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• #1 Pertussis infection: Epidemiology, microbiology, and pathogenesis – UpToDate

  https://www.uptodate.com/contents/pertussis-infection-epidemiology-microbiology-and-pathogenesis

  Pertussis, also known as „whooping cough,” is a highly contagious respiratory illness caused by Bordetella pertussis. […] The microbiology, epidemiology, and pathogenesis of pertussis are reviewed here. […] Pertussis is caused by the gram-negative coccobacillus B. pertussis, a strict human pathogen with no known animal or environmental reservoir. […] Pertussis is a highly contagious respiratory illness. In adolescents and adults, infection may result in a protracted cough and is occasionally associated with substantial morbidity. In children, and particularly infants, morbidity is more often substantial, and the disease may be fatal.

• #2 Pertussis – Infectious Diseases – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/infectious-diseases/gram-negative-bacilli/pertussis

  Infection with B. pertussis occurs only in humans; there are no animal reservoirs. […] Transmission is mainly via droplets of respiratory secretions that contain B. pertussis (a small, nonmotile, gram-negative coccobacillus) from infected patients, particularly during the catarrhal and early paroxysmal stages. The infection is highly contagious and causes disease in 80% of close contacts. […] The catarrhal stage begins insidiously, generally with sneezing, lacrimation, or other signs of coryza; anorexia; listlessness; and a troublesome, hacking nocturnal cough that gradually becomes diurnal. […] After 10 to 14 days, the paroxysmal stage begins with an increase in the severity and frequency of the cough. […] The white blood cell count is usually between 15,000 and 20,000/mcL (15 and 20 109/L) but may be normal or as high as 60,000/mcL (60 109/L), usually with 60 to 80% small lymphocytes.

• #3 Pertussis Pathogenesis—What We Know and What We Don’t Know

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3952676/

  Pertussis is a worldwide public health threat. Bordetella pertussis produces multiple virulence factors that have been studied individually, and many have recently been found to have additional biological activities. Nevertheless, how they interact to cause the disease pertussis remains unknown. […] Despite this extensive body of knowledge, woefully little is known about the mechanisms by which these factors act in concert to cause whooping cough in humans. […] The mechanisms of microbial pathogenesis and the roles of individual components can be put into a working context by considering the proven or hypothesized contribution of each virulence factor to specific pathogenic processes. […] Components of B. pertussis that are likely virulence factors include proteins categorized as toxins and adhesins, as well as other molecules that interact with host cells to alter their function.

• #4 Scholarly Article or Book Chapter | Bordetella pertussis pathogenesis: current and future challenges | ID: wp988t10w | Carolina Digital Repository

  https://cdr.lib.unc.edu/concern/articles/wp988t10w?locale=en

  Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. […] In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. […] Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. […] We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies.

• #5 Bordetella – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK7813/

  Transmission is by droplets. The bacteria colonize only ciliated cells of the respiratory mucosa, and they multiply rapidly. […] The roles of the various toxins in pathogenesis are unclear. […] The agent of whooping cough is transmitted primarily via droplets. Infection results in colonization and rapid multiplication of the bacteria on the mucous membranes of the respiratory tract. Bacteremia does not occur. Electron microscopic studies have demonstrated that phase I strains of Bordetella pertussis adhere only to the tuft of ciliated cells in the mucosa of the human respiratory tract; no attachment to nonciliated cells was observed. Convincing experimental data indicate that the adherence of Bordetella pertussis to human cilia is effected by a synergistic action of pertussis toxin and filamentous hemagglutinin, each acting as a bivalent bridge between the bacterium and the ciliary receptor.

• #6 Whooping cough – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/whooping-cough/symptoms-causes/syc-20378973

  Whooping cough is an illness that can spread easily. It’s also called pertussis. An infection with bacteria causes it. […] A type of bacteria called Bordetella pertussis causes whooping cough. When an infected person coughs or sneezes, tiny germ-filled droplets spray into the air. Anyone who happens to be nearby can breathe in the droplets. The bacteria that cause whooping cough also can spread when people are together for a long time. Or these germs can spread when people share breathing space, such as while holding a newborn on your chest.

• #7 Whooping cough – Wikipedia

  https://en.wikipedia.org/wiki/Whooping_cough

  The bacterium Bordetella pertussis causes pertussis, which is spread easily through the coughs and sneezes of an infected person. […] After the bacteria are inhaled, they initially adhere to the ciliated epithelium in the nasopharynx. Surface proteins of B. pertussis, including filamentous hemagglutinin and pertactin, mediate attachment to the epithelium. The bacteria then multiply. […] The bacteria secrete several toxins. Tracheal cytotoxin (TCT), a fragment of peptidoglycan, kills ciliated epithelial cells in the airway and thereby inhibits the mechanism which clears the airways of mucus and debris. TCT may contribute to the cough characteristic of pertussis. Pertussis toxin causes lymphocytosis by an unknown mechanism. The elevated number of white blood cells leads to pulmonary hypertension, a major cause of death by pertussis. In infants who develop encephalopathy, cerebral hemorrhage and cortical atrophy occur, likely due to hypoxia.

• #8 Bordetella pertussis | Mechanisms of Pathogenicity

  https://mechpath.com/2017/12/19/bordetella-pertussis/

  Pertussis, also known as whooping cough (uncontrollable violent coughing), is an infection of the respiratory system originating from the bacterium Bordetella pertussis. This bacterial pathogen colonizes and multiplies in the upper and lower respiratory tracts. It is highly contagious as it is transferred by coughing or sneezing through airborne droplets. […] Upon inhalation of contaminated aerosols, the bacteria adhere to the epithelium, which is the protective tissue that surrounds the respiratory airways such as the nasopharynx and trachea. After the attachment process, B. pertussis will start to multiply and produce virulence factors that help the microorganism thrive and cause disease. The collective effect of these factors allows the bacteria to cause damage to the host and elude its immune system.

• #9 Bordetella pertussis pathogenesis: current and future challenges | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3235

  Bordetella spp. produce many virulence factors that contribute to pathogenesis, including toxins, adhesion factors, iron-acquisition systems and surface structures. […] Future goals include improving the efficacy of vaccines, protecting unvaccinated infants from infection and developing better treatment strategies for infants who become infected with B. pertussis. Achieving these goals requires a more thorough understanding of the mechanisms that are used by B. pertussis to establish infection and cause disease. […] In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into B. pertussis virulence-factor function. […] Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. […] This study quantifies the amount of adenylate cyclase toxin (ACT) in nasopharyngeal washes of infants and baboons infected with B. pertussis and suggests that physiologically relevant concentrations of ACT are much lower than the concentrations that are used in many in vitro experiments. […] This study confirms T3SS activity in clinical isolates of B. pertussis, which suggests that laboratory adaptation might lead to loss of T3SS protein expression and, contradictory to previous understanding, that T3SS is probably important for B. pertussis virulence.

• #10 Pertussis toxin – Wikipedia

  https://en.wikipedia.org/wiki/Pertussis_toxin

  Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection. […] PT clearly plays a central role in the pathogenesis of pertussis although this was discovered only in the early 1980s. […] PT is released from B. pertussis in an inactive form. Following PT binding to a cell membrane receptor, it is taken up in an endosome, after which it undergoes retrograde transport to the trans-Golgi network and endoplasmic reticulum. At some point during this transport, the A subunit (or protomer) becomes activated, perhaps through the action of glutathione and ATP. PT catalyzes the ADP-ribosylation of the i subunits of the heterotrimeric G protein. This prevents the G proteins from interacting with G protein-coupled receptors on the cell membrane, thus interfering with intracellular communication. The Gi subunits remain locked in their GDP-bound, inactive state, thus unable to inhibit adenylate cyclase activity, leading to increased cellular concentrations of cAMP.

• #11 Pertussis Toxin: The Nuts and Bolts – The Native Antigen Company

  https://thenativeantigencompany.com/pertussis-toxin-the-nuts-and-bolts/

  Bordetella pertussis is a gram-negative, aerobic bacterium that causes whooping cough. […] Pertussis toxin (PTX) is a key toxin produced by B. pertussis to modulate immune responses that aid invasion and immune evasion. […] PTX is actively secreted through a Ptl secretion system, where it is thought to bind non-specifically to various mammalian cell-surface receptors. […] PTXs S1 subunit is a member of the ADP-ribosylating family of toxins, which function by transferring an ADP-ribose moiety from cellular NAD+ to intracellular host proteins, resulting in their inactivation and subsequent cellular dysfunction. […] By modulating cAMP activity, PTX is able to disrupt cellular signalling mechanisms and prevent a robust immune response. […] One of the common effects of B. pertussis infection is a build-up of cAMP in phagocytes, which inhibits typical immune responses to bacterial infection, such as phagocytosis and induction of nitric oxide synthesis.

• #12 Pertussis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Pertussis_pathophysiology

  Bordetella pertussis produces multiple antigenic and biologically active virulence factors responsible for the clinical manifestations of pertussis. These virulence factors include: Pertussis toxin (PT) undergoes ADP-ribosylation of G proteins to disrupt signal transduction in host cells. Filamentous hemagglutinin (FHA) is a surface protein responsible for the interaction and adhesion between host cells and Bordetella pertussis. FHA is a component of the acellular DTaP vaccine. Adenylate cyclase toxin (ACT) delivers an adenylate cyclase domain into the host cell and increases the intracellular cAMP concentration. Following cAMP delivery, phagocyte activity is inhibited, and phagocytes undergo apoptosis. Pertactin (PRN) defends Bordetella pertussis against the host neutrophils (immunomodulation). PRN is a component of the acellular DTaP vaccine. Tracheal cytotoxin (TCT) is responsible for the death of host respiratory cells using intracellular IL-1 and nitric oxide. Lipooligosaccharide (LOS) is a unique outer membrane component that is thought to play a role in clinical manifestations of pertussis. Unknown virulence mechanism. Dermonecrotic toxin (DNT) de-aminates signaling proteins (similar mechanism to Pasteurella multicida leukotoxin). Fimbriae (FIM) are surface appendages to adhere to host cells and avoid host immune cells (immunomodulation). FIM is a component of the acellular DTaP vaccine.

• #12 Pertussis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Pertussis_pathophysiology

  Pertussis is primarily a toxin-mediated disease. Bordetella pertussis is highly contagious and is usually transmitted to the human host by direct contact with aerolized mucus of infected individuals. B. pertussis attaches to the cilia of the respiratory epithelial cells, proliferates and produces virulence factors that paralyze the cilia, and causes inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. B. pertussis utilizes virulence factors – including pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), adenylate cyclase toxin (ACT), tracheal cytotoxin (TCT), lipooligosaccharide (LOS), and dermonecrotic toxin (DNT) – to attach, proliferate, and evade the host immune system. […] The bacterium produces toxins (virulence factors) that paralyze the cilia, and cause inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. Bordetella pertussis has tropism for pulmonary tissue and rarely disseminates to other organs. The steps involved in the pathogenesis of pertussis include the following: Inoculation, Attachment to the respiratory epithelium, Proliferation, Production of virulence factors (toxins), Evasion of host immune cells, Tissue destruction.

• #13 pertussis-pathogenesis-clinical-findings-and-complications | Calgary Guide

  https://calgaryguide.ucalgary.ca/pertussis-pathogenesis-clinical-findings-and-complications/pertussis-pathogenesis-clinical-findings-complications/

  Pertussis pathogenesis clinical findings complications […] Bordetella pertussis bacterium enters the airway via droplets B. pertussis binds to ciliated epithelial cells and multiplies, colonizing the nasopharynx B. pertussis produces multiple toxins (e.g. pertussis toxin, tracheal toxin) which damage mucosal cells Pertussis toxin produces cyclic AMP (cAMP) and disrupts normal intracellular signalling, impairing the immune response initially […] Initial immune dampening allows the bacteria to take hold and begin replicating. During this incubation period, the bacteria has not yet replicated to the point of causing symptoms. […] Tracheal cytotoxin released by B. pertussis impairs normal cilia function and ciliary beating in the trachea […] B. pertussis is a Gram-negative strict aerobe An effective vaccine exists to prevent infection by B. pertussis Pertussis most commonly infects children.

