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Recent months have seen an increase in pertussis cases in several countries across the Northern and Southern hemispheres. The lack of immune stimulation during the COVID-19 pandemic due to the reduced circulation of Bordetella pertussis, the pathogen responsible for pertussis, is likely to have led to increased population susceptibility which has been magnified the typical three to five yearly cyclical peaks in activity. Maternal immunization for pertussis proves highly effective in protecting infants under three months of age. It's also critical for immunizers and parents to maintain high and timely immunization uptake to ensure infants receive maximum early protection when they are most at risk of severe disease., Competing Interests: Declarations of competing interest AK is the Vice President for academia and strategy of the RCOG. All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bordetella pertussis, the bacterium responsible for whooping cough, remains a significant public health challenge despite the existing licensed pertussis vaccines. Current acellular pertussis vaccines, though having favorable reactogenicity and efficacy profiles, involve complex and costly production processes. In addition, acellular vaccines have functional challenges such as short-lasting duration of immunity and limited antigen coverage. Filamentous hemagglutinin (FHA) is an adhesin of B. pertussis that is included in all multivalent pertussis vaccine formulations. Antibodies to FHA have been shown to prevent bacterial attachment to respiratory epithelial cells, and T cell responses to FHA facilitate cell-mediated immunity. In this study, FHA's mature C-terminal domain (MCD) was evaluated as a novel vaccine antigen. MCD was conjugated to virus-like particles via SpyTag-SpyCatcher technology. Prime-boost vaccine studies were performed in mice to characterize immunogenicity and protection against the intranasal B. pertussis challenge. MCD-SpyVLP was more immunogenic than SpyTag-MCD antigen alone, and in Tohama I strain challenge studies, improved protection against challenge was observed in the lungs at day 3 and in the trachea and nasal wash at day 7 post-challenge. Furthermore, a B. pertussis strain encoding genetically inactivated pertussis toxin was used to evaluate MCD-SpyVLP vaccine immunity. Mice vaccinated with MCD-SpyVLP had significantly lower respiratory bacterial burden at both days 3 and 7 post-challenge compared to mock-vaccinated animals. Overall, these data support the use of SpyTag-SpyCatcher VLPs as a platform for use in vaccine development against B. pertussis and other pathogens., Competing Interests: The authors declare no conflict of interest.

Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of Bordetella pertussis and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.

Introduction: Whooping cough, also known as pertussis, remains a significant challenge as a vaccine-preventable disease worldwide. Since the switch from the whole-cell Pertussis (wP) vaccine to the acellular Pertussis vaccine (aP), cases of whooping cough have increased in countries using the aP vaccine. Understanding the immune system's response to pertussis vaccines and infection is crucial for improving current vaccine efficacy., Areas Covered: This review of the literature using PubMed records offers an overview of the qualitative differences in antibody and T cell responses to B. pertussis (BP) in vaccination and infection, and their potential association with decreased efficacy of the aP vaccine in preventing infection and subclinical colonization. We further discuss how asymptomatic infections and carriage are widespread among vaccinated human populations, and explore methodologies that can be employed for their detection, to better understand their impact on adaptive immune responses and identify key features necessary for protection against the disease., Expert Opinion: An underappreciated human BP reservoir, stemming from the decreased capacity of the aP vaccine to prevent subclinical infection, offers an alternative explanation for the increased incidence of clinical disease and recurrent outbreaks.

Background: Changes to pertussis vaccination programmes can have impacts on disease burden that should be estimated independently from factors such as age- and period-related trends. We used age-period-cohort (APC) models to explore pertussis incidence in Manitoba over a 25-year period (1992-2017)., Methods: We identified all laboratory-confirmed cases of pertussis from Manitoba's Communicable Diseases Database and calculated age-standardized incidence rates. We used APC models to investigate trends in pertussis incidence., Results: During the study period, 2479 cases were reported. Age-standardized rates were highest during a large outbreak in 1994 (55 cases/100 000 person-years), with much lower peaks in 1998, 2012 and 2016. We saw strong age and cohort effects in the APC models, with a steady decrease in incidence with increasing age and increased risk in the cohort born between 1980 and 1995., Conclusions: The highest risk for pertussis was consistently in young children, regardless of birth cohort or time period. The 1981 programme change to an adsorbed whole-cell pertussis vaccine with low effectiveness resulted in reduced protection in the 1981-95 birth cohort and contributed to the largest outbreak of disease during the 25-year study period., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: Although pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006-2008., Methods: We assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies., Results: We included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: - 21.0, 24.0) in the period 15-364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15-364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6-11 years) than younger (0-5 years) children, it was lower at 12-13 years than after 14 years., Conclusion: VE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy., (© 2021. © Crown 2021 as represented by the Government of Ontario.)

Pertussis (whooping cough) is a respiratory infection caused by Bordetella pertussis. All ages are susceptible. In the prevaccine era, almost all children became infected. Pertussis is particularly dangerous in young infants, who account for practically all hospitalizations and deaths, but clinical disease is burdensome at any age. Widespread use of pertussis vaccines dramatically reduced cases, but concern over adverse reactions led to the replacement of standard whole-cell by acellular pertussis vaccines that contain only a few selected pertussis antigens and are far less reactogenic. Routine administration of acellular pertussis vaccines combined with diphtheria and tetanus toxoids is recommended in infancy with toddler and preschool boosters, at age 11, and during pregnancy. Boosting in the second half of every pregancy is critical to protection of the newborn. Waning of vaccine immunity over time has become an increasing concern, and several new pertussis vaccines are being evaluated to address this problem., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Pertussis, mainly caused by Bordetella pertussis, is a severe respiratory disease that can be fatal, especially in young infants. Vaccines, massively implemented since the middle of the last century, have substantially reduced the pertussis incidence, but have not been able to fully control the disease. One of the shortcomings of current pertussis vaccines is their inability to prevent infection by and transmission of B. pertussis, in contrast to immunity following natural infection. We have developed the live attenuated nasal vaccine BPZE1 and have shown that it prevents both disease and B. pertussis infection in preclinical models. This vaccine is now in clinical development. However, the initial clinical studies have suggested that vaccine take is hampered by pre-existing antibodies to pertactin. Here, we have constructed a pertactin-deficient BPZE1 derivative called BPZE1P in order to overcome this limitation. BPZE1P colonized the murine respiratory tract as efficiently as BPZE1 and induced antibodies at levels similar to those elicited by BPZE1. In the presence of pre-existing antibodies induced by acellular pertussis vaccination, BPZE1P colonized the mouse respiratory tract more efficiently than BPZE1. Both vaccines protected equally well the murine lungs and noses from challenge with laboratory and clinical strains of B. pertussis, including pertactin-deficient strains, against which current acellular pertussis vaccines are less efficient. BPZE1P may thus be an interesting alternative to BPZE1 to overcome vaccine take limitations due to pre-existing antibodies to pertactin., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [LS, ASD and CL are co-inventors of patents on BPZE1, which were licensed to ILiAD Biotechnologies. No conflict of interest is declared by the other author.], (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (i.n.) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (phosphate-buffered saline [PBS]), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particles (IRI-1501). We utilized two study designs: short term (challenged 35 days after priming vaccination) and long term (challenged 6 months after boost). The short-term study demonstrated that immunization with i.n. vaccine candidates decreased the bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant B. pertussis -specific IgG antibodies in both the serum and lung and increased numbers of anti- B. pertussis IgG-secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the i.n. vaccines correlated with protection, suggesting that long-term antibody responses can be protective., (Copyright © 2021 Wolf et al.)

Background: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using electronic health record (eHR) databases in Europe. Proof-of-concept studies were designed to assess the proposed processes and system for generating the required evidence to perform B/R assessment and near-real time monitoring of vaccines. We aimed to test B/R methodologies for vaccines, using the comparison of the B/R profiles of whole-cell (wP) and acellular pertussis (aP) vaccine formulations in children as an example., Methods: We used multi-criteria decision analysis (MCDA) to structure the B/R assessment combined with individual-level state transition modelling to build the B/R effects table. In the state transition model, we simulated the number of events in two hypothetical cohorts of 1 million children followed from first pertussis dose till pre-school-entry booster (or six years of age, whichever occurred first), with one cohort receiving wP, and the other aP. The benefits were reductions in pertussis incidence and complications. The risks were increased incidences of febrile convulsions, fever, hypotonic-hyporesponsive episodes, injection-site reactions and persistent crying. Most model parameters were informed by estimates (coverage, background incidences, relative risks) from eHR databases from Denmark (SSI), Spain (BIFAP and SIDIAP), Italy (Pedianet) and the UK (RCGP-RSC and THIN). Preferences were elicited from clinical and epidemiological experts., Results: Using state transition modelling to build the B/R effects table facilitated the comparison of different vaccine effects (e.g. immediate vaccine risks vs long-term vaccine benefits). Estimates from eHR databases could be used to inform the simulation model. The model results could be easily combined with preference weights to obtain B/R scores., Conclusion: Existing B/R methodology, modelling and estimates from eHR databases can be successfully used for B/R assessment of vaccines., Competing Interests: Declaration of Competing Interest Tom de Smedt, Hanne-Dorthe Emborg, Giorgia Danieli, Talita Duarte-Salles, Consuelo Huerta, Elisa Martin-Merino, Gino Picelli and Lara Tramontan declared no potential conflicts of interest. Kaatje Bollaerts and Daniel Weibel received consultancy fees from GSK for work unrelated to the submitted work. Miriam Sturkenboom declared that she has received grants from Novartis, CDC and Bill & Melinda Gates Foundation, for work unrelated to the submitted work. Edouard Ledent and Vincent Bauchau declared that he is employed by GSK and holds company shares., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The Accelerated Development of Vaccine benefit-risk Collaboration in Europe (ADVANCE) public-private collaboration, aimed to develop and test a system for rapid benefit-risk monitoring of vaccines using healthcare databases in Europe. The objective of this proof-of-concept (POC) study was to test the feasibility of the ADVANCE system to generate incidence rates (IRs) per 1000 person-years and incidence rate ratios (IRRs) for risks associated with whole cell- (wP) and acellular- (aP) pertussis vaccines, occurring in event-specific risk windows in children prior to their pre-school-entry booster., Methods: The study population comprised almost 5.1 million children aged 1 month to <6 years vaccinated with wP or aP vaccines during the study period from 1 January 1990 to 31 December 2015. Data from two Danish hospital (H) databases (AUH and SSI) and five primary care (PC) databases from, UK (THIN and RCGP RSC), Spain (SIDIAP and BIFAP) and Italy (Pedianet) were analysed. Database-specific IRRs between risk vs. non-risk periods were estimated in a self-controlled case series study and pooled using random-effects meta-analyses., Results: The overall IRs were: fever, 58.2 (95% CI: 58.1; 58.3), 96.9 (96.7; 97.1) for PC DBs and 8.56 (8.5; 8.6) for H DBs; convulsions, 7.6 (95% CI: 7.6; 7.7), 3.55 (3.5; 3.6) for PC and 12.87 (12.8; 13) for H; persistent crying, 3.9 (95% CI: 3.8; 3.9) for PC, injection-site reactions, 2.2 (95% CI 2.1; 2.2) for PC, hypotonic hypo-responsive episode (HHE), 0.4 (95% CI: 0.4; 0.4), 0.6 (0.6; 0.6) for PC and 0.2 (0.2; 0.3) for H; and somnolence: 0.3 (95% CI: 0.3; 0.3) for PC. The pooled IRRs for persistent crying, fever, and ISR, adjusted for age and healthy vaccinee period were higher after wP vs. aP vaccination, and lower for convulsions, for all doses. The IRR for HHE was slightly lower for wP than aP, while wP was associated with somnolence only for dose 1 and dose 3 compared with aP., Conclusions: The estimated IRs and IRRs were comparable with published data, therefore demonstrating that the ADVANCE system was able to combine several European healthcare databases to assess vaccine safety data for wP and aP vaccination., Competing Interests: Declaration of Competing Interest Caitlin Dodd, Talita Duarte-Salles, Gino Picelli, Lara Tramontan, Giorgia Danieli, Ana Correa, Chris McGee, Elisa Martín-Merino, Consuelo Huerta, Hanne-Dorthe Emborg, Kaatje Bollaerts, Klara Berencsi declared no conflicts of interest. Daniel Weibel declared personal fees from GSK outside the submitted work. Olivia Mahaux, Francois Haguinet and Vincent Bauchau declared that they are employed by GSK and hold shares from GSK. Lina Titievsky declared that she is employed Pfizer and holds stocks from Pfizer. Miriam Sturkenboom declared that she has received grants from Novartis, CDC and the Bill & Melinda Gates Foundation outside the submitted work., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Because the increasing morbidity of pertussis in all age groups worldwide, the quality of pertussis vaccines has aroused a common concern. To improve the quality of pertussis vaccine in research and production, the effects of manufacture processes on post-translational modifications (PTMs) of bioactive proteins in pertussis vaccine were investigated by a liquid chromatography quadruple - time of flight mass spectrometer (LC-Q-TOF) method in this study. The main bioactive proteins in pertussis vaccine studied include pertussis toxin (PT), pertactin (PRN) and filamentous hemagglutinin (FHA). The main manufacture processes focused are fermentation techniques, purification techniques and storage conditions. The results show that FHA and PRN are rather stable against PTM as only deamidation (Asn) was detected, which is believed to be due to their larger sizes of the bioactive proteins. For PT, however, all the manufacture processes studied have shown significant effects on types and sites of PTMs. Modifications of oxidation and demethylation (Met) occurred in the PT proteins produced by B. pertussis strain Tohama and stored in suspension in saline solution. However, they were not observed in the PT samples produced from stain CS and stored in powders. Carbamylation (Arg) on multiple sites (in S3, S4 and S5) was observed in the PT produced from 5th generation strain CS of B. pertussis. The high abundance ratio of carbamylation modification was potentially a negative effect on the detoxification of PT, since unmodified Lys was the active site for detoxification. The results obtained in this study provide information for making protection strategies against PTMs in pertussis vaccine in manufacture and storage., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Despite high vaccination coverage using acellular (ACV) and whole-cell pertussis (WCV) vaccines, the resurgence of pertussis is observed globally. Genetic divergence in circulating strains of Bordetella pertussis has been reported as one of the contributing factors for the resurgence of the disease. Our current knowledge of B. pertussis genetic evolution in circulating strains is mostly based on studies conducted in countries using ACVs targeting only a few antigens used in the production of ACVs. To better understand the adaptation to vaccine-induced selection pressure, it will be essential to study B. pertussis populations in developing countries which are using WCVs. India is a significant user and global supplier of WCVs. We report here comparative genome analyses of vaccine and clinical isolates reported from India. Whole-genome sequences obtained from vaccine strains: WCV (J445, J446, J447 and J448), ACV (BP165) were compared with Tohama-I reference strain and recently reported clinical isolates from India (BPD1, BPD2). Core genome-based phylogenetic analysis was also performed using 166 isolates reported from countries using ACV., Results: Whole-genome analysis of vaccine and clinical isolates reported from India revealed high genetic similarity and conserved genome among strains. Phylogenetic analysis showed that clinical and vaccine strains share genetic closeness with reference strain Tohama-I. The allelic profile of vaccine strains (J445:ptxP1/ptxA2/prn1/fim2-1/fim3-1; J446: ptxP2/ptxA4/prn7/fim2-2/fim3-1; J447 and J448: ptxP1/ptxA1/ prn1/fim2-1/fim3-1), which matched entirely with clinical isolates (BPD1:ptxP1/ptxA1/prn1/fim2-1 and BPD2: ptxP1/ptxA1/prn1/fim2-1) reported from India. Multi-locus sequence typing (MLST) demonstrated the presence of dominant sequence types ST2 and primitive ST1 in vaccine strains which will allow better coverage against circulating strains of B. pertussis., Conclusions: The study provides a detailed characterization of vaccine and clinical strains reported from India, which will further facilitate epidemiological studies on genetic shifts in countries which are using WCVs in their immunization programs.

Infants aged under one year are at the highest risk of severe complications or death from pertussis infection. Prompt vaccination with a three dose course at two, three and four months of age decreases the amount of time they are vulnerable following waning of maternal antibodies. In Wales, uptake of all three doses of the primary course of pertussis containing vaccine is high. However, timeliness and equity at a population level have not been previously reported. This analysis included 163,733 children born from 1st January 2013 to 31st December 2017. In this cohort 87.9% received the first dose of a pertussis containing vaccine by 12 weeks of age, 87.1% had received all three doses by 24 weeks of age, and 96.3% received three doses by 52 weeks of age. Differences in uptake between those living in the most deprived and least deprived quintiles of Lower Super Output Area (LSOA) were smaller than differences in timeliness, but statistically significant. In 2017 the difference in timely uptake between those living in the most and least deprived quintiles was 4%, 5% and 7% for doses one, two and three respectively. There was a difference of 10% in the proportion of infants receiving all three primary vaccinations on time between the most and least deprived quintile of LSOAs. Consideration is needed on interventions that will help improve timeliness such as enhanced follow up of defaulters, electronic communication between primary care data systems, enhanced health visitor intervention and opportunistic vaccination in those who fail to attend scheduled vaccination appointments. There is also the need for routine monitoring of timeliness and further research into what influences delayed vaccination., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Richard Roberts and Anne McGowan declare a non-personal non-specific conflict of interest in relation to Astra Zeneca, GSK, MSD, Pfizer, Sanofi and Seqirus who all sponsor the annual Wales Immunisation Conference up to a maximum of £2000.]., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14-15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15-19-years-old to infants <1-year-old decreased following introduction of the Tdap program and were significantly halved during the 2009-2012 post-Tdap versus 2000-2003 pre-Tdap period. This program impact, however, is tempered by the observation that pertussis incidence among 15-19-year-olds was already lower than any other pediatric age group, following gradual decline from pre-teen rates even before the Tdap program. The risk of hospitalization among adolescents 15-19-years-old was also low throughout at <1/100,000. Furthermore, IRRs increased in 2013-2017 when an increasing proportion of 15-19-year-olds were primed with acellular pertussis vaccine only, suggesting short-lived Tdap booster-dose effectiveness that warrants further monitoring., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pertussis persists in Manitoba despite the universal availability of pertussis vaccines. Recent cases have included previously vaccinated individuals, raising concerns about declining vaccine effectiveness (VE). We measured pertussis VE and duration of protection using Manitoba's provincial immunization and communicable disease registries., Methods: Using a nested case-control design, individuals with laboratory-confirmed pertussis in Manitoba diagnosed between April 1, 1992, and March 31, 2015, were matched to up to five population-based controls on age, gender, geography, and case physician or number of physician visits. Conditional logistic regression was used to estimate VE against pertussis for both the whole-cell (wP) and acellular (aP) pertussis vaccines. Duration of protection was assessed using time since last dose., Results: Data on 534 eligible cases and 2614 controls were available for analysis. The adjusted VE estimate for aP-containing vaccines was 85% (95%CI: 74-91%); VE was 89% (66-96%) one to three years after the last vaccination. The adjusted VE of wP-containing vaccines was -15% (-91-31%) during a large outbreak in 1994 and 1995 compared to 35% (-26-66%) during non-outbreak years., Conclusions: Our estimates suggest that the aP vaccine was effective in preventing pertussis since its introduction in Manitoba. VE was lower during a large outbreak, highlighting the importance of separately analyzing outbreak periods when estimating pertussis VE over time., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

