Pertussis immunisation in infancy and atopic outcomes: A protocol for a population-based cohort study using linked administrative data

INTRODUCTION: The burden of IgE-mediated food allergy in Australian born children is reported to be among the highest globally. This illness shares risk factors and frequently coexists with asthma, one of the most common noncommunicable diseases of childhood. Findings from a case-control study suggest that compared to immunisation with acellular pertussis vaccine, early priming of infants with whole-cell pertussis vaccine may be associated with a lower risk of subsequent IgE-mediated food allergy. If whole-cell vaccination is protective of food allergy and other atopic diseases, especially if protective against childhood asthma, the population-level effects could justify its preferential recommendation. However, the potential beneficial effects of whole-cell pertussis vaccination for the prevention of atopic diseases at a population-scale are yet to be investigated. METHODS AND ANALYSIS: Analyses of population-based record linkage data will be undertaken to compare the rates of admissions to hospital for asthma in children aged between 5 and 15 years old, who were born in Western Australia (WA) or New South Wales (NSW) between 1997 and 1999 (329,831) when pertussis immunisation in Australia transitioned from whole-cell to acellular only schedules. In the primary analysis we will estimate hazard ratios and 95% confidence intervals for the time-to-first-event (hospital admissions as above) using Cox proportional hazard models in recipients of a first dose of whole-cell versus acellular pertussis-containing vaccine before 112 days old (~4 months of age). Similarly, we will also fit time-to-recurrent events analyses using Andersen-Gill models, and robust variance estimates to account for potential within-child dependence. Hospitalisations for all-cause anaphylaxis, food anaphylaxis, venom, all-cause urticaria and atopic dermatitis will also be examined in children who received at least one dose of pertussis-containing vaccine by the time of the cohort entry, using analogous statistical methods. Presentations to the emergency departments will be assessed separately using the same statistical approach.