Pneumococcal conjugate vaccine coverage and indirect protection against invasive pneumococcal disease and pneumonia hospitalisations in Australia: a retrospective record linkage cohort study
Background: There is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCV) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among under-vaccinated Australian children. Methods: Birth and vaccination records, IPD notifications and hospitalisations were individually linked for children aged < five years, born between 2001 and 2012 in two Australian states (New South Wales and Western Australia; 1.37 million children). Using Poisson regression models, we examined the association between PCV coverage, in small geographical units, and the incidence of (1) 7-valent PCV (PCV7)-type IPD, (2) all-cause pneumonia and (3) pneumococcal and lobar pneumonia hospitalisation in under-vaccinated children. Under-vaccinated children received < two doses of PCV at < 12 months of age and no doses at ≥ 12 months of age. Potential confounding variables were selected for adjustment a priori with the assistance of a directed acyclic graph. The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on addressed at birth only) and unmeasured confounders. Findings There were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% CI 0.958-0.975, p-value <0.001), and pneumonia hospitalisations (all-cause pneumonia: aIRR 0.991 95% CI 0.990-0.994, p-value<0.001) among under-vaccinated children. Subgroup analyses for children < four months old, urban, rural and Indigenous populations showed similar trends, although effects were smaller for rural and Indigenous populations. Fifty-percent coverage of PCV7 among children < five years of age prevented up to 72.5% (95% CI 51.6-84.4) of PCV7-type IPD among under-vaccinated children, while 90% coverage prevented 95.2% (95% CI 89.4-97.8). Conclusions In this study we observed substantial indirect protection at low PCV coverage, challenging assumptions high vaccine coverage is required.