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A key goal of pertussis control is to protect infants too young to be vaccinated, the age group most vulnerable to this highly contagious respiratory infection. In the last decade, maternal immunization has been deployed in many countries, successfully reducing pertussis in this age group. Because of immunological blunting, however, this strategy may erode the effectiveness of primary vaccination at later ages. Here, we systematically reviewed the literature on the relative risk (RR) of pertussis after primary immunization of infants born to vaccinated vs. unvaccinated mothers. The four studies identified had ≤6 years of follow-up and large statistical uncertainty (meta-analysis weighted mean RR: 0.71, 95% CI: 0.38-1.32). To interpret this evidence, we designed a new mathematical model with explicit blunting mechanisms and evaluated maternal immunization's short- and long-term impact on pertussis transmission dynamics. We show that transient dynamics can mask blunting for at least a decade after rolling out maternal immunization. Hence, the current epidemiological evidence may be insufficient to rule out modest reductions in the effectiveness of primary vaccination. Irrespective of this potential collateral cost, we predict that maternal immunization will remain effective at protecting unvaccinated newborns, supporting current public health recommendations., (© 2024. The Author(s).)

Routine vaccination with pertussis vaccines has been successful in driving down pertussis mortality and morbidity globally. Despite high vaccination coverage, countries such as Australia, USA, and UK have experienced increase in pertussis activity over the last few decades. This may be due to local pockets of low vaccination coverage that result in persistence of pertussis in the population and occasionally lead to large outbreaks. The objective of this study was to characterize the association between pertussis vaccination coverage and sociodemographic factors and pertussis incidence at the school district level in King County, Washington, USA. We used monthly pertussis incidence data for all ages reported to the Public Health Seattle and King County between January 1, 2010 and December 31, 2017 to obtain school district level pertussis incidence. We obtained immunization data from the Washington State Immunization Information System to estimate school-district level vaccination coverage as proportion of 19-35 month old children fully vaccinated with ≥4 doses of the Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccine in a school district. We used two methods to quantify the effects of vaccination coverage on pertussis incidence: an ecological vaccine model and an endemic-epidemic model. Even though the effect of vaccination is modeled differently in the two approaches, both models can be used to estimate the association between vaccination coverage and pertussis incidence. Using the ecological vaccine model, we estimated the vaccine effectiveness of 4 doses of Diphtheria-Tetanus-acellular-Pertussis vaccine to be 83% (95% credible interval: 63%, 95%). In the endemic-epidemic model, under-vaccination was statistically significantly associated with epidemic risk of pertussis (adjusted Relative Risk, aRR: 2.76; 95% confidence interval: 1.44, 16.6). Household size and median income were statistically significantly associated with endemic pertussis risk. The endemic-epidemic model suffers from ecological bias, whereas the ecological vaccine model provides less biased and more interpretable estimates of epidemiological parameters, such as DTaP vaccine effectiveness, for each school district., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO's Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care to 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia during 2015. Our Southern Africa Mother Infant Pertussis Study (SAMIPS) prospectively monitored a cohort of mother/infant pairs across infants' first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for respiratory syncytial virus (RSV) and Bordetella pertussis . Our retrospective analysis of the SAMIPS cohort found that symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins., Competing Interests: Zacharia Mupila and Lawrence Mwananyanda are employed by Right to Care Zambia., (©2023 Gunning et al.)

