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

Huong Le; Nicholas de Klerk; Christopher C Blyth; Heather Gidding; Parveen Fathima; Hannah C Moore

doi:10.1016/j.vaccine.2023.06.085

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

Vaccine. 2023 Jul 31;41(34):5029-5036. doi: 10.1016/j.vaccine.2023.06.085. Epub 2023 Jul 6.

Authors

Huong Le¹, Nicholas de Klerk², Christopher C Blyth³, Heather Gidding⁴, Parveen Fathima⁵, Hannah C Moore⁶

Affiliations

¹ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia; School of Population Health, Curtin University, Perth, Australia. Electronic address: huong.le@telethonkids.org.au.
² Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia.
³ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia; Department of Infectious Diseases, Perth Children's Hospital, Perth, Australia; PathWest Laboratory Medicine, Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia.
⁴ The University of Sydney Northern Clinical School, St Leonards, NSW, Australia; Women and Babies Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia; School of Population Health, UNSW Medicine, University of NSW, Sydney, NSW, Australia; National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, Sydney, NSW, Australia.
⁵ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia; Department of Health, Government of Western Australia, Perth, Australia.
⁶ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia; School of Population Health, Curtin University, Perth, Australia.

PMID: 37407408
DOI: 10.1016/j.vaccine.2023.06.085

Abstract

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.

Keywords: Causal inference; Children; Instrumental variable; Quasi-natural experiment; RSV infections; Seasonal influenza vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Australia
Child
Child, Preschool
Female
Hospitalization
Humans
Infant
Influenza Vaccines*
Influenza, Human* / epidemiology
Influenza, Human* / prevention & control
Pregnancy
Respiratory Syncytial Virus Infections* / epidemiology
Respiratory Syncytial Virus Infections* / prevention & control
Respiratory Syncytial Virus, Human*
Seasons

Substances

Influenza Vaccines