Pneumococcal Meningitis in Adults after Introduction of PCV7 and PCV13, Israel, July 2009-June 20151

Abstract

The indirect effect of pneumococcal conjugate vaccine on adult pneumococcal meningitis has not been thoroughly investigated. We present data from active surveillance on pneumococcal meningitis in adults in Israel occurring during July 2009-June 2015. Pneumococcal meningitis was diagnosed for 221 patients, 9.4% of all invasive pneumococcal disease (IPD) cases. Although overall IPD incidence decreased during the study period, meningitis increased nonsignificantly from 0.66 to 0.85 cases/100,000 population. Incidence of vaccine type (VT) pneumococcal meningitis (VT13) decreased by 70%, but non-VT13 pneumococcal meningitis increased from 0.32 to 0.75 cases/100,000 population (incident rate ratio 2.35, 95% CI 1.27-4.35). Pneumococcal meningitis patients were younger and healthier than nonmeningitis IPD patients, and 20.2% had a history of previous head surgery or cerebrospinal fluid leak compared with <2.0% of nonmeningitis patients (p<0.0001). Non-VT13 types that rarely cause IPD (15B/C, 6C, 23A, 23B, 24F) seem to be emerging as common causes of meningitis.

Keywords: Israel; PCV13; PCV7; S. pneumoniae; Streptococcus pneumoniae; adults; bacteria; indirect effects; invasive pneumococcal disease; meningitis; nationwide surveillance; pneumococcal conjugate vaccine; pneumococcal meningitis; serotype replacement; streptococci; vaccine.

Figure 1

Incidence of meningitis and nonmeningitis IPD in patients >18 years of age, Israel, July 1, 2009–June 30, 2015. Introduction of PCV7 and PCV13 into the pediatric national immunization plan are depicted with arrows; 95% Poisson CIs are depicted for overall IPD and meningitis IPD. IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine.

Figure 2

Proportion ceftriaxone-nonsusceptible isolates among all Streptococcus pneumoniae isolates acquired from patients with invasive pneumococcal disease, by 2-year period, Israel, July 1, 2009–June 30, 2015. Ceftriaxone-nonsusceptible isolates were those that could grow at a concentration above ceftriaxone’s MIC (>1 µg/mL). *In 2009–2011, the 1 ceftriaxone-nonsusceptible isolate was serotype 14. †In 2011–2013, the 5 ceftriaxone-nonsusceptible isolates included 2 of serotype 19F and 1 each of serotypes 19A, 34, and 23B. ‡In 2013–2015, the ceftriaxone-nonsusceptible isolates were serotypes 23F (n = 2) and 19A (n = 3), and 1 was not typeable.

Figure 3

Incidence of pneumococcal meningitis in patients >18 years of age, by VT, Israel, July 1, 2009–June 30, 2015. The total number of cases per year are shown, and the introductions of PCV7 and PCV13 into the pediatric national immunization plan are depicted with arrows. *Serotypes included in the VT13 vaccine but not in the VT7 vaccine. PCV, pneumococcal conjugate vaccine; VT, vaccine type.

Figure 4

Comparison of serotypes causing pneumococcal meningitis during the first and last 2-year periods of study, Israel, July 1, 2009–June 30, 2011, and July 1, 2013–June 30, 2015. Only common serotypes (those occurring in >5% of cases in either the first 2-year period [n = 62] or last 2-year period [n = 81]) were included. *p<0.05; †p<0.1; ‡serotypes covered by pneumococcal conjugate vaccine 13.

Figure 5

Serotypes associated with meningitis and nonmeningitis invasive pneumococcal disease, Israel, July 1, 2009–June 30, 2015. Only major serotypes (those totaling >3% of all Streptococcus pneumoniae isolates from all study years) were included. *p<0.1; †p<0.05; ‡p<0.005; §serotypes covered by pneumococcal conjugate vaccine 13.