  Meningitis Trust and Big Lottery Fund, UK.
authors.affiliation: University College London Institute of Child Health, London, UK. r.viner@ucl.ac.uk
authors.forename: Russell M
authors.initials: RM
authors.lastname: Viner
authors.forename: Robert
authors.initials: R
authors.lastname: Booy
authors.forename: Helen
authors.initials: H
authors.lastname: Johnson
authors.forename: W John
authors.initials: WJ
authors.lastname: Edmunds
authors.forename: Lee
authors.initials: L
authors.lastname: Hudson
authors.forename: Helen
authors.initials: H
authors.lastname: Bedford
authors.forename: Ed
authors.initials: E
authors.lastname: Kaczmarski
authors.forename: Kaukab
authors.initials: K
authors.lastname: Rajput
authors.forename: Mary
authors.initials: M
authors.lastname: Ramsay
authors.forename: Deborah
authors.initials: D
authors.lastname: Christie
mesh_terms: D000293:Adolescent; D000367:Age Factors; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D004185:Disability Evaluation; D056344:Executive Function; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007360:Intelligence; D008297:Male; D008568:Memory / Q000502:physiology; D008585:Meningitis, Meningococcal / Q000150:complications* / Q000209:etiology* / Q000821:virology; D008589:Meningococcal Infections / Q000150:complications* / Q000175:diagnosis*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies