{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:52:54Z","timestamp":1753890774296,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Rapid transmission, a critical contributory factor in outbreaks of invasive meningococcal disease, requires na\u00efve populations of sufficient size and intermingling. We examined genomic variability and transmission dynamics in a student population subject to an 11-fold increase in carriage of a hypervirulent <jats:italic>Neisseria meningitidis<\/jats:italic> serogroup W ST-11 clone. Phylogenetic clusters, mutation and recombination rates were derived by bioinformatic analyses of whole-genome sequencing data. Transmission dynamics were determined by combining observed carriage rates, cluster sizes and distributions with simple SIS models. Between 9 and 15 genetically-distinct clusters were detected and associated with seven residential halls. Clusters had low mutation accumulation rates and infrequent recombination events. Modeling indicated that effective contacts decreased from 10 to 2 per day between the start and mid-point of the university term. Transmission rates fluctuated between 1 and 4% while the R(t) for carriage decreased from an initial rate of 47 to 1. Decreases in transmission values correlated with a rise in vaccine-induced immunity. Observed carriage dynamics could be mimicked by populations containing 20% of super spreaders with 2.3-fold higher effective contact rates. We conclude that spread of this hypervirulent ST-11 meningococcal clone depends on the levels of effective contacts and immunity rather than genomic variability. Additionally, we propose that super-spreaders enhance meningococcal transmission and that a 70% MenACWY immunization level is sufficient to retard, but not fully prevent, meningococcal spread in close-contact populations.<\/jats:p>","DOI":"10.3389\/fgene.2020.579411","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T06:39:25Z","timestamp":1607323165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Rapid Transmission of a Hyper-Virulent Meningococcal Clone Due to High Effective Contact Numbers and Super Spreaders"],"prefix":"10.3389","volume":"11","author":[{"given":"Jonathan C.","family":"Holmes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke R.","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil J.","family":"Oldfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.J.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher D.","family":"Bayliss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0025-5564(99)00047-4","article-title":"Comparison of deterministic and stochastic Sis and Sir models in discrete time.","volume":"163","author":"Allen","year":"2000","journal-title":"Math. Biosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1093\/bioinformatics\/btp347","article-title":"ABACAS: algorithm-based automatic contiguation of assembled sequences.","volume":"25","author":"Assefa","year":"2009","journal-title":"Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2015.20.28.21188","article-title":"Targeted vaccination of teenagers following continued rapid endemic expansion of a single meningococcal group W clone (sequence type 11 clonal complex), United Kingdom 2015.","volume":"20","author":"Campbell","year":"2015","journal-title":"Euro Surveill."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","article-title":"trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses.","volume":"25","author":"Capella-Guti\u00e9rrez","year":"2009","journal-title":"Bioinformatics"},{"key":"B5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1574-6976.2006.00052.x","article-title":"Lessons from meningococcal carriage studies.","volume":"31","author":"Caugant","year":"2007","journal-title":"FEMS Microbiol. Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"B64","DOI":"10.1016\/j.vaccine.2009.04.061","article-title":"Meningococcal carriage and disease - population biology and evolution.","volume":"27","author":"Caugant","year":"2009","journal-title":"Vaccine"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-2193","article-title":"Effectiveness and duration of protection of one dose of a meningococcal conjugate vaccine.","volume":"139","author":"Cohn","year":"2017","journal-title":"Pediatrics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"164","DOI":"10.4161\/viru.18639","article-title":"Mechanism of meningeal invasion by Neisseria meningitidis.","volume":"3","author":"Coureuil","year":"2012","journal-title":"Virulence"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1101\/gr.2289704","article-title":"Mauve: multiple alignment of conserved genomic sequence with rearrangements.","volume":"14","author":"Darling","year":"2004","journal-title":"Genome Res."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/438293a","article-title":"Dimensions of superspreading.","volume":"438","author":"Galvani","year":"2005","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.03068-19","article-title":"Localised hypermutation is the major driver of meningococcal genetic variability during persistent asymptomatic carriage.","volume":"11","author":"Green","year":"2020","journal-title":"mBio"},{"key":"B12","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1093\/infdis\/jiz275","article-title":"Potentiation of phase variation in outer-membrane proteins during spread of the hyperinvasive Neisseria meningitidis serogroup W ST-11 lineage.","volume":"220","author":"Green","year":"2019","journal-title":"J. Infect. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e420","DOI":"10.1016\/S1473-3099(17)30307-9","article-title":"The basic reproduction number (R0) of measles: a systematic review.","volume":"17","author":"Guerra","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1137\/S0036144500371907","article-title":"The mathematics of infectious diseases.","volume":"42","author":"Hethcote","year":"2000","journal-title":"SIAM Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1111\/1469-0691.12308","article-title":"Mathematical modelling and prediction in infectious disease epidemiology.","volume":"19","author":"Huppert","year":"2013","journal-title":"Clin. Microbiol. Infect."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-595","article-title":"BIGSdb: scalable analysis of bacterial genome variation at the population level.","volume":"11","author":"Jolley","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1093\/cid\/ciu881","article-title":"Increase in endemic Neisseria meningitidis capsular group W sequence Type 11 complex associated with severe invasive disease in England and Wales.","volume":"60","author":"Ladhani","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01974-14","article-title":"Emergence of a new epidemic Neisseria meningitidis serogroup A Clone in the African meningitis belt: high-resolution picture of genomic changes that mediate immune evasion.","volume":"5","author":"Lamelas","year":"2014","journal-title":"mBio"},{"key":"B19","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature04153","article-title":"Superspreading and the effect of individual variation on disease emergence.","volume":"438","author":"Lloyd-Smith","year":"2005","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2016.21.45.30395","article-title":"An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain. Scotland and Sweden. July to August 2015.","volume":"21","author":"Lucidarme","year":"2016","journal-title":"Euro Surveill."},{"key":"B21","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1086\/527401","article-title":"Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity.","volume":"197","author":"Maiden","year":"2008","journal-title":"J. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vev003","article-title":"Editor\u2019s Choice: RDP4: detection and analysis of recombination patterns in virus genomes.","volume":"1","author":"Martin","year":"2015","journal-title":"Virus Evol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.idm.2016.12.003","article-title":"Mathematical models of SIR disease spread with combined non-sexual and sexual transmission routes.","volume":"2","author":"Miller","year":"2017","journal-title":"Infect. Dis. Model."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050074","article-title":"Social contacts and mixing patterns relevant to the spread of infectious diseases.","volume":"5","author":"Mossong","year":"2008","journal-title":"PLoS Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.3201\/eid2306.161768","article-title":"Rise in group W meningococcal carriage in university students, United Kingdom.","volume":"23","author":"Oldfield","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1093\/infdis\/jix596","article-title":"Limited impact of adolescent meningococcal ACWY vaccination on Neisseria meningitidis serogroup W carriage in university students.","volume":"217","author":"Oldfield","year":"2018","journal-title":"J. Infect. Dis."},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-07235-5","article-title":"Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection.","volume":"9","author":"Pandey","year":"2018","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"crossref","first-page":"e510","DOI":"10.1016\/j.ijid.2010.06.020","article-title":"Super-spreaders in infectious diseases.","volume":"15","author":"Stein","year":"2011","journal-title":"Int. J. Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1093\/aje\/kwi160","article-title":"Dynamic models of meningococcal carriage, disease, and the impact of serogroup C conjugate vaccination.","volume":"162","author":"Trotter","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.puhe.2016.12.010","article-title":"University vaccine campaign increases meningococcal ACWY vaccine coverage.","volume":"145","author":"Turner","year":"2017","journal-title":"Public Health"},{"key":"B31","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.idm.2017.06.002","article-title":"Reproduction numbers of infectious disease models.","volume":"2","author":"van den Driessche","year":"2017","journal-title":"Infect. Dis. Model."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2020.579411\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T06:39:27Z","timestamp":1607323167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2020.579411\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,7]]},"references-count":31,"alternative-id":["10.3389\/fgene.2020.579411"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2020.579411","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2020,12,7]]},"article-number":"579411"}}