Pertussis

The bacterium Bordetella pertussis causes disease by producing various virulence and adhesion factors, among them pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and agglutinogens (Agg), also called fimbriae (FIM) "Typical" pertussis or whooping cough starts with unspecific respiratory symptoms (catarrhal phase) followed by severe coughing spasms with whoops and vomiting (paroxysmal phase) and only after weeks or months disease severity slowly wanes (convalescent phase). "Atypical pertussis" with unspecific, long-lasting coughing episodes is seen in adolescents and adults; very young infants may die from apnoea. B. pertussis is transmitted by droplets, and neither infection nor vaccination produce long lasting protection. Macrolide antibiotics are given to patients and their contacts to reduce spread of the organism; however, antibiotics do NOT change the duration or course of the disease once symptoms are present. Whole cell pertussis vaccines (wP) consist of whole inactivated B. pertussis-cells, whereas acellular vaccines (aP) consist of one to five single components like PT, FHA, PRN or FIM. Pertussis vaccines are currently only available as combination vaccines with tetanus und diphtheria (DTP). Among these are DTwP; DTaP; TdaP; and various DTP-combinations with Hib, IPV, HBV vaccines. Whole cell pertussis (DTwP) combination vaccines are more reactogenic, whereas DTaP vaccines are generally well tolerated. Some DTwP had good efficacy/effectiveness (90%), it was low (40%) with others. Vaccine efficacy of DTaP vaccines ranges between 70% and 90%. As with most vaccines, efficiency is higher for severe disease. While pertussis vaccines did control clinical disease, protection is limited. Vaccination is recommended for all infants (three doses) worldwide with a booster in the second year of life. Many countries give additional doses at school entry and in adolescents, and some to adults. Vaccination of pregnant women effectively protects newborn infants and is increasingly recommended.

Pertussis

The bacterium Bordetella pertussis causes disease by producing various virulence and adhesion factors, among them pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and agglutinogens (Agg), also called fimbriae (FIM) "Typical" pertussis or whooping cough starts with unspecific respiratory symptoms (catarrhal phase) followed by severe coughing spasms with whoops and vomiting (paroxysmal phase) and only after weeks or months disease severity slowly wanes (convalescent phase). "Atypical pertussis" with unspecific, long-lasting coughing episodes is seen in adolescents and adults; very young infants may die from apnoea. B. pertussis is transmitted by droplets, and neither infection nor vaccination produce long lasting protection. Macrolide antibiotics are given to patients and their contacts to reduce spread of the organism; however, antibiotics do NOT change the duration or course of the disease once symptoms are present. Whole cell pertussis vaccines (wP) consist of whole inactivated B. pertussis-cells, whereas acellular vaccines (aP) consist of one to five single components like PT, FHA, PRN or FIM. Pertussis vaccines are currently only available as combination vaccines with tetanus und diphtheria (DTP). Among these are DTwP; DTaP; TdaP; and various DTP-combinations with Hib, IPV, HBV vaccines. Whole cell pertussis (DTwP) combination vaccines are more reactogenic, whereas DTaP vaccines are generally well tolerated. Some DTwP had good efficacy/effectiveness (90%), it was low (40%) with others. Vaccine efficacy of DTaP vaccines ranges between 70% and 90%. As with most vaccines, efficiency is higher for severe disease. While pertussis vaccines did control clinical disease, protection is limited. Vaccination is recommended for all infants (three doses) worldwide with a booster in the second year of life. Many countries give additional doses at school entry and in adolescents, and some to adults. Vaccination of pregnant women effectively protects newborn infants and is increasingly recommended.

Spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Competitive interactions between pathogen strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures, however, this has rarely been measured due to inadequate data and analytical tools. Bordetella pertussis (B. pertussis), responsible for 160,000 deaths annually, provides a rare natural experiment as many countries have switched from whole cell vaccines to acellular vaccines, which have very different immunogenic properties. Here we use 3,344 sequences from 23 countries and build phylogenetic models to reveal that B. pertussis has substantial diversity within communities, with the relative fitness of local genotypes changing in response to switches in vaccine policy. We demonstrate that the number of transmission chains circulating within subnational regions is strongly associated with host population size. It takes 5-10 years for individual lineages to be homogeneously distributed throughout Europe or the United States. Increased fitness of pertactin-deficient strains following implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of national vaccine policies in shifting local diversity of a pathogen that still poses a large burden on global public health.

