Immune boosting and the perils of interpreting pertussis seroprevalence studies

Seroepidemiology has significant potential for uncovering the unreported burden of infectious diseases. However, for diseases without well-defined serological correlates of protection, the phenomenon of immune boosting--whereby pathogen exposure triggers a detectable immune response without causing a transmissible infection--can complicate the interpretation of seroprevalence data from serosurveys. This issue is relevant to pertussis, a highly contagious and vaccine-preventable disease that remains a significant public health concern worldwide. Here, we aimed to evaluate the reliability of pertussis serosurveys--in particular, how immune boosting may cause these studies to overestimate transmissible infections--based on a population-based model of pertussis transmission that tracked the dynamics of infection, immune boosting, and seropositivity of IgG against pertussis toxin. By fitting this model to seroprevalence data from the late whole-cell pertussis vaccine era in six European countries, we estimated immunity conferred by infection or vaccination to last, on average, for several decades. We then predicted the prevalence and positive predictive value (PPV)--the proportion of true positives-- of seropositivity in serosurveys among adult age groups across twelve countries broadly representative of transmission patterns worldwide. Overall, we predicted a low PPV across multiple scenarios, especially in young adults aged 20-39 years, where it dropped below 50% in almost all tested scenarios. Thus, the common interpretation of seroprevalence as a measure of recent infections may lead to an overly pessimistic view of pertussis circulation. Our model is applicable to numerous other infectious disease systems and may be used to efficiently synthesize evidence from multiple data streams, including case-based and seroprevalence data.