Meningococcal carriage in adolescents in the United Kingdom to inform timing of an adolescent vaccination strategy

Jeppesen, Catherine A.; Snape, Matthew D.; Robinson, Hannah; Gossger, Nicoletta; John, Tessa M.; Voysey, Merryn; Ladhani, Shamez; Okike, Ifeanyichukwu; Oeser, Clarissa; Kent, Alison; Oliver, Jennifer; Taylor, Pippa; Morales-Aza, Begonia; Clarke, Stuart C.; Casey, Michelle; Martins, Filipa; Kitchin, Nicholas; Anderson, Annaliesa S.; Jones, H; Jansen, Kathrin U.; Eiden, Joseph; Pedneault, Louise; Heath, Paul T; Finn, Adam; Faust, Saul N; Pollard, Andrew J.

doi:10.1016/j.jinf.2015.02.006

Cited by 62 publications

(63 citation statements)

References 27 publications

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“…Recent development of serogroup B meningococcal vaccines highlights the importance of pharyngeal carriage data, particularly in adolescents and young adults to inform implementation strategies. A study on the carriage prevalence in high risk populations showed that serogroups B and Y were most common in the UK, with carriage up to 6.5% and 5.5% respectively, increasing throughout adolescence 15 and suggesting that immunization to help protect against serogroup Y IMD would be best placed in the early teenage years or before to decrease transmission.…”

Section: Discussionmentioning

confidence: 99%

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013

Bröker

Emonet

Fazio

et al. 2015

Human Vaccines & Immunotherapeutics

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Section: Discussionmentioning

confidence: 99%

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013

Bröker

Emonet

Fazio

et al. 2015

Human Vaccines & Immunotherapeutics

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“…8 Although this methodology has been applied to the study of Nm carriage, 9 no information on colonization density of Nm has been reported. The presence of more bacteria may be associated with higher rates of transmission and thus be important for evaluation of vaccine indirect effects.…”

Section: A C C E P T E Dmentioning

confidence: 99%

“…qPCR assays may also be used to identify capsular groups more reliably than agglutination antisera in pharyngeal Nm in which levels of capsular expression are often downregulated. 9,10 We applied qPCR to the detection, quantification and characterization of Nm from oropharyngeal swabs, to compare the performance of this approach with conventional techniques and to work out how best to apply it to the study of the potential impact of new generation meningococcal vaccines on carriage and transmission. We describe for the first time the distribution of density of Nm oropharyngeal colonization in a sample of healthy young adults.…”

Section: A C C E P T E Dmentioning

confidence: 99%

“…Study 1: a four center study performed in 2011-12 in the UK in school and first year university students, aged 10-25 years and reported previously. 9 Permission was obtained from the sponsor of the study to retain the heads of pharyngeal swabs collected from all subjects at the third study visit, after they had been used to inoculate agar plates immediately after being taken. Instead of discarding them, they were broken off into containers with 1.5mL STGG broth, all prepared in one batch.…”

Section: A C C E P T E Dmentioning

confidence: 99%

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Density Distribution of Pharyngeal Carriage of Meningococcus in Healthy Young Adults

Finn

Morales-Aza

Sikora

et al. 2016

Pediatric Infectious Disease Journal

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Background: Improved understanding of Neisseria meningitidis (Nm) carriage biology and better methods for detection and quantification would facilitate studies of potential impact of new vaccines on colonization and transmission in adolescents. Methods:We performed plate cultures on 107 oropharyngeal swabs stored frozen in STGG broth and previously positive for Nm. We compared quantitative (q)PCR detection of Nm in 601 STGG-swabs with culture. Using qPCR (n=87), a log-phase broth culture standard curve and semi-quantitative plate cultures (n=68), we measured density of carriage. We compared qPCR genogrouping of DNA extracts from STGG-swabs and from plate culture lawns (n=110) with purified isolates (n=80).Results: Swab storage resulted in only 10% loss of culture sensitivity. Direct sodC qPCR Nm detection yielded more positives (87/601, 14.5%) than culture (80/601, 13.3%). Most samples (57/110) positive by culture were also positive by qPCR and vice versa, but discrepancies (single positives) were frequent among low density samples. sodC qPCR was positive in 79/80 isolates but in only 65 by ctrA qPCR. Density both by culture and qPCR varied across 4 orders of magnitude with the majority being low (<50 bacteria-gene copies/mL) and a minority being high (>1000). Genogrouping qPCRs yielded more positive results when performed on DNA extracts from lawn cultures. Conclusions:We provide the first description of the distribution of Nm carriage density. This could be important for understanding transmission dynamics and population-level effectiveness of adolescent vaccine programs. Storage of swabs frozen in STGG for batched laboratory analysis facilitates carriage studies and direct sodC qPCR for Nm combined with qPCR genogrouping of lawn culture extracts provides accurate, detailed description of colonization.

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“…This ongoing decrease was expected because, to date, the incidence of MenC disease is still very low (16), suggesting that the samples used in this study were collected during a period with low MenC carriage and therefore a low chance of natural boosting of MenC-specific immunity (3). In coherence, a recently published carriage study from the UK found very low levels of MenC carriage up to 13 years after the introduction of MenC vaccination (17). It is assumed that MenC-specific functional antibody levels will continue to decrease with time and that herd effects will eventually fade away.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of Meningococcal Serogroup C-Specific Functional Antibody Levels Up to 15 Years after a Single Immunization with a Meningococcal Serogroup C Conjugate Vaccine during Adolescence

Stoof

Ravenhorst

Rooijen

et al. 2017

Clin Vaccine Immunol

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Adolescent vaccination is now considered the key factor for offering direct protection against meningococcal disease but also for reducing carriage and transmission and, in this way, establishing herd protection. This study estimated age-dependent patterns in functional meningococcal serogroup C (MenC) antibody kinetics after primary MenC conjugate (MenCC) vaccination in adolescents. Serum samples (n ϭ 1,676) were drawn from 2006 to 2011 from individuals aged 9 to 18 years at the time of primary MenCC vaccination in 2002. Functional antibody levels were measured with a serum bactericidal antibody assay (SBA) using rabbit complement. SBA titers gradually declined with time. Up to 9 years after primary vaccination, SBA titers were estimated to be higher in individuals who were aged 13 to 18 years at priming than in those who were aged 9 to 10 years at priming. Based on a linear mixed model, the higher functional antibody levels with age seem to be due to the achievement of higher peak levels upon vaccination rather than to lower rates of decline. It is estimated that 35 to 50% of individuals who received a single primary MenCC vaccination at an age of 9 to 18 years in 2002 will still have sufficient protective antibody levels 15 years later. Using a linear mixed model based on cohort data for a single dated serum sample per person, we were able to estimate the level of protection against MenC up to 15 years after a single vaccination. The current study shows that analysis of antibody kinetics can be done using crosssectional serology data and is therefore relevant for future serosurveillance studies.

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Meningococcal carriage in adolescents in the United Kingdom to inform timing of an adolescent vaccination strategy

Abstract: If vaccination is to precede the adolescent rise in MenB carriage, these data suggest it should take place in early adolescence. Studies assessing vaccine impact should use molecular methods to detect carriage.

Cited by 62 publications

References 27 publications

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013

Density Distribution of Pharyngeal Carriage of Meningococcus in Healthy Young Adults

Kinetics of Meningococcal Serogroup C-Specific Functional Antibody Levels Up to 15 Years after a Single Immunization with a Meningococcal Serogroup C Conjugate Vaccine during Adolescence

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