The Path to New Pediatric Vaccines against Pertussis

Whooping cough, or pertussis, mostly caused by Bordetella pertussis, is a respiratory disease that affects all age groups, but severe and fatal pertussis occurs almost exclusively in young children. The widespread use of whole-cell and, more recently, of acellular vaccines has substantially reduced the disease incidence. However, it has not been eliminated in any part of the world and has made a worrisome rebound in several areas. Cocoon and maternal immunization have been implemented in several countries but have their intrinsic limitations. To effectively control pertussis, novel vaccines are needed that protect against disease and prevent B. pertussis infection and transmission, which is not the case for current vaccines. Several approaches are contemplated, including alternative administration routes, such as nasal immunization, improvement of acellular vaccines by adding more antigens and T-cell-promoting adjuvants, and the development of novel vaccines, such as outer membrane vesicles and live attenuated vaccines. Among them, only a live attenuated vaccine has so far been assessed for safety and immunogenicity in preclinical models other than mice and is in clinical development. Before any of these vaccines can be used in neonates, extensive safety and immunogenicity assessment in pre-clinical neonatal models and in carefully designed clinical trials is necessary. The aim of this review is to discuss the current pertussis problem, implemented strategies to resolve it, the value of animal models and novel vaccine approaches.

Simultaneous Determination of Antibodies to Pertussis Toxin and Adenylate Cyclase Toxin Improves Serological Diagnosis of Pertussis

Serological diagnosis of pertussis is mainly based on anti-pertussis toxin (PT) IgG antibodies. Since PT is included in all acellular vaccines (ACV), serological assays do not differentiate antibodies induced by ACVs and infection. Adenylate cyclase toxin (ACT) is not included in the ACVs, which makes it a promising candidate for pertussis serology with the specific aim of separating infection- and ACV-induced antibodies. A multiplex lateral flow test with PT and ACT antigens was developed to measure serum antibodies from pertussis-seropositive patients (n = 46), healthy controls (n = 102), and subjects who received a booster dose of ACV containing PT, filamentous hemagglutinin, and pertactin (n = 67) with paired sera collected before and one month after the vaccination. If the diagnosis was solely based on anti-PT antibodies, 98.5–44.8% specificity (before and after vaccination, respectively) and 78.2% sensitivity were achieved, whereas if ACT was used in combination with PT, the sensitivity of the assay increased to 91.3% without compromising specificity. No increase in the level of anti-ACT antibodies was found after vaccination. This exploratory study indicates that the use of ACT for serology would be beneficial in combination with a lower quantitative cutoff for anti-PT antibodies, and particularly in children and adolescents who frequently receive booster vaccinations.

Pertussis in the Voronezh Region: Epidemiology and Vaccination

Relevance. In recent years, the increase in the incidence of pertussis has been observed in many countries despite high vaccination coverage of the child population.Purpose: was to study the epidemiological features of whooping cough in the Voronezh region for the period from 2008 to 2018 years.Methods. The research material was data the annual form No. 2, 5, 6 of Rosstat for 2008 through 2018. Statistical data processing was performed using Microsoft Excel 2007.Results. The epidemiological features of pertussis in the Voronezh region for the period from 2008 to 2018 have been studied. Despite the high coverage of preventive vaccinations in children of the first years of life, in recent years, the incidence of pertussis increased the average Russian rates by 3,5 times. In the age structure of the diseased there was a tendency to increase the proportion of schoolchildren and adults. Analysis of the reports showed that half of the cases were vaccinated at the prescribed age, but the interval after vaccination before the illness was an average of 9 years.Conclusions. In recent years, there has been a tendency to an increase in the incidence of whooping cough in the Voronezh region. The incidence of vaccinated indicates the natural extinction of post-vaccination immunity to school age and requires a decision on the introduction of revaccination of schoolchildren with actual acellular vaccines.

