Whooping Cough

Aka: Whooping Cough, Bordetella pertussis, Pertussis

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II. Epidemiology

  1. Incidence
    1. Worldwide: 30-50 million cases/year with 300,000 deaths/year
    2. U.S.
      1. General Population
        1. Peak (2012): 48,277 cases in U.S. (>8.5 cases per 100,000)
        2. In 2018, there were 15,609 reported cases in U.S.
      2. Infants: 88.7 per 100,000 in 2012
      3. Mortality: 18 deaths (mostly infants) in 2012
  2. 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
  3. 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]
  4. 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 apnea, Pneumonia, Seizures and death

III. Causes

  1. Bordetella pertussis (most common)
  2. Bordetella parapertussis
  3. Bordatella Bronchiseptica

IV. Pathophysiology

  1. Extremely contagious with 80-100% secondary attack rate in those susceptible
  2. Droplet spread with inhalation into airways
  3. Pertussis releases toxins that damage the respiratory epithelium and result in mucosal injury
  4. 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
  5. Toxins (4)
    1. Pertussis Toxin
      1. B-Binding Subunit attaches to Target Cells
      2. A-Action Subunit
        1. Toxin binds membrane G Proteins which activate membrane bound adenylate cyclase
        2. Results in increased cAMP, with secondary inhibition of Macrophage and neutrophil Phagocytosis
    2. Extracytoplasmic adenylate cyclase
      1. Suppresses inflammatory cell chemotaxis and Phagocytosis
    3. Filamentous Hemagglutinin
      1. Binds ciliated epithelial cells
    4. Tracheal Cytotoxin
      1. Attacks respiratory epithelial cell

V. Findings: Signs and Symptoms

  1. 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)
  2. 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 or afebrile
    3. Malaise
    4. Mild Conjunctivitis
    5. Mild dry cough
    6. Pharyngitis
    7. Rhinorrhea or Rhinitis
    8. Sneezing
    9. Lacrimation
  3. Paroxysmal cough Stage (2-4 weeks with peak at 2 weeks, may persist up to 10 weeks)
    1. Infants under age 6 months
      1. Apnea (mortality risk)
      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 and flailing limbs with coughing spasms
    2. Older infants, children and adults
      1. Gradually progressive cough in spasms to severe, Staccato 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
          1. Sensation of Strangulation or suffocation can be significantly anxiety provoking
        4. Post-tussive Emesis may occur
        5. Typically breathing is unencumbered between Coughing Fits
          1. 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
  4. Convalescent Stage (2-3 weeks, may last months in young infants)
    1. Bacteria clear within 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

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

VII. Diagnosis

  1. See Bordetella Pertussis Test
  2. 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
  3. 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]
  4. Factors most predictive of Pertussis
    1. Inspiratory Whooping (esp. in children LR+ 2.9 vs adults LR+ 1.2)
    2. Posttussive Emesis (LR+ 1.7)
    3. Paroxysmal cough (adults LR+ 1.2)

VIII. Labs: Specific Bordatella Testing

  1. See Bordetella Pertussis Test
  2. Bordatella PCR (preferred first-line)
    1. Sample obtained with nasopharyngeal Dacron or nylon swab with results back in 1-2 days
    2. Efficacy
      1. Sufficient accuracy alone (Pertussis Culture was previously recommended for confirmation)
      2. Test Sensitivity: 77 to 97%
        1. Much better Test Sensitivity than Pertussis Culture
        2. Test Sensitivity best in first 3-4 weeks (wanes after 3-4 weeks)
      3. Test Specificity: 88 to 97%
        1. False Negatives after 4 weeks of cough
        2. Lower Test Specificity than culture (higher False Positive Rate)
  3. Bordatella Pertussis Culture
    1. Indicated during Pertussis outbreaks and for strain identification
    2. Sample obtained with nasopharyngeal Dacron or nylon swab
      1. Requires special transport media and culture conditions
      2. Results are delayed 7-10 days
    3. Efficacy
      1. Test Sensitivity: 20 to 80%
        1. Low Test Sensitivity (best in first two weeks)
        2. False Negatives occur at >2 weeks from cough onset (esp. if after Antibiotics started)
      2. Test Specificity: 100%
  4. Pertussis Serology
    1. Indicated in late presentation from onset of cough (4-12 weeks)
    2. Efficacy
      1. Test Sensitivity: 65%
      2. Test Specificity: 92%
        1. False Positives in recently vaccinated patients (within last year)
        2. False Positives in infants age <6 months (maternal antibodies)
  5. Avoid unhelpful tests
    1. Direct fluorescent Antibody assays
      1. Low Test Sensitivity and Test Specificity

