Pertussis

Pertussis, or whooping cough, is a highly infectious disease of the respiratory tract caused by the gram-negative bacteria Bordetella pertussis. The disease is mainly transmitted via airborne droplets and most commonly occurs in children. Typically, pertussis manifests in three stages, with the second and third stages characterized by intense paroxysmal coughing that is followed by a distinctive whooping sound on inhalation and, in some cases, vomiting. Young infants may not develop the typical cough, and often present with apnea and cyanosis instead. The disease is most often diagnosed via laboratory tests, especially detection of B. pertussis in bacterial culture. However, as test results may take time to obtain, treatment should be initiated as soon as clinical suspicion of pertussis arises. Subsequent management includes hospitalization of high-risk patients (e.g., infants) and antibiotic therapy with macrolides. These may lessen the length and severity of the disease if administered early, while also reducing infectivity and further disease transmission. Macrolides are also the drug of choice for post-exposure prophylaxis (PEP), which is recommended for all people with a recent history of exposure to pertussis. PEP is administered regardless of the individual immunization status, as both vaccination and prior infection may shorten the disease course, but do not provide full immunity.

• Typically a childhood disease (particularly children aged < 1 year); however, older patients are increasingly affected. ^[1][2]
• High rate of infections in newborns: Tdap vaccine is recommended for pregnant women between weeks 27 and 36 of gestation. ^[2][3]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: Bordetella pertussis is a gram‑negative, obligate aerobic coccobacillus.
• Transmission: airborne droplet (through coughing); direct contact with oral or nasal secretions
• Infectivity
  • Without antibiotic treatment: 4–6 weeks
  • With treatment: ∼ 5 days
  • Highly virulent
• Incubation period: on average 7–10 days (range 4–21 days)

References:^[2]

• Proliferation of Bordetella pertussis on ciliated epithelial cells of the respiratory mucosa → production of virulence factors (e.g., tracheal cytotoxin) → paralysis of respiratory epithelium cilia and inflammation → secretion of inflammatory exudate into respiratory tract → compromise of small airways → cough, pneumonia, cyanosis ^[4]
• Bordetella pertussis produces pertussis toxin → ADP-ribosylation of the α subunit of G_i protein → inhibition of Gi protein → adenylate cyclase disinhibition → cAMP accumulation → impaired cell signaling pathways ^[5]
• Pertussis toxin is responsible for most of the systemic manifestations associated with whooping cough (e.g. hypoglycemia, lymphocytosis, modulation of host immune response).
• Neither vaccination nor actual infection confers complete or lifelong immunity.

Catarrhal stage (1–2 weeks)

• Nonspecific symptoms similar to an upper respiratory infection (mild cough, watery nasal discharge, rarely low-grade fever)
• Possibly conjunctivitis

Paroxysmal stage (2–6 weeks)

• Intense paroxysmal coughing (often occurring at night)
  • Followed by a deep and loud inhalation or high-pitched whooping sound
  • Accompanied by tongue protrusion , gagging, and struggling for breath
  • Possibly accompanied by cyanosis
  • Increases in frequency and severity throughout the stage
  • Followed by the expulsion of phlegm or posttussive vomiting (risk of dehydration)
• Potential bleeding of the conjunctiva, petechiae, and venous congestion
• Infants (< 6 months) may only develop apnea and not the characteristic cough.

Convalescent stage (weeks to months)

• Progressive reduction of symptoms
• Coughing attacks may persist over several weeks before resolving

The typical whooping cough manifests mainly in children aged 6 months to 5 years. The individual stages of the disease may be indistinguishable in young infants and adults.

Catarrhal stage manifests with Coryza, while the Paroxysmal stage manifests with Posttussive vomiting and whooPing cough.

References:^[6][7]

A presumptive diagnosis of pertussis may be made based on clinical history and findings. However, if possible, laboratory tests should be performed to confirm the diagnosis.