Pertussis in the Voronezh Region: Epidemiology and Vaccination

Relevance. In recent years, the increase in the incidence of pertussis has been observed in many countries despite high vaccination coverage of the child population.Purpose: was to study the epidemiological features of whooping cough in the Voronezh region for the period from 2008 to 2018 years.Methods. The research material was data the annual form No. 2, 5, 6 of Rosstat for 2008 through 2018. Statistical data processing was performed using Microsoft Excel 2007.Results. The epidemiological features of pertussis in the Voronezh region for the period from 2008 to 2018 have been studied. Despite the high coverage of preventive vaccinations in children of the first years of life, in recent years, the incidence of pertussis increased the average Russian rates by 3,5 times. In the age structure of the diseased there was a tendency to increase the proportion of schoolchildren and adults. Analysis of the reports showed that half of the cases were vaccinated at the prescribed age, but the interval after vaccination before the illness was an average of 9 years.Conclusions. In recent years, there has been a tendency to an increase in the incidence of whooping cough in the Voronezh region. The incidence of vaccinated indicates the natural extinction of post-vaccination immunity to school age and requires a decision on the introduction of revaccination of schoolchildren with actual acellular vaccines.

Bordetella infection

Bordetella are small Gram-negative coccobacilli, of which Bordetella pertussis is the most important human pathogen. Bordetella pertussis is the cause of whooping cough, which remains one of the 10 leading causes of death among children less than five years old. Transmission of this highly infectious organism is primarily by aerosolized droplets. The preferred diagnostic methods are polymerase chain reaction detection from nasopharyngeal samples and serology (IgG antibodies to pertussis toxin). Macrolide antibiotics are recommended if started within four weeks of illness onset. Preventing severe disease in young children remains the primary goal, hence schedules consist of a three-dose infant series and subsequent booster doses. Acellular vaccines enable immunization schedules to include adolescents and adults. Acellular pertussis vaccine given to pregnant women reduces the risk of pertussis in young infants. Antibiotic prophylaxis is given when there is an infant at risk of exposure.

A qPCR assay for Bordetella pertussis cells that enumerates both live and dead bacteria

Bordetella pertussis is the causative agent of whooping cough, commonly referred to as pertussis. Although the incidence of pertussis was reduced through vaccination, during the last thirty years it has returned to high levels in a number of countries. This resurgence has been linked to the switch from the use of whole-cell to acellular vaccines. Protection afforded by acellular vaccines appears to be short-lived compared to that afforded by whole cell vaccines. In order to inform future vaccine improvement by identifying immune correlates of protection, a human challenge model of B. pertussis colonisation has been developed. Accurate measurement of colonisation status in this model has required development of a qPCR-based assay to enumerate B. pertussis in samples that distinguishes between viable and dead bacteria. Here we report the development of this assay and its performance in the quantification of B. pertussis from human challenge model samples. This assay has future utility in diagnostic labs and in research where a quantitative measure of both B. pertussis number and viability is required.

Assays for Determining Pertussis Toxin Activity in Acellular Pertussis Vaccines

Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This toxin is responsible for many physiological effects on the host, but it is also immunogenic and in its detoxified form is the main component of all ACVs. In producing toxoid for vaccines, it is vital to achieve a balance between sufficiently detoxifying PTx to render it safe while maintaining enough molecular structure that it retains its protective immunogenicity. To ensure that the first part of this balancing act has been successfully achieved, assays are required to accurately measure residual PTx activity in ACV products accurately. Quality control assays are also required to ensure that the detoxification procedures are robust and stable. This manuscript reviews the methods that have been used to achieve this aim, or may have the potential to replace them, and highlights their continuing requirement as vaccines that induce a longer lasting immunity are developed to prevent the re-occurrence of outbreaks that have been observed recently.