Whooping Cough Diseases Research Articles

Atangana-Baleanu Fractional Dynamics of Predictive Whooping Cough Model with Optimal Control Analysis

Whooping cough, or pertussis, is an infectious disease that causes serious threats to people of all ages, specifically to infant and young children, all over the world. Due to the severe impact on health, it is necessary to construct a mathematical model that can be used to predict future dynamics of the disease, as well as to suggest strategies to eliminate the disease in an optimal way. For this, we constructed a new Atangana–Baleanu fractional model for whooping cough disease to predict the future dynamics of the disease, as well as to suggest strategies to eliminate the disease in an optimal way. We prove that the proposed model has a unique solution that is positive and bounded. To measure the contagiousness of the disease, we determined the reproduction number R0 and used it to examine the local and global stability at equilibrium points that have symmetry. Through sensitivity analysis, we determined parameters of the model that are most sensitive to R0. The ultimate aim of this research was to analyze different disease prevention approaches in order to find the most suitable one. For this, we included the vaccination and quarantine compartments in the proposed model and formulated an optimal control problem to assess the effect of vaccination and quarantine rates on disease control in three distinct scenarios. Firstly, we study the impact of vaccination strategy and conclude the findings with a graphical presentation of the results. Secondly, we examine the impact of quarantine strategy on whooping cough infection and its possible elimination from society. Lastly, we implement vaccination and quarantine strategies together to visualize their combined effect on infection control. In addition to the study of the optimal control problem, we examine the effect of the fractional order on disease dynamics, as well as the impact of constant vaccination and quarantine rates on disease transmission and control. The numerical results reveal that the optimal control strategy with vaccination and quarantine together would be more effective in reducing the spread of whooping cough infection. The implementation of the Toufik–Atangana-type numerical scheme for the solution of the fractional optimal control problem is another contribution of this article.

A SEIR Epidemic Model of Whooping Cough‐Like Infections and Its Dynamically Consistent Approximation

Whooping cough is a highly transmitted disease around the world. According to the World Health Organization (WHO), 0.15 million cases had reported globally in 2018. Most of the Asian and African states are infected regions. Through the study, we investigated the whole population into the four classes susceptible (S), exposed (E), infected (I), and vaccinated or recovered (R). The transmission dynamics of whooping cough disease are studied analytically and numerically. Analytical analyses are positivity, boundedness, reproduction number, equilibria, and local and global stabilities. In numerical analysis, we developed an implicit numerical integration scheme consistent with the biological problem’s properties. The analysis of the implicit method for the said model is dynamically consistent, positive, and bounded. Furthermore, an implicit numerical integration scheme is suitable for studying a particular epidemic model such as the whooping cough disease.

Evaluation of pertussis antibody levels and related factors in maternal and cord blood, 2020

Abstract Background Pregnancy immunization is recommended to protect babies against pertussis, which has a high mortality and morbidity during infancy, but whooping cough vaccine is not given to pregnant women in Turkey. In this study, pertussis antibodies in maternal and cord blood were investigated. Methods The study group was one hundred and fifty-four mothers who gave birth at Hacettepe University Hospitals in Ankara, from July to October 2020. The information of the mothers was collected by questionnaire and sera were taken. In this descriptive epidemiological study, anti-PT and anti-FHA were investigated with ELISA (EUROIMMUN B. Pertussis toxin (PT) IgG, Filamentous Hemagglutinin (FHA) IgG) method in maternal and cord-paired sera, the limit value was accepted as 10 IU/ml. Anti-ACT was investigated in the sera of 79 mothers who were anti-PT or anti-FHA positive by Immunblot (EUROIMMUN Adenylate Cyclase Toxin (ACT) IgG) method. Correlation analysis of continuous numerical variables was performed. The difference between categorical variables was evaluated with the Chi-Square test. Results Mean (SD) maternal age, gestational age and birth weight were 30.1 (5.1) years, 38.5 (0.9) weeks, 3307 (441) g, respectively. Anti-PT and anti-FHA are at protective levels in 18.8% and 48.1% of the mothers, respectively. Anti-PT and anti-FHA are at the protective level in 38.3% and 55.8% of the cord, respectively. Anti-FHA positivity is 63.3% between the ages of 25 and under, 38.6% between the ages of 26-35, and 69.6% at the age of 36 and over (p = 0.005). 72.4% of mothers with anti-PT positive and 67.6% of mothers with anti-FHA positive were anti-ACT antibody positive. Anti-ACT positive mothers were immunized by having the disease, not by vaccine. Anti-PT and anti-FHA antibody levels in maternal and cord blood are highly correlated. Conclusions Protective level of pertussis antibodies in maternal and cord blood is low. Most mothers are immunized with pertussis infection, not vaccine. Key messages The amount of pertussis antibodies in maternal and cord blood is low in Turkey and maternal immunization is needed. The addition of pertussis-containing vaccines to pregnant immunization is important to protect babies from whooping cough disease, which remains a major public health problem.