Introduction: The re-emergence of pertussis has occurred in the past two decades in developed countries. The highest morbidity and mortality is seen among infants. Vaccination in pregnancy is recommended to reduce the pertussis burden in infants., Methods: We developed and validated an agent-based model to characterize pertussis epidemiology in Alberta. We computed programmatic effectiveness of pertussis vaccination during pregnancy (PVE) in relation to maternal vaccine coverage and pertussis disease reporting thresholds. We estimated the population preventable fraction (PFP) of different levels of maternal vaccine coverage against counterfactual "no-vaccination" scenario. We modeled the effect of immunological blunting and measured protection through interruption of exposure pathways., Results: PVE was inversely related to duration of passive immunity from maternal immunization across most simulations. In the scenario of 50% maternal vaccine coverage, PVE was 87% (95% quantiles 82-91%), with PFP of 44% (95% quantiles 41-45%). For monthly age intervals of 0-2, 2-4, 4-6 and 6-12, PVE ranged between 82 and 99%, and PFP ranged between 41 and 49%. At 75% maternal vaccine coverage, PVE and PFP were 90% (95% quantiles 86-92%) and 68% (95% quantiles 65-69%), respectively. At 50% maternal vaccine coverage and 10% blunting, PVE and PFP were 86% (95% quantiles 77-87%) and 43% (95% quantiles 39-44%), respectively, while at 50% blunting, the corresponding values of PVE and PFP were 76% (95% quantiles 70-81%) and 38% (95% quantiles 35-40%). PVE attributable to interruption of exposure pathways was 54-57%., Conclusions: Our model predicts significant reduction in future pertussis cases in infants due to maternal vaccination, with immunological blunting slightly moderating its effectiveness. The model is most sensitive to maternal vaccination coverage. The interruption of exposure pathways plays a role in the reduction of pertussis burden in infants due to maternal immunization. The effect of maternal immunization on population other than infants remains to be elucidated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Pertussis has resurfaced in the UK, with incidence levels not seen since the 1980s. While the fundamental causes of this resurgence remain the subject of much conjecture, the study of historical patterns of pathogen diffusion can be illuminating. Here, we examined time series of pertussis incidence in the boroughs of Greater London from 1982 to 2013 to document the spatial epidemiology of this bacterial infection and to identify the potential drivers of its percolation. The incidence of pertussis over this period is characterized by 3 distinct stages: a period exhibiting declining trends with 4-year inter-epidemic cycles from 1982 to 1994, followed by a deep trough until 2006 and the subsequent resurgence. We observed systematic temporal trends in the age distribution of cases and the fade-out profile of pertussis coincident with increasing national vaccine coverage from 1982 to 1990. To quantify the hierarchy of epidemic phases across the boroughs of London, we used the Hilbert transform. We report a consistent pattern of spatial organization from 1982 to the early 1990s, with some boroughs consistently leading epidemic waves and others routinely lagging. To determine the potential drivers of these geographic patterns, a comprehensive parallel database of borough-specific features was compiled, comprising of demographic, movement and socio-economic factors that were used in statistical analyses to predict epidemic phase relationships among boroughs. Specifically, we used a combination of a feed-forward neural network (FFNN), and SHapley Additive exPlanations (SHAP) values to quantify the contribution of each covariate to model predictions. Our analyses identified a number of predictors of a borough's historical epidemic phase, specifically the age composition of households, the number of agricultural and skilled manual workers, latitude, the population of public transport commuters and high-occupancy households. Univariate regression analysis of the 2012 epidemic identified the ratio of cumulative unvaccinated children to the total population and population of Pakistan-born population to have moderate positive and negative association, respectively, with the timing of epidemic. In