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Integrated Genomic Surveillance of Invasive Meningococcal Disease in Scotland 2015-2022, Following the Introduction of Routine Infant MenB Vaccination

27 Pages Posted: 4 Aug 2022

See all articles by Charlene MC Rodrigues

Charlene MC Rodrigues

University of Oxford - Department of Zoology

Laura MacDonald

Government of the United Kingdom - Public Health Scotland

Roisin Ure

Government of the United Kingdom - Bacterial Respiratory Infection Service

Martin CJ Maiden

University of Oxford - Department of Zoology

Andrew Smith

Government of the United Kingdom - Bacterial Respiratory Infection Service

J. Claire Cameron

Government of the United Kingdom - Public Health Scotland

More...

Abstract

Background: In September 2015, the UK was first to introduce protein-based meningococcal vaccine 4CMenB (‘Bexsero®’) into a national infant immunisation schedule. Following successful control of serogroup C, Y, and W invasive meningococcal disease (IMD) by conjugate polysaccharide vaccines, Bexsero® targeted serogroup B IMD, the most prevalent meningococcal serogroup in 2015. As Bexsero® contains four variable subcapsular proteins, non-homologous meningococcal variants potentially evade Bexsero®-induced protection. Using genomic, microbiological, and epidemiological data we investigated IMD cases in children <5 years of age following Bexsero® implementation.

Methods: IMD cases reported in Scotland between 1st September 2015-30th June 2022 were identified. Patient demographics and vaccination status retrieved, respective meningococcal genotypic antigenic variants determined and used to assess potential vaccine coverage in fully vaccinated, partially vaccinated, and unvaccinated children.

Findings: Eighty-two serogroup B IMD cases occurred in children <5 years, 34/82 of whom received ≥1 Bexsero® dose. Amongst fully vaccinated children with IMD (19/34): none were infected with meningococci deduced to be vaccine-preventable; 2/19 were infected with non-preventable meningococci; and for 15/19 deductions were not possible. Of the 15/34 partially vaccinated children, 7/15 were infected by vaccine-preventable meningococci and 2/15 infected with non-preventable meningococci. There were 48 IMD cases in unvaccinated children, 40/48 were ineligible for vaccination, but 20/48 had vaccine-preventable IMD.

Interpretation: In fully vaccinated children, these data suggest high Bexsero® efficacy for preventing disease with meningococci deduced to be sensitive to vaccine-induced immune responses. Further, they suggest that a single Bexsero® dose provides poor protection against vaccine-preventable meningococci. Despite high Bexsero® uptake, 33% of vaccine-eligible children with IMD had missed vaccine doses, emphasising the importance of vaccination according to schedule.  We conclude that rapid national epidemiological, microbiological, and genomic, data can assess vaccine effectiveness post-introduction.

Funding Information: This work was part of the NHS clinical care pathways for meningococcal disease in Scotland, UK, Wellcome Trust grant Thrasher Fund grant 15512 to CMCR.

Declaration of Interests: All authors having no conflicts to declare.

Ethics Approval Statement: The Public Health Scotland Order 2019 in Article 9(2)(i) places an obligation on Public Health Scotland to engage in the control of spread of infectious diseases in accordance with section 43 of the National Health Service (Scotland) Act 1978. In accordance with Sections 15, 16(5), and 21(2) of the Public Health etc. (Scotland) Act 2008, PHS is obliged to process data in relation to notifiable diseases, health risk states of patients, notifiable organisms, and carrying out public health investigations, and as such, individual patient consent is not required.

Keywords: Vaccination, Bexsero, 4CMenB, breakthrough cases, genomics, WGS, MenDeVAR, BAST, meningococcal infections

Suggested Citation

Rodrigues, Charlene MC and MacDonald, Laura and Ure, Roisin and Maiden, Martin CJ and Smith, Andrew and Cameron, J. Claire, Integrated Genomic Surveillance of Invasive Meningococcal Disease in Scotland 2015-2022, Following the Introduction of Routine Infant MenB Vaccination. Available at SSRN: https://ssrn.com/abstract=4178039 or http://dx.doi.org/10.2139/ssrn.4178039

Charlene MC Rodrigues

University of Oxford - Department of Zoology ( email )

Laura MacDonald

Government of the United Kingdom - Public Health Scotland ( email )

United States

Roisin Ure

Government of the United Kingdom - Bacterial Respiratory Infection Service ( email )

Martin CJ Maiden (Contact Author)

University of Oxford - Department of Zoology ( email )

Andrew Smith

Government of the United Kingdom - Bacterial Respiratory Infection Service ( email )

J. Claire Cameron

Government of the United Kingdom - Public Health Scotland ( email )

United States

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