Whooping Cough

Aka: Whooping Cough, Bordetella pertussis, Pertussis

II. Epidemiology

Incidence
1. U.S. (2012)
  1. General Population: 41,000 cases/year (8.5 cases per 100,000)
  2. Infants: 88.7 per 100,000
  3. Mortality: 18 deaths (mostly infants)
2. Worldwide: 30-50 million cases/year with 300,000 deaths/year
Pertussis still affects children more than adults
1. Infants younger than 6 months represent 38% of U.S. cases
2. Children under age 5 years represent 71% of U.S. cases
Pertussis is a common cause of adult Chronic Cough
1. Pertussis is responsible for 20% of adults and teens with severe cough >2 weeks presenting to ED
  1. Senzilet (2001) Clin Infect Dis 32:1691-7 [PubMed]
2. Most cases in children occur in over age 10 years
3. With waning immunity, teens and adults are reservoir
  1. Immunity wanes by as much as 42% per year since last DTaP
  2. Klein (2012) N Engl J Med 367(11): 1012-9 [PubMed]
Infants are infected by adults
1. Infants account for most of Pertussis-related mortality (especially under age 3 months)
2. Infant immunity <1 year is incomplete
3. Infants comprise >50% of all childhood infections
4. Infection most severe in infants including death

III. Etiologies

Bordetella pertussis (most common)
Bordetella parapertussis
Bordatella Bronchiseptica

IV. Pathophysiology

Extremely contagious with 80-100% secondary attack rate in those susceptible
Droplet spread with inhalation into airways
Pertussis releases toxins that damage the respiratory epithelium and result in mucosal injury
Incubation period: 7 to 10 days (incubation may be as long as 3 weeks)
1. Contrast with most viral infections which incubate for a few days

V. Findings: Signs and symptoms

General Findings
1. Variable severity based on age and immunity
2. Pertussis without classic Paroxysmal coughing spasms is common
  1. Especially in teens and adults with prolonged cough (>30% of Pertussis cases)
3. Exam is often normal (although fine rales may be present)
Catarrhal Stage (1-2 weeks, may be as short as a few days in infants <3 month)
1. Indistinguishable from a Common Cold (but highly contagious)
2. Low grade fever
3. Malaise
4. Mild Conjunctivitis
5. Mild cough
6. Pharyngitis
7. Rhinorrhea or Rhinitis
8. Sneezing
9. Lacrimation
Paroxysmal cough Stage (2-4 weeks with peak at 2 weeks)
1. Infants under age 6 months
  1. Apnea
  2. Cyanosis
  3. Bradycardia
  4. Persistent cough (not in spasms, and whooping is uncommon)
  5. Decreased oral intake
  6. Choking or gagging
  7. Gasping
  8. Face reddened
2. Older infants, children and adults
  1. Gradually progressive cough in spasms to severe Coughing Fits
    1. Starts as a dry, intermittent cough before progressing to a Paroxysmal cough
    2. Coughing spasms result from difficult clearing thick mucus in the trachea and Bronchi
    3. Patient feels as if cannot breath during coughing fit
    4. Typically breathing is unencumbered between Coughing Fits
    5. Post-tussive Emesis may occur
    6. May be asymptomatic between coughing episodes
  2. Inspiratory whoop
    1. Most common in young children
      1. Uncommon under age 6 months, and in teens and adults
    2. High pitched whooping sound triggered by gasping after a severe coughing spell
    3. Occurs when a deep breath is taken against a closed glottis
  3. Associated secondary conditions (from severe coughing spells)
    1. Subconjunctival Hemorrhage
    2. Back Pain
    3. Post-tussive Emesis
    4. Mallory Weiss Tear
    5. Cyanosis
    6. Cough Syncope
    7. Cough fracture (Rib Fracture)
    8. Petechiae (face and trunk)
    9. Pneuomothorax
    10. Pneumomediastinum
    11. Abdominal Hernia or Inguinal Hernia
    12. Urinary Incontinence
    13. Rectal Prolapse
Convalescent Stage (2-3 weeks, may last months in young infants)
1. Bacteria clear with 3-4 weeks of infection onset
2. Respiratory epithelium remains damaged following acute infection
  1. Prolonged recovery represents healing time
3. Coughing spasms resolve over 1-3 months (“80 day cough”)

