Non-specific benefit of seasonal influenza vaccine on respiratory syncytial virus-hospitalisations in children: An instrumental variable approach using population-based data.

Background: Seasonal influenza vaccine is effective against influenza hospitalisations, but little is known about non-specific effects of the vaccine on other respiratory pathogens with similar seasonal patterns. We aimed to assess the causal impact of seasonal influenza vaccine on laboratory-confirmed hospitalisations for respiratory syncytial virus (RSV) in children using an instrumental variable (IV) strategy.
Methods: We used probabilistically linked population-based data on childhood immunisations, births, deaths, hospitalisations, perinatal factors, and microbiology test results (2000-2013) of all Western Australian (WA) children born 2000-2012, observed longitudinally until the earliest of 7 years of age or 31 December 2013. We exploited a unique natural experiment created from the WA's state-funded preschool influenza vaccination policy commencing in 2008 and used this as an instrument for children's seasonal influenza vaccination status. We estimated a system of two simultaneous probit equations: determinants of influenza vaccine uptake, and determinants of RSV-confirmed hospitalisation.
Results: Influenza vaccine coverage was low prior to 2008 but increased to 36 % in children aged 6-23 months in 2009. The majority (90 %) of RSV-hospitalisations occurred in children <2 years. Receipt of influenza vaccine reduced RSV-hospitalisations, especially in those <2 years with a rate reduction of 2.27 per 1000 (95 % CI: -3.26; -1.28), and a smaller rate reduction of 0.53 per 1000 (95 % CI: -1.04; -0.02) in those 2-7 years. Over the 5-year period (2008-2013), the state-funded preschool-influenza vaccine program resulted in 1,193 fewer RSV-hospitalisations. Of these, 793 (67 %) were in young children <2 years.
Conclusions: To our knowledge, this is the first analysis utilising an IV estimation strategy on a population level to assess the causal impact of seasonal influenza vaccine on risk of RSV-hospitalisations. We estimated a small protective effect that warrants further investigation.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HCM has received travel support to attend a real-world influenza vaccine policy summit sponsored by Seqirus and was a member of the Independent Scientific Steering Committee; has received honoraria for participation in Merk Sharpe and Dohme (Australia) Expert Input Forums on RSV epidemiology and is in receipt of a Merck Investigator Studies Program; none of these are related to the work reported in this manuscript. HG has served on a Seqirus advisory board unrelated to this research. HCM reports financial support was provided by Stan Perron Charitable Foundation. CCB reports financial support was provided by National Health and Medical Research Council. HCM reports a relationship with Merck Sharp & Dohme (Australia) Pty Limited that includes: funding grants and paid expert testimony. HG reports a relationship with Seqirus Vaccines Ltd that includes: consulting or advisory.
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