Intranasal inoculation with Bordetella pertussis confers protection without inducing classical whooping cough in baboons.

The resurgence of whooping cough in many countries highlights the crucial need for a better understanding of the pathogenesis of respiratory infection by Bordetella pertussis. Exposure of baboons to B. pertussis by the intranasal and intra-tracheal routes is a recently described preclinical model that reproduces both B. pertussis infection of humans and whooping cough disease. Here, we tested both intranasal and intranasal+intra-tracheal exposure routes and assessed their impact on disease development and immunity. Young baboons were intranasally exposed to the B1917 clinical isolate, representative of circulating strains in Europe, or its green-fluorescent protein expressing derivative. Animals were followed for pertussis symptoms and bacterial colonization and by in vivo probe-based confocal laser endomicroscopy (pCLE) imaging. Sero-conversion and protection against subsequent infection were then evaluated. Seroconversion and bacterial colonization of both the nasopharynx and trachea was observed in baboons exposed to B. pertussis by the intranasal route only, and also in those animals challenged by both the intranasal and intra-tracheal routes together. However, baboons exposed solely by the intranasal route developed only mild clinical symptoms, with no paroxysmal cough. These animals were protected against re-infection by B. pertussis. Intranasal exposure of baboons to B. pertussis does not induce disease but elicits immune mechanisms that protect them from subsequent exposure to the bacteria. These findings suggest that the intranasal route of inoculation in this non-human primate model could be used in the pre-clinical evaluation of nasal candidate vaccines against pertussis.

Production of Highly Active Recombinant Dermonecrotic Toxin of Bordetella Pertussis.

Pathogenic Bordetella bacteria release a neurotropic dermonecrotic toxin (DNT) that is endocytosed into animal cells and permanently activates the Rho family GTPases by polyamination or deamidation of the glutamine residues in their switch II regions (e.g., Gln63 of RhoA). DNT was found to enable high level colonization of the nasal cavity of pigs by B. bronchiseptica and the capacity of DNT to inhibit differentiation of nasal turbinate bone osteoblasts causes atrophic rhinitis in infected pigs. However, it remains unknown whether DNT plays any role also in virulence of the human pathogen B. pertussis and in pathogenesis of the whooping cough disease. We report a procedure for purification of large amounts of LPS-free recombinant DNT that exhibits a high biological activity on cells expressing the DNT receptors Cav3.1 and Cav3.2. Electron microscopy and single particle image analysis of negatively stained preparations revealed that the DNT molecule adopts a V-shaped structure with well-resolved protein domains. These results open the way to structure–function studies on DNT and its interactions with airway epithelial layers.

A Whooping Cough Education Module for WIC Clients in Utah.

Clients in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) are required to complete education modules quarterly to maintain eligibility. The purposes of this project were to: (1) create a whooping cough vaccination education module for WIC clients; (2) evaluate baseline perceptions of WIC clients on the whooping cough vaccine and disease; and (3) evaluate whooping cough knowledge following completion of the module. A decline in vaccination rates among infants and children using WIC services was reported by a local WIC program director who requested whooping cough vaccination education materials. This quality improvement project included development of a whooping cough education module and evaluation of learning. Learning was evaluated using a pre- and posttest design. Client feedback was solicited via open-ended questions. Quantitative analysis was performed on visual analog-type questions with paired t-tests and a Cohen's d. Content analysis was conducted on open-ended items. The module was designed by a team of vaccination experts and included general definitions, signs and symptoms during the three stages of disease, recommendations to prevent whooping cough, and vaccination recommendations. Learning of users of the module was then evaluated. After using the module, clients indicated they were significantly more likely to vaccinate themselves and their child against whooping cough, and to recommend the vaccination to their family members. The greatest concern of participants about whooping cough was how it affected infants. Participants reported they learned new information on disease seriousness, recognition of symptoms, and treatment options but still requested additional information on the whooping cough disease and vaccine. A whooping cough education module is an effective strategy to improve whooping cough knowledge and promote the whooping cough vaccine.

