Elsevier

The Lancet Neurology

Volume 11, Issue 9, September 2012, Pages 774-783
The Lancet Neurology

Articles
Outcomes of invasive meningococcal serogroup B disease in children and adolescents (MOSAIC): a case-control study

https://doi.org/10.1016/S1474-4422(12)70180-1Get rights and content

Summary

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.

Findings

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.

Interpretation

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.

Funding

Meningitis Trust and Big Lottery Fund, UK.

Introduction

Every year, 500 000 cases of invasive meningococcal disease causing 50 000 deaths are reported worldwide.1, 2 In countries using serogroup C meningococcal polysaccharide-protein conjugate vaccines, about 90% of invasive meningococcal disease is now caused by serogroup B Neisseria meningitidis.1, 2 The incidence of invasive meningococcal disease is now 0·35 per 100 000 in the USA, is 2·0 per 100 000 in the UK, and ranges from 0·30 to 8·90 cases per 100 000 population in most of Europe and the Americas.1, 2

Serogroup B meningococcal disease is now the commonest cause of life-threatening septicaemia and meningitis in children in many high-income and middle-income countries. It largely affects children younger than 5 years, with a case-fatality rate of about 5%.3 Effective vaccines for serogroup B meningococcal infection have proved difficult to develop. New vaccines have recently undergone phase 3 trials,4, 5 and are currently being assessed for introduction by national agencies in many countries. Analyses are hampered by the scarcity of robust data on the burden of deficit after serogroup B meningococcal disease, which is likely to differ from that of serogroup C disease.2 We undertook a case-control study (Meningococcal outcomes in adolescents and in children, MOSAIC) to examine the disease burden in survivors of serogroup B meningococcal disease in childhood.

Section snippets

Study design and participants

We undertook a population-based case-control study, with children with meningococcal disease recruited from the UK Meningococcal Reference Unit (MRU), which identifies more than 92% of meningococcal disease reported in England, UK.6 Eligible cases were survivors with serogroup B meningococcal disease proven by culture or PCR from any normally sterile site, notified from a hospital in one of five adjacent English regions (East Midlands, West Midlands, East of England, Southeast of England, and

Results

Of 537 participants with previous serogroup B meningococcal disease who were available for recruitment, 246 (46%) were recruited, of which one withdrew during assessment (figure). The recruited participants were highly similar to unrecruited individuals in terms of age at disease (p=0·9), sex (p=0·4), and severity of disease (median length of hospital stay was 5 days [IQR 4] in both groups; p=0·4; data not shown). Non-recruited children with serogroup B meningococcal disease were more likely to

Discussion

We present comprehensive data about outcomes of survival of serogroup B meningococcal disease in childhood. Survivors were significantly more likely than matched controls to have a range of objectively measured deficits across various domains. About a tenth had major sequelae resulting in major physical or neurological disability, including major amputations, very low IQ, seizures, moderately severe bilateral hearing loss, and major hearing loss. Additionally, just over a third of survivors had

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