B. pertussis is a human-specific pathogen and the causative agent of whooping cough. The ongoing resurgence in pertussis incidence in high income countries is likely due to faster waning of immunity and increased asymptomatic colonization in individuals vaccinated with acellular pertussis (aP) vaccine relative whole-cell pertussis (wP)-vaccinated individuals. This has renewed interest in developing more effective vaccines and treatments and, in support of these efforts, defining pertussis vaccine correlates of protection and the role of vaccine antigens and toxins in disease. Pertussis and its toxins have been investigated by scientists for over a century, yet we still do not have a clear understanding of how pertussis toxin (PT) contributes to disease symptomology or how anti-PT immune responses confer protection. This review covers PT's role in disease and evidence for its protective role in vaccines. Clinical data suggest that PT is a defining and essential toxin for B. pertussis pathogenesis and, when formulated into a vaccine, can prevent disease. Additional studies are required to further elucidate the role of PT in disease and vaccine-mediated protection, to inform the development of more effective treatments and vaccines.

Introduction: Pertussis in Latin America continues to cause periodic epidemics with substantial morbidity particularly among young children. The disease has persisted despite long-standing vaccination programs in the region. Areas covered: We conducted a systematic review to characterize the recent epidemiology of pertussis in Latin America and Hispanic Caribbean. We undertook a holistic approach and attempted to include all available data concerning pertussis that may explain the changing dynamics of the disease. Expert opinion: There are wide disparities in the reported annual incidence rates of pertussis both within and between countries in the region. General trends in pertussis incidence are difficult to ascertain due to the heterogeneity in the epidemiological data. Available data suggests that the disease burden has changed over the years such that now it predominantly affects those <1 year. Coverage with three doses of the pertussis vaccine has been highly variable, and very few countries have consistently achieved ≥90% coverage annually since 2000. There remain inequalities in vaccination coverage in some regions/localities and specific groups, which sustains the risk of pertussis dissemination. The WHO considers that maternal pertussis immunization provides protection to infants too young to be vaccinated; >10 Latin American countries currently recommend vaccination of pregnant women.

Background: Pertussis is still frequently reported in Canada. In Alberta, pertussis incidence ranged from 1.8 to 20.5 cases per 100,000 persons for 2004-2015. Most cases occurred in those aged <15 years. In Alberta, acellular formulations replaced whole-cell in 1997. We investigated pertussis vaccine effectiveness (VE) using a test-negative design (TND) study., Methods: We included all persons who had a real-time PCR laboratory test for Bordetella pertussis between January 1, 2010 and August 31, 2015, in the province of Alberta, Canada. Vaccination history was obtained from Alberta's immunization repository. Vaccination status was classified as complete, incomplete, or unvaccinated, based on the province's vaccination schedule. Persons who had received ≥one dose of whole cell vaccine were excluded from analysis. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for pertussis infection by time since last vaccination. We adjusted for vaccination status, age, sex, neighbourhood income, urban/rural status, and the presence of a co-morbid condition. VE was calculated as [(1 - aOR) * 100]., Results: Of the 12,149 tests available, 936 (7.7%) were positive for Bordetella pertussis. Among the full cohort, VE was 90% (95% CI 87-92%) at 1 year, 81% (95% CI 77-85%) at 1-3 years, 76% (95% CI 68-82%) at 4-7 years, and 37% (95% CI 11-56%) at 8 or more years since a last dose of acellular pertussis vaccine., Conclusions: Pertussis VE was highest in the first year after vaccination, then declined noticeably as years since a last vaccination increased. Our results suggest that a large number of adolescents and adults are susceptible to infection with Bordetella pertussis. Regular boosters throughout childhood, adolescence, and during pregnancy may be needed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Bordetella pertussis is the etiological agent of whooping cough, a bacterial infection of especially children, which may be fatal without treatment. In frame of studies to investigate putative effects of vaccination on host-pathogen interaction and clonal distribution of strains, in addition to Corynebacterium diphtheriae and Clostridium tetani toxoid vaccines, also whole-cell and acellular pertussis vaccines were analyzed by mass spectrometry., Data Description: LC-MS/MS spectra were generated and analyzed using B. pertussis genome data and proteins present in whole-cell and acellular pertussis vaccines were identified. Subcellular localization of proteins and presence of signal peptides was determined bioinformatically.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

The evolution of Bordetella pertussis from a common ancestor similar to Bordetella bronchiseptica has occurred through large-scale gene loss, inactivation and rearrangements, largely driven by the spread of insertion sequence element repeats throughout the genome. B. pertussis is widely considered to be monomorphic, and recent evolution of the B. pertussis genome appears to, at least in part, be driven by vaccine-based selection. Given the recent global resurgence of whooping cough despite the wide-spread use of vaccination, a more thorough understanding of B. pertussis genomics could be highly informative. In this chapter we discuss the evolution of B. pertussis, including how vaccination is changing the circulating B. pertussis population at the gene-level, and how new sequencing technologies are revealing previously unknown levels of inter- and intra-strain variation at the genome-level.

