Meningococcal carriage in periods of high and low invasive meningococcal disease incidence in the UK: comparison of UKMenCar1-4 cross-sectional survey results

Abstract

Background: The incidence of invasive meningococcal disease in the UK decreased by approximately four times from 1999 to 2014, with reductions in serogroup C and serogroup B disease. Lower serogroup C invasive meningococcal disease incidence was attributable to implementation of the meningococcal serogroup C conjugate vaccine in 1999, through direct and indirect protection, but no vaccine was implemented against serogroup B disease. UK Meningococcal Carriage surveys 1-3 (UKMenCar1-3), conducted in 1999, 2000, and 2001, were essential for understanding the impact of vaccination. To investigate the decline in invasive meningococcal disease incidence, we did a large oropharyngeal carriage survey in 2014-15, immediately before the changes to meningococcal vaccines in the UK national immunisation schedule.

Methods: UKMenCar4 was a cross-sectional survey in adolescents aged 15-19 years who were enrolled from schools and colleges geographically local to one of 11 UK sampling centres between Sept 1, 2014, and March 30, 2015. Participants provided an oropharyngeal swab sample and completed a questionnaire on risk factors for carriage, including social behaviours. Samples were cultured for putative Neisseria spp, which were characterised with serogrouping and whole-genome sequencing. Data from this study were compared with the results from the UKMenCar1-3 surveys (1999-2001).

Findings: From the 19 641 participants (11 332 female, 8242 male, 67 not stated) in UKMenCar4 with culturable swabs and completed risk-factor questionnaires, 1420 meningococci were isolated, with a carriage prevalence of 7·23% (95% CI 6·88-7·60). Carriage prevalence was substantially lower in UKMenCar4 than in the previous surveys: carriage prevalence was 16·6% (95% CI 15·89-17·22; 2306/13 901) in UKMenCar1 (1999), 17·6% (17·05-18·22; 2873/16 295) in UKMenCar2 (2000), and 18·7% (18·12-19·27; 3283/17 569) in UKMenCar3 (2001). Carriage prevalence was lower for all serogroups in UKMenCar4 than in UKMenCar1-3, except for serogroup Y, which was unchanged. The prevalence of carriage-promoting social behaviours decreased from 1999 to 2014-15, with individuals reporting regular cigarette smoking decreasing from 2932 (21·5%) of 13 650 to 2202 (11·2%) of 19 641, kissing in the past week from 6127 (44·8%) of 13 679 to 7320 (37·3%) of 19 641, and attendance at pubs and nightclubs in the past week from 8436 (62·1%) of 13 594 to 7662 (39·0%) of 19 641 (all p<0·0001).

Interpretation: We show that meningococcal carriage prevalence in adolescents sampled nationally during a low incidence period (2014-15) was less than half of that in an equivalent population during a high incidence period (1999-2001). Disease and carriage caused by serogroup C was well controlled by ongoing vaccination. The prevalence of behaviours associated with carriage declined, suggesting that public health policies aimed at influencing behaviour might have further reduced disease.

Funding: Wellcome Trust, UK Department of Health, and National Institute for Health Research.

Figure 1

Invasive meningococcal disease incidence in the England and Wales from 1984–85 to 2016–17, by capsular serogroup Laboratory-confirmed disease cases, including culture-confirmed and PCR-confirmed disease, are stratified by epidemiological year. Coloured bars represent different capsular serogroups measured by dot-blot ELISA or siaD PCR. The lines below the graph show the changes in UK vaccination policy over this period for the MCC vaccine, the quadrivalent ACWY polysaccharide conjugate vaccine, and the protein-based vaccine 4CMenB (Bexsero [GlaxoSmithKline, Brentford, UK] is the only brand available). The timing of the four UK Meningococcal Carriage surveys are shown in relation to periods of high and low incidence of invasive meningococcal disease. Disease incidence data were obtained from the Meningococcal Reference Unit of Public Health England. Infant refers to those aged <12 months; toddler refers to those aged 12–13 months, and adolescent refers to those aged 13–15 years. *A catch-up campaign was implemented in 2000 to all individuals younger than 18 years, and in 2002 for all individuals younger than 25 years. 4CMenB=four-component meningococcal serogroup B. MCC=meningococcal serotype C conjugate.

Figure 2

Carriage rates and odds ratios for carriage by age (A) Oropharyngeal carriage rates for adolescents aged 15–19 years in the UK for UKMenCar1 in 1999 (2306 meningococci isolates from 13 901 participants) and UKMenCar4 in 2014–15 (1420 meningococci isolates from 19 641 participants). The p values for the difference between the two surveys are p=0·00027 for the 15-year-old age group and p<0·0001 for all other age groups. (B) Odds ratios for carriage by age in the two carriage surveys; the data are also presented in appendix p 7. UKMenCar=UK Meningococcal Carriage.

Figure 3

Association between adolescent meningococcal carriage prevalence and invasive disease incidence Bars indicate the measured carriage prevalence of meningococci in adolescents from UKMenCar1 (1999; 13 901 participants), UKMenCar2 (2000; 16 295 participants), UKMenCar3 (2001; 17 569 participants), and UKMenCar4 (2014–15; 19 641 participants; appendix p 9). Lines indicate England and Wales incidence (per 100 000 population) of invasive meningococcal disease caused by each genogroup over time. The predominant carried meningococcal clonal complexes in UKMenCar1–3 and UKMenCar4 are shown. The y-axes for genogroup B are scaled differently compared with those of the other genogroups to present the data more clearly. Disease incidence data were obtained from the Meningococcal Reference Unit of Public Health England. cc=clonal complex. UKMenCar=UK Meningococcal Carriage.

Figure 4

Distribution of meningococcal clonal complexes in UKMenCar1–4 surveys Proportions of the nine most frequently occurring clonal complexes of meningococci are shown for the four UKMenCar studies. A clonal complex was assigned to 2102 of 2306 meningococci in UKMenCar1, 2692 of 2873 in UKMenCar2, 3109 of 3283 in UKMenCar3, and 1326 of 1420 in UKMenCar4. cc=clonal complex. UKMenCar=UK Meningococcal Carriage.

Figure 5

Risk factors for carriage among UK adolescents in UKMenCar1–4 (A) Meningococcal carriage rates by frequency of risk factors in UKMenCar1, the adolescent UK carriage survey done in 1999 (n=13 919). Figure reproduced unchanged under CC BY. (B) Meningococcal carriage rates by frequency of risk factors in UKMenCar4, the adolescent UK carriage survey done in 2014–15 (n=19 641). Visits to pubs or nightclubs were categorised differently between UKMenCar1 and UKMenCar4. UKMenCar=UK Meningococcal Carriage.