addition to providing a comprehensive overview of contemporary pertussis transmission in a large metropolitan population, this study has identified the characteristics that determine the spatial spread of this bacterium across the boroughs of London., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Waning of immunity after vaccination with the acellular Pertussis (aP) vaccine has been proposed as one of the main reasons for pertussis resurgence in the US. In this study, we estimated time-varying vaccine effectiveness after 5 doses of aP vaccine., Methods: We conducted a retrospective cohort study among children 5-9 years old (born between 2008 and 2012) living in King County, Washington, USA, who participated in the Washington State Immunization Information System. We estimated time-varying vaccine effectiveness after 5 doses of aP using smoothed scaled Schoenfeld residuals obtained from fitting Cox proportional hazards models to the data as well as piecewise constant Poisson regression., Results: There were 55 pertussis cases in this cohort, of whom 22 (40%) were fully-vaccinated and 33 (60%) were under-vaccinated. Vaccine effectiveness (VE) remained high for up to 42 months after the fifth dose (VE(t) = 89%; 95% CI: 64%, 97%) as estimated using survival analysis methods and up to 4 years (VE(t) = 93%; 95% CI: 67%, 98%) as estimated using Poisson regression., Conclusion: We did not find evidence for waning of vaccine effectiveness for up to four years after 5 doses of aP among 5 -9 years old children in King County, WA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Importance: In most countries, the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is administered as a 3-dose infant series followed by additional booster doses in the first 5 years of life. Short-term immunity from the DTaP vaccine can depend on the number, timing, and interval between doses. Not receiving doses in a timely manner might be associated with a higher pertussis risk., Objective: To examine the association between number and timeliness of vaccine doses and age-specific pertussis risk., Design, Setting, and Participants: This population-based, retrospective cohort study used Washington State Immunization Information System data and pertussis surveillance data from Public Health Seattle and King County, Washington. Included participants were children aged 3 months to 9 years born or living in King County, Washington, between January 1, 2008, and December 31, 2017. Data were analyzed from June 30 to December 1, 2019., Exposures: Being undervaccinated (receiving fewer than recommended doses at a given age) or delayed vaccination (not receiving doses within time frames recommended by Centers for Disease Control and Prevention)., Main Outcomes and Measures: Suspected, probable, and confirmed pertussis diagnosis., Results: A total of 316 404 children (median age, 65.2 months [interquartile range, 35.3-94.1 months]; 162 025 boys [51.2%]) as of December 31, 2017, with 17.4 million person-months of follow-up were included in the analysis. A total of 19 943 children (6.3%) had no vaccines recorded in the Immunization Information System, 116 193 (36.7%) received a vaccine with a delay, and 180 268 (56.9%) were fully vaccinated with no delay. Delayed vaccination and undervaccination rates were higher for older children (17.6% delayed or undervaccinated at age 2 months for dose 1 at 3 months vs 41.6% at age 5 years for dose 5) but improved for successive birth cohorts (52.2% for 2008 birth cohort vs 32.3% for 2017 birth cohort). Undervaccination was significantly associated with higher risk of pertussis for the 3-dose primary series (adjusted relative risk [aRR], 4.8; 95% CI, 3.1-7.6), the first booster (aRR, 3.2; 95% CI, 2.3-4.5), and the second booster (aRR, 4.6; 95% CI, 2.6-8.2). However, delay in vaccination among children who received the recommended number of vaccine doses was not associated with pertussis risk., Conclusions and Relevance: The results of this cohort study suggest that undervaccination is associated with higher pertussis risk. Short delays in vaccine receipt may be less important if the age-appropriate number of doses is administered, but delaying doses is not recommended. Ensuring that children receive all doses of pertussis vaccine, even if there is some delay, is important.