• #14 Pertussis toxin – Wikipedia

  https://en.wikipedia.org/wiki/Pertussis_toxin

  Increased intracellular cAMP affects normal biological signaling. The toxin causes several systemic effects, among which is an increased release of insulin, causing hypoglycemia. Whether the effects of pertussis toxin are responsible for the paroxysmal cough remains unknown. […] As a result of this unique mechanism, PT has also become widely used as a biochemical tool to ADP-ribosylate GTP-binding proteins in the study of signal transduction.

• #15 15.3E: Whooping Cough – Biology LibreTexts

  https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/15%3A_Diseases/15.03%3A_Bacterial_Diseases_of_the_Respiratory_System/15.3E%3A_Whooping_Cough

  Pertussis is caused by the bacteria, Bordetella pertussis, a gram-negative, aerobic coccobacillus capsulate of the genus Bordetella. Bordetella pertussis infects its host by colonizing lung epithelial cells. The bacterium contains a surface protein, filamentous haemagglutinin adhesin, which binds to the sulfatides found on the cilia of epithelial cells. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from an organism s lungs, and the body responds by sending the host into a coughing fit. These coughs expel some bacteria into the air, which are free to infect other hosts. […] B. pertussis has the ability to inhibit the function of a hosts immune system, through virulence factors. Its virulence factors include pertussis toxin, filamentous hmagglutinin, pertactin, fimbria, and tracheal cytotoxin. The pertussis toxin, or PTx, inhibits G protein coupling that regulates an adenylate cyclase-mediated conversion of ATP to cyclic AMP. The end result is that phagocytes convert too much ATP to cyclic AMP, which can cause disturbances in cellular signaling mechanisms. This prevents phagocytes from correctly responding to an infection. PTx, formerly known as lymphocytosis -promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes. This can lead to a condition known as lymphocytosis, which is a large increase in the number of lymphocytes in an organisms blood. […] Whooping cough is caused by the bacteria Bordetella pertussis, which infects the respiratory system. Bordetella pertussis produces a number of virulence factors, notably Ptx, which inhibits the ability of phagocytes to respond to infections. This helps Bordetella pertussis spread throughout a host.

• #16 Pertussis Pathogenesis—What We Know and What We Don’t Know

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3952676/

  PT and ACT are active modulators of host defenses. […] ACT (which acts locally) and PT (which acts locally and systemically) disrupt endogenous signaling pathways by producing cAMP (ACT) or catalyzing covalent modification of key molecules in host signaling pathways (PT). […] Although the ability of PMN to kill B. pertussis in vitro has been demonstrated and the biological activities of several virulence factors appear to be directed at neutralizing PMN functions, it remains unclear how this bacterium is cleared in immune or nonimmune hosts. […] Clinical pertussis resulting from infection with B. pertussis is a contemporary medical and public health problem. Although many so-called virulence factors have been identified and studied, the mechanisms by which these (and yet-to-be-recognized products) result in pertussis remain primarily conjectural, based on in vitro studies and use of bacterial mutants in rodent models.

• #17 Chapter 16: Pertussis | Pink Book | CDC

  https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-16-pertussis.html

  Pertussis is primarily a toxin-mediated disease. The bacteria attach to the cilia of the respiratory epithelial cells, produce toxins that paralyze the cilia, and cause inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. Pertussis antigens appear to allow the organism to evade host defenses in that lymphocytosis is promoted but chemotaxis is impaired. […] Previously it was thought that B. pertussis did not invade the tissues. However, studies have shown the bacteria to be present in alveolar macrophages.

• #18 Bordetella pertussis | Mechanisms of Pathogenicity

  https://mechpath.com/2017/12/19/bordetella-pertussis/

  Early in the infection, the pertussis toxin causes a major delay in the recruitment of white blood cells to the site of infection by blocking chemokine production, a signal molecule that is normally sent from the invaded cells to announce danger. This delay allows the bacteria to multiply and achieve further colonization. It continues by making the host cells hypersensitive to histamine, a compound that promotes leakiness in the vascular membrane. This leakiness causes the contents of the blood vessels to be absorbed by the tissue below the epithelial cells and causes swelling. This swelling inflicts pressure on the epithelial layer and promotes mucus production, causing the respiratory airways to narrow, making it more difficult to breathe in extreme cases.

• #19 Bordetella – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK7813/

  Studies of numerous Bordetella pertussis toxins and their corresponding biologic activities have yielded plausible explanations for many of the symptoms of whooping cough. These include, for example, the frequent occurrence of absolute lymphocytosis (an unusual phenomenon in bacterial infections), hypoglycemia, and the adjuvant effect of pertussis toxin on the immune response to unrelated antigens. The finding that phase I isolates of Bordetella bronchiseptica produce almost complete ciliostasis within 3 hours in ciliated epithelial cell outgrowths from canine tracheal explants may be explained by the action of adenylate cyclase toxin and tracheal cytotoxin. The same toxins evidently inhibit the phagocytic activities of the host. In humans, an initial local peribronchial lymphoid hyperplasia occurs, accompanied or followed by necrotizing inflammation and leukocyte infiltration in parts of the larynx, trachea, and bronchi. Usually, peribronchiolitis and variable patterns of atelectasis and emphysema also develop.

• #20 Pertussis: Practice Essentials, Background, Etiology and Pathophysiology

  https://emedicine.medscape.com/article/967268-overview

  Humans are the sole reservoir for B pertussis and B parapertussis. B pertussis, a gram-negative pleomorphic bacillus, is the main causative organism for pertussis. B pertussis spreads via aerosolized droplets produced by the cough of infected individuals, attaching to and damaging ciliated respiratory epithelium. B pertussis also multiplies on the respiratory epithelium, starting in the nasopharynx and ending primarily in the bronchi and bronchioles. […] A mucopurulent sanguineous exudate forms in the respiratory tract. This exudate compromises the small airways (especially those of infants) and predisposes the affected individual to atelectasis, cough, cyanosis, and pneumonia. The lung parenchyma and bloodstream are not invaded; therefore, blood culture results are negative. […] Transmission of pertussis can occur through direct face-to-face contact, through sharing of a confined space, or through contact with oral, nasal, or respiratory secretions from an infected source. In a study of pertussis in 4 US states, out of 264 infants with the disease, the infants mother was the source of pertussis in 32% of cases, and another family member was the source in 43% of cases. […] Young infants, especially those born prematurely, and patients with underlying cardiac, pulmonary, neuromuscular, or neurologic disease are at high risk of contracting the disease and for complications.

• #21 Whooping Cough (Pertussis)

  https://www.uspharmacist.com/article/whooping-cough-pertussis

  B pertussis multiplies on the respiratory epithelium, beginning in the nasopharynx and ending in the bronchi and bronchioles. A mucopurulent sanguineous exudate forms in the respiratory tract, which compromises small airways (especially those of infants) and predisposes the affected individual to atelectasis, cough, cyanosis, and pneumonia. Lung parenchyma and bloodstream are generally not invaded; therefore, blood culture labs are usually negative.

• #22 Bordetella – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK7813/

  To date, there is no plausible explanation for the development of the paroxysmal coughing syndrome characteristic of pertussis. According to Pittman, pertussis is mediated by pertussis toxin and is characterized by a two-stage process infection (colonization) and disease thus resembling other bacterial toxicoses such as diphtheria, tetanus, and cholera. This fascinating idea can be accepted only if it is clearly demonstrated that pertussis toxin causes paroxysmal coughing. Such a demonstration is lacking. Moreover, paroxysmal coughing occurs in infections with Bordetella parapertussis, which does not synthesize pertussis toxin. On the other hand, an additional infection with Bordetella pertussis cannot be excluded in such cases. There is no convincing explanation for the acute encephalopathy sometimes observed in pertussis. Research into the pathogenetic mechanisms of pertussis are hampered by the lack of an adequate animal model showing the characteristic paroxysmal coughing syndrome and by the limited opportunity to perform direct studies of the respiratory tract of babies and children.

• #23

  https://link.springer.com/article/10.1007/BF01974634

  Whooping cough can be caused by either Bordetella pertussis or Bordetella parapertussis. Although the two species share an almost complete DNA identity, Bordetella parapertussis does not produce pertussis toxin, which is thought to be the main virulence factor of Bordetella pertussis. […] The results indicate that pertussis toxin may not play a decisive role in causing the typical symptoms of whooping cough, such as paroxysmal coughing, whooping and vomiting.

