Bordetella pertussis

Background

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

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)

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.

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

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

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

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

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

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

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