Pertussis on the Rise: Population Dynamical Effects of Waning Immunity

Incidence of whooping cough, or pertussis, caused primarily by the bacteria Bordetella pertussis and secondarily by B. parapertussis, has been increasing for the past two to three decades in most developed countries despite high vaccine coverage. In addition to an overall increase in cases, there has been a shift in the age distribution with a much larger number and proportion of cases now found in teenagers and adults. However, the age group most at risk of severe disease and death is infants, and they are not fully protected by the vaccine until after the third dose of vaccine, given between six and twelve months of age in most places. It is therefore important to design vaccine policy to maximize indirect protection of infants. A number of hypotheses have been put forward to explain the recent changes in pertussis epidemiology. The three primary ones involve evolution of the pathogen population [92], importance of age-specific contact rates [105], and loss of population-level herd immunity through waning individual immunity combined with reduced exposure to circulating pathogen [1,77]. The work presented here primarily explores evidence for the third of these hypotheses using a two-pronged approach: (1) statistical modeling of contemporary age-specific incidence and vaccine history data from Massachusetts and Norway, and (2) mechanistic modeling that connects the within host immune dynamics to population level epidemiology in contemporary Massachusetts and pre-vaccine era Copenhagen, Denmark. I show that in both Norway and Massachusetts the seasonality of pertussis infections varies between age groups, with school-age children experiencing peak incidence in the winter, infants in the summer, and adults less clearly defined, showing that chains of transmission partially age-segregate. There is consistent evidence from the two regions of temporary vaccine-induced immunity that lasts 5-10 years. Moreover, infections are occurring more quickly after vaccination now than they did ten or fifteen years ago in both locations. I hypothesize that these changes can be explained by low incidence in the current era providing little natural immune boosting (the anamnestic response), thereby allowing immunity to wane fully, such that clinical disease and transmission occur more frequently upon re-exposure. I evaluate this hypothesis by encapsulating it in a pair of mathematical models, one deterministic, one stochastic, and compare its predictions regarding age, total incidence, and dynamics against historical pre-vacine and contemporary data. I find that the deterministic, unforced model with a rapid anamnestic response predicts the shift in age distribution and increase in incidence with high vaccine coverage. The seasonally forced, stochastic model is able to recapitulate the observed dynamics from Copenhagen in the prevaccine era. We find that the presence of rapid boosting allows for a shorter duration of immunity, thereby reconciling current clinical estimates of the duration of infection-induced immunity with prevaccine-era dynamics. Additionally, we show that the intermittent large outbreaks observed in prevaccineera Copenhagen may result from highly intermingled basins of attraction for ghosts of multiannual cyclic attractors.