Evaluation of outbreak response immunization in the control of pertussis using agent-based modeling

BACKGROUND Pertussis control remains a challenge due to recently observed effects of waning immunity to acellular vaccine and suboptimal vaccine coverage. Multiple outbreaks have been reported in different ages worldwide. For certain outbreaks, public health authorities can launch an outbreak response immunization (ORI) campaign to control pertussis spread. We investigated effects of an outbreak response immunization targeting young adolescents in averting pertussis cases. METHODS We developed an agent-based model for pertussis transmission representing disease mechanism, waning immunity, vaccination schedule and pathogen transmission in a spatially-explicit 500,000-person contact network representing a typical Canadian Public Health district. Parameters were derived from literature and calibration. We used published cumulative incidence and dose-specific vaccine coverage to calibrate the model's epidemiological curves. We endogenized outbreak response by defining thresholds to trigger simulated immunization campaigns in the 10-14 age group offering 80% coverage. We ran paired simulations with and without outbreak response immunization and included those resulting in a single ORI within a 10-year span. We calculated the number of cases averted attributable to outbreak immunization campaign in all ages, in the 10-14 age group and in infants. The count of cases averted were tested using Mann-Whitney U test to determine statistical significance. Numbers needed to vaccinate during immunization campaign to prevent a single case in respective age groups were derived from the model. We varied adult vaccine coverage, waning immunity parameters, immunization campaign eligibility and tested stronger vaccination boosting effect in sensitivity analyses. RESULTS 189 qualified paired-runs were analyzed. On average, ORI was triggered every 26 years. On a per-run basis, there were an average of 124, 243 and 429 pertussis cases averted across all age groups within 1, 3 and 10 years of a campaign, respectively. During the same time periods, 53, 96, and 163 cases were averted in the 10-14 age group, and 6, 11, 20 in infants under 1 (p < 0.001, all groups). Numbers needed to vaccinate ranged from 49 to 221, from 130 to 519 and from 1,031 to 4,903 for all ages, the 10-14 age group and for infants, respectively. Most sensitivity analyses resulted in minimal impact on a number of cases averted. DISCUSSION Our model generated 30 years of longitudinal data to evaluate effects of outbreak response immunization in a controlled study. Immunization campaign implemented as an outbreak response measure among adolescents may confer benefits across all ages accruing over a 10-year period. Our inference is dependent on having an outbreak of significant magnitude affecting predominantly the selected age and achieving a comprehensive vaccine coverage during the campaign. Economic evaluations and comparisons with other control measures can add to conclusions generated by our work.