• #24

  https://step2.medbullets.com/infectious-dis/121806/pertussis

  bacteria colonizes mucosal surface […] pertussis toxin binds to and activates adenylate cyclase by inhibiting Gi […] impairs phagocytosis, allowing the bacteria to survive […] tracheal cytotoxin […] impairs cilia, preventing normal clearance of respiratory secretions […] low lung volume at the beginning of inspiration causes strong inspiration and inspiratory whoop

• #25

  https://step1.medbullets.com/microbiology/104070/bordetella-pertussis

  bacteria colonizes mucosal surface […] pertussis toxin binds to and activates adenylate cyclase by inhibiting Gi […] impairs phagocytosis, allowing the bacteria to survive […] tracheal cytotoxin […] peptidoglycan fragment that impairs cilia, preventing normal clearance of respiratory secretions […] low lung volume at the beginning of inspiration causes strong inspiration and inspiratory whoop.

• #26 Immunity to the respiratory pathogen Bordetella pertussis | Mucosal Immunology

  https://www.nature.com/articles/mi201254

  Bordetella pertussis causes whooping cough, a severe respiratory tract infection in infants and children, and also infects adults. Studies in murine models have shown that innate immune mechanisms involving dendritic cells, macrophages, neutrophils, natural killer cells, and antimicrobial peptides help to control the infection, while complete bacterial clearance requires cellular immunity mediated by T-helper type 1 (Th1) and Th17 cells. […] Protective immunity generated by wP appears to be mediated largely by Th1 cells, whereas less efficacious alum-adjuvanted aP induce strong antibody Th2 and Th17 responses. New generation aP that induce Th1 rather than Th2 responses are required to improve vaccine efficacy and prevent further spread of B. pertussis. […] Although no single correlate of immunity has emerged, considerable progress has been made in our understanding of the complex mechanisms of protective immunity to B. pertussis. Studies in humans have been complemented by more revealing experiments in murine respiratory challenge models.

• #27 Immunity to the respiratory pathogen Bordetella pertussis | Mucosal Immunology

  https://www.nature.com/articles/mi201254

  Studies on cellular immunity to B. pertussis have shown that recovery from whooping cough in children is associated with the induction of interferon (IFN)–secreting T helper type 1 (Th1) cells. […] Complementary studies in mice have shown that IFN- is required for the control of B. pertussis infection in the respiratory tract; mice lacking this cytokine or its receptor develop disseminating and lethal infection. […] Furthermore, experiments involving cell depletion or adoptive transfer have provided convincing evidence of a role for Th1 cells in clearance of a primary infection or following immunization with wP. […] By contrast, immunization of mice with aP induces Th2-type responses, which promote humoral immunity, but do not appear to be as effective as Th1 cells in clearance of B. pertussis from the respiratory tract. […] Thus, the failure of alum-adjuvanted aP to induce Th1 responses, and hence IFN- secretion, may be one explanation for the increasing incidence of pertussis in populations using aP.

• #28 The Role of Type I and III Interferons in the Pathogenesis of Bordetella pertussis Infection and Disease.

  https://archive.hshsl.umaryland.edu/entities/publication/f4a885f2-66ce-4e3e-9b98-12ec198586d9

  Bordetella pertussis is a Gram-negative bacterial pathogen that infects human respiratory tracts and is the causative agent for the disease pertussis, otherwise known as whooping cough. […] Using RNA-sequencing transcriptomics we investigated lung gene expression responses to Bordetella pertussis infection in adult mice, revealing that type I and III interferon (IFN) responses and signaling pathways may play an important role in promoting inflammatory responses. […] In B. pertussis infected mice, lung type I/III IFN responses correlated with increased proinflammatory cytokine expression and lung inflammatory pathology. […] In direct contrast, infant mice didn’t upregulate type I/III IFNs in response to B. pertussis infection and were protected from lethal infection by increased type I IFN signaling, indicating age dependent effects of type I/III IFN signaling during B. pertussis infection.

• #29 The Role of Type I and III Interferons in the Pathogenesis of Bordetella pertussis Infection and Disease.

  https://archive.hshsl.umaryland.edu/entities/publication/f4a885f2-66ce-4e3e-9b98-12ec198586d9

  The induction of type I/III IFNs was found to be MyD88 dependent, and TLR9 and STING were identified as DNA sensing pattern recognition receptors required for type I/III IFN responses, as well as for typical levels of lung inflammatory pathology. […] This observation, coupled with results showing DNase treatment of B. pertussis-infected mice causing reduced lung pathology, indicated a DNA dependent induction of type I/III IFNs, making these targets for therapeutic intervention.

• #30 Does vaccination reduce the virulence of the bacteria responsible for whooping cough? | Institut Pasteur

  https://www.pasteur.fr/en/research-journal/news/does-vaccination-reduce-virulence-bacteria-responsible-whooping-cough

  Following an analysis of bacterial samples from infants with whooping cough, scientists from the National Reference Center (CNR) for Whooping Cough and other Bordetellosis have revealed that the most severe forms of the disease are associated with specific strains expressing a key vaccine antigen. This discovery suggests that the bacteria may have evolved into less virulent and therefore less dangerous forms because of mass vaccination. […] Over the past decade, scientists at the National Reference Center (CNR) for Whooping Cough and other Bordetella Infections monitoring the bacteria responsible for whooping cough, Bordetella pertussis (B. pertussis), have also observed a rise in strains lacking the expression of one of the vaccine antigens, pertactin. This reflects an adaptation of the pathogen to widespread vaccination with acellular vaccines: the strains that do not produce pertactin partly evade the immune response in vaccinated individuals and spread more effectively than the original strains which expressed the antigen.

• #31 Does vaccination reduce the virulence of the bacteria responsible for whooping cough? | Institut Pasteur

  https://www.pasteur.fr/en/research-journal/news/does-vaccination-reduce-virulence-bacteria-responsible-whooping-cough

  The link between the most severe forms of whooping cough and the presence of pertactin suggests that vaccination exerts selective pressure on B. pertussis, causing the bacteria to evolve towards less virulent strains lacking pertactin. In other words, widespread vaccination could reduce the severity of the disease and decrease the risk of severe whooping cough in infants.

• #32 Pertussis: Common Questions and Answers | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/0800/p186.html

  Some strains have shifted away from displaying the acellular vaccine antigens (i.e., pertussis toxin, pertactin, fimbriae 2 or 3, and filamentous hemagglutinin). These are known as vaccine antigen deficient strains or escape mutants. Even without this shift, immunity wanes in most patients because of uncertain causes. […] Immunity typically wanes two to four years after administration of the acellular pertussis vaccine, although this can occur as early as one year postvaccination. Individuals with natural infection also experience waning immunity, including children with a history of pertussis. […] Antibiotics are intended to prevent transmission of pertussis to others and do not shorten the disease course or improve symptoms. Azithromycin (Zithromax) is the preferred treatment for pertussis because of its favorable safety profile, but use of other macrolides (erythromycin, clarithromycin) or trimethoprim/sulfamethoxazole is an acceptable alternative.

• #33 Appendix C: Animal Models for the Study of Whooping Cough and the Testing of Vaccine Materials | Adverse Effects of Pertussis and Rubella Vaccines | The National Academies Press

  https://nap.nationalacademies.org/read/1815/chapter/14

  Bordetella pertussis does not naturally cause disease in animals. Nevertheless, experiments in animals have made important contributions to the present, although incomplete, understanding of pertussis. […] Most of the information about pertussis gained from animal models has come from the study of mice. […] Using intranasal inoculation of infant mice, Weiss and colleagues (1983, 1984) showed that mutant strains of B. pertussis lacking pertussis toxin (PT) or extracytoplasmic adenylate cyclase were much less virulent than the wild-type (naturally occurring) organism. […] In summary, B. pertussis is a complex organism, multiple factors having been proposed as possible contributors to its virulence. Their role in whooping cough has not been clearly established. Without better understanding of the organism and the human disease, it cannot be concluded with confidence that data from animal models relate to findings in humans.

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