VI. Differential Diagnosis

Catarrhal stage
1. Viral Upper Respiratory Infection (e.g. Adenovirus)
2. High fever suggests alternative diagnosis
Paroxysmal stage
1. See Cough Causes
2. Mycoplasma pneumoniae
3. Chlamydia pneumoniae
4. RSV Bronchiolitis (esp. infants)
Convalescent stage with persistent cough
1. See Chronic Cough
2. Asthma
3. Gastroesophageal Reflux
4. Acute Sinusitis with post nasal drainage

VII. Labs

Specific bordatella testing
1. See Bordetella Pertussis Test
2. Bordatella PCR (preferred first-line)
  1. Sufficient accuracy alone (Pertussis Culture was previously recommended for confirmation)
  2. Much better Test Sensitivity than culture (best in first two weeks, wanes after 3-4 weeks)
    1. False negatives after 4 weeks of cough
  3. Lower Test Specificity than culture (higher False Positive Rate)
3. Bordatella Pertussis Culture
  1. Low Test Sensitivity (best in first two weeks)
  2. False negatives occur at >2 weeks from cough onset
  3. High Specificity
4. Pertussis Serology
  1. Consider in late presentation from onset of cough (4-12 weeks)
Complete Blood Count
1. Leukocytosis (esp. Lymphocytosis) from 15,000 to as high as 100,000
2. Higher White Blood Cell Counts are associated with worse prognosis

VIII. Imaging

Chest XRay
1. Indications
  1. Pneumonia in Children suspected (Dyspnea, Tachypnea, Hypoxia)
2. Findings
  1. Normal in most cases
  2. Right heart border may appear “shaggy”
  3. Secondary Pneumonia with other Bacteria complicates 20% of cases
Echocardiogram indications
1. Pulmonary Hypertension suspected in severely ill children

IX. Diagnosis

See Bordetella Pertussis Test
Cough for less than one week is typically of viral origin
1. Consider Pertussis when cough persists for longer than 2 weeks, especially when worsens over time or
2. During local outbreaks or known Pertussis contact
Clinical suspicion criteria (CDC clinical case definition)
1. Major Criteria: Acute cough for 14 days
2. Minor criteria (requires one)
  1. Paroxysmal cough
  2. Post-tussive Emesis
  3. Inspiratory Whoop
  4. Pertussis outbreak
3. Precaution
  1. Requiring minor criteria misses a significant number of Pertussis cases
    1. Do not rely solely on CDC clinical case definition for Pertussis diagnosis (esp. minor criteria)
  2. Cornia (2010) JAMA 304(8): 890-6 [PubMed]

X. Management: General

Pertussis is a clinical diagnosis (see diagnosis above)
1. Classic paroxysms of cough and the associated whoop, are often absent in adults
2. Consider Pertussis in any patient with Chronic Cough, especially with suspected waning immunity
Hospital Admission Indications
1. All infants <4 months (and consider ICU admission)
  1. High risk of apnea and death
2. Infants older than 4 months with severe symptoms, apnea, Cyanosis
3. Children with serious comorbidity
  1. Cardiopulmonary disease
  2. Neurologic or muscular disorders
4. Very high White Blood Cell Counts (associated with worse prognosis)
General Measures in severe cases (typically infants and young children)
1. Exchange Transfusion
2. Extracorporeal Membrane Oxygenation (ECMO)
Treatment and reporting are based on clinical suspicion
1. Test and treat empirically at time of testing if clinically suspect
  1. Do not delay antibiotics for test confirmation
    1. Test will return about the time a 5 day antibiotic course is completed
  2. Early treatment within 1-2 weeks has the best efficacy in preventing spread to contacts
  3. Antibiotics do not however otherwise alter course, complication rate or mortality
    1. Antibiotics eradicate B. Pertussis from nasopharynx
    2. Altunaiji (2007) Cochrane Database Syst Rev (3): CD004404 [PubMed]
2. Antibiotic indications (for Pertussis treatment)
  1. Age <12 months: Within 6 weeks of onset of cough
  2. Age >12 months: Within 3 weeks of onset of cough
3. Quarantine at time of diagnosis for 5 full days on antibiotics
  1. Or more if longer than three weeks since symptom onset
4. Treat close contacts (asymptomic contacts need not be quarantined)
5. Report clinically suspected cases before confirmation
Antibiotic dosing
1. Azithromycin (preferred first line option)
  1. Avoid shorter 3 day courses due to lack of supporting evidence
  2. Child: 10 mg/kg orally on day 1 and then 5 mg/kg daily for days 2-5
  3. Adult: 500 mg orally on day 1 and then 250 mg daily for days 2-5
2. Other Macrolides
  1. Clarithromycin
    1. Child: 7.5 mg/kg twice daily for 7 days
    2. Adult: 500 mg orally twice daily for 7 days
  2. Erythromycin delayed release tablet
    1. Child: 40-60 mg/kg/day divided three to four times daily orally for 14 days
      1. Use with caution in young infants (risk of Hypertrophic Pyloric Stenosis)
    2. Adults: 666 mg orally three times daily orally for 14 days
3. Other agents with some efficacy against Pertussis (not as effective as Macrolides)
  1. Bactrim
    1. Indicated for Macrolide allergy or GI intolerance
    2. Do not use in pregnancy, Lactation, age <2 months
    3. Dosing
      1. Child: 8/40 mg/kg trimethoprim/sulfamethoxazole divided twice daily for 14 days
      2. Adult: Bactrim DS (160/800) one tablet twice daily for 14 days
  2. Clindamycin
    1. Avoid unless unable to use Macrolides or Bactrim`