Recent pertussis resurgence in numerous countries may be driven by asymptomatic infections. Most pertussis surveillance studies are cross-sectional and cannot distinguish asymptomatic from pre-symptomatic infections. Longitudinal surveillance could overcome this barrier, providing more information about the true burden of pertussis at the population level. Here we analyze 17,442 nasopharyngeal samples from a longitudinal cohort of 1320 Zambian mother/infant pairs. Our analysis has two elements. First, we demonstrate that the full range of IS481 qPCR CT values provides insight into pertussis epidemiology, showing concordance of low and high CT results over time, within mother/infant pairs, and in relation to symptomatology. Second, we exploit these full-range qPCR data to demonstrate a high incidence of asymptomatic pertussis, including among infants. Our results demonstrate a wider burden of pertussis infection than we anticipated in this population, and expose key limitations of threshold-based interpretation of qPCR results in infectious disease surveillance., Competing Interests: CG, CG, WM, LM, DT, RP, GK, ZM, PR No competing interests declared, (© 2021, Gill et al.)

Introduction: Reliable information on rates of up-to-date coverage and timely administration of routine childhood immunisations are critical for guiding public health efforts worldwide, yet prospective observation of vaccination programmes within individual communities is rare. Here, we provide a longitudinal analysis of the directly observed administration of a three-dose primary vaccination series to infants in a low-resource community in Lusaka, Zambia., Methods: Throughout 2015, we recruited a longitudinal birth cohort of mother/infant pairs (initial enrolment, 1981 pairs; attending, 1497 pairs) from the periurban informal settlement of Chawama compound, located in Lusaka, Zambia. We prospectively monitored the administration of scheduled diphtheria-tetanus-pertussis (DTP) vaccinations across the first 14-18 weeks of life. We analysed study attendance and vaccine coverage, both overall and stratified by age group. We employed Kaplan-Meier analyses to estimate delays in age-appropriate administration of vaccine doses. We also assessed schedule timing violations, including early and compressed dose administration., Results: At study completion, first dose (DTP1) rates were high (92.9% of attending), whereas third dose completion (DTP3) rates were far lower (61.9%). Missed vaccinations and study dropout both contributed to the low DTP3 completion rates. DTP1 was administered very late (at or after 10 weeks) to 61 infants (4.1%). DTP1 was administered too early to 64 infants (4.3%), and 77 (5.1%) received consecutive doses below the minimum recommended spacing of 28 days., Conclusions: We observe substantial individual variation in the timing of early childhood DTP doses, though following this birth cohort proved challenging. Our results indicate that timely administration of both DTP1 and DTP3 remains a challenge in this community. These directly-observed, individual-based results provide an important counterpoint to more course-grained, survey-based national and province estimates of up-to-date vaccine coverage. This study also highlights the challenges of vaccine hesitancy and suboptimal utilisation of (no-cost) healthcare services in a low-resource urban setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Despite high vaccine coverage in many parts of the world, pertussis is resurging in a number of areas in which acellular vaccines are the primary vaccine administered to infants and young children. This is attributed in part to the suboptimal and short-lived immunity elicited by acellular pertussis vaccines and to their inability to prevent nasal colonization and transmission of the etiologic agent Bordetella pertussis In response to this escalating public health concern, the National Institute of Allergy and Infectious Diseases held the workshop "Overcoming Waning Immunity in Pertussis Vaccines" in September 2019 to identify issues and possible solutions for the defects in immunity stimulated by acellular pertussis vaccines. Discussions covered aspects of the current problem, gaps in knowledge and possible paths forward. This review summarizes presentations and discussions of some of the key points that were raised by the workshop., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Measles, an acute viral disease, continues to be an important cause of childhood mortality worldwide. Infection with the measles virus is thought to be associated with a transient but profound period of immune suppression. Recently, it has been claimed that measles-induced immune manipulation lasts for about 30 months and results in increased susceptibility to other co-circulating infectious diseases and more severe disease outcomes upon infection. We tested this hypothesis using model-based inference applied to parallel historical records of measles and whooping cough mortality and morbidity. Specifically, we used maximum likelihood to fit a mechanistic transmission model to incidence data from three different eras, spanning mortality records from 1904 to 1912 and 1922 to 1932 and morbidity records from 1946 to 1956. Our aim was to quantify the timing, severity and pathogenesis impacts of measles-induced immune modulation and their consequences for whooping cough epidemiology across a temporal gradient of measles transmission. We identified an increase in susceptibility to whooping cough following recent measles infection by approximately 85-, 10- and 36-fold for the three eras, respectively, although the duration of this effect was variable. Overall, while the immune impacts of measles may be strong and clearly evident at the individual level, their epidemiological signature in these data appears both modest and inconsistent. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.

Importance: The United States has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high estimated vaccine coverage. Short-lived immunity induced by diphtheria-tetanus-acellular pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden, but the duration of protection conferred by DTaP vaccines remains incompletely quantified., Objective: To assess the duration of immunity and the effectiveness of DTaP vaccines in US children., Design, Setting, and Participants: A mathematical, age-structured model of pertussis transmission, previously validated empirically on incidence data in Massachusetts, was used in this simulation study to assess the duration of DTaP immunity most consistent with the empirical values of the relative increase in the odds of acquiring pertussis from recent epidemiologic studies in the United States. The study included 5 simulated cohorts of children born between January 1, 2001, and December 31, 2005, followed up between the ages of 5 and 9 years (study period, January 1, 2006, to December 31, 2014). Statistical analysis was performed from May 1 to December 1, 2017., Interventions: Vaccination with DTaP according to the US immunization schedule, with a range of assumptions regarding the degree of waning immunity., Main Outcomes and Measures: Vaccine effectiveness and relative change in the odds of acquiring pertussis (odds ratio) in children aged 5 to 9 years, duration of DTaP immunity, and vaccine population-level impact., Results: This study found a marked association between the degree of waning immunity, vaccine effectiveness, and the odds ratio. Counterintuitively, the odds ratio was positively associated with vaccine effectiveness, as a consequence of nonlinear, age-assortative transmission dynamics. Based on the empirical odds ratios (1.33; 95% CI, 1.23-1.43), it was estimated that vaccine effectiveness exceeded 75% in children aged 5 to 9 years and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose., Conclusions and Relevance: The results of this study suggest that temporal trends in the odds of acquiring pertussis are an unreliable measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. Control strategies should be based on the best available estimates of vaccine properties and the age structure of the transmission network.

