Effect of Pneumococcal Conjugate Vaccines on Pneumococcal Meningitis, England and Wales, July 1, 2000-June 30, 2016

Abstract

We describe the effects of the 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines on pneumococcal meningitis in England and Wales during July 1, 2000-June 30, 2016. Overall, 84,473 laboratory-confirmed invasive pneumococcal disease cases, including 4,160 (4.9%) cases with meningitis, occurred. PCV7 implementation in 2006 did not lower overall pneumococcal meningitis incidence because of replacement with non-PCV7-type meningitis incidence. Replacement with PCV13 in 2010, however, led to a 48% reduction in pneumococcal meningitis incidence by 2015-16. The overall case-fatality rate was 17.5%: 10.7% among patients <5 years of age, 17.3% among patients 5-64 years of age, and 31.9% among patients >65 years of age. Serotype 8 was associated with increased odds of death (adjusted odds ratio 2.9, 95% CI 1.8-4.7). In England and Wales, an effect on pneumococcal meningitis was observed only after PCV13 implementation. Further studies are needed to assess pneumococcal meningitis caused by the replacing serotypes.

Keywords: England; PCV13; PCV7; Streptococcus pneumoniae; Wales; bacteria; case fatality rate; case-fatality rate; conjugate vaccines; epidemiology; immunization; incidence; invasive pneumococcal disease; meningitis; pneumococcal meningitis; serotype; serotype 8.

Figure 1

Corrected trends in incidence of pneumococcal meningitis and nonmeningitis cases by Streptococcus pneumoniae serotype, age group, and epidemiologic year, England and Wales, July 1, 2000–June 30, 2016. A–H) Meningitis (A, C, E, G) and nonmeningitis (B, D, F, H) cases in patients <5 years of age (A, B); patients 5–64 years of age (C, D); patients >65 years of age (E, F); and patients of all ages (G, H). The raw numbers of cases for each year were corrected for missing serotype and age with the assumption that cases with missing data for age, serotype, or both had the same age and serotype distribution as those cases for which this information was known; cases were also corrected for annual changes in population denominators in each age group (13).The vertical lines denote the introduction of PCV7 and PCV13 into the national childhood immunization program. PCV7 refers to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, and additional PCV13 refers to serotypes 1, 3, 5, 6A, 7F, and 19A. Non-PCV13 refers to all other serotypes. PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine.

Figure 2

Mean annual number of pneumococcal meningitis cases among patients of all ages by Streptococcus pneumoniae serotype and period, England and Wales, July 1, 2000–June 30, 2016. The pre-PCV7 period refers to July 1, 2000–June 30, 2006, pre-PCV13 period July 1, 2008–June 30, 2010, and PCV13 period July 1, 2011–June 30, 2016. PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine. For cases diagnosed during the PCV13 period (July 1, 2011–June 30, 2016), we used multivariable logistic regression to calculate the odds of meningitis vs. nonmeningitis. O, other serotypes.

Figure 3

Contribution of individual Streptococcus pneumoniae serotypes to pneumococcal meningitis and nonmeningitis cases for all age groups after PCV13 introduction, England and Wales, July 1, 2011–June 30, 2016. We included the non-PCV13 serotypes that involved >10 cases. PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine. O, other serotypes.

Figure 4

Distribution of pneumococcal meningitis cases in children <5 years of age, by month of age and Streptococcus pneumoniae serotype group, England and Wales, July 1, 2000–June 30, 2016. PCV7 refers to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, and additional PCV13 refers to serotypes 1, 3, 5, 6A, 7F, and 19A. PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine.

Figure 5

Pneumococcal meningitis cases, by Streptococcus pneumoniae serotype and severity, England and Wales, July 1, 2015–June 30, 2016. We included the non-PCV13 serotypes that involved >10 cases. O, other serotypes; PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine.