Bordetella Pertussis
Diseases

Author: Gian Maria Frontuto
Date: 12/04/2014

Description

B.Pertussis, belonging to the genus Bordetella, is a Gram – capsulated bacterium; it presents a cocco-bacillary shape and it is aerobic obliged. It is the aetiological agent of hooping cough.

PATHOGENESIS

B. Pertussis is a bacterium that produces numerous virulence factors that have been studied individually and some of which possess additional biological activities. It remains unknown, however, how these interact to cause whooping cough.
Infection by B. Pertussis occurs through contact of this bacterium with ciliated epithelial cells of the respiratory tract, subsequent bacterial proliferation and final damage to the respiratory epithelium with general impairment caused by proinflammatory factors and cytokines.
B.Pertussis produces two adhesion proteins, named pertactin and filamentous hemagglutinin, that contain an Arg-Gly-Asp sequence that binds the integrin proteins of ciliated cells membranes promoting the adherence of the bacterium to the epithelium. These proteins also bind the CR3 receptor of macrophages promoting phagocytosis of the bacterium capable of survival and intracellular replication. It is also produces pertussis toxin that contains a toxic subunit, S1, and five binding subunits named S2 S3 S4 S5: S2 subunit binds lattosilceramide present on epithelial cells, S3 subunit binds phagocytic cells causing the increase of CR3 on the cell surface thus promoting the mechanism of bacterial adhesion and phagocytosis previously described.
Localized and systemic manifestation of the disease are conducted through the different toxins produced by B.Pertussis:
_ S1 subunit of pertussis toxin presents ADP-ribosylating activity for G proteins of membrane that regulate adenylyl cyclase activity. That toxin inactivates the inhibitory protein Giα that controls this activity causing an increase of intracellular concentration of cAMP and, as result, of mucus and respiratory secretion.
_ Adenylyl cyclase/hemolysin is a dual function toxin which is activated in target cells catalysing the conversion of ATP to cAMP and inhibiting chemotaxis, phagocytosis and killing by leukocytes.
_ The dermonecrotic toxin is liable for localized destruction of the tissues.
_ The tracheal cytotoxin is monomer of bacterial peptidoglycan which causes ciliostasis and ciliated cells loss due to his interference with DNA synthesis which prevent cells regeneration. It also stimulates the production of inflammatory molecules as IL-1.

  • Microbiologia Medica, Patrick R. Murray, Ken S. Rosenthal, Michael A. Pfaller, ELSEVIER, 2010

EPIDEMIOLOGY

Pertussis is a human endemic disease in the world even with an incidence significantly decreased following the introduction of vaccines in 1949. In the past whooping cough struck more frequently children while today it is widespread among adolescents and adults.
In case of infection, their symptoms can be persistent and displeasing, such as prolonged cough, but symptoms may be mild as most of them have been vaccinated against the disease. The greater concern is the risk of disease transmission by infected adolescents and adults against unvaccinated children who are most vulnerable to the symptoms. The number of infected each year is estimated to be between 20 and 40 million people with a number of deaths that varies between 200 000 and 400 000 that includes for most unvaccinated children. Although the true incidence of the disease is underestimated, the improvement of diagnostic tests and the recognition of milder forms of the disease have resulted in an increase of reported cases.

  • Microbiologia Medica, Patrick R. Murray, Ken S. Rosenthal, Michael A. Pfaller, ELSEVIER, 2010

CLINICAL MANIFESTATION

Whooping cough is contracted through inhalation of infected aerosols and, after an incubation period of 7/10 days of B. pertussis, is manifested in three phases:
_ The catarrhal phase is characterized by serous rhinorrhea, sneezing, fever and slight illness. Since at this stage the bacteria reaches its peak, while the disease is not yet diagnosed, sick people are the greatest source of risk of infection for healthy people.
_ The paroxysmal phase occurs after 1-2 weeks and is characterized by the destruction of the ciliated cells of the respiratory tract. The subject in this phase have a paroxysmal cough defined as “whooping cough” in which more coughing follows one another compulsively followed by an inspiratory shriek during the inspiratory phase. During the paroxysmal phase the airways present an obstruction partially caused by mucus.
_ The convalescent phase occurs after 2-4 weeks with paroxysmal cough decreasing in frequency and severity but with the possibility that there might be any secondary complications.

  • Microbiologia Medica, Patrick R. Murray, Ken S. Rosenthal, Michael A. Pfaller, ELSEVIER, 2010

DIAGNOSIS TREATMENT PREVENTION

Diagnosis in based on clinical suspicion with subsequent collection of diagnostic specimens such as nasopharyngeal aspirate which is collected from infected patients and seeded on a suitable culture media such as Regan-Lowe agar for carrying out the laboratory tests. The sensitivity of the culture is influenced by multiple patient-related factors such as the stage of the disease, the possible use of antibiotics, the quality of the sample and the conditions of transport and culture methods.
B. Pertussis requires an incubation period of about 7-10 days but, despite the optimal conditions for growth, less than half of patients have a positive culture. Pertussis therapy is mainly supportive with administration of antibiotics (such as penicillins and macrolides) to reduce the duration of infectivity and avoid complications; this effect is however limited as the disease is usually recognised in paroxysmal phase in which the peak of infectivity is now past.
Vaccination is compulsory and is carried along with the tetanus and diphtheria within the first year of life with reminders of school age.

  • Microbiologia Medica, Patrick R. Murray, Ken S. Rosenthal, Michael A. Pfaller, ELSEVIER, 2010
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