Pertussis

Pertussis, or whooping cough, is a highly infectious disease of the respiratory tract caused by the gram-negative bacterium Bordetella pertussis. This disease spreads via droplet transmission (and to a lesser extent via fomites) 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. Patients who meet the suspected case definition for pertussis should be started on antibiotic therapy for pertussis and confirmatory laboratory studies (usually PCR or culture) should be conducted. Postexposure prophylaxis for pertussis is recommended for all close contacts and high-risk individuals (e.g., infants) regardless of immunization status. Pertussis immunization is part of the routine immunization schedule; while immunization reduces the severity of illness it does not provide full immunity.

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

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: Bordetella pertussis is a gram‑negative, obligate aerobic coccobacillus.
• Transmission: droplet transmission, fomite transmission ^[4][5]
• 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:^[1][6]

• 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 ^[7]
• 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 ^[8]
• 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.

Pertussis classically has three stages: catarrhal, paroxysmal, and convalescent. Symptoms may vary, however, based on age and immunization status; vaccinated individuals tending to have a milder illness without characteristic whooping. ^[1][9]

Catarrhal stage (1–2 weeks) ^[9]

• Nonspecific symptoms similar to an upper respiratory infection, e.g.:
  • Mild cough
  • Watery nasal discharge
  • Rarely low-grade fever
  • Possibly conjunctivitis
• Patients are highly infectious.

Paroxysmal stage (2–6 weeks) ^[9]

• Intense paroxysmal coughing (often occurring at night)
  • Followed by a deep and loud inhalation or high-pitched whooping sound
  • Accompanied by struggling for breath, gagging, and tongue protrusion
  • 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 present with: ^[1][6]
  • Apneic episodes
  • Paroxysmal coughing but no characteristic whoop ^[1]

Convalescent stage (weeks to months) ^[9]

• Progressive reduction of symptoms
• Coughing attacks may persist over several weeks before resolving.
• Patients have an increased susceptibility to respiratory infections.

The typical pattern of paroxysmal cough with whooping manifests mainly in unvaccinated children. Infants < 6 months of age, vaccinated individuals, and adults may not whoop and may not follow the classic stages of pertussis. ^[1][9]

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

Approach ^[1][10]

• Perform confirmatory studies for any patient that meets the suspected case definition for pertussis. ^[9]
• The choice of diagnostic test depends on duration since symptom onset. ^[9][11][12]
  • First 1–4 weeks: Obtain PCR ± culture.
  • Between 4—12 weeks: Consider a serum sample for serology. ^[9][12]
• For infants < 3 months, consider a CBC.
  • Lymphocyte-predominant leukocytosis is common in infants and young children. ^[6]
  • An absolute lymphocyte count of > 20,000 cells/μL is a classic diagnostic finding and suggests a poor prognosis. ^[1][9]

Suspected case definition for pertussis ^[11][12][13]

Cough is present for any duration (with a low threshold for suspicion in infants), with ≥ 1 of the following: ^[9][13]

• Paroxysmal coughing
• Whooping on inspiration
• Posttussive vomiting
• Apnea ^[11][12]
• Known contact with confirmed case
• Living in an area with a pertussis outbreak

The presence of fever suggests an alternative diagnosis (see “Differential diagnoses of pertussis”). ^[9][13]

Confirmatory studies

PCR and/or cultures should be used for patients who present ≤ 4 weeks since cough onset. Serology should be used for patients who present > 4 weeks after developing symptoms.

PCR ^[1][6][11]

• Preferred test ^[9]
  • High sensitivity
  • Rapid results
  • Unaffected by antibiotic therapy or previous vaccination ^[1]
• Specimen collection
  • Preferred: nasopharyngeal swab
  • Alternative: saline nasopharyngeal aspirate

Bacterial culture ^[1][6][11]

• Gold standard ^[9]
  • 100% specificity
  • Use is limited by:
    • Long growth time (7–10 days)
    • Low sensitivity, especially in patients who are taking antibiotics or have been immunized ^[1]
• Indications ^[9][14]
  • Alternative when PCR is not available
  • In addition to PCR for strain identification
• Specimen collection method
  • Preferred: nasopharyngeal swab
  • Alternative: saline nasopharyngeal aspirate

Pertussis serology ^[6][9][11]

• Used for patients who meet all the following criteria:
  • 4–12 weeks since cough onset ^[1][6]
  • Age ≥ 6 months ^[9]
  • ≥ 1 year since the last vaccination dose
• Findings: ↑ IgG antibodies to pertussis toxin

The CDC only accepts positive culture or PCR for disease reporting; serology is, however, suggested for use in outbreak settings. ^[6][12]

Direct fluorescent antibody testing and blood cultures are not recommended because of low specificity and sensitivity. ^[6][11][15]

• 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.

Approach ^[6]

• Start antibiotic therapy in suspected pertussis without waiting for diagnostic confirmation. ^[6][9][10]
• Assess patients for admission criteria for pertussis and admit if present.
  • Consider the need for ICU/PICU consult.
  • Infants with pertussis should be admitted to a facility able to escalate care. ^[6][16]
• Provide supportive care, e.g.: ^[17]
  • Respiratory support ^[16]
  • Frequent suctioning
  • Management of dehydration and hypovolemia
  • Nutritional support
• Initiate measures to prevent onward transmission of pertussis.
• After treatment, offer the acellular pertussis vaccine to stable unvaccinated patients. ^[1]

Symptomatic treatment of cough (e.g., with corticosteroids, antihistamines, albuterol) is not recommended, as there is no evidence symptomatic treatments reduce cough or duration of hospitalization. ^[9][18]

Pertussis is a nationally notifiable disease. ^[9]

