Pertussis (Whooping Cough)

Pertussis, or whooping cough, is a potentially life-threatening highly contagious bacterial infection of the respiratory tract caused by Bordetella pertussis. The disease has 3 clinical stages, the second and third of which are characterized by an intense paroxysmal cough, an inspiratory whoop, and post-tussive vomiting. Pertussis can be prevented by a vaccine that is administered as part of most routine vaccinations and usually started at the age of 6 weeks. Diagnosis is based on the clinical history and confirmed by the detection of the organism via culture or polymerase chain reaction. If pertussis is suspected, immediate antibiotic therapy with macrolides should be initiated, even if laboratory confirmation is pending.

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Epidemiology and Etiology

Epidemiology

  • Incidence worldwide: 24 million cases per year
  • Deaths worldwide: approximately 161,000 per year
  • Incidence in the United States: 15,000 cases in 2018
  • More common in developing countries, with the highest mortality rate in infants 
  • Common and more severe in infants < 1 year of age (usually no or scant maternal passive immunity unless the mother was given a Tdap booster vaccine in the early third trimester)
    • Increasingly more common in adolescents, as protective immunity of vaccination wanes after 4–12 years

Etiology

  • Infection with the bacterium Bordetella pertussis (a gram-negative coccobacillus)
  • Transmission occurs through airborne droplets (coughing, sneezing, or speaking) or direct contact with oral or nasal secretions of an infected individual.
  • High infectivity for approximately 3 weeks after the cough begins if untreated (only 5 days with treatment)
  • Incubation period: 7–10 days

Pathophysiology

  • Infection through the inhalation of airborne droplets containing B. pertussis 
  • Bacteria adhere to and damage the ciliated epithelium of the nasopharynx, causing inhibition of the mucociliary elevator (may spread to the bronchial tree and lungs in severe cases).
    • Bacteria also evade intracellular digestion and thereby evade the immune system of the host.
  • Virulence factors (e.g., tracheal cytotoxin, dermonecrotic toxin, adenylate cyclase ) cause inflammation and destruction of the cilia.
    → secretion of inflammatory exudate into the respiratory tract (RT)
    → impairs the removal of mucus and debris from the RT → higher risk of secondary infections
  • Organisms have been found in alveolar macrophages as well as the ciliated respiratory epithelial cells of the lower RT, which may explain the prolonged duration of cough. 
  • Pertussis toxin produces most of the systemic manifestations associated with whooping cough (e.g., lymphocytosis, pulmonary hypertension).
Bordetella pertussis causing whooping cough

Pathophysiology of Bordetella pertussis causing whooping cough

Image by Lecturio.

Clinical Presentation

First stage: catarrhal

  • Lasts 1–2 weeks
  • Presents with nonspecific symptoms of an upper respiratory tract infection:
    • Mild cough
    • Low-grade fevers
    • Coryza (i.e., runny nose)
    • Sneezing
    • Conjunctivitis

Second stage: paroxysmal

  • Lasts 2–8 weeks 
  • Presents with characteristic paroxysms of intense cough followed by an inspiratory “whooping” sound
    • Typically absent in infants, who instead present with periods of apnea due to the inability of their respiratory muscles to produce strong coughing
  • Post-tussive vomiting, shortness of breath (dyspnea), and cyanosis can occur

Third stage: convalescent

  • Lasts 4 weeks on average, but may extend for months
  • Characterized by the progressive reduction of all symptoms

Diagnosis

  • Diagnosis is strongly suspected with clinical history but requires laboratory confirmation.
  • History: possible contact with other “whooping cough” cases and vaccination (as the vaccine does not provide full protection, pertussis needs to be considered even in vaccinated children!)
  • Laboratory tests:
    • Nasopharyngeal swab → culture (gold standard) or polymerase chain reaction
      • Only reliable during the first 2–3 weeks of the infection
    • Complete blood count shows nonspecific lymphocytosis.
    • Serology testing can be used up to several weeks after the onset of symptoms.
      • A 2-fold rise in the antibody titer against pertussis is diagnostic.
Gram stain of the bacteria Bordetella pertussis

Gram stain of the bacteria Bordetella pertussis

Image: “Gram stain of the bacteria Bordetella pertussis” by CDC/Public Health Image Library. License: Public Domain

Management and Prevention

Supportive care

  • Hospitalization may be required for infants who present with apnea and respiratory distress.
  • Oxygen administration may be required in severe cases.
  • Antitussive therapy has not been shown to be effective.

Medical therapy

  • Macrolides (e.g., azithromycin, clarithromycin, erythromycin)
    • Reduce the spread of pertussis but do not affect the clinical course
    • Azithromycin as first-line choice for infants < 1 month of age
    • In the case of allergies to macrolides, trimethoprim-sulfamethoxazole is used.

Prevention

  • Active immunization through the administration of diphtheria-tetanus toxoids and acellular pertussis vaccine (DTaP)
    • Only 80%–90% effective
    • 5 doses in total (at ages 2, 4, 6, and 18 months; and 5 years)
    • Booster vaccine needed at 11–18 years of age (10 years following the last dose) or in pregnant women (in the third trimester) with the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap)

Differential Diagnosis

  • Bronchitis: a lower respiratory tract infection that leads to inflammation of the bronchi
  • Pneumonia: a respiratory infection characterized by inflammation of the alveolar space and/or the interstitial tissue of the lungs
  • Croup: also known as laryngotracheobronchitis, a disease usually caused by a viral infection or, rarely, by a bacterial infection that results in swelling inside the trachea; interferes with normal breathing
  • Foreign body aspiration: the aspiration of an object that becomes lodged in the larynx, trachea, or bronchi. A potentially life-threatening emergency that usually occurs in children < 3 years of age

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