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Journal of the Pediatric Infectious... Sep 2019Effective diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines became available in the 1930s, and they were put into routine use in the United States in the... (Review)
Review
Effective diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines became available in the 1930s, and they were put into routine use in the United States in the 1940s. Their use reduced the average rate of reported pertussis cases from 157 in 100 000 in the prevaccine era to <1 in 100 000 in the 1970s. Because of alleged reactions (encephalopathy and death), several countries discontinued (Sweden) or markedly decreased (United Kingdom, Germany, Japan) use of the vaccine. During the 20th century, Bordetella pertussis was studied extensively in animal model systems, and many "toxins" and protective antigens were described. A leader in B pertussis research was Margaret Pittman of the National Institutes of Health/US Food and Drug Administration. She published 2 articles suggesting that pertussis was a pertussis toxin (PT)-mediated disease. Dr Pittman's views led to the idea that less-reactogenic acellular vaccines could be produced. The first diphtheria, tetanus, pertussis (DTaP) vaccines were developed in Japan and put into routine use there. Afterward, DTaP vaccines were developed in the Western world, and definitive efficacy trials were carried out in the 1990s. These vaccines were all less reactogenic than DTwP vaccines, and despite the fact that their efficacy was less than that of DTwP vaccines, they were approved in the United States and many other countries. DTaP vaccines replaced DTwP vaccines in the United States in 1997. In the last 13 years, major pertussis epidemics have occurred in the United States, and numerous studies have shown the deficiencies of DTaP vaccines, including the small number of antigens that the vaccines contain and the type of cellular immune response that they elicit. The type of cellular response a predominantly, T2 response results in less efficacy and shorter duration of protection. Because of the small number of antigens (3-5 in DTaP vaccines vs >3000 in DTwP vaccines), linked-epitope suppression occurs. Because of linked-epitope suppression, all children who were primed by DTaP vaccines will be more susceptible to pertussis throughout their lifetimes, and there is no easy way to decrease this increased lifetime susceptibility.
Topics: Antibodies, Bacterial; Antigens, Bacterial; Bordetella pertussis; Diphtheria-Tetanus-Pertussis Vaccine; Germany; Humans; Immunity; Japan; Pertussis Toxin; Pertussis Vaccine; Sweden; Time Factors; United Kingdom; United States; Whooping Cough
PubMed: 30793754
DOI: 10.1093/jpids/piz005 -
Toxins Sep 2019is 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... (Review)
Review
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 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.
Topics: Animals; Hemagglutinins; Humans; Immunoglobulins, Intravenous; Pertussis Toxin; Pertussis Vaccine; Vaccination
PubMed: 31546599
DOI: 10.3390/toxins11100557 -
American Journal of Preventive Medicine Jan 2021India's childhood vaccination coverage has increased amid the implementation of national health policies intended to improve immunization levels. However, there is a...
INTRODUCTION
India's childhood vaccination coverage has increased amid the implementation of national health policies intended to improve immunization levels. However, there is a dearth of contemporary studies comparing state-level childhood vaccination rates across India's highly diverse states and territories. This study assesses SES-based inequalities in childhood vaccination by state for 2002-2013.
METHODS
National surveys from 2002 to 2004, 2007 to 2008, and 2012 to 2013 were used for analyses. Household SES was assessed using an asset index created through principal component analysis. Full vaccination comprised 1 dose bacille Calmette-Guerin, 3 doses diphtheria-pertussis-tetanus vaccine, 3 doses oral polio vaccine, and 1 dose measles-containing vaccine at age 12-60 months. Inequality analyses were stratified by 3 time periods and by government-designated high focus group versus non-high focus group states.
RESULTS
Childhood vaccination steadily increased between 2002 and 2013 in high focus group states but fell in some non-high focus group states, whereas SES-based vaccination inequalities generally decreased in both. In 2012-2013, rural areas had lower vaccination rates than urban areas in high focus group states but similar vaccination rates as urban areas in non-high focus group states. Increases in vaccination rates were not consistently accompanied by improvements in SES-based inequalities in vaccination.
CONCLUSIONS
Childhood vaccination in India has improved overall, although increases are more pronounced in high focus group states than in non-high focus group states over the study period. The gap in coverage between these states decreased over time owing in part to the latter experiencing reductions in full vaccination rates during 2007-2013. SES-based vaccination disparities persist in India, highlighting the need to improve vaccination rates for all children, especially those from disadvantaged and underserved groups.
