Pneumococcal conjugate vaccine coverage and indirect protection against invasive pneumococcal disease and pneumonia hospitalisations in Australia: a retrospective record linkage cohort study
Authors: Chan Jocelyn , Gidding Heather F , Blyth Christopher C , Fathima Parveen , Jayasinghe Sanjay , McIntyre Peter B , Moore Hannah C , Mulholland Kim , Nguyen Cattram D , Andrews Ross , Russell Fiona M 
Published: July 2021

AbstractBackgroundThere 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.MethodsBirth 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.FindingsThere 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).ConclusionsIn this study we observed substantial indirect protection at low PCV coverage, challenging assumptions high vaccine coverage is required.Author summaryWhy was this study done?Pneumococcal conjugate vaccines (PCVs) reduce the burden of pneumococcal disease in vaccinated and unvaccinated populations through both direct and indirect (herd) effects.The indirect effects comprise a substantial component of overall vaccine impact, contributing to the cost-effectiveness of the vaccine but little is known about what factors contribute to herd protection, including vaccination coverage.In this study, we examined association between PCV coverage and indirect effects within in diverse populations within AustraliaWhat did the researchers do and find?Using a large dataset of 1.3 million children from two states in Australia, we quantified the relationship between PCV coverage within small geographical units and indirect protection against pneumococcal disease. We also performed similar analyses for infants too young to be fully vaccinated, urban, rural and Indigenous populations.There were strong inverse relationships between PCV coverage and the incidence of severe invasive disease due to vaccine types and pneumonia hospitalisations among under-vaccinated children i.e. higher coverage were associated with greater reductions in disease due to indirect effects. We also found substantial indirect effects at relatively low levels of PCV coverage. We estimated that 50% and 90% coverage of 7-valent PCV (PCV7) among children under five years of age prevented almost three-quarters (72.5%, 95% CI 51.6-84.4) and almost all (95.2%, 95% CI 89.4-97.8) of PCV7-type severe invasive disease, respectively. For pneumonia, we estimated that 50% and 90% coverage was sufficient to prevent one-third (33.3%, 95% CI 27.3-38.8) and about half (51.7%, 95% CI 43.7-58.6) of all-cause pneumonia hospitalisations among under-vaccinated children.These trends were similar for children less than four months old, urban, rural and Indigenous populations, although these effects were smaller for rural and Indigenous populations. There was also a trend towards decreasing incidence of PCV13-type IPD among under-vaccinated children as PCV13 coverage increased.What do these findings mean?Our results challenge existing assumptions that high PCV coverage is required to achieve substantial indirect protection.Understanding the determinants of indirect effects are particularly urgent as countries that have controlled vaccine-type pneumococcal disease consider using reducing the number of PCV doses (from three to two). Reduced dose schedules have the potential to significantly lower program costs while maintaining vaccine impact, providing indirect protection is achieved and preserved.