We present new evidence that the immunity conferred against pertussis by the DTaP acellular vaccine wanes more slowly than widely believed., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The recent resurgence of pertussis in England and Wales has been marked by infant deaths and rising cases in teens and adults. To understand which age cohorts are most responsible for these trends, we employed three separate statistical methods to analyze high-resolution pertussis reports from 1982 to 2012. The fine-grained nature of the time-series allowed us to describe the changes in age-specific incidence and contrast the transmission dynamics in the 1980s and during the resurgence era. Our results identified infants and school children younger than 10 years of age as a core group, prior to 2002: pertussis incidence in these populations was predictive of incidence in other age groups. After 2002, no core groups were identifiable. This conclusion is independent of methodology used. Because it is unlikely that the underlying contact patterns substantially changed over the study period, changes in predictability likely result from the introduction of more stringent diagnostics tests that may have inadvertently played a role in masking the relative contributions of core transmission groups., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The increase in whooping cough (pertussis) incidence in many countries with high routine vaccination coverage is alarming, with incidence in the US reaching almost 50,000 reported cases per year, reflecting incidence levels not seen since the 1950s. While the potential explanations for this resurgence remain debated, we face an urgent need to protect newborns, especially during the time window between birth and the first routine vaccination dose. Maternal immunisation has been proposed as an effective strategy for protecting neonates, who are at higher risk of severe pertussis disease and mortality. However, if maternally derived antibodies adversely affect the immunogenicity of the routine schedule, through blunting effects, we may observe a gradual degradation of herd immunity. 'Wasted' vaccines would result in an accumulation of susceptible children in the population, specifically leading to an overall increase in incidence in older age groups. In this Perspective, we discuss potential long-term epidemiological effects of maternal immunisation, as determined by possible immune interference outcomes., (This article is copyright of The Authors, 2017.)

Background:  The increase in the incidence of whooping cough (pertussis) in many countries with high vaccination coverage is alarming. Maternal pertussis immunization has been proposed as an effective means of protecting newborns during the interval between birth and the first routine dose. However, there are concerns regarding potential interference between maternal antibodies and the immune response elicited by the routine schedule, with possible long-term population-level effects., Methods:  We formulated a transmission model comprising both primary routine and maternal immunization. This model was examined to evaluate the long-term epidemiological effects of routine and maternal immunization, together with consequences of potential immune interference scenarios., Results:  Overall, our model demonstrates that maternal immunization is an effective strategy in reducing the incidence of pertussis in neonates prior to the onset of the primary schedule. However, if maternal antibodies lead to blunting, incidence increases among older age groups. For instance, our model predicts that with 60% routine and maternal immunization coverage and 30% blunting, the incidence among neonates (0-2 months) is reduced by 43%. Under the same scenario, we observe a 20% increase in incidence among children aged 5-10 years. However, the downstream increase in the older age groups occurs with a delay of approximately a decade or more., Conclusions:  Maternal immunization has clear positive effects on infant burden of disease, lowering mean infant incidence. However, if maternally derived antibodies adversely affect the immunogenicity of the routine schedule, we predict eventual population-level repercussions that may lead to an overall increase in incidence in older age groups., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. Still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. Resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. In this review, we first present 1980-2012 incidence data from 63 countries and show that pertussis resurgence is not universal. We further argue that the large geographical variation in trends probably precludes a simple explanation, such as the transition from whole-cell to acellular pertussis vaccines. Reviewing available evidence, we then propose that prevailing views on pertussis epidemiology are inconsistent with both historical and contemporary data. Indeed, we summarize epidemiological evidence showing that natural infection and vaccination both appear to provide long-term protection against transmission and disease, so that previously infected or vaccinated adults contribute little to overall transmission at a population level. Finally, we identify several promising avenues that may lead to a consistent explanation of global pertussis epidemiology and to more effective control strategies., (© 2016 The Author(s).)