SUPPLEMENT INFORMATION
This article is part of a supplement entitled Global Vaccination Equity, which is sponsored by the Global Institute for Vaccine Equity at the University of Michigan School of Public Health.
Topics: Child; Child, Preschool; Diphtheria-Tetanus-Pertussis Vaccine; Humans; Immunization Programs; India; Infant; Vaccination; Vaccination Coverage
PubMed: 33097336
DOI: 10.1016/j.amepre.2020.06.034 -
Applied Microbiology and Biotechnology Feb 2022Despite considerable progress in the understanding of clinical pertussis, the contemporary emergence of antimicrobial resistance for Bordetella pertussis and an... (Review)
Review
Despite considerable progress in the understanding of clinical pertussis, the contemporary emergence of antimicrobial resistance for Bordetella pertussis and an evolution of concerns with acellular component vaccination have both sparked a renewed interest. Although simian models of infection best correlate with the observed attributes of human infection, several animal models have been used for decades and have positively contributed in many ways to the related science. Nevertheless, there is yet the lack of a reliable small animal model system that mimics the combination of infection genesis, variable upper and lower respiratory infection, systemic effects, infection resolution, and vaccine responses. This narrative review examines the history and attributes of non-primate animal models for pertussis and places context with the current use and needs. Emerging from the latter is the necessity for further such study to better create the optimal model of infection and vaccination with use of current molecular tools and a broader range of animal systems. KEY POINTS: • Currently used and past non-primate animal models of B. pertussis infection often have unique and focused applications. • A non-primate animal model that consistently mimics human pertussis for the majority of key infection characteristics is lacking. • There remains ample opportunity for an improved non-primate animal model of pertussis with the use of current molecular biology tools and with further exploration of species not previously considered.
Topics: Animals; Bordetella pertussis; Disease Models, Animal; Humans; Pertussis Vaccine; Vaccination; Whooping Cough
PubMed: 35103810
DOI: 10.1007/s00253-022-11798-1 -
JAMA Pediatrics Apr 2023Infants younger than 1 year have the highest burden of pertussis morbidity and mortality. In 2011, the US introduced tetanus toxoid, reduced diphtheria toxoid, and...
IMPORTANCE
Infants younger than 1 year have the highest burden of pertussis morbidity and mortality. In 2011, the US introduced tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy to protect infants before vaccinations begin.
OBJECTIVE
To assess the association of maternal Tdap vaccination during pregnancy with the incidence of pertussis among infants in the US.
DESIGN, SETTING, AND PARTICIPANTS
In this ecologic study, a time-trend analysis was performed of infant pertussis cases reported through the National Notifiable Diseases Surveillance System between January 1, 2000, and December 31, 2019, in the US. Statistical analysis was performed from April 1, 2020, to October 31, 2022.
EXPOSURES
Maternal Tdap vaccination during pregnancy.
MAIN OUTCOMES AND MEASURES
Pertussis incidence rates were calculated and compared between 2 periods-the pre-maternal Tdap vaccination period (2000-2010) and the post-maternal Tdap vaccination period (2012-2019)-for 2 age groups: infants younger than 2 months (target group of maternal vaccination) and infants aged 6 months to less than 12 months (comparison group). Incidence rate differences between the 2 age groups were modeled using weighted segmented linear regression. The slope difference between the 2 periods was estimated to assess the association of maternal Tdap vaccination with pertussis incidence among infants.
RESULTS
A total of 57 460 pertussis cases were reported in infants younger than 1 year between 2000 and 2019; 19 322 cases (33.6%) were in infants younger than 2 months. During the pre-maternal Tdap vaccination period, annual pertussis incidence did not change among infants younger than 2 months (slope, 3.29 per 100 000 infants per year; P = .28) but increased slightly among infants aged 6 months to less than 12 months (slope, 2.10 per 100 000 infants per year; P = .01). There was no change in the difference in incidence between the 2 age groups (slope, 0.08 per 100 000 infants per year; P = .97) during the pre-maternal Tdap vaccination period overall. However, in the post-maternal Tdap vaccination period, incidence decreased among infants younger than 2 months (slope, -14.53 per 100 000 infants per year; P = .001) while remaining unchanged among infants aged 6 months to less than 12 months (slope, 1.42 per 100 000 infants per year; P = .29). The incidence rate difference between the 2 age groups significantly decreased during the post-maternal Tdap vaccination period (slope, -14.43 per 100 000 infants per year; P < .001). Pertussis incidence rate differences were significantly different between the pre-maternal and post-maternal Tdap vaccination periods (slope difference, -14.51 per 100 000 infants per year; P = .01).