Admission criteria for pertussis

• Admit patients with features of severe disease, e.g.: ^[6][17]
  • Patients of any age with:
    • Pneumonia
    • Signs of respiratory failure (i.e., cyanosis, apnea)
    • CNS complications (e.g., seizure)
  • In infants with:
    • Apnea
    • Difficulty feeding
• Consider admission for patients with risk factors for severe pertussis, e.g.: ^[6][19][20]
  • Individuals of any age with a history of:
    • Immunocompromise
    • Pulmonary disease (e.g., COPD, asthma)
    • Neurologic disorders
    • Genetic disease
  • Infants with any of the following characteristics:
    • Age < 4 months
    • Prematurity
    • Low birth weight
    • Mother who did not receive a pertussis vaccine during pregnancy

Infants < 6 months are at the highest risk for morbidity and mortality, especially those with a history of preterm delivery or inadequate maternal immunization. ^[6][20]

Antibiotic therapy for pertussis ^[1][6][9]

• First-line: macrolides
  • Preferred: azithromycin (off-label) ^[6][9]
  • Alternative
    • Erythromycin ^[6]
    • Clarithromycin ^[6]
• Allergy/intolerance to macrolides: Consider trimethoprim/sulfamethoxazole: (off-label). ^[6]

Antibiotic therapy decreases transmission of pertussis but may not improve the duration or severity of symptoms, especially if started at a later clinical stage. ^[1][11]

Monitor infants < 6 weeks of age who are being treated with azithromycin or erythromycin for hypertrophic pyloric stenosis. ^[6]

• Start immediate antibiotic therapy for pertussis.
• Provide supportive therapy (e.g., respiratory support) as needed.
• Send PCR and/or culture to confirm the diagnosis.
• Assess admission criteria for pertussis and admit if present.
• Initiate measures to prevent onward transmission of pertussis.
• Perform contact tracing to determine who should be offered postexposure prophylaxis for pertussis.
• Notify the state health department.

• Infection: otitis media
• Respiratory
  • Bordetella pertussis pneumonia
  • Hemoptysis, atelectasis, pneumothorax
• Cardiac: pulmonary hypertension ^[6]
• Neurologic: seizures, encephalopathy with possible permanent damage
• Sudden infant death ^[6]

References:^[21][22][23]

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

• In children > 6 months: usually good; lengthy convalescence, but full recovery
• In children < 6 months: increased risk of complications; mortality highest in children < 2 months ^[1][6]

Primary prevention of pertussis ^[24][25][26]

• Vaccine: the acellular pertussis vaccine is available as a combination vaccine that also contains the diphtheria vaccine and tetanus vaccine.
• Choice of vaccine depends on age: ^[1]
  • Children < 7 years of age: DTaP vaccine
  • Children ≥ 7 years of age and adults: Tdap vaccine ^[1]
• Primary course
  • Recommended at 2, 4, 6, and 15–18 months and at 4–6 years
  • Adults who were not vaccinated as children should receive a one-time dose of Tdap.
  • See “ACIP immunization schedule” for details on routine and catch-up schedules.
• Booster
  • All individuals aged 11–12 years ^[6]
  • During each pregnancy: one-time dose, preferably at 27–36 weeks of gestation
  • Adults who receive a routine tetanus booster with Tdap will also be boosted against pertussis. ^[9][26]
• Contraindications ^[24][26]
  • Absolute contraindications: anaphylactic reaction to or encephalopathy from previous pertussis vaccination
  • Relative contraindications include:
    • Moderate to severe acute illness
    • Uncontrolled or evolving neurological disorders (e.g., Guillain-Barré syndrome or seizures)
    • Arthus reaction

Pertussis vaccination helps reduce severity, but infection can still occur because the immunity from vaccination (as well as infection) is short-lived and there has been a rise in vaccine antigen-deficient strains. ^[9]

Ensure all close contacts (e.g., family members, caregivers) of infants have received all the recommended age-appropriate pertussis vaccines (DTaP, Tdap). ^[1][6][9]

Prevention of onward transmission of pertussis

Approach ^[6][11]

• Use droplet precautions when evaluating patients.
• Advise isolation precautions for pertussis for suspected or confirmed cases.
  • The duration of isolation precautions varies based on treatment status: ^[1]
    • Treated patients: until 5 days of antibiotic therapy have been completed
    • Untreated patients: > 3 weeks since cough onset
  • For patients in the community: ^[6]
    • Advise avoiding contact with high-risk individuals (i.e., pregnant women, infants, and children).
    • Children who attend daycare/school and staff in childcare and healthcare settings should remain at home.
  • For hospitalized patients: Place the patient in a side room with droplet precautions. ^[11]
• Perform contact tracing to determine who should be offered postexposure prophylaxis for pertussis.
• Pertussis is a notifiable disease; ensure the state health department has been contacted.

Postexposure prophylaxis for pertussis ^[6][10]

• Indications ^[11]
  • All close contacts of an individual pertussis with, regardless of age and vaccination status ^[1]
  • High-risk individuals with possible exposure, e.g.:
    • Infants
    • Pregnant women (third trimester)
    • Any individual who cares for infants and/or pregnant women (e.g., health care or daycare workers)
    • Immunocompromised individuals ^[9]
    • Individuals with chronic comorbidities (e.g., respiratory conditions) ^[9]
• Prophylactic measures
  • Administer antibiotic therapy for pertussis within 21 days of contact exposure. ^[9]
  • Advise isolation precautions for pertussis until 5 days of antibiotic therapy has been completed. ^[27]
  • Ensure all asymptomatic individuals are up-to-date with acellular pertussis vaccine according to the ACIP immunization schedule. ^[1][11]