Pertussis has reemerged as a major public health concern in many countries where it was once considered well controlled. Although the mechanisms responsible for continued pertussis circulation and resurgence remain elusive and contentious, many countries have nevertheless recommended booster vaccinations, the timing and number of which vary widely. Here, using a stochastic, age-stratified transmission model, we searched for cost-effective booster vaccination strategies using a genetic algorithm. We did so assuming four hypothesized mechanisms underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II) frequent primary vaccine failure, (III) waning of vaccine-derived protection, and (IV) vaccine "leakiness." For scenarios I-IV, successful booster strategies were identified and varied considerably by mechanism. Especially notable is the inability of booster schedules to alleviate resurgence when vaccines are leaky. Critically, our findings argue that the ultimate effectiveness of vaccine booster schedules will likely depend on correctly pinpointing the causes of resurgence, with misdiagnosis of the problem epidemiologically ineffective and economically costly.

Recent much-publicized increases in pertussis case reports in some countries with high vaccine coverage have raised concerns about its current and future control. The ubiquity of this trend, however, remains unexamined. In an attempt to paint a global picture, we used case counts to determine which countries experienced statistically significant trends in incidence over the past two decades and to map changes in incidence during this period. These data reveal that pertussis resurgence is not a universal phenomenon. The heterogeneity in incidence trends, even in countries with superficially similar demography, socioeconomic conditions and vaccination programmes, is striking and requires explanation. In this opinion piece, we review and assess the multifaceted proposed explanations incorporating evolution, population dynamics, and the details of immunization programmes. While we do not solve the riddle that is pertussis epidemiology, we highlight critical aspects that are likely to hold the key to understanding its worldwide epidemiology.

Pertussis incidence has been rising in some countries, including the UK, despite sustained high vaccine coverage. We questioned whether it is possible to explain the resurgence without recourse to complex hypotheses about pathogen evolution, subclinical infections, or trends in surveillance efficiency. In particular, we investigated the possibility that the resurgence is a consequence of the legacy of incomplete pediatric immunization, in the context of cohort structure and age-dependent transmission. We constructed a model of pertussis transmission in England and Wales based on data on age-specific contact rates and historical vaccine coverage estimates. We evaluated the agreement between model-predicted and observed patterns of age-specific pertussis incidence under a variety of assumptions regarding the duration of immunity. Under the assumption that infection-derived immunity is complete and lifelong, and regardless of the duration of vaccine-induced immunity, the model consistently predicts a resurgence of pertussis incidence comparable to that which has been observed. Interestingly, no resurgence is predicted when infection- and vaccine-derived immunities wane at the same rate. These results were qualitatively insensitive to rates of primary vaccine failure. We conclude that the alarming resurgence of pertussis among adults and adolescents in Britain and elsewhere may simply be a legacy of historically inadequate coverage employing imperfect vaccines. Indeed, we argue that the absence of resurgence at this late date would be more surprising. Our analysis shows that careful accounting for age dependence in contact rates and susceptibility is prerequisite to the identification of which features of pertussis epidemiology want additional explanation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

Prediction and control of the geographical spread of emerging pathogens has become a central public health issue. Because these infectious diseases are by definition novel, there are few data to characterize their dynamics. One possible solution to this problem is to apply lessons learnt from analyses of historical data on familiar and epidemiologically similar pathogens. However, the portability of the spatial ecology of an infectious disease in a different epoch to other infections remains unexamined. Here, we study this issue by taking advantage of the recent re-emergence of pertussis in the United States to compare its spatial transmission dynamics throughout the 1950s with the past decade. We report 4-year waves, sweeping across the continent in the 1950s. These waves are shown to emanate from highly synchronous foci in the northwest and northeast coasts. In contrast, the recent resurgence of the disease is characterized by 5.5-year epidemics with no particular spatial structure. We interpret this to be the result of dramatic changes in patterns of human movement over the second half of the last century, together with changing age distribution of pertussis. We conclude that extrapolation regarding the spatial spread of contemporaneous pathogens based on analyses of historical incidence may be potentially very misleading.

Resolving the long-term, population-level consequence of vaccine-induced immunity to pertussis is a key challenge for control strategies and vaccine development. Controlled vaccine efficacy studies provide invaluable information; however, they are limited in scope by their sample size and follow-up duration. Long-term time series of incidence data collected by public health institutions provide insight at a broader scale, especially when the data are spatially explicit and age stratified. By using modern ecological and statistical methodolgies, which are reviewed in this paper, new insights into the duration of transmission-blocking immunity and the age-specific patterns of transmission can be gained. Recent advances in computing power and statistical software development will increasingly make these methods available to public health practitioners, vaccine developers and academics alike.