Vaccines and vaccination against pertussis (whooping cough) have had one of the longest and most complex history, with alternating splendour and public disbelief, enthusiasm and concerns, overall resulting in changes in composition and replacement of vaccines, and associated vaccination strategies, including use of different vaccines in different countries, with no apparent equals for other bacterial vaccines. Of this both frustrating and exciting venue no end has been reached. In this note, I am shortly recapitulating the history of pertussis vaccines, from the inactivated, whole-cell vaccine to the acellular ones, with their merits and limitations, particularly concerning the debated issue of waning immunity, and a glimpse on a new vaccine proposal. Some reflections on the complexity and apparent peculiarity of this field are also made to the final scope of discussing aspects of the evolving strategies of disease control in a high-income country.

Bordetella pertussis is the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the United States since the switch from the whole-cell pertussis vaccines (wP) to the acellular pertussis vaccines (aP; diphtheria-tetanus-acellular-pertussis vaccine/tetanus-diphtheria-pertussis vaccine). Adenylate cyclase toxin (ACT) is a major virulence factor of B. pertussis that is (i) required for establishment of infection, (ii) an effective immunogen, and (iii) a protective antigen. The C-terminal repeats-in-toxin domain (RTX) of ACT is sufficient to induce production of toxin-neutralizing antibodies. In this study, we characterized the effectiveness of vaccines containing the RTX antigen against experimental murine infection with B. pertussis RTX was not protective as a single-antigen vaccine against B. pertussis challenge, and adding RTX to 1/5 human dose of aP did not enhance protection. Since the doses of aP used in murine studies are not proportionate to mouse/human body masses, we titrated the aP from 1/20 to 1/160 of the human dose. Mice receiving 1/80 human aP dose had bacterial burden comparable to those of naive controls. Adding RTX antigen to the 1/80 aP base resulted in enhanced bacterial clearance. Inclusion of RTX induced production of antibodies recognizing RTX, enhanced production of anti-pertussis toxin, decreased secretion of proinflammatory cytokines, such as interleukin-6, and decreased recruitment of total macrophages in the lung. This study shows that adding RTX antigen to an appropriate dose of aP can enhance protection against B. pertussis challenge in mice., (Copyright © 2018 American Society for Microbiology.)

After a decade of decreases in the incidence of vaccine-preventable diseases, in the late 1980s the incidence began to increase. Four vaccine preventable diseases, including pertussis, caused major epidemics, and children were the most vulnerable during these outbreaks. Due to waning immunity, genomic changes, and inadequate herd immunity in adults, infants and children are at risk for contracting pertussis. Pertussis is a vaccine-preventable disease. Pertussis is difficult to diagnose early because the presentation is similar to common problems such as bronchitis or upper respiratory infections. School nurses should be able to identify signs and symptoms in the earliest stage possible to prevent transmission and refer for treatment early. The purpose of this article is to provide school nurses with information to understand the disease and identify individuals infected with pertussis.

The introduction of a whole-cell vaccine against Bordetella pertussis, the causative agent of whooping cough, dramatically reduced disease incidence. Unfortunately, the whole-cell formulation also induces severe reactions in some infants. Because of this, acellular vaccines have been developed, but they are used exclusively in high-income countries. However, the acellular vaccines do not provide long-term protection, and despite the use of routine boosters, the disease is on the rise. In this issue of the JCI, da Silva Antunes and colleagues demonstrate that the whole-cell vaccines promote long-term polarization toward Th1 and Th17 responses, while the acellular vaccines induce Th2 polarization. Moreover, this polarization is long term, as the response to acellular boosters is dependent on the initial vaccine given in infancy. The authors speculate that Tregs may be induced by initial acellular vaccine administration. The results of this study have important implications for the development of pertussis vaccination strategies that would induce Th1 and Th17 polarization.

Despite high vaccination rates, the incidence of whooping cough has steadily been increasing in developing countries for several decades. The current acellular pertussis (aP) vaccines all include the major protective antigen pertussis toxin (PTx) and are safer, but they appear to be less protective than infection or older, whole-cell vaccines. To better understand the attributes of individual antibodies stimulated by aP, we isolated plasmablast clones recognizing PTx after booster immunization of two donors. Five unique antibody sequences recognizing native PTx were recovered and expressed as recombinant human IgG1 antibodies. The antibodies all bind different epitopes on the PTx S1 subunit, B oligomer, or S1-B subunit interface, and just one clone neutralized PTx in an in vitro assay. To better understand the epitopes bound by the nonneutralizing S1-subunit antibodies, comprehensive mutagenesis with yeast display provided a detailed map of the epitope recognized by antibodies A8 and E12. Residue R76 is required for antibody A8 binding and is present on the S1 surface but is only partially exposed in the holotoxin, providing a structural explanation for A8's inability to neutralize holotoxin. The B-subunit-specific antibody D8 inhibited PTx binding to a model receptor and neutralized PTx in vitro as well as in an in vivo leukocytosis assay. This is the first study, to our knowledge, to identify individual human antibodies stimulated by the acellular pertussis vaccine and demonstrates the feasibility of using these approaches to address outstanding issues in pertussis vaccinology, including mechanisms of accelerated waning of protective immunity despite repeated aP immunization., (Copyright © 2018 Acquaye-Seedah et al.)

Introduction: Vaccination in pregnancy has been shown to be effective for the prevention of influenza and pertussis in infants, providing support for similar strategies to prevent group B streptococcus and respiratory syncytial virus infections that represent a large burden in pediatric population., Areas Covered: This review addresses the principle of maternal immunization, efficacy and safety of both pertussis and seasonal influenza vaccines and presents available data on group B streptococcus and respiratory syncytial virus that are in development for administration during pregnancy., Expert Commentary: Complementary data is needed to help in understanding pertussis vaccine mechanisms, improving influenza vaccine efficacy and addressing the interference phenomenon which is when maternal antibodies interfere with the infant vaccine response. Several knowledge gaps need to be filled in group B streptococcus and respiratory syncytial virus vaccines research.

