Deciphering the impacts of vaccination and immunity on pertussis epidemiology in Thailand

Type Journal Article - Proceedings of the National Academy of Sciences
Title Deciphering the impacts of vaccination and immunity on pertussis epidemiology in Thailand
Volume 110
Issue 23
Publication (Day/Month/Year) 2013
Page numbers 9595-9600
Pertussis is a highly infectious respiratory disease that is currently responsible for nearly 300,000 annual deaths worldwide, primarily in infants in developing countries. Despite sustained high vaccine uptake, a resurgence in pertussis incidence has been reported in a number of countries. This resurgence has led to critical questions regarding the transmission impacts of vaccination and pertussis immunology. We analyzed pertussis incidence in Thailand—both age-stratified and longitudinal aggregate reports—over the past 30 y. To dissect the contributions of waning pertussis immunity and repeat infections to pertussis epidemiology in Thailand following a pronounced increase in vaccine uptake, we used likelihood-based statistical inference methods to evaluate the support for multiple competing transmission models. We found that, in contrast to other settings, there is no evidence for pertussis resurgence in Thailand, with each model examined pointing to a substantial rise in herd immunity over the past 30 y. Using a variety of empirical metrics, we verified our findings by documenting signatures of changing herd immunity over the study period. Importantly, this work leads to the conclusion that repeat infections have played little role in shaping pertussis epidemiology in Thailand. Our results are surprisingly emphatic in support of measurable impact of herd immunity given the uncertainty associated with pertussis epidemiology.

Pertussis, or whooping cough, was historically considered a serious disease of childhood. Because of the high burden of morbidity and mortality associated with pertussis (1), routine vaccination programs were implemented in many developed countries during the 1940s and 1950s that led, in some instances, to a 99% reduction in reported incidence (2, 3). The success of these vaccination programs in reducing pertussis notifications led to optimism over its potential eradication, a sentiment that has since been replaced by widespread concern following high-profile outbreaks in populations with long-standing immunization, with the United States and Australia arguably experiencing the largest impacts of these resurgences (4??–7).

Recent attempts to explain contemporary pertussis epidemiology have largely attributed the resurgence to the immunological consequences of vaccination and natural infection. In turn, uncertainty surrounding the role of a number of potentially key players has been highlighted, including the duration of naturally acquired and vaccine-induced immunity (8??–11), limited natural immune boosting following the introduction of vaccine programs (10, 12), loss of vaccine efficacy resulting from antigenic divergence (13, 14), and, crucially, whether vaccines prevent pertussis transmission or simply reduce the incidence of disease (15?–17). To assess the population-level consequences of immunity, we confront high-resolution incidence reports in Thailand with modern techniques for statistical inference to provide a mechanistic interpretation of the transmission impact of vaccination on pertussis immunity in Thailand. Using a series of competing transmission models, we demonstrate that declines in pertussis incidence coinciding with increases in vaccine uptake between 1984 and 1989 arose following reduction in pertussis circulation. Indeed, the maximum-likelihood estimate associated with each model points to a small or negligible transmission contribution of repeat infections, with vaccination effectively generating herd immunity.

To verify our conclusions, we use several empirical metrics to demonstrate that there is a true increase in herd immunity. We document dramatic changes in patterns of pertussis epidemiology, and quantify shifts in population measures of herd immunity. We report that over the time span of this study, there was a drastic decline in reported pertussis cases from Thailand, an effect that is especially pronounced among infants. Coincident with reduced incidence, we also found a rise in the critical community size. Overall, these observations are consistent with reduced pertussis circulation in Thailand.

Our findings shed light on key hotly debated aspects of pertussis epidemiology. First, these results indicate that current pediatric immunization programs in Thailand have successfully reduced pertussis transmission. Second, there is no empirical evidence for a resurgence in Thailand, with circulation of Bordetella pertussis effectively controlled by current vaccines. Finally, repeat infections appear to play an insignificant role in pertussis epidemiology in Thailand.

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