J. Claire Cameron

Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity

BACKGROUND In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. METHODS Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 samples, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. RESULTS A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06); these meningococci also exhibited high rates of capsule expression. CONCLUSIONS The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.

Social Behavior and Meningococcal Carriage in British Teenagers

Understanding predisposing factors for meningococcal carriage may identify targets for public health interventions. Before mass vaccination with meningococcal group C conjugate vaccine began in autumn 1999, we took pharyngeal swabs from ≈14,000 UK teenagers and collected information on potential risk factors. Neisseria meningitidis was cultured from 2,319 (16.7%) of 13,919 swabs. In multivariable analysis, attendance at pubs/clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with increased risk for meningococcal carriage (p<0.001). Carriage in those with none of these risk factors was 7.8%, compared to 32.8% in those with all 3. Passive smoking was also linked to higher risk for carriage, but age, sex, social deprivation, home crowding, or school characteristics had little or no effect. Social behavior, rather than age or sex, can explain the higher frequency of meningococcal carriage among teenagers. A ban on smoking in public places may reduce risk for transmission.

Changes in Serogroup and Genotype Prevalence Among Carried Meningococci in the United Kingdom During Vaccine Implementation

Background. Herd immunity is important in the effectiveness of conjugate polysaccharide vaccines against encapsulated bacteria. A large multicenter study investigated the effect of meningococcal serogroup C conjugate vaccine introduction on the meningococcal population. Methods. Carried meningococci in individuals aged 15–19 years attending education establishments were investigated before and for 2 years after vaccine introduction. Isolates were characterized by multilocus sequence typing, serogroup, and capsular region genotype and changes in phenotypes and genotypes assessed. Results. A total of 8462 meningococci were isolated from 47 765 participants (17.7%). Serogroup prevalence was similar over the 3 years, except for decreases of 80% for serogroup C and 40% for serogroup 29E. Clonal complexes were associated with particular serogroups and their relative proportions fluctuated, with 12 statistically significant changes (6 up, 6 down). The reduction of ST-11 complex serogroup C meningococci was probably due to vaccine introduction. Reasons for a decrease in serogroup 29E ST-254 meningococci (from 1.8% to 0.7%) and an increase in serogroup B ST-213 complex meningococci (from 6.7% to 10.6%) were less clear. Conclusions. Natural fluctuations in carried meningococcal genotypes and phenotypes a can be affected by the use of conjugate vaccines, and not all of these changes are anticipatable in advance of vaccine introduction.

Intussusception incidence among infants in the UK and Republic of Ireland: A pre-rotavirus vaccine prospective surveillance study

Highlights • The pre-rotavirus vaccine incidence of intussusception among UK and Irish infants was 24.8 and 24.2/100,000 live births.• The highest incidence (50.3/100,000 live births) occurred in the fifth month of life (for England).• A seasonal trend in intussusception was observed with the incidence significantly increased during winter and spring.• Baseline rates will inform rotavirus vaccine-safety policy by enabling comparison with post-introduction incidence.

Risk of hospitalisation with fever following MenB vaccination: self-controlled case series analysis

Objective To investigate a possible association between fever admissions and 4 component Meningococcal B (4CMenB). Design 4CMenB is given at 8 and 16 weeks in the first year of life. Self-controlled case series using linked routinely collected healthcare data, where the risk period was the 3 days immediately following receipt of a vaccine dose. Patients Children aged under 1 year in Scotland preintroduction and postintroduction of 4CMenB vaccine (pre—September 2014 to August 2015 and post—September 2015 to June 2016). Main outcome measures Hospitalisations for fever attributable to 4CMenB vaccine. Results The postintroduction model showed an increased risk in the 3 days after dose 1 (relative incidence (RI), 10.78; 95% CI: 8.31 to 14.00) and dose 3 (RI, 9.80; 95% CI: 7.10 to 13.62), with a smaller increased risk after dose 2 (RI, 2.20; 95% CI: 1.27 to 3.82). The magnitude of these effects was greater than in the preintroduction model. The attributable fractions were 90.7%, 54.8% and 89.7%, equating to 162, 14 and 84 vaccine attributable cases per 100 000 doses, respectively. This is equivalent to 102 extra hospitalisations in Scotland annually, based on a birth cohort of 55 100 and extrapolated to 1430 across the UK based on a birth cohort of 777 165. Conclusion There is an increased risk of hospital admission with fever within 3 days of the routine childhood immunisations at 8 and 16 weeks following introduction of 4CMenB vaccine. The results indicate that further understanding of the current use of prophylactic paracetamol is needed. Communication to parents and health professionals may also need to be re-examined, and guidance on the use of prophylactic paracetamol reinforced.