Although the resurgence of pertussis in nations with long-standing vaccination programs has raised serious concerns about the effectiveness of current immunization policy, the epidemiology of resurgence remains poorly understood. We analyzed pertussis notifications in US states obtained from the National Notifiable Disease Surveillance System from 1951 to 2010 to explore the timing, spatial pattern and consistency of resurgence across the country. Here we show that resurgence occurred at different times in different states, spread out over a transition period of roughly three decades. Further, despite this spatial variation, broad patterns in pertussis epidemiology can be described by two dominant phases: (1) a period of decline ending in the mid-1970s, followed by (2) nationwide resurgence. Together, these patterns explain 89.7% of the variation in US case notifications between 1951 and 2005. This resurgence was interrupted, however, by a synchronized downturn in 2005 that continues to the present in many large states. The causes of these two transitions in pertussis epidemiology remain hotly debated, though our findings suggest that evolution of the Bordetella pertussis bacterium, loss of immunity and persistent transmission among adults, and demographic drivers are more probable explanations than changes in reporting or the introduction of acellular vaccines., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The epidemiology of whooping cough (pertussis) remains enigmatic. A leading cause of infant mortality globally, its resurgence in several developed nations--despite the availability and use of vaccines for many decades--has caused alarm. We combined data from a singular natural experiment and a detailed contact network study to show that age-specific contact patterns alone can explain shifts in prevalence and age-stratified incidence in the vaccine era. The practical implications of our results are notable: Ignoring age-structured contacts is likely to result in misinterpretation of epidemiological data and potentially costly policy missteps.

Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable.

Understanding the mechanisms that generate oscillations in the incidence of childhood infectious diseases has preoccupied epidemiologists and population ecologists for nearly two centuries. This body of work has generated simple yet powerful explanations for the epidemics of measles and chickenpox, while the dynamics of other infectious diseases, such as whooping cough, have proved more challenging to decipher. A number of authors have, in recent years, proposed that the noisy and somewhat irregular epidemics of whooping cough may arise due to stochasticity and its interaction with nonlinearity in transmission and seasonal variation in contact rates. The reason underlying the susceptibility of whooping cough dynamics to noise and the precise nature of its transient dynamics remain poorly understood. Here we use household data on the incubation period in order to parametrize more realistic distributions of the latent and infectious periods. We demonstrate that previously reported phenomena result from transients following the interaction between the stable annual attractor and unstable multiennial solutions.

Recent studies have demonstrated that ecological interference among some childhood diseases may have important dynamic consequences. An interesting question is, when would we expect the interference effect to be pronounced? To address the issue, here we develop a seasonally forced two-disease age-structured model, using empirically derived age-specific force of infection (ASFOI) for numerous infections of childhood. Our comparative numerical analysis shows that when the ASFOIs for the two diseases largely overlap, the dynamics predicted by the two-disease model are generally different from those predicted by the analogous single-disease model, suggesting strong fingerprints of disease interference. When the ASFOIs overlap less, on the other hand, both diseases behave as predicted by the single-disease model, suggesting weak interference. We conclude that age structure is an important factor that should be taken into account in order to explore the underlying mechanisms of disease interference.

Measles and pertussis are ubiquitous vaccine-preventable diseases, which remain an important public health problem in developing countries. Hence, developing a deep understanding of their transmission dynamics remains imperative. To achieve this, we compared the impact of vaccination at both individual and population levels in a Senegalese rural community. This study represents the first such comparative study in tropical conditions and constitutes a point of comparison with other studies of disease dynamics in developed countries. Changes in the transmission rates of infections are reflected in their mean ages at infection and basic reproductive ratio calculated before and after vaccination. We explored persistence of both infections in relation to population size in each village and found the inter-epidemic period for the whole area using wavelets analysis. As predicted by epidemiological theory, we observed an increase in the mean age at infection and a decrease in the reproductive ratio of both diseases. We showed for both the pre- vaccination and vaccine eras that persistence depends on population size. After vaccination, persistence decreased and the inter-epidemic period increased. The observed changes suggest that vaccination against measles and pertussis induced a drop in their transmission. Similarities in disease dynamics to those of temperate regions such as England and Wales were also observed.

