Invasive Pneumococcal Disease after Routine Pneumococcal Conjugate Vaccination in Children, England and Wales

Shamez N. Ladhani

, Mary P.E. Slack, Nick J. Andrews, Pauline A. Waight, Ray Borrow, and Elizabeth Miller

Author affiliations: Author affiliations: Health Protection Services Colindale, London, UK (S.N. Ladhani, M.P.E. Slack, N.J Andrews, P.A Waight, E. Miller); Health Protection Agency, Manchester, UK (R. Borrow)

Abstract

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3–59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006–March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.

In September 2006, the United Kingdom introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national childhood immunization program for receipt at 2, 4, and 13 months of age (1). At the same time, a 12-month catch-up campaign was initiated that offered 2 vaccine doses to 2–8-month-old infants and 1 dose to 12–24-month-old children (1). The program rapidly achieved high vaccine coverage (2) and was highly effective (3), resulting in a rapid reduction in invasive pneumococcal disease (IPD) caused by the serotypes in PCV7 (PCV7-IPD; serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F), particularly in children < 2 data-blogger-escaped-2009="2009" data-blogger-escaped-98="98" data-blogger-escaped-a="a" data-blogger-escaped-age="age" data-blogger-escaped-by="by" data-blogger-escaped-decreased="decreased" data-blogger-escaped-for="for" data-blogger-escaped-href="http://wwwnc.cdc.gov/eid/article/19/1/12-0741_article.htm?s_cid=eid-gDev-email#r4" data-blogger-escaped-of="of" data-blogger-escaped-pcv7-ipd="pcv7-ipd" data-blogger-escaped-whom="whom" data-blogger-escaped-years="years" title="4">4
). Because conjugate vaccines induce high antibody levels that reduce carriage in vaccinated children and, therefore, transmission of Streptococcus pneumoniae to others, PCV7-IPD also declined by >75% in older age groups through indirect protection (herd immunity) (4). Moreover, although this reduction was offset by an increase in IPD caused by serotypes not included in PCV7 (serotype replacement disease), IPD decreased 34% overall across all age groups during 2009–10 (56% in children <2 a="a" age="age" href="http://wwwnc.cdc.gov/eid/article/19/1/12-0741_article.htm?s_cid=eid-gDev-email#r4" of="of" title="4" years="years">4). The introduction of a 13-valent vaccine (PCV13) in April 2010 provided protection against 2 of the key replacing serotypes, 7F and 19A (5); however, concern remains about the potential for further replacement disease with non-PCV13 serotypes. After PCV7 introduction, the Health Protection Agency (HPA) collected detailed clinical information about all laboratory-confirmed IPD cases in children eligible for PCV7 in England and Wales. To predict the potential long-term effect of higher-valent vaccines on childhood IPD, an understanding is needed of the characteristics of children in whom IPD developed and of the infecting serotypes during the PCV7 period. We describe the distribution of known risk factors, clinical features, and outcome of illness in children with IPD in the cohort eligible for PCV7 in England and Wales.