Bordetella pertussis - Whooping Cough

Indications for Testing

Patients with predominant complaint of persistent cough, especially in the absence of fever, sore throat, hoarseness, tachypnea or wheeze

Criteria for Diagnosis

CDC criteria for Bordetella pertussis infection

Laboratory Testing

Culture or PCR recommended by CDC to confirm case
- PCR
  - Highly sensitive for diagnosis of B. pertussis – must use nasopharyngeal swab for highest sensitivity and specificity
  - Useful in patients during early and mid phase of suspected pertussis disease (<3 weeks)
  - Antibiotic treatment may reduce sensitivity
  - Will detect B. parapertussis and may cross react with B. holmesii
- Nasopharyngeal culture
  - Follow up to PCR
  - Considered gold standard but is frequently negative in adults
  - Recommended only during the first 3 weeks of illness (sensitivity decreases steeply if specimen is >2 weeks from onset of cough)
  - Do not use cotton or calcium alginate swabs for collection
Serological testing
- B. pertussis IgA, IgG, IgM testing (ELISA and Immunoblot)
  - Serological testing does not satisfy CDC criteria for diagnosis due to non-standardization of testing among laboratories
  - Useful for evaluating immune status

Differential Diagnosis

Chlamydia pneumoniae
Adenovirus
Mycoplasma pneumoniae
Parainfluenza Virus 1, 2, 3
Influenza
Asthma
Acute exacerbation of chronic bronchitis
Cytomegalovirus
Legionella pneumophila
Hantavirus
Metapneumovirus

Pertussis is a highly infectious and contagious disease commonly referred to as whooping cough. It is caused by the bacterium Bordetella pertussis.

Epidemiology

Incidence – 1-5/100,000
- Recent resurgence of disease in industrialized countries
Age – peak incidence <6 months or >14 years of age
- Primarily seen in those with waning immunity from childhood vaccination (immunity begins to wane during early adolescence)
- Significant incidence in unimmunized infants <1 year
Occurrence – infection occurs most frequently in late spring and summer
Transmission
- Adult and teenage children with common cold symptoms are significant reservoirs of the organism and the source of outbreaks in highly susceptible populations
- Transmitted by respiratory droplets (B. pertussis causes disease only in humans)
  - Infection rates >90% in susceptible populations

Organism

B. pertussis is a gram-negative pleomorphic coccobacillus
Multiple virulence factors are produced that aid in organism attachment and production of disease
- Pertussis toxin is responsible for many disease effects
B. parapertussis is a related species that may cause a milder form of pertussis syndrome

Clinical Presentation

Nonspecific viral upper respiratory tract infection-like symptoms
- Disease spread often not recognized due to mild symptoms in immunized persons
- Secondary spread common in families and schools
After 7-10 day incubation, a prolonged course ensues consisting of 3 overlapping stages
- Catarrhal (1-2 weeks post infection [PI])
- Paroxysmal coughing (1-4 weeks PI)
- Convalescent (4-6 weeks PI)
Partially immune persons and infants >6 months may not manifest all of the typical symptoms
- Paroxysmal coughing may be absent
Classic pertussis is generally diagnosed clinically
- Inspiratory whoop
- Lymphocytosis
- Paroxysmal cough
- Posttussive vomiting
Atypical pertussis may occur with mild or absent symptoms in adults and previously vaccinated children
- Atypical pertussis is common, endemic and usually unrecognized in adults
Secondary complications
- Respiratory
  - Bronchitis
  - Laryngitis
  - Pneumonia
  - Pneumothorax
- Nonrespiratory
  - Complications resulting from severe cough
    - Epistaxis
    - Rectal prolapse
    - Rib fracture
    - Subconjunctival hemorrhage
  - Central nervous system
    - Deafness
    - Encephalitis
    - Seizures
  - Hemolytic uremic syndrome
- Death – fulminant course more common in very young infants

Treatment

Antibiotics
- Treatment given early after onset of symptoms reduces communicability and may reduce duration and severity of disease
- Prophylaxis for household contacts

Prevention

Vaccination
Pediatric age groups – combined Hib and TDaP
Adult revaccination
- Recommended during teen years and in patients ≥30 years (TDaP)

Tests generally appear in the order most useful for common clinical situations

Test name: Bordetella pertussis/parapertussis by PCR

ARUP #: 0065080

Methodology: Qualitative Polymerase Chain Reaction

Use:

The method of choice for direct detection of B. pertussis or B. parapertussis for patients with cough and no previous antibiotic therapy

Adult patients with persistent cough in whom pertussis is suspected
Children with epidemiological and clinical features of disease

Limitations:

Patients with pertussis may remain PCR-positive for variable periods following treatment

Negative result does not rule out the presence of B. pertussis DNA in concentrations below detection level of assay