IX. Labs: Other

  1. Complete Blood Count
    1. Significant Leukocytosis during the paroxysmal stage
    2. Leukocytosis (esp. Lymphocytosis) from 15,000 to as high as 100,000
    3. Leukocytosis >20,000 with >50% Lymphocytes is highly suggestive of Pertussis in infants <3 months
    4. Higher White Blood Cell Counts are associated with worse course (consider hospitalization)

X. Imaging

  1. 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
  2. Echocardiogram indications
    1. Pulmonary Hypertension suspected in severely ill children

XI. Management: General

  1. 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
  2. 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)
  3. Severe Pertussis with Hyperleukocytosis, Pulmonary Hypertension (typically infants and young children)
    1. Exchange Transfusion
      1. Improved survival in severe Pertussis and severe Leukocytosis
      2. Kuperman (2014) Transfusion 54(6): 1630-3 [PubMed]
    2. Extracorporeal Membrane Oxygenation (ECMO)
      1. Indicated in severe Pulmonary Hypertension or Critical Illness (but poor outcomes)
      2. De Barry (2005) Pediatr Surg Int 21(8): 692-4 [PubMed]
  4. 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
        1. Effective in reducing disease spread if started in the first 21 days of onset
      3. Antibiotics do not however otherwise alter course, complication rate or mortality
        1. Antibiotics eradicate B. Pertussis from nasopharynx (hence decreasing spread)
        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
    6. Other measures
      1. Corticosteroids have not been found effective in reducing cough or hospitalization length of stay
  5. 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. Trimethoprim/sulfamethoxazole (Bactrim, Septra)
        1. Indicated for Macrolide allergy or gastrointestinal intolerance (or Macrolide resistance)
        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`

XII. Management: Prevention of spread

  1. 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
  2. Post-exposure Prophyaxis
    1. Indications: Exposure to source patient within 21 days of cough onset
      1. Household exposures
      2. Other close contacts (including healthcare workers who did not wear masks)
      3. Infants under 6 months, pregnant women in third trimester or Immunocompromised
    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 yet been given

XIII. Prevention

  1. 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. VaccineAntigen deficient strains (escape mutants) have become more common
      1. VaccineAntigens include Pertussis toxin, fimbriae 2, 3, filamentous hemagglutinin, Pertussis toxin
      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]
    3. Immunity wanes 2-4 years (even as early as 1 year) after each acellular Pertussis Vaccine
      1. Repeated pertussis Vaccination in adults has poor efficacy in preventing childhood Pertussis
      2. Vaccinated patients have reduced severity of illness, but may still become infected and the transmit the infection
    4. Infants too young to vaccinate are responsible for 85% of Pertussis deaths
      1. Resulted in recommendation as of 2012 to repeat pertussis Vaccination in third trimester of all pregnancies
      2. Passive Immunity in the first 3 months of life is a key current strategy for young infant protection
  2. Diphtheria Tetanus Acellular Pertussis Vaccine (DTaP)
    1. Primary Series for 5 doses by age 5 years
  3. 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 between 27 and 36 weeks (repeat with each pregnancy)

XIV. Complications

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

XV. Resources

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

XVI. References

  1. Aldeen and Rosenbaum (2017) 1200 Questions Emergency Medicine Boards, 3rd ed, Wolters Kluwer, Baltimore, p. 121
  2. Coffman (2005) Hospital Physician
  3. Gilbert (2001) Sanford Antimicrobial, p. 25
  4. Harrison and Ruttan (2019) Crit Dec Emerg Med 33(7): 3-12
  5. Harrison and Ruttan (2023) Crit Dec Emerg Med 38(2): 23-31
  6. Takhar and Herbert in Majoewsky (2013) EM:Rap 13(4): 2-3
  7. Birkebaek (1999) Clin Infect Dis 29:1239-42 [PubMed]
  8. Gregory (2006) Am Fam Physician 74:420-7 [PubMed]
  9. Kline (2013) Am Fam Physician 88(8): 507-14 [PubMed]
  10. Kline (2021) Am Fam Physician 104(2): 186-92 [PubMed]
  11. Tiwari (2005) MMWR Recomm Rep 54(RR-14): 1-16 [PubMed]

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