Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England

Stephen A. Clark; Jay Lucidarme; Georgina Angel; Aiswarya Lekshmi; Begonia Morales-Aza; Laura Willerton; Helen Campbell; Steve J. Gray; Shamez Ladhani; Mike Wade; Mary Ramsay; Julie Yates; Adam Finn; Raymond Borrow

doi:10.1038/s41598-019-46483-3

Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England

Stephen A. Clark^*, Jay Lucidarme, Georgina Angel, Aiswarya Lekshmi, Begonia Morales-Aza, Laura Willerton, Helen Campbell, Steve J. Gray, Shamez Ladhani, Mike Wade, Mary Ramsay, Julie Yates, Adam Finn, Raymond Borrow

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Between April 2016 and September 2017, four cases of group B meningococcal disease were reported among sixth-form college students in Bristol, UK. Culture and non-culture whole genome sequencing was utilised and demonstrated that the four genomes of the responsible ST-41 strains clustered closely on a sub-lineage of ST-41/44 clonal complex. The outbreak resulted in two fatalities. A distinct social group associated with one of the cases was selected for vaccination with 4CMenB and pharyngeal swabbing. In vitro culturing, multiple real-time PCR assays (sodC, ctrA and siaD_B) and a PorA PCR-sequencing assay were used to detect meningococcal colonisation and a carriage rate of 32.6% was observed. Furthermore, a high proportion of the pharyngeal swabs (78.3%) yielded a Factor H-Binding Protein (fHbp) nucleotide allele suggesting that the antigenic gene is prevalent among non-meningococcal flora, most likely Neisseria commensals. This may have implications for fHbp as a vaccine antigen should it be shown to influence bacterial colonisation.

Original language	English
Article number	9990
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-46483-3
Publication status	Published - 1 Dec 2019

Bibliographical note

Funding Information:
Non-culture whole genome sequencing services were provided by the Pathogen Genomics Unit at University College London. This publication made use of the Neisseria Multi Locus Sequence Typing website (https:// pubmlst.org/neisseria/) developed by Keith Jolley and sited at the University of Oxford (Jolley & Maiden 2010, BMC Bioinformatics, 11:595). The development of this site has been funded by the Wellcome Trust and European Union. The genomic data generated in this publication are available in the PubMLST database. This publication made use of the Meningitis Research Foundation Meningococcus Genome Library (http://www.meningitis.org/ research/genome), developed by Public Health England, the Wellcome Trust Sanger Institute and the University of Oxford as a collaboration. A project initially funded by the Meningitis Research Foundation.

Funding Information:
Competing Interests: S.A.C., J.L., A.L., L.W., S.J.G. and R.B. have performed contract research on behalf of Public Health England for GlaxoSmithKline (GSK), Pfizer and Sanofi-Pasteur. A.F. has research grants, held by the University of Bristol, funded by GSK and Pfizer. All other authors report no conflicts of interest.

Publisher Copyright:
© 2019, The Author(s).

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Clark, S. A., Lucidarme, J., Angel, G., Lekshmi, A., Morales-Aza, B., Willerton, L., Campbell, H., Gray, S. J., Ladhani, S., Wade, M., Ramsay, M., Yates, J., Finn, A., & Borrow, R. (2019). Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England. Scientific Reports, 9(1), Article 9990. https://doi.org/10.1038/s41598-019-46483-3

@article{eea3472278e64eeea72f4f50d401b6d2,

title = "Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England",

abstract = "Between April 2016 and September 2017, four cases of group B meningococcal disease were reported among sixth-form college students in Bristol, UK. Culture and non-culture whole genome sequencing was utilised and demonstrated that the four genomes of the responsible ST-41 strains clustered closely on a sub-lineage of ST-41/44 clonal complex. The outbreak resulted in two fatalities. A distinct social group associated with one of the cases was selected for vaccination with 4CMenB and pharyngeal swabbing. In vitro culturing, multiple real-time PCR assays (sodC, ctrA and siaDB) and a PorA PCR-sequencing assay were used to detect meningococcal colonisation and a carriage rate of 32.6% was observed. Furthermore, a high proportion of the pharyngeal swabs (78.3%) yielded a Factor H-Binding Protein (fHbp) nucleotide allele suggesting that the antigenic gene is prevalent among non-meningococcal flora, most likely Neisseria commensals. This may have implications for fHbp as a vaccine antigen should it be shown to influence bacterial colonisation.",

