The impact of the pneumococcal conjugate vaccine on the epidemiology and aetiology of childhood pneumonia

PhD ThesisBackground The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced routinely in the UK in September 2006 and replaced by PCV13 from April 2010. Aims To evaluate the impact of PCV7 on the incidence of all-cause community-acquired pneumonia (CAP) in children. Also to investigate the aetiology of CAP before and after the introduction of PCV as well as serotype the pneumococcal infections. Methods Enrolled children were from North East England (excluding Cumbria) who were aged 0–16 years and presented with clinical and radiological features suggestive of pneumonia. Epidemiology survey was prospectively undertaken in 2008–2009 at 11 hospitals in North East England. Data were compared to those from a similar survey undertaken in the same hospitals in 2001–2002. Aetiology studies were prospectively conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) in Newcastle and Middlesbrough. Investigations included culture, serology, immunofluorescence antibody, urinary pneumococcal antigen and PCR assays. Epidemiology Results A total of 542 children were enrolled, of which 74% were aged <5 years. PCV7 uptake was 90.7%. The annual incidence of pneumonia was 11.8/10 000 (95% CI 10.9–12.9), and the hospitalisation rate was 9.9/10 000 (95% CI 9.0–10.9). Compared to 2001, there was a 19% (95% CI 8–29) reduction in the annual rate of CAP in those aged <5 years, and in those <2 years a 33.1% (95% CI 20–45) reduction in the annual incidence of CAP and 38.1% (95% CI 24–50) reduction in hospitalisation rates. However, for those unvaccinated aged ≥5 years, there was no difference in the annual incidence of CAP and hospitalisation rate between both surveys. Since 2001, the overall reduction in annual incidence was 17.7% (95% CI 8–26) and for hospitalisation 18.5% (95% CI 8–28). Aetiology Results A total of 401 children were enrolled; 241 and 160 respectively in the pre- and post- vaccine studies (73% aged <5 years), for whom at least one diagnostic investigation had been performed. Identification of a definite pathogen was higher post-vaccine (61%) than pre-vaccine (48.5%) [p=0.019]. Rates of bacterial infections were not different between post- and pre-vaccine (17.5% versus 24%, p=0.258). Viral (31%) and mixed infections (12.5%) found more often post-vaccine than pre-vaccine (19.5% [p=0.021] and 5% [p=0.015] respectively). Pneumococcal detection post-vaccine was substantially improved when PCR assays were used compared to culture (21.6% versus 6%, p=0.0004). A serotype was identified in 75% (18/24) post-vaccine including serotypes 1 (44.4%), 3 (27.8%), 19A (22.2%) and 7A/F (5.6%). Conclusions PCV7 has reduced both the annual incidence and rate of hospitalisation of pneumonia in children, particularly those aged