Background: A significant increase in pertussis incidence occurred in Brazil, from 2011 to 2014, despite high coverage of childhood immunization with whole-cell-pertussis (wP) containing vaccines. This study presents pertussis surveillance data from São Paulo state and discusses the challenges to interpret them considering pertussis cyclic epidemic behavior, the introduction of new diagnostic techniques and new vaccination strategies, and enhanced disease awareness during epidemics., Methods: Observational study including pertussis cases reported to the Surveillance System in São Paulo state, from January 2001 to December 2015. Pertussis cases data were retrieved from the National Notifiable Diseases Information System (SINAN) website and from São Paulo state Epidemiological Surveillance Center (CVE/SP) database. Vaccination coverage and homogeneity data were collected from the Unified Health System Department of Informatics (DATASUS). We presented cases distribution by year, age group and diagnostic criteria and calculated pertussis incidence rates. The proportions of cases among different age groups were compared using chi-square test for trend., Results: Infants less than 1 year of age were the most affected during the whole period, but the proportions of cases in this age group had a significant decreasing trend, with significant increase in the proportions of cases reported among older age groups (1-4, 5-10 and ≥20 years). Cases among infants aged less than 6 months represented ≥90% of all cases in children less than 1 year of age in all but 2 years (2012 and 2015). A non-significant decrease in the proportion of cases among infants aged < 2 months was observed in parallel to a significant increase in the proportion of cases in infants aged 6-11 months., Conclusions: A pertussis outbreak has occurred in a state with universal use of wP vaccine. The disease cyclic behavior has probably had a major role in the increased incidence rates registered in São Paulo state, from 2011 to 2014, as well as in the decreased incidence in 2015. Maternal vaccination cannot explain the drop in the number of cases among all age groups, in 2015, as herd protection is not expected, but may have had an impact on the number of cases in infants aged < 2 months.

Pertussis and rotavirus vaccines have been the subject of several controversies over the years. In this paper the authors discuss facts and myths behind these controversies and also suggest solutions to overcome some limitations of these vaccines. The whole-cell pertussis vaccine (wPV) came into disrepute due to the associated adverse reactions, resulting in its replacement by acellular pertussis vaccine (aPV) in industrialized nations in 1990s. Although wPV is known to have more side effects; but they are usually minor. Whole-cell pertussis containing vaccine is being used safely in the National Immunization programme in India from many years. Another controversy erupted during 2009-2010, when there were reports of resurgence of pertussis cases among adolescents and adults, from developed nations. Present literature review raises doubts about long term protection offered by aPV, when compared with wPV. In spite of prevailing controversy, acellular pertussis containing vaccines should be acceptable, if timely delivery of primary and booster doses is ensured; including vaccination of adolescents and pregnant women. Initial rotavirus vaccine was withdrawn from the market because of increased risk of intussusception. Although three new generation rotavirus vaccines are currently available for use in India, but doubts about their efficacy, long term protection and safety still exists. Present literature review found them to be safe and moderately efficacious because of reasonable good cross protection. Even a moderately efficacious vaccine like rotavirus vaccine could significantly improve the outcome if disease burden is high. Therefore, it is being included in National Immunization Programme of India.

Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis. However, after the introduction of the whole-cell pertussis vaccine (wP), the annual incidence rates of the disease progressively declined. Despite this result, the inclusion of wP in the national immunization schedule of infants and young children was debated regarding its safety. Several efforts to produce vaccines based on B. pertussis components capable of evoking protective immunity with no or limited adverse events were made. Of these others, five pertussis antigens were considered possible components of acellular vaccines (aPs): pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and fimbria proteins 2 and 3. However, the introduction of aPs was followed by a slight but progressive increase in the incidence of pertussis. This paper discusses the potential reasons for reduced aPs efficacy. Moreover, it attempts to evaluate the real effectiveness of aPs and the potential differences between available preparations. Data analysis showed that several boosters are needed to maintain protection against pertussis and additional studies are needed to confirm the antigens that should be included in aPs to improve the prevention of pertussis.

Pertussis or whooping cough, a highly infectious respiratory infection, causes significant morbidity and mortality in infants. In adolescents and adults, pertussis presents with atypical symptoms often resulting in under-diagnosis and under-reporting, increasing the risk of transmission to more vulnerable groups. Maternal vaccination against pertussis protects mothers and newborns. This evaluation assessed the cost-effectiveness of adding maternal dTpa (reduced antigen diphtheria, Tetanus, acellular pertussis) vaccination to the 2016 nationally-funded pertussis program (DTPa [Diphtheria, Tetanus, acellular Pertussis] at 2, 4, 6, 18 months, 4 years and dTpa at 12-13 years) in Australia. A static cross-sectional population model was developed using a one-year period at steady-state. The model considered the total Australian population, stratified by age. Vaccine effectiveness against pertussis infection was assumed to be 92% in mothers and 91% in newborns, based on observational and case-control studies. The model included conservative assumptions around unreported cases. With 70% coverage, adding maternal vaccination to the existing pertussis program would prevent 8,847 pertussis cases, 422 outpatient cases, 146 hospitalizations and 0.54 deaths per year at the population level. With a 5% discount rate, 138.5 quality-adjusted life-years (QALYs) would be gained at an extra cost of AUS$ 4.44 million and an incremental cost-effectiveness ratio of AUS$ 32,065 per QALY gained. Sensitivity and scenario analyses demonstrated that outcomes were most sensitive to assumptions around vaccine effectiveness, duration of protection in mothers, and disutility of unreported cases. In conclusion, dTpa vaccination in the third trimester of pregnancy is likely to be cost-effective from a healthcare payer perspective in Australia.

We describe the detection of Bordetella holmesii as a cause of whooping cough in Spain. Prevalence was 3.9% in 2015, doubling to 8.8% in 2016. This emergence raises concern regarding the contribution of B. holmesii to the reemergence of whooping cough and the effectiveness of the pertussis vaccine.

