First statewide meningococcal B vaccine program in infants, children and adolescents: evidence for implementation in South Australia.

Invasive meningococcal disease (IMD) is an uncommon but life-threatening infection caused by Neisseria meningitidis. Serogroups B, C, W and Y cause most IMD cases in Australia. The highest incidence occurs in children under 5 years of age. A second peak occurs in adolescents and young adults, which is also the age of highest carriage prevalence of N. meningitidis. Meningococcal serogroup B (MenB) disease predominated nationally before 2016 and has remained the predominant cause of IMD in South Australia with 82% of cases, compared with 35% in New South Wales, 35% in Queensland, 9% in Victoria, 29% in Western Australia and 36% nationally in 2016. MenB vaccination is recommended by the Australian Technical Advisory Group on Immunisation for infants up to 2 years of age and adolescents aged 15-19 years (age 15-24 years for at-risk groups, such as people living in close quarters or smokers), laboratory workers with exposure to N. meningitidis, and Aboriginal and Torres Strait Islander children from age 2 months to 19 years. Due to the epidemiology and disease burden from MenB, a meningococcal B vaccine program has been implemented in South Australia for individuals with age-specific incidence rates higher than the mean rate of 2.8/100 000 population in South Australia in the period 2000-2017, including infants, young children (< 4 years) and adolescents (15-20 years). Program evaluation of vaccine effectiveness against IMD is important. As observational evidence also suggests 4CMenB may have an impact on Neisseria gonorrhoeae with genetic homology between bacterial species, the vaccine impact on gonorrhoea will also be assessed.

Effectiveness and impact of the 4CMenB vaccine against invasive serogroup B meningococcal disease and gonorrhoea in an infant, child, and adolescent programme: an observational cohort and case-control study.

BACKGROUND: A programme of vaccination with the four-component serogroup B meningococcal (4CMenB) vaccine was introduced in South Australia for infants and children aged 0-3 years on Oct 1, 2018, and for senior school students in school years 10 and 11 (aged 15-16 years) and young adults aged 17-20 years on Feb 1, 2019. We aimed to evaluate vaccine effectiveness and impact on serogroup B meningococcal disease and gonorrhoea 2 years after implementation of the programme. METHODS: We did a cohort and case-control study among those targeted by the South Australia 4CMenB vaccination programme. We obtained disease notification data from SA Health, Government of South Australia, and vaccine coverage data from the South Australian records of the Australian Immunisation Register. Vaccine effectiveness was estimated as the reduction in the odds of infection using the screening and case-control methods. Vaccine impact was estimated as incidence rate ratios (IRRs), obtained by comparing case numbers in each year following the start of the vaccination programme with cases in the equivalent age cohort during the pre-vaccination programme years. We used Poisson or negative binomial models, as appropriate, with adjustment for changes in the incidence of serogroup B meningococcal disease in age cohorts not eligible for vaccination through the state programme. FINDINGS: 4CMenB vaccine coverage 2 years after introduction of the childhood vaccination programme was 94·9% (33 357 of 35 144 eligible individuals) for one dose, 91·4% (26 443 of 28 922) for two doses, and 79·4% (15 440 of 19 436) for three doses in infants. The one-dose (77·1%, 16 422 of 21 305) and two-dose (69·0%, 14 704 of 21 305) coverage was highest in adolescents born in 2003 (approximately year 10 students). 2 years after implementation of the childhood vaccination programme, incidence of serogroup B meningococcal disease was significantly reduced compared with before programme implementation in infants aged 12 weeks to 11 months (adjusted IRR [aIRR] 0·40 [95% CI 0·23-0·69], p=0·0011), but not in those aged 1 year (0·79 [0·16-3·87], p=0·77), 2 years (0·75 [0·18-3·14], p=0·70), or 4 years (3·00 [0·47-18·79], p=0·24). aIRRs were not calculable in those aged 3 or 5 years because of no cases occurring after programme implementation. aIRR for serogroup B meningococcal disease was 0·27 (0·06-1·16, p=0·078) in adolescents aged 15-18 years 2 years after implementation of the adolescent and young adult programme, and 1·20 (0·70-2·06, p=0·51) in those aged 19-21 years in the first year. Two-dose vaccine effectiveness against serogroup B meningococcal disease was estimated to be 94·2% (95% CI 36·6-99·5) using the screening method and 94·7% (40·3-99·5) using the case-control method in children, and 100% in adolescents and young adults (no cases reported after implementation). Estimated two-dose vaccine effectiveness against gonorrhoea in adolescents and young adults was 32·7% (8·3-50·6) based on the case-control method using age-matched individuals with chlamydia infection as controls. INTERPRETATION: 4CMenB vaccine shows sustained effectiveness against serogroup B meningococcal disease 2 years after introduction in infants and adolescents, and moderate effectiveness against gonorrhoea in adolescents. The high vaccine effectiveness against serogroup B meningococcal disease is likely due to high coverage in the target age groups and close antigenic match between the 4CMenB vaccine and the disease-associated serogroup B meningococcal strains circulating in South Australia. COVID-19-related physical distancing policies might have contributed to further declines in serogroup B meningococcal disease cases during the programme's second year. FUNDING: SA Health, Government of South Australia.

Evaluating the effectiveness of the 4CMenB vaccine against invasive meningococcal disease and gonorrhoea in an infant, child and adolescent program: protocol.

Invasive meningococcal disease causes significant morbidity and mortality worldwide, with serogroup B being one of the predominant serogroups in Australia for many years. The South Australian (SA) State Government recently funded the introduction of a 4CMenB vaccination program for infants, children and adolescents. In addition to protecting against invasive meningococcal disease, emerging evidence suggests the 4CMenB vaccine may also be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. The proposed project aims to evaluate the effectiveness of the SA 4CMenB vaccination program against invasive meningococcal disease and gonorrhoea through a combination of observational studies using routine surveillance and research data. The main methodological approaches involve an interrupted time series regression model, screening, and case-control analyses with different sets of controls to estimate vaccine impact and effectiveness. These analyses are designed to minimize potential biases inherent in all observational studies and to provide critical data on the effectiveness of the 4CMenB vaccine against two diseases of major global public health concern.