Developing methods for anticipating the emergence or reemergence of infectious diseases is both important and timely; however, traditional model-based approaches are stymied by uncertainty surrounding the underlying drivers. Here, we demonstrate an operational, mechanism-agnostic detection algorithm for disease (re-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down. Specifically, we used computer simulations to train a supervised learning algorithm to detect the dynamical footprints of (re-)emergence present in epidemiological data. Our algorithm was then challenged to forecast the slowly manifesting, spatially replicated reemergence of mumps in England in the mid-2000s and pertussis post-1980 in the United States. Our method successfully anticipated mumps reemergence 4 years in advance, during which time mitigation efforts could have been implemented. From 1980 onwards, our model identified resurgent states with increasing accuracy, leading to reliable classification starting in 1992. Additionally, we successfully applied the detection algorithm to 2 vector-transmitted case studies, namely, outbreaks of dengue serotypes in Puerto Rico and a rapidly unfolding outbreak of plague in 2017 in Madagascar. Taken together, these findings illustrate the power of theoretically informed machine learning techniques to develop early warning systems for the (re-)emergence of infectious diseases. This study develops an operational algorithm for the detection of the (re-)emergence of infectious disease. The authors illustrate its utility by successfully applying it to four (re-)emerging threats—mumps, pertussis, dengue and plague, providing early warning that could enable intervention measures. [ABSTRACT FROM AUTHOR]

Pertussis reemergence is underpinned by slowly waning immunity to both whole-cell and acellular vaccines together with incomplete past vaccination coverage. The problem of pertussis: The recent rise of pertussis in developed countries has generated controversy as to its cause. Domenech de Cellès et al. modeled pertussis transmission using incidence data from Massachusetts, United States. They found little evidence that the switch to the acellular vaccine contributed to the Massachusetts outbreaks. Instead, waning vaccine-conferred immunity, as opposed to vaccine failure to mount a full or even partial immune response, best explained the local rise in pertussis cases along with a historical gap in vaccination coverage. Simulations suggested that administering existing boosters to children may be an effective strategy to halt pertussis transmission. The resurgence of pertussis over the past decades has resulted in incidence levels not witnessed in the United States since the 1950s. The underlying causes have been the subject of much speculation, with particular attention paid to the shortcomings of the latest generation of vaccines. We formulated transmission models comprising competing hypotheses regarding vaccine failure and challenged them to explain 16 years of highly resolved incidence data from Massachusetts, United States. Our results suggest that the resurgence of pertussis is a predictable consequence of incomplete historical coverage with an imperfect vaccine that confers slowly waning immunity. We found evidence that the vaccine itself is effective at reducing overall transmission, yet that routine vaccination alone would be insufficient for elimination of the disease. Our results indicated that the core transmission group is schoolchildren. Therefore, efforts aimed at curtailing transmission in the population at large, and especially in vulnerable infants, are more likely to succeed if targeted at schoolchildren, rather than adults. [ABSTRACT FROM AUTHOR]

Prediction and control of the geographical spread of emerging pathogens has become a central public health issue. Because these infectious diseases are by definition novel, there are few data to characterize their dynamics. One possible solution to this problem is to apply lessons learnt from analyses of historical data on familiar and epidemiologically similar pathogens. However, the portability of the spatial ecology of an infectious disease in a different epoch to other infections remains unexamined. Here, we study this issue by taking advantage of the recent re-emergence of pertussis in the United States to compare its spatial transmission dynamics throughout the 1950s with the past decade. We report 4-year waves, sweeping across the continent in the 1950s. These waves are shown to emanate from highly synchronous foci in the northwest and northeast coasts. In contrast, the recent resurgence of the disease is characterized by 5.5-year epidemics with no particular spatial structure. We interpret this to be the result of dramatic changes in patterns of human movement over the second half of the last century, together with changing age distribution of pertussis. We conclude that extrapolation regarding the spatial spread of contemporaneous pathogens based on analyses of historical incidence may be potentially very misleading. [ABSTRACT FROM AUTHOR]