Bordetella pertussis

Background

Microbiology

• Small, Gram-negative coccobacillus
• Fastidious, slow-growing, and strictly aerobic
• Catalase positive non-fermentative
• Pertussis toxin helps it to evade the host defenses

Pathophysiology

• Four steps to infection: attachment, evasion of host defenses, local damage, and systemic manifestations
• Virulence determined by filamentous hemagglutinin (FHA) and fimbriae (FIM) adhesins
  • Required for tracheal colonization
  • Pertussis toxin (PT) also plays a role
• Adenylate cyclase toxin (ACT) and PT allow it to evade host defenses
  • ACT inhibits macrophages by catalysing ATP to cAMP
  • PT delays neutrophil recruitment by suppressing G protein signaling pathways
• Tracheal cytotoxin (TCT) produces NO and damages the tracheal epitheleal cells
• Few systemic manifestations because it doesn't enter circulation

Clinical Manifestations

• Presents with cough lasting 14 days or more, with paroxysms of coughing, an inspiratory whoop, and post-tussive vomiting
• Incubation period of 7 to 10 days on average (range 5 to 21 days)

Young Children

• Three stages:
  1. Catarrhal stage, with rhinorrhea, nonpurulent conjuctivitis, occasional cough, and a low-grade fever; lasts 1 to 2 weeks.
  2. Paroxysmal stage, with fits of coughing and an inspiratory whoop; lasts 1 to 6 weeks. May have post-tussive emesis. Occasionally associated with hyperinsulinemia and hypoglycemia in infants.
  3. Convalescent stage, with the cough slowly resolving over 1 to 6 weeks, occasionally up to 8 weeks.

Adults

• Can present atypically, with less whooping and less post-tussive vomiting
• Coughing is seen in most patients, lasting longer than 21 days
  • Mean duration 36 to 48 days
• Post-tussive vomiting is suggestive of pertussis

Carrier State

• Transient nasopharyngeal carriage in immunized children

Complications

• Case-fatality rate of 1% in children under 6 months
• Pneumonia is the most common complication, either caused by the disease itself for by coinfection (especially RSV)
• Encephalopathy is a rare complication, usually in unimmunized children
  • Begins weeks 2 to 4 after cough, with seizures and focal neurologic deficits
• Pulmonary hypertension
• Pneumonia and urinary incontinence are common in older patients
• The paroxysms of coughing can also cause subconjunctival hemorrhages, syncope, and rib fractures

Diagnosis

• Nasopharyngeal swab/aspirate culture
  • Sensitivity 15 to 80%
• PCR
• Serology
  • Antibodies (IgG and IgA) against GHA, agglutinogen, or PT
    • IgG rises 2 to 3 weeks after infection or immunization (1 week after booster)
    • Look for a two-fold increase in IgG to diagnose acute infection
  • Antigens including PT

Management

• Treat within 21 days of symptom onset (except if <1 mo. old, treat regardless of duration)
• In children
  • Azithromycin 10 mg/kg on day 1 followed by 5 mg/kg/d for 4 days
  • Erythomycin 40-50 mg/kg/d divided qid for 7-14 days
  • Clarithromycin 15 mg/kg/d divided bid for 7 days
  • Azithromycin for children <1 year
• In infants <1 mo, azithromycin 10 mg/kg/d for 5 days
• In adults
  • Azithromycin 500mg followed by 250 mg daily for 4 more days
  • Erythomycin 500 mg qid for 7-14 days
  • Clarithromycin 500 mg bid for 7 days

Prevention

Infection Control

• Droplet precautions
• Duration
  • Treated: after 5 days of effective treatment
  • Untreated: after 3 weeks from onset of paroxysms
• Communicable from onset of catarrhal stage to 3 weeks after onset of coughing or paroxysms

Post-Exposure Prophylaxis

• Consider prophylaxis of close contacts (face-to-face within 3 feet), third-trimester pregnancy, infants, and healthcare workers
• Should be considered up to 21 days following last contact
• Options include:
  • Azithromycin 500 mg for one day followed by 250 mg for 4 more days
  • Erythromycin 500 mg qid for 7 to 14 days
  • Clarithromycin 500 mg bid for 7 days

Immunization

• Options include whole-cell (DTP) and acellular (DTaP or Tdap)
  • Acellular removed lipopolysaccharide so is less reactive, but is as or more effective than whole cell
    • There was a fear of encephalopathy and SIDS with DTP
    • Acellular has PT, the two hemagluttinins, and protectin
  • DTaP (diphtheria toxoid, tetanus toxoid, and acellular pertussis, pediatric formula)
    • Given at 2, 4, 6, and 18 months, with booster at 4-6 years
  • Tdap booster once in adulthood, and with every pregnancy for women (third trimester)
• None of the vaccines carry life-long immunity; even the immunity from the acellular pertussis vaccine wanes after 4-5 years