Pneumococcal Conjugate Vaccines Are Protective Against Respiratory Syncytial Virus Hospitalizations in Infants: A Population-Based Observational Study

Abstract

Background Pneumococcal conjugate vaccines (PCV) reduced the risk of respiratory syncytial virus (RSV) in a randomised clinical trial. We aimed to assess the real-world effectiveness of PCV on RSV-hospitalisations among Western Australian infants. Methods We conducted a population-based cohort study of births 2000-2012, using probabilistically linked individual-level immunisation, hospitalisation, respiratory microbiology testing and perinatal data. We performed Cox proportional hazard models with time varying exposure (receipt of infant PCV doses) against the first RSV-confirmed hospitalisation 0-12 months adjusted for perinatal and socio-demographic factors. Results From 360,994 children, three-dose PCV coverage in Aboriginal infants ranged from 29-51% in 2001-04 when PCV was funded for Aboriginal children only. Following universal funding in 2005, coverage increased to 85% for Aboriginal and 73% for non-Aboriginal infants. RSV-hospitalisation rates were highest in young infants 0-5 months (22.5/1000) and more than two times higher in Aboriginal infants than in non-Aboriginal infants. Receipt of 3 or more PCV doses in the universal funded period was associated with a 30% reduction in RSV-hospitalisation in Aboriginal infants (adjusted hazard ratio, aHR 0.70 [95% confidence interval, CI 0.46-1.06]) and 21% reduction in non-Aboriginal infants (aHR 0.79 [95% CI 0.63-0.99]) compared with unvaccinated infants. Conclusions Prior to the introduction of RSV vaccines, our study suggests that universal childhood PCV vaccination may result in a reduction in severe RSV infections in children and maybe important for countries who are yet to consider PCV programs.

Impact of pneumococcal conjugate vaccine 13 introduction on severe lower respiratory tract infections associated with respiratory syncytial virus or influenza virus in hospitalized children in Ulaanbaatar, Mongolia

“…Hospitalization data during 1996-2012 in Western Australia did not show an impact of PCV on RSV infection, particularly, in Aboriginal infants [16] . In contrast a population-based birth cohort in Western Australia during 2000-2012 showed a 21-30% reduction in RSV hospitalization [17] . All these studies, mainly in high-income countries, suggest there may be a positive additional effect of PCV on RSV and influenza viral infections in young children; however, it is not clear whether this effect will also be observed inxbrk LMICs.…”

“…Since 2000, when the first pneumococcal conjugate vaccine (PCV) was licensed, the use of PCV in high-income countries has led to substantial reductions in pneumococcal disease and associated mortality. PCV has also shown an impact on LRTIs associated with RSV and influenza in some settings [14] , [15] , [16] , [17] . A retrospective time series analysis of US hospitalization data from 1992/1993 to 2008/2009 reported a significant decline in RSV-coded hospitalizations in children aged <1 year (−18.0%), 4 years after the 7-valent PCV (PCV7) introduction in 2001 across 18 states [15] .…”

Modelling respiratory syncytial virus age-specific risk of hospitalisation in term and preterm infants

“…Infants born preterm are the largest risk group predisposed to higher rates of severe RSV illness, but other groups include First Nations infants (RSV-hospitalisation rates approximately double the rate of non-First Nations children [ 50 ]), those with congenital heart disease, and those with chromosomal abnormalities including Trisomy 21 (ALRI hospitalisation rates are 3–8 times higher than children with no birth defects [ 51 ]). Our model structure could be extended to include these other risk groups if sufficient data are available for parameterisation, enabling targeted advice to policymakers for high-risk group specific interventions, for example, the option of an additional dose in a high-risk infant’s second RSV season.…”

Cohort profile: A population-based record linkage platform to address critical epidemiological evidence gaps in respiratory syncytial virus and other respiratory infections

“…Population sub-groups such as infants born preterm [15], First Nations infants [16], children with comorbidities, and those with congenital anomalies [17] may be suffering from a disproportionate burden of acute lower respiratory infection (ALRI). However, RSV and other respiratory pathogen-specific data in these high-risk groups are limited.…”

“…While our current focus is on RSV and the platform was built with RSV in mind, the Respiratory Infections Linked Data Platform will provide a valuable resource for wider epidemiological research on other respiratory viruses and infections in the future. Members of our team have longstanding expertise using linked population data in previous analyses, including the evaluation of maternal influenza and pertussis vaccine safety and effectiveness [18,19], and direct and indirect effects of maternal [20][21][22] and childhood [16,23] vaccines, which has aided the design of this platform and will assist with investigations of all respiratory infections. The Respiratory Infections data platform will enable evaluation of the direct and indirect effects of maternal RSV vaccines and/or monoclonal antibodies on RSV and non-RSV hospitalisations.…”