CONCLUSIONS AND RELEVANCE
In this study, following maternal Tdap vaccine introduction, a sustained decrease in pertussis incidence was observed among infants younger than 2 months, narrowing the incidence gap with infants aged 6 months to less than 12 months. These findings suggest that maternal Tdap vaccination is associated with a reduction in pertussis burden in the target age group (<2 months) and that further increases in coverage may be associated with additional reductions in infant disease.
Topics: Pregnancy; Female; Infant; Humans; Whooping Cough; Incidence; Diphtheria-Tetanus-acellular Pertussis Vaccines; Pertussis Vaccine; Tetanus; Diphtheria; Vaccination
PubMed: 36745442
DOI: 10.1001/jamapediatrics.2022.5689 -
Vaccine Nov 2022BPZE1 is a live, attenuated pertussis vaccine derived from B. pertussis strain Tohama I modified by genetic removal or inactivation of 3 B. pertussis toxins: pertussis... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
BPZE1 is a live, attenuated pertussis vaccine derived from B. pertussis strain Tohama I modified by genetic removal or inactivation of 3 B. pertussis toxins: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin. This Phase 2a study evaluated the safety and immunogenicity of liquid or lyophilized BPZE1 vaccine administered intranasally by needleless tuberculin syringe or mucosal atomization device (VaxINator) at two dose levels.
METHODS
Fifty healthy male and non-pregnant female participants 18-49 years of age were enrolled. Participants were randomized 3:3:3:1 to a single lyophilized dose of 10 colony forming units (CFU) BPZE1, 10 CFU BPZE1, placebo via VaxINator device, or a single liquid dose of 10 CFU BPZE1 via tuberculin syringe. Reactogenicity was assessed for 14 days. Blood was obtained pre-vaccination; on Day 8 (safety); and on Days 15, 29, and 181 (immunogenicity). Nasal wick and swab samples were obtained at baseline and on Days 29 and 181 for assessment of mucosal antibody responses and clearance of BPZE1.
RESULTS
Across all groups, 35/50 (70 %) experienced at least one local adverse event (AE) and 31/50 (62 %) experienced at least one systemic AE, with similar AE frequencies observed between the highest 10 CFU BPZE1 and placebo groups. There were no severe or serious AEs during the study. At Day 29, seroconversion (≥2-fold rise from baseline in serum IgG or IgA) to at least 2 pertussis antigens was observed in 73 % in the 10 CFU BPZE1 VaxINator group, 60 % in the 10 CFU BPZE1 group delivered via tuberculin syringe, 27 % of participants in the 10 CFU BPZE1 VaxINator group, and 20 % in the placebo VaxINator group. No participants were colonized with BPZE1 at Day 29 post vaccination.
DISCUSSION
Lyophilized BPZE1 vaccine was well tolerated and immunogenic at the highest dose (10 CFU) delivered intranasally by VaxINator device and was not associated with any SAEs or prolonged shedding of BPZE1. Further evaluation of BPZE1 is warranted.
Topics: Adult; Male; Female; Humans; Pertussis Vaccine; Bordetella pertussis; Whooping Cough; Tuberculin; Administration, Intranasal; Vaccines, Attenuated; Immunogenicity, Vaccine
PubMed: 36220716
DOI: 10.1016/j.vaccine.2022.09.075 -
Microbial Genomics Dec 2023Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32...
Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32 isolates sourced from three different surveillance programmes in South Africa between 2015 and 2019. Genome sequences were characterized using multilocus sequence typing, vaccine antigen genes (, , , and ) and overall genome structure. All isolates were sequence type 2 and harboured the pertussis toxin promoter allele . The dominant genotype was 3122 (31/32, 96.9 %), with no pertactin-deficient or other mutations in vaccine antigen genes identified. Amongst 21 isolates yielding closed genome assemblies, eight distinct genome structures were detected, with 61.9 % (13/21) of the isolates exhibiting three predominant structures. Increases in case numbers are probably not due to evolutionary changes in the genome but possibly due to other factors such as the cyclical nature of disease, waning immunity due to the use of acellular vaccines and/or population immunity gaps.