History ^[7]

• Clinical diagnosis possible in patients with a cough lasting ≥ 2 weeks and at least one of the following symptoms:
  • Coughing paroxysms
  • Whooping on inspiration
  • Vomiting following coughing attack
  • Apnea (in infants)
• Inquire about immunization history and possible contact with infectious persons.

Laboratory tests ^[8][9]

• Blood count: lymphocyte-predominant leukocytosis (50,000–60,000/μL) that corresponds with disease severity
• Pathogen detection (to confirm the diagnosis)
  • Culture (gold standard) or PCR: samples from deep nasopharyngeal aspiration or posterior nasopharyngeal swab
  • Serology: unsuitable for early diagnosis because antibody detection (IgA, IgG, IgM) first occurs after a period of 2–4 weeks

As B. pertussis only grows on respiratory epithelium, blood cultures are always negative.

• Bordetella parapertussis infection
• Respiratory syncytial virus bronchiolitis
• Pneumonia, particularly due to Chlamydia trachomatis or Mycoplasma pneumoniae
• Croup (laryngotracheobronchitis)
• Foreign body aspiration

The differential diagnoses listed here are not exhaustive.

General approach ^[10]

• Early initiation of treatment, especially in high-risk patients (e.g., infants), while confirmatory laboratory tests are pending
• Hospitalization and monitoring: infants < 4 months; severe cases (e.g., respiratory distress, cyanosis, apnea, inability to feed)
• Oxygen administration with humidification
• Increased fluid intake and nutritional support
• If necessary, sedation

Medical therapy ^[11][12]

• Macrolides (e.g., azithromycin, clarithromycin, erythromycin)
  • In children > 1 month and adults: any macrolide ; If macrolides are not tolerated, use trimethroprim-sulfamethoxazole.
  • Infants < 1 month: azithromycin
• Early administration may lessen symptoms of the catarrhal stage and early paroxysmal stage.
• Late antibiotic administration has little influence on disease severity but reduces infectivity.

• Infection: otitis media
• Respiratory
  • Bordetella pertussis pneumonia
  • Hemoptysis, atelectasis, pneumothorax
• Neurologic: seizures, encephalopathy with possible permanent damage

References:^[13][14]

We list the most important complications. The selection is not exhaustive.

• In children > 3 months: very good; lengthy convalescence, but full recovery
• In children < 3 months: mortality 1–3%, particularly due to apnea
• Increased risk for complications
  • Premature infants
  • Children < 6 months
  • People with underlying cardiac, pulmonary, neurologic, or neuromuscular disease

References:^[10]

Immunization ^[2][15][16]

• Children
  • Routine immunization: DTaP vaccine (diphtheria, tetanus, and pertussis) at 2, 4, 6, and 15–18 months and at 4–6 years (see “Immunization schedule”)
  • Booster vaccination: Tdap vaccine
    • Single dose at 7–10 years of age if immunization is incomplete
    • Single-dose boost at 11–18 years of age, at least 10 years following the last dose
  • Contraindications: known anaphylactic reactions, encephalopathy following previous vaccination ^[17]
• Adults
  • One-time dose of Tdap
  • In particular, pregnant women; and people in contact with newborns should be vaccinated .

Post-exposure prophylaxis ^[18][19][20]

• Indications
  • All household contacts of a pertussis case, regardless of their vaccination status
  • People at high risk of developing severe pertussis, including:
    • Infants younger than 12 months
    • Pregnant individuals in their third trimester of pregnancy
    • Individuals with conditions that may be exacerbated by a pertussis infection (e.g., immunocompromization due to HIV, conditions affecting the lungs)
  • People who have close contact with others at high risk of developing severe pertussis (e.g., workers in neonatal intensive care units, childcare settings, or maternity wards)
• Regimen: choice of antibiotics is identical to treatment recommendations (see “Therapy” above)
• Isolation
  • Required for 5 days after initiation of antibiotic therapy
  • Without antibiotic treatment: minimum of 3 weeks after the onset of first symptoms

Pertussis is a notifiable disease. ^[21]