The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice

The type III secretion system (T3SS) of pathogenic bordetellae employs a self-associating tip complex protein Bsp22. This protein is immunogenic during infections by Bordetella bronchiseptica and could be used as a protective antigen to immunize mice against B. bronchiseptica challenge. Since low-passage clinical isolates of the human pathogen Bordetella pertussis produce a highly homologous Bsp22 protein (97% homology), we examined its vaccine and diagnostic potential. No Bsp22-specific antibodies were, however, detected in serum samples from 36 patients with clinically and serologically confirmed whooping cough disease (pertussis syndrome). Moreover, although the induction of Bsp22 secretion by the laboratory-adapted 18323 strain in the course of mice lung infection was observed, the B. pertussis 18323-infected mice did not mount any detectable serum antibody response against Bsp22. Furthermore, immunization with recombinant Bsp22 protein yielded induction of high Bsp22-specific serum antibody titers but did not protect mice against an intranasal challenge with B. pertussis 18323. Unlike for B. bronchiseptica, hence, the Bsp22 protein is nonimmunogenic, and/or the serum antibody response to it is suppressed, during B. pertussis infections of humans and mice.

A practical approach for exploration and modeling of the design space of a bacterial vaccine cultivation process

A licensed pharmaceutical process is required to be executed within the validated ranges throughout the lifetime of product manufacturing. Changes to the process, especially for processes involving biological products, usually require the manufacturer to demonstrate that the safety and efficacy of the product remains unchanged by new or additional clinical testing. Recent changes in the regulations for pharmaceutical processing allow broader ranges of process settings to be submitted for regulatory approval, the so-called process design space, which means that a manufacturer can optimize his process within the submitted ranges after the product has entered the market, which allows flexible processes. In this article, the applicability of this concept of the process design space is investigated for the cultivation process step for a vaccine against whooping cough disease. An experimental design (DoE) is applied to investigate the ranges of critical process parameters that still result in a product that meets specifications. The on-line process data, including near infrared spectroscopy, are used to build a descriptive model of the processes used in the experimental design. Finally, the data of all processes are integrated in a multivariate batch monitoring model that represents the investigated process design space. This article demonstrates how the general principles of PAT and process design space can be applied for an undefined biological product such as a whole cell vaccine. The approach chosen for model development described here, allows on line monitoring and control of cultivation batches in order to assure in real time that a process is running within the process design space.

Evaluation of a critical process parameter: Oxygen limitation during cultivation has a fully reversible effect on gene expression of Bordetella pertussis

Modern (bio)pharmaceutical process development requires thorough investigation of all process parameters that are critical to product quality. The impact of a disturbance of such a parameter during processing needs to be known so that a rational decision can be made about the release of the product. In cultivation processes the dissolved oxygen (DO) concentration is generally accepted as being a critical parameter. In this article the impact of a 90 min period of oxygen limitation during the cultivation of the strictly aerobic Bordetella pertussis bacterium is investigated. The cultivation is the most important process step for the manufacturing of a vaccine against whooping cough disease. Samples were taken immediately before and after oxygen limitation and at the end of cultivation of four oxygen limited and three control cultivations. DNA microarray analysis of the full transcriptome of the B. pertussis bacterium revealed that a 90 min period of oxygen limitation has a substantial effect on overall gene expression patterns. In total 104 genes were identified as a significant hit at any of the sample points, of which 58 were directly related to oxygen limitation. The other genes were mainly affected towards the end of cultivation. Of all genes involved in oxygen limitation none were identified to show a significant difference between the oxygen limited and control cultivations at the end of the batch. This indicates a fully reversible effect of oxygen limitation on gene expression. This finding has implications for the risk assessment of dissolved oxygen concentration as a critical process parameter.

PAT for vaccines: The first stage of PAT implementation for development of a well-defined whole-cell vaccine against whooping cough disease

Since variation in process time and process output is commonly accepted to be inevitable for biological processes, application of Process Analytical Technologies (PAT) on these processes is challenging. In this paper the applicability of PAT on the cultivation of Bordetella pertussis bacteria as part of the manufacture of a vaccine against whooping cough disease is investigated. Scrutinizing and eliminating the most prominent sources of variance make the cultivation process step highly reproducible. Furthermore, the use of DNA microarrays allows investigation of how disturbances influence cellular physiology and product quality. Marker genes for product quality were identified, providing the means to quantitatively assess product quality, which is hardly possible using the mandatory animal tests for product quality. The tools and results described in this paper, combined with suitable on line measurements, can make full PAT application for this process step possible. Ultimately, the process can be designed and controlled towards consistent end product quality.