False positives for B. pertussis may occur in samples containing B. holmesii DNA

False positives for B. parapertussis may occur in samples containing B. bronchiseptica DNA

5 days of appropriate treatment can negate PCR results

Test name: Bordetella pertussis Culture

ARUP #: 0060117

Methodology: Standard reference procedures for Bordetella pertussis culture and identification

Use:

Gold standard test for diagnosing pertussis in children

May test for B. pertussis in adults who have consistent epidemiological and clinical features of disease

In addition, order B. pertussis by PCR

Limitations:

Highly specific only in acute disease phase

Rarely positive in adults

Negative culture does not exclude the possibility of B. pertussis infection

Successful culture requires special media and incubation up to 7 days; also highly dependent on specimen collection, transportation and laboratory techniques

Diagnostic sensitivity <60% when specimen obtained after early catarrhal stage or after treatment with certain antibiotics; reduced sensitivity in adults and vaccinated patients

Test name: Bordetella pertussis Antibodies, IgA, IgG, and IgM by ELISA with Reflex to Immunoblot

ARUP #: 2001775

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot

Use:

Diagnose disease in adults with atypical pertussis symptoms who have paroxysmal coughing persisting for several weeks

Base treatment decisions on result of IgM immunoblot instead of ELISA test; IgM by ELISA may produce false-positive results

If IgA or IgM greater than or equal to 1.2 U/mL, IgA or IgM immunoblot will be added; if IgG greater than or equal to 2.5 U/mL, IgG immunoblot will be added

Limitations:

IgG antibodies can only be used to diagnose active infection when paired sera are available and a rise in antibody level can be demonstrated

Significant rise may not always be demonstrated as peak levels of IgG may be reached before the first sample is collected; therefore, both IgA and IgM antibody levels should be measured to diagnose active disease

Additional Tests Available

Test name: Bordetella pertussis Antibodies, IgA, IgG, & IgM by Immunoblot

ARUP #: 2004328

Methodology: Qualitative Immunoblot

Comments:

Test for presence of toxin to confirm B. pertussis

Test name: Bordetella pertussis Antibodies, IgA & IgG by ELISA with Reflex to Immunoblot

ARUP #: 2001774

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot

Comments:

If IgA greater than or equal to 1.2 U/mL, IgA immunoblot will be added; if IgG greater than or equal to 2.5 U/mL, IgG immunoblot will be added

Test name: Bordetella pertussis Antibody, IgG by ELISA

ARUP #: 2005268

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Bordetella pertussis Antibody, IgG by ELISA with Reflex to Immunoblot

ARUP #: 2001768

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot

Comments:

If IgG greater than or equal to 2.5 U/mL, IgG immunoblot will be added

Test name: Bordetella pertussis Antibody, IgM by ELISA with Reflex to Immunoblot

ARUP #: 2001769

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot

Comments:

Base treatment decisions on result of IgM immunoblot instead of ELISA test; IgM by ELISA may produce false-positive results

If IgM greater than or equal to 1.2 U/mL, IgM immunoblot will be added

Test name: Gram Stain

ARUP #: 0060101

Methodology: Stain/Microscopic Exam

Comments:

Test name: Bordetella pertussis DFA

ARUP #: 2004667

Methodology: Direct Fluorescent Antibody Stain

Comments:

Less sensitive than PCR

Test name: Bordetella pertussis Antibodies, IgG and IgM by ELISA with Reflex to Immunoblot

ARUP #: 2001784

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot

Comments:

Diagnose active disease in adults with atypical pertussis symptoms who have paroxysmal coughing that has persisted for several weeks

Base treatment decisions on result of IgM immunoblot instead of ELISA test; IgM by ELISA may produce false-positive results

Order B. pertussis culture concurrently (sensitivity of culture is >60% in adults, vaccinated patients, or after antibiotic treatment)

Often difficult to diagnose without a comparison of acute and convalescent samples; may be difficult to differentiate between vaccine effects and pertussis infection

Pertussis serology may be helpful in laboratory confirmation of disease in adults but cannot be used during acute disease phase

Sensitivity 55%; however, sensitivity decreases progressively during course of disease

If IgM greater than or equal to 1.2 U/mL, IgM immunoblot will be added; if IgG greater than or equal to 2.5 U/mL, IgG immunoblot will be added

Test name: Bordetella pertussis Antibody, IgA by Immunoblot

ARUP #: 2004316

Methodology: Qualitative Immunoblot

Comments:

Test name: Bordetella pertussis Antibody, IgG by Immunoblot

ARUP #: 2004327

Methodology: Qualitative Immunoblot

Comments:

Test name: Bordetella pertussis Antibody, IgM by Immunoblot