Increase of invasive pneumococcal disease in children temporally associated with RSV outbreak in Quebec: a time-series analysis

Abstract

Background: Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections.

Methods: We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated.

Findings: A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics.

Interpretation: These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions targeting RSV, such as vaccines, for IPD prevention should be considered.

Funding: The study was supported by a grant from the Quebec Ministry of Health and Social Services ('ministère de la Santé et des Services sociaux du Québec'). Publication was supported by a grant from "Fondation de l'Assistance Publique - Hôpitaux de Paris et de l'Alliance « Tous Unis contre le Virus » (Fondation de France/Institut Pasteur/APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award.

Keywords: Child; Invasive pneumococcal disease; Pneumococcal conjugate vaccine; Respiratory syncytial virus; Respiratory viral infection; Time series analysis.

Fig. 1

Evolution of the monthly incidence of IPD across age groups in Quebec, January 2013–January 2022, N = 7712. A) <5 years. B) 5–64 years. C) ≥65 years. The black line shows the observed monthly incidence of IPD, the red line shows the monthly incidence of IPD estimated by the model (quasi-Poisson regression modeling), the dotted blue line shows the expected monthly incidence of IPD if no intervention had occurred (quasi-Poisson regression modeling). Pre-NPI period, PCV13 implemented: from January 2013 to May 2018. Pre-NPI period, PCV10 implemented: from June 2018 to February 2020. Period 2, NPIs implemented: From March 2020 to February 2021. Period 3, NPIs partially relaxed: From March 2021 to January 2022. Abbreviations: IPD: invasive pneumococcal disease. NPIs: non-pharmaceutical interventions.

Fig. 2

Evolution of the monthly number of positive tests for respiratory viruses over time, in Quebec, January 2013–January 2022. A) RSV. B) Influenza. C) Parainfluenza 1. D) Parainfluenza 2. E) Parainfluenza 3. F) Parainfluenza 4. G) Adenovirus. H) Human metapneumovirus. I) Common coronavirus (non-SARS-CoV-2). The black line shows the observed monthly incidence of IPD, the red line shows the monthly incidence of IPD estimated by the model (quasi-Poisson regression modeling), the dotted blue line shows the expected monthly incidence of IPD if no intervention had occurred (quasi-Poisson regression modeling). Pre-NPI period, PCV13 implemented: from January 2013 to May 2018. Pre-NPI period, PCV10 implemented: from June 2018 to February 2020. Period 2, NPIs implemented: From March 2020 to February 2021. Period 3, NPIs partially relaxed: From March 2021 to January 2022. Abbreviations: IPD: invasive pneumococcal disease. NPIs: non-pharmaceutical interventions.