Introduction: We summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. Globally Bordetella pertussis is one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission. To improve vaccine strategies, a greater understanding of human B. pertussis colonisation is required. This article summarises a protocol and does not contain any results., Methods and Analysis: A controlled human colonisation model will be developed over two phases. In phase A, a low dose of the inoculum will be given intranasally to healthy participants. This dose will be escalated or de-escalated until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the exposed volunteers without causing disease. The colonisation period, shedding and exploratory immunology will be assessed during a 17-day inpatient stay and follow-up over 1 year. The dose of inoculum that achieves 70% colonisation will then be confirmed in phase B, comparing healthy participants exposed to B. pertussis with a control group receiving a sham inoculum., Ethics and Dissemination: This study has been approved by the ethical committee reference: 17/SC/0006, 24 February 2017. Findings will be published in peer-reviewed open access journals as soon as possible., Competing Interests: Competing interests: HDG hasreceived sponsorship from Abbvie to attend a clinical paediatric rheumatology course. SF acts on behalf of the University ofSouthampton/University Hospital Southampton NHS Foundation trust as chief and principal investigator for clinical trials Sponsored by vaccine andantimicrobial manufacturers but receives no personal payments for the work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Rising pertussis incidence has prompted a number of countries to implement maternally targeted vaccination strategies to protect vulnerable infants, but questions remain about the optimal design of such strategies. We simulated pertussis transmission within an individual-based model parameterized to match Australian conditions, explicitly linking infants and their mothers to estimate the effectiveness of alternative maternally targeted vaccination strategies (antenatal delivery vs. postnatal delivery) and the benefit of revaccination over the course of multiple pregnancies. For firstborn infants aged less than 2 months, antenatal immunization reduced annual pertussis incidence by 60%, from 780 per 100,000 firstborn children under age 2 months (interquartile range (IQR), 682-862) to 315 per 100,000 (IQR, 260-370), while postnatal vaccination produced a minimal reduction, with an incidence of 728 per 100,000 (IQR, 628-789). Subsequent infants obtained limited protection from a single antenatal dose, but revaccinating mothers during every pregnancy decreased incidence for these infants by 58%, from 1,878 per 100,000 subsequent children under age 2 months (IQR, 1,712-2,076) to 791 per 100,000 (IQR, 683-915). Subsequent infants also benefited from household-level herd immunity when antenatal vaccination for every pregnancy was combined with a toddler booster dose at age 18 months; incidence was reduced to 626 per 100,000 (IQR, 548-691). Our approach provides useful information to aid consideration of alternative maternally targeted vaccination strategies and can inform development of outcome measures for program evaluation., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The goals of this article are to review the pertussis cocooning strategy, which has been recommended in France since 2004 to protect infants not yet vaccinated from becoming infected by vaccinating their immediate entourage, and to present room for improvement. The analysis of the literature between 2004 and 2015 shows that pertussis vaccine coverage in new parents is lower than 50% and that attempts that have already been implemented to increase it are effective. Pertussis vaccine coverage improvement requires all health actors to collaborate and be trained in informing and motivating parents to get vaccinated before, during and after pregnancy (the parents then will act as relays to their relatives); generalization in maternity wards of systematic checking of the vaccination card; extension to the midwives of the right to prescribe and administer pertussis vaccine to spouses; vaccination facilitation in maternity wards with the support of health organizations. Exchange and sharing of experiences between health care professionals are essential. Pregnancy is the ideal period to promote pertussis vaccination., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii-specific serum antibodies might play an important role in protection. Immuno-proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA-like protein of B. holmesii. An aBH vaccine prepared from a BipA-like protein-deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA-like protein plays an important role in the protective efficacy of aBH vaccine., (© 2016 The Societies and John Wiley & Sons Australia, Ltd.)

Introduction: Pertussis or whooping cough is a respiratory disease caused by Bordetella pertussis or, to a lesser extent, by B. parapertussis. Vaccines against pertussis have been widely used for more than 50 years and have led to a significant reduction of morbidity and mortality. However, even in countries with a high vaccine coverage, the disease is still not well controlled. Surveillance is urgently needed., Areas Covered: This review summarizes surveillance methods and gives examples that may be used when setting up a surveillance program or analyzing an outbreak. Expert commentary: Pertussis surveillance is urgently required in order to define the burden of disease, to adapt vaccine strategies according to the type of pertussis vaccine used and to follow the evolution of the bacteria.

For the development of a third generation of pertussis vaccine that could improve the control of the disease, it was proposed that the immune responses induced by the classic whole cell vaccine (wP) or after infection should be used as a reference point. We have recently identified a vaccine candidate based on outer membrane vesicles (OMVs) derived from the disease etiologic agent that have been shown to be safe and protective in mice model of infection. Here we characterized OMVs-mediated immunity and the safety of our new candidate. We also deepen the knowledge of the induced humoral response contribution in pertussis protection. Regarding the safety of the OMVs based vaccine (TdapOMVsBp,) the in vitro whole blood human assay here performed, showed that the low toxicity of OMVs-based vaccine previously detected in mice could be extended to human samples. Stimulation of splenocytes from immunized mice evidenced the presence of IFN-γ and IL-17-producing cells, indicated that OMVs induces both Th1 and Th17 response. Interestingly TdapOMVsBp-raised antibodies such as those induced by wP and commercial acellular vaccines (aP) which contribute to induce protection against Bordetella pertussis infection. As occurs with wP-induced antibodies, the TdapOMVsBp-induced serum antibodies efficiently opsonized B. pertussis. All the data here obtained shows that OMVs based vaccine is able to induce Th1/Th17 and Th2 mixed profile with robust humoral response involved in protection, positioning this candidate among the different possibilities to constitute the third generation of anti-pertussis vaccines., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Diagnosis of pertussis remains a challenge, and consequently research on the risk of disease might be biased because of misclassification. We quantified this misclassification and corrected for it in a case-control study of children in Philadelphia, Pennsylvania, who were 3 months to 6 years of age and diagnosed with pertussis between 2011 and 2013. Vaccine effectiveness (VE; calculated as (1 - odds ratio) × 100) was used to describe the average reduction in reported pertussis incidence resulting from persons being up to date on pertussis-antigen containing vaccines. Bayesian techniques were used to correct for purported nondifferential misclassification by reclassifying the cases per the 2014 Council of State and Territorial Epidemiologists pertussis case definition. Naïve VE was 50% (95% confidence interval: 16%, 69%). After correcting for misclassification, VE ranged from 57% (95% credible interval: 30, 73) to 82% (95% credible interval: 43, 95), depending on the amount of underreporting of pertussis that was assumed to have occurred in the study period. Meaningful misclassification was observed in terms of false negatives detected after the incorporation of infant apnea to the 2014 case definition. Although specificity was nearly perfect, sensitivity of the case definition varied from 90% to 20%, depending on the assumption about missed cases. Knowing the degree of the underreporting is essential to the accurate evaluation of VE., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination., Design and Settings: A prospective observational study conducted in 2 New Zealand regions., Participants: Women in their 28th-38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination., Main Outcomes Measures: Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions., Results: 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related., Conclusions: Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine., Trial Registration Number: ACTRN12613001045707., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

This article presents the World Health Organization's (WHO) recommendations for the use of vaccines against Bordetella pertussis from the WHO position paper on Pertussis vaccines: WHO position paper--August 2015, recently published in the Weekly Epidemiological Record (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2015;90(August(35)):433-60). This position paper summarizes the most recent developments in the field of pertussis disease and its prevention by vaccination. It includes the WHO position on the choice of Pertussis vaccine as well as on the use of additional strategies, particularly vaccination during pregnancy, for prevention of early infant mortality. This document replaces the first WHO position paper on vaccines against disease caused by Pertussis published in 2010 (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2010;85(October(40)):385-400) and incorporates the revised guidance on the choice of pertussis vaccines published in July 2014 (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2014;89(July(30)):337-44). Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2014 and April 2015 meetings. The evidence presented at the meetings can be accessed at http://www.who.int/immunization/sage/previous/en/index.html., (Copyright © 2016 The World Health Organization. Published by Elsevier Ltd.. All rights reserved.)