National hospital data for intussusception: Data linkage and retrospective analysis to assess quality and use in vaccine safety surveillance

OBJECTIVES To assess the quality of national Hospital Episode Statistics (HES) data for intussusception, and evaluate this routinely collected database for rotavirus vaccine safety surveillance by estimating pre-vaccination trends in intussusception hospitalisation. METHODS Data linkage was performed between HES and prospective intussusception data from the British Paediatric Surveillance Unit (BPSU), followed by capture-recapture analysis to verify HES data quality. Inclusion criteria were infants aged less than 12 months and admitted for intussusception to National Health Service (NHS) hospitals in England from March 2008 to March 2009. To estimate pre-vaccination incidence rates of intussusception, we performed a retrospective analysis of HES data. Infants aged less than 12 months and admitted for intussusception to NHS hospitals in England between 1995 and 2009 were included. RESULTS Data linkage between 254 cases of intussusception identified in HES data and 190 cases reported via the BPSU resulted in 163 cases common to both data sources. Of remaining 91 cases in HES, 37 had confirmed intussusception. HES data accuracy was 78.7% (200 confirmed/254 cases) and completeness for intussusception was 86% (163 matched/190 BPSU cases) compared to 81.5% (163 matched/200 HES cases) for BPSU. A total of 233 (95% CI: 227.4 to 238.8) intussusception cases were estimated for the infant population (2008 to 2009). For retrospective analysis, of 6462 intussusception admissions in HES data (1995 to 2009), 1594 (24.7%) were duplicate admissions. A declining trend in intussusception incidence was observed in the infant population, from 86/100,000 in 1997 to 34/100,000 in 2009 (60% reduction, P<0.001). Cosinor modelling showed an excess of cases among infants in winter and spring (P<0.001, n=4957, 1995 to 2009). CONCLUSION National hospital data capture the majority of admissions for intussusception and should be considered for the post-implementation surveillance of rotavirus vaccine safety in England.

Genomic Surveillance of 4CMenB Vaccine Antigenic Variants among Disease-Causing Neisseria meningitidis Isolates, United Kingdom, 2010-2016.

In September 2015, 4CMenB meningococcal vaccine was introduced into the United Kingdom infant immunization program without phase 3 trial information. Understanding the effect of this program requires enhanced surveillance of invasive meningococcal disease (IMD) Neisseria meningitidis isolates and comparison with prevaccination isolates. Bexsero Antigen Sequence Types (BASTs) were used to analyze whole-genome sequences of 3,073 prevaccine IMD N. meningitidis isolates obtained during 2010−2016. Isolates exhibited 803 BASTs among 31 clonal complexes. Frequencies of antigen peptide variants were factor H binding protein 1, 13.4%; Neisserial heparin-binding antigen 2, 13.8%; Neisseria adhesin A 8, 0.8%; and Porin A-VR2:P1.4,10.9%. In 2015−16, serogroup B isolates showed the highest proportion (35.7%) of exact matches to >1 Bexsero components. Serogroup W isolates showed the highest proportion (93.9%) of putatively cross-reactive variants of Bexsero antigens. Results highlighted the likely role of cross-reactive antigens. BAST surveillance of meningococcal whole-genome sequence data is rapid, scalable, and portable and enables international comparisons of isolates.

HPV vaccine: positive insights from universal adolescent HepB vaccination

The introduction of universal adolescent HPV vaccination in schools has a positive outlook

Public policy for meningococcal vaccination

ABSTRACT On an individual basis, meningococcal disease is consistently shown to be one of the most feared potential childhood infections. On a population level, any clustering of cases or increase in disease requires proactive health protection management, while epidemics can be devastating. It is therefore no surprise that developing protective meningococcal vaccines and effective strategies for their implementation has been a continuing public health priority for some decades.

A mixed-methods study to identify factors associated with MenACWY vaccine uptake, barriers and motivations towards vaccination among undergraduate students

Background: In response to an outbreak of severe meningococcal disease caused by serogroup W, the UK introduced the meningococcal ACWY (MenACWY) for adolescents and new university students as a control measure. Objective: To estimate MenACWY vaccine uptake and identify factors associated with uptake, barriers and motivations towards vaccination among university students. Design: Mixed methods including a cross-sectional survey, 7 interviews and 1 focus group. Setting: A Scottish university between April and May 2016. Methods: Inclusion criteria were <25 years and attending university for the first time (MenACWY eligible). All first-year undergraduates (n = 5,808) were invited to take part in the survey via email, and qualitative participants were recruited through the survey. The final sample consisted of 768 students, representing 13% (768/5,808) of the target population. Results: MenACWY uptake among the sample was 71.5% (549/768). Older students (22–24 years) were less likely than younger students (18 years) to have been vaccinated [adjusted odds ratio (aOR) = 0.21; 95% confidence interval (CI) = 0.06–0.77], and male students were less likely to be vaccinated than female students (aOR = 0.667; 95% CI = 0.45–0.96). In comparison to international students, domestic students had a significantly higher odds of vaccination (aOR = 3.89; 95% CI = 2.64–5.72). Communication barriers were most frequently identified as reasons for non-vaccination. Most vaccination occurred before starting university (76.7%, 421/549), highlighting access barriers. Meningococcal disease knowledge was low; a significant association (p < 0.001) was found between knowledge and vaccination uptake. Some participants were unaware of their vaccination history. They perceived meningococcal disease as severe, but disease risk as low. Key motivations were knowledge of the benefits of vaccines, influence of others and social responsibility. Conclusion: Students outside main UK-based, core age cohorts were under-immunised and focused efforts are needed to improve vaccination rates. Future student vaccination programmes could focus on raising awareness of the serious implications of meningococcal disease. Additional benefit may be gained from emphasising the benefits of vaccinations for society as a whole.