B Part of It protocol: a cluster randomised controlled trial to assess the impact of 4CMenB vaccine on pharyngeal carriage ofNeisseria meningitidisin adolescents

Abstract

IntroductionSouth Australia (SA) has the highest notification rate of invasive meningococcal disease in Australia with the majority of cases due to serogroup B. Neisseria meningitidis is carried in the pharynx, with adolescents having the highest rates of carriage. A vaccine designed to offer protection against serogroup B (4CMenB) is licensed in Australia. The SA MenB vaccine carriage study aims to assess the impact of 4CMenB on carriage of N. meningitidis in adolescents.Methods and analysisThis is a parallel cluster randomised controlled trial enrolling year 10, 11 and 12 school students (approximately 16–18 years of age) throughout SA, in metropolitan and rural/remote areas. Schools are randomised to intervention (4CMenB vaccination at baseline) or control (4CMenB vaccination at study completion) with randomisation stratified by school size and socioeconomic status, as measured by the Index of Community Socio-Educational Advantage (Australian Curriculum). Oropharyngeal swabs will be taken from all students at visit 1, and 12 months later from year 11 and 12 students. Students unvaccinated in 2017 will receive vaccine at the 12-month follow-up. Carriage prevalence of N. meningitidis will be determined by PCR at baseline and 12 months following 4CMenB vaccination and compared with carriage prevalence at 12 months in unvaccinated students. A questionnaire will be completed at baseline and 12 months to assess risk factors associated with carriage. The primary outcome of carriage prevalence of disease causing N. meningitidis at 12 months will be compared between groups using logistic regression, with generalised estimating equations used to account for clustering at the school level. The difference in carriage prevalence between groups will be expressed as an OR with 95% CI.Ethics and disseminationThe study was approved by the Women’s and Children’s Health Network Human Research Ethics Committee (WCHN HREC). The protocol, informed consent forms, recruitment materials, social media and all participant materials have been reviewed and approved by the WCHN HREC and updated on ClinicalTrials.gov. Results will be published in international peer-reviewed journals and presented at national and international conferences. The study findings will be provided in public forums and to study participants and participating schools.Trial registration numberACTRN12617000079347. NCT03089086; Pre-results.

B Part of It study: a longitudinal study to assess carriage of Neisseria meningitidis in first year university students in South Australia

“…Our direct swab PCR method in the pilot study mirrored study processes for a large RCT. 9 In a UK study of over 2899 sample pairs, the sensitivity and specificity of direct swab PorA PCR compared to plating and then PCR of the isolate were 0.66 and 0.99 respectively. 13 The ability to grow isolates on selective agar were similar at 6 and 16 hours, however there was significant loss (46%) of isolates in samples frozen at 48 hours after collection.…”

“…During 2017 and 2018, all year 10, 11, and 12 students in South Australia were offered 4CMenB vaccination as part of a cluster randomised trial to assess the impact of the 4CMenB vaccine on carriage. 9 Understanding the prevalence of N. meningitidis and risk factors for pharyngeal carriage are important precursors to the introduction of meningococcal vaccine programs. 4 Prevalence of carriage increases in adolescents, peaking at around 19 years of age.…”

“…Over 34,000 students are to be immunised through their school immunisation providers, as well as have oropharyngeal swabs collected over a 3-month period. 9 Due to vast transport distances in the RCT (up to 1800km), we needed to establish the loss of isolate yield with different times to sample freezing.…”

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

“…There are limited safety and effectiveness data on adolescent 4CMenB vaccination population programs. SA is the first place globally to implement such an extensive program and already has the largest cohort of adolescents vaccinated with 4CMenB through the SA MenB vaccine herd immunity study . Over 56 000 doses of 4CMenB were administered to adolescents from 2017 to 2018, with no safety signals identified …”

Economic evaluation of meningococcal vaccines: considerations for the future

“…Regarding meningococcal vaccination, additional studies will be required to discern whether herd effects play a role in the effectiveness of MenB vaccination programs, as has been demonstrated for vaccines targeting other serogroups [31][32][33][34]. A cluster-randomized study is currently under way in Australia to investigate MenB-4C (Bexsero ® , 4CMenB; GlaxoSmithKline Vaccines, Srl, Siena, Italy) for effects on carriage, and by extension, transmission [35]. Results from this study coupled with an adolescent study under way in the United Kingdom [36] may elucidate whether adolescent MenB vaccination programs could produce a herd effect.…”