Topics: Humans; Bordetella pertussis; Whooping Cough; South Africa; Pertussis Vaccine; Genomics
PubMed: 38117675
DOI: 10.1099/mgen.0.001162 -
Scientific Reports May 2023Autoagglutination (Agg) of Bordetella pertussis is often observed in clinical laboratory. However, its causal factors and frequency in circulating strains are unknown....
Autoagglutination (Agg) of Bordetella pertussis is often observed in clinical laboratory. However, its causal factors and frequency in circulating strains are unknown. Repeated single colony isolation enabled us to detect an Agg mutant in the supernatant of an Agg strain of B. pertussis. Whole-genome sequencing and immunoblot analysis disclosed that the Agg mutant had a single C-deletion in its fim3 promoter region (Pfim3) which abolished Fim3 fimbriae production. A B. pertussis fim3-knock out mutant also lacked the Agg phenotype. Agg clinical isolates were detected a higher production of Fim3 than Fim3-producing Agg isolates. B. pertussis is known to harbor multiple Pfim3 poly(C) lengths within a single strain culture and our newly developed PCR/LDR assay revealed that Agg isolates harbor the highest Pfim3 poly-14C abundance. We evaluated the frequency of autoagglutination in clinical B. pertussis isolates collected in Japan between 1994 and 2018 (n = 203). Fim3 production was confirmed for 190 isolates and 74.7% of them displayed the Agg phenotype. The Agg phenotype was strongly associated with Pfim3 poly-14C abundance. Taken together, our findings demonstrated that B. pertussis autoagglutination occurs in response to high Fim3 levels and the Agg strain has predominated in Japan over the past two decades.
Topics: Humans; Bordetella pertussis; Whooping Cough; Fimbriae, Bacterial; Phenotype; Pertussis Vaccine
PubMed: 37165008
DOI: 10.1038/s41598-023-34672-0 -
International Journal of Infectious... Oct 2019Pertussis is a highly infectious respiratory disease caused by Bordetella pertussis. Infants and young children are particularly at risk of severe and life-threatening... (Review)
Review
Pertussis is a highly infectious respiratory disease caused by Bordetella pertussis. Infants and young children are particularly at risk of severe and life-threatening disease. Infectious older individuals may transmit Bordetella pertussis to unprotected infants. Pertussis control measures have even failed in some countries with high pertussis vaccination coverage rates, leading to increased incidence rates. In 2014, this caused the World Health Organization to declare pertussis resurgent in some countries and led to recommendations regarding pertussis surveillance and national immunization programs. Despite the resurgence of pertussis, epidemiology of the disease in Southeast Asia has received little attention. In this narrative review, we describe pertussis surveillance systems, control measures, epidemiologic trends, and region-specific pertussis research in Southeast Asia. We also make recommendations for the intensification of pertussis surveillance and research in the region.
Topics: Asia, Southeastern; Bordetella pertussis; Humans; Immunization Programs; Pertussis Vaccine; Whooping Cough
PubMed: 31369823
DOI: 10.1016/j.ijid.2019.07.016 -
Zhonghua Liu Xing Bing Xue Za Zhi =... Mar 2023Pertussis is an acute, highly infectious respiratory disease caused by , and is one of the leading causes of infant disease and death worldwide. The pertussis vaccine... (Review)
Review
Pertussis is an acute, highly infectious respiratory disease caused by , and is one of the leading causes of infant disease and death worldwide. The pertussis vaccine has been used in the expanded program on immunization globally since 1974 and the vaccination coverage remains high. In recent years, the pertussis incidence rate increased, even pertussis outbreaks occurred, in more and more countries or areas after years with low incidence level. The disease burden of pertussis has been seriously underestimated, and the prevention and control of pertussis is facing many challenges. This article reviews the epidemic status of pertussis worldwide, the factors affecting the reemergence of pertussis, and the challenges in the prevention and control to provide a reference for prevention and control of pertussis.
Topics: Infant; Humans; Whooping Cough; Vaccination; Pertussis Vaccine; Bordetella pertussis; Disease Outbreaks
PubMed: 36942347
DOI: 10.3760/cma.j.cn112338-20220825-00737