XI. Management: Prevention of spread

Quarantine
1. Pertussis patients are off work and out of school
2. May return after 5 days on antibiotics or sooner if 3 weeks after paroxysmal stage ends
Post-exposure Prophyaxis
1. Indications
  1. Household exposures and other close contacts (including healthcare workers who did not wear masks)
    1. Especially infants under 6 months and pregnant women in third trimester AND
    2. Exposure to source patient within 21 days of cough onset
2. Protocol
  1. Contacts are typically asymptomatic and need not be quarantined
  2. Use same antibiotic course as above
  3. Monitor contacts for 3 weeks for onset of symptoms
3. Post-exposure Vaccination indications
  1. Age <7 years, if four doses of DTaP have not been completed
  2. Age 4 to 6 years, if fifth DTaP has not been given

XII. Prevention

Precautions
1. Adults are often the vector of Pertussis transmission to unimmunized or underimmunized children
  1. Adults tend to have subclinical persentations that are often missed
2. Pertactin (a key Immunization component) is absent in some U.S. Pertussis strains as of 2013
  1. May result in decreased Immunization efficacy if pertactin-negative strains become more common
  2. Queenan (2013) N Engl J Med 368(6): 583-4 [PubMed]
Diphtheria Tetanus Acellular Pertussis Vaccine (DTaP)
1. Primary Series for 5 doses by age 5 years
Tdap (Boostrix, Adacel)
1. Age 7-10 years old for single catch-up dose if Primary Series with <5 DTaP doses or unknown status
2. Age 11-18 years old: Single dose pimary series booster
3. Age 18-64 years old: Single Tdap to replace any of the every 10 year Tetanus boosters
4. Pregnant women in third trimester (repeat with each pregnancy)

XIII. Complications

Infants
1. Hospitalization
2. Apnea (50% of infants)
3. Superimposed Bacterial Pneumonia (20% of infants, with high mortality rate)
4. Dehydration
5. Encephalopathy
6. Death (rate has been rising for infants)
Teens and adults
1. See Findings
2. Prolonged cough (up to 6 weeks)
3. Weight loss (33%)
4. Urinary Incontinence (28%)
5. Syncope (6%)
6. Cough fracture (4%, Rib Fracture associated with severe coughing spells)
7. Secondary Bacterial Pneumonia (2-4%)
8. Otitis Media (most common infectious complication)

XIV. Resources

CDC Pertussis
1. http://www.cdc.gov/pertussis/

XV. References

Aldeen and Rosenbaum (2017) 1200 Questions Emergency Medicine Boards, 3rd ed, Wolters Kluwer, Baltimore, p. 121
Coffman (2005) Hospital Physician
Gilbert (2001) Sanford Antimicrobial, p. 25
Harrison and Ruttan (2019) Crit Dec Emerg Med 33(7): 3-12
Takhar and Herbert in Majoewsky (2013) EM:Rap 13(4): 2-3
Birkebaek (1999) Clin Infect Dis 29:1239-42 [PubMed]
Gregory (2006) Am Fam Physician 74:420-7 [PubMed]
Kline (2013) Am Fam Physician 88(8): 507-14 [PubMed]
Tiwari (2005) MMWR Recomm Rep 54(RR-14): 1-16 [PubMed]

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