Pertussis or whooping cough has been given many names over the centuries. It was first recognized in the Middle Ages and since then various epidemics have been described. Jules Bordet and Octave Gengou isolated Bordetella pertussis, a causative agent for whooping cough, in Paris more than 100 years ago, which created an excellent opportunity to invent a vaccine. In 1914 the whole-cell pertussis vaccine was invented, then in the 1940s it was combined with tetanus and diphtheria toxoids to become DTP and it became widely available. A successive decrease in the incidence of the disease has since been observed. The vaccine has been about 80 % effective in preventing serious disease and death from pertussis. The disadvantage is that the vaccine offers protection for 5-10 years after the last dose of the full vaccination course. The second issue is the question of how to prevent side effects of the whole-cell vaccine. In the 1990s, the acellular vaccine was introduced in the US and gradually replaced the whole-cell vaccine. About 10 years later, a possible failure with the new vaccine has been observed, that is a lack of long-term protection. Nowadays, both vaccines are used, with the acellular vaccine being vastly predominant in most developed countries. Pertussis incidence has increased since the 1980s, but new prevention strategies include booster doses for specific age groups.

Objective: Pertussis is a highly virulent vaccine preventable disease that remains a global challenge. This study aimed to assess community knowledge of pertussis infection as well as awareness and uptake of adult pertussis booster vaccine., Methods: A cross-sectional survey was conducted of randomly selected households in South Australia by Computer Assisted Telephone Interviews in 2011. Survey data were weighted to the age, gender and geographical area profile of the population., Results: From 3124 randomly sampled contactable households, 1967 interviews were conducted (participation rate 63%) with individuals aged 18-93 years, including 608 parents of children aged <18 years. The majority of respondents (97%) had heard of pertussis (whooping cough) and 18% reported that a household member had previously contracted whooping cough infection. Most respondents considered whooping cough to be highly contagious (73%) and severe for infants (89%). Over half (51%) of those surveyed were aware that family members commonly transmit pertussis to infants. Despite high knowledge, pertussis vaccine uptake was low, with only 10% of respondents reporting pertussis vaccination in the previous five years. Whilst 61% of respondents were aware of the availability of an adult pertussis booster vaccine, only 8% (n=154) reported their Family Physician had discussed it with them. If provided free, 77% agreed that they would be more likely to accept a booster pertussis vaccination. Independent predictors of recent pertussis vaccination included higher education, larger household size, perception of greater disease severity for infants and discussion with a Family Physician about pertussis vaccination., Conclusions: Whilst knowledge regarding transmission and severity of Bordetella pertussis was high, uptake of pertussis vaccination for adults is remarkably low amongst the South Australian community. Improved awareness regarding the availability of a booster pertussis vaccine through Family Physicians and/or provision of funded pertussis vaccination for adults has the potential to improve pertussis vaccine coverage., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Pertussis (whooping cough) is a respiratory disease caused by the bacterium Bordetella pertussis. Despite the implementation of immunization programs and high vaccine coverage in most jurisdictions, pertussis is still one of the most common vaccine-preventable diseases, suggesting that the current vaccines and immunization schedules have not been sufficiently effective. Several factors are thought to contribute to this. The acellular pertussis vaccine that has been used in many jurisdictions since the 1990s is less effective than the previously used whole-cell vaccine, with immunity waning over time. Both whole-cell and acellular pertussis vaccines are effective at reducing disease severity but not transmission, resulting in outbreaks in vaccinated cohorts. In this review, we discuss various limitations of the current approaches to protection from pertussis and outline various options for reducing the burden of pertussis on a population level., (© Published by Oxford University Press on behalf of FEMS 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

During a pertussis epidemic in 2011-2012 the Western Australian (WA) Department of Health implemented a 'cocooning' programme, offering free pertussis-containing vaccine (dTpa) to new parents. We assessed the impact of vaccinating parents with dTpa on the incidence of pertussis infection in newborns. Births in WA during 2011-2012 were linked to a register of parental pertussis vaccinations and to notified reports of laboratory-proven pertussis in children <6 months of age. Parents who received dTpa during the four weeks after their child's birth were defined as 'vaccinated postpartum.' Cox proportional-hazards methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of pertussis infection among infants born to parents vaccinated postpartum vs. unvaccinated parents, adjusted for maternal age, geographic region, timing of birth, and number of siblings. Of 64,364 live-births, 43,480 (68%) infants had at least one vaccinated parent (60% of mothers and 36% of fathers). After excluding records where parent(s) were either vaccinated prior to the birth, vaccinated >28 days after the birth, the vaccination date was uncertain, or the child died at birth (n=42), the final cohort contained 53,149 children, 118 of whom developed pertussis. There was no difference in the incidence of pertussis among infants whose parents were both vaccinated postpartum compared to those with unvaccinated parents (1.9 vs 2.2 infections per 1000 infants; adjusted HR 0.91; 95%CI 0.55-1.53). Similarly, when assessed independently, maternal postpartum vaccination was not protective (adjusted HR 1.19; 95%CI 0.82-1.72). Supplemental sensitivity analyses which varied the time period for parental vaccination and accounted for under-reporting of vaccination status did not significantly alter these findings. In our setting, vaccinating parents with dTpa during the four weeks following delivery did not reduce pertussis diagnoses in infants. WA now provides dTpa vaccine to pregnant women during the third trimester., (Copyright © 2015 Elsevier Ltd. All rights reserved.)