author = "Clark, {Stephen A.} and Jay Lucidarme and Georgina Angel and Aiswarya Lekshmi and Begonia Morales-Aza and Laura Willerton and Helen Campbell and Gray, {Steve J.} and Shamez Ladhani and Mike Wade and Mary Ramsay and Julie Yates and Adam Finn and Raymond Borrow",

note = "Funding Information: Non-culture whole genome sequencing services were provided by the Pathogen Genomics Unit at University College London. This publication made use of the Neisseria Multi Locus Sequence Typing website (https:// pubmlst.org/neisseria/) developed by Keith Jolley and sited at the University of Oxford (Jolley & Maiden 2010, BMC Bioinformatics, 11:595). The development of this site has been funded by the Wellcome Trust and European Union. The genomic data generated in this publication are available in the PubMLST database. This publication made use of the Meningitis Research Foundation Meningococcus Genome Library (http://www.meningitis.org/ research/genome), developed by Public Health England, the Wellcome Trust Sanger Institute and the University of Oxford as a collaboration. A project initially funded by the Meningitis Research Foundation. Funding Information: Competing Interests: S.A.C., J.L., A.L., L.W., S.J.G. and R.B. have performed contract research on behalf of Public Health England for GlaxoSmithKline (GSK), Pfizer and Sanofi-Pasteur. A.F. has research grants, held by the University of Bristol, funded by GSK and Pfizer. All other authors report no conflicts of interest. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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Clark, SA , Lucidarme, J, Angel, G, Lekshmi, A, Morales-Aza, B, Willerton, L, Campbell, H, Gray, SJ, Ladhani, S, Wade, M, Ramsay, M, Yates, J, Finn, A & Borrow, R 2019, 'Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England', Scientific Reports, vol. 9, no. 1, 9990. https://doi.org/10.1038/s41598-019-46483-3

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AU - Lucidarme, Jay

AU - Angel, Georgina

AU - Lekshmi, Aiswarya

AU - Morales-Aza, Begonia

AU - Willerton, Laura

AU - Campbell, Helen

AU - Gray, Steve J.

AU - Ladhani, Shamez

AU - Wade, Mike

AU - Ramsay, Mary

AU - Yates, Julie

AU - Finn, Adam

AU - Borrow, Raymond

N1 - Funding Information: Non-culture whole genome sequencing services were provided by the Pathogen Genomics Unit at University College London. This publication made use of the Neisseria Multi Locus Sequence Typing website (https:// pubmlst.org/neisseria/) developed by Keith Jolley and sited at the University of Oxford (Jolley & Maiden 2010, BMC Bioinformatics, 11:595). The development of this site has been funded by the Wellcome Trust and European Union. The genomic data generated in this publication are available in the PubMLST database. This publication made use of the Meningitis Research Foundation Meningococcus Genome Library (http://www.meningitis.org/ research/genome), developed by Public Health England, the Wellcome Trust Sanger Institute and the University of Oxford as a collaboration. A project initially funded by the Meningitis Research Foundation. Funding Information: Competing Interests: S.A.C., J.L., A.L., L.W., S.J.G. and R.B. have performed contract research on behalf of Public Health England for GlaxoSmithKline (GSK), Pfizer and Sanofi-Pasteur. A.F. has research grants, held by the University of Bristol, funded by GSK and Pfizer. All other authors report no conflicts of interest. Publisher Copyright: © 2019, The Author(s).

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N2 - Between April 2016 and September 2017, four cases of group B meningococcal disease were reported among sixth-form college students in Bristol, UK. Culture and non-culture whole genome sequencing was utilised and demonstrated that the four genomes of the responsible ST-41 strains clustered closely on a sub-lineage of ST-41/44 clonal complex. The outbreak resulted in two fatalities. A distinct social group associated with one of the cases was selected for vaccination with 4CMenB and pharyngeal swabbing. In vitro culturing, multiple real-time PCR assays (sodC, ctrA and siaDB) and a PorA PCR-sequencing assay were used to detect meningococcal colonisation and a carriage rate of 32.6% was observed. Furthermore, a high proportion of the pharyngeal swabs (78.3%) yielded a Factor H-Binding Protein (fHbp) nucleotide allele suggesting that the antigenic gene is prevalent among non-meningococcal flora, most likely Neisseria commensals. This may have implications for fHbp as a vaccine antigen should it be shown to influence bacterial colonisation.

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Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England

Abstract

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