Impact of Vaccine Schedule Change on Pertussis Epidemiology in France: A Modelling and Serological Study

Background: In 2013, France modified its pertussis vaccination schedule to remove one dose at 3 months of age and change the age of the booster dose from 16 to 11 months. We aimed to assess the subsequent impact on pertussis epidemiology in France. Methods: We analysed the PCR test results of nasopharyngeal swabs (N=7493) collected from symptomatic outpatients aged 2-20 years old between 2012 and 2019 in France. We developed a Poisson regression model in which the number of positive cases by year and age depended on the year, age group, population size of each age group and a proxy of waning immunity that could vary with vaccine schedule. We also compared the anti-pertussis toxin (PT) antibody levels of 315 children born before and after the vaccine schedule change. Findings: The model that best fitted the 2012-2018 epidemiological data supported a faster waning of immunity following vaccination with the new vaccine schedule. Four years after vaccination, the risk of developing pertussis was 2.1 (95% CI, 1.7-2.2) times higher for children vaccinated according to the new schedule than those vaccinated according to the previous schedule. The model correctly predicted the age distribution of cases in 2019. Anti-PT IgG levels were significantly lower in children born after implementation of the new schedule, compared to children born before. Interpretation: A shorter-lived protection induced by the 2/4+11 vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in 2-5-year olds. Funding Statement: This project was funded by the INCEPTION interdisciplinary project at Institut Pasteur, “Understanding whooping cough resurgence in Europe by combining genomic, epidemiological and sociological approaches” (French Government Investissements d’Avenir grant ANR-16-CONV-0005). This work received financial support from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant n_ANR-10-LABX-62-IBEID). Institutional support was provided by Institut Pasteur and Sante publique France. Declaration of Interests: None to declare. Ethics Approval Statement: The data collection received approval by French supervisory ethics authority (CNIL, n°1474593), and was approved by the local Institutional Review board (N° 2020 1028160733). All data processing and storage comply with the General Data Protection Regulation (GDPR) and ethical standards of the National Research Committee. This study was conducted in accordance with the Helsinki Declaration, with informed consent obtained from each patient’s guardians.