II. Epidemiology
-
Incidence
- Worldwide: 30-50 million cases/year with 300,000 deaths/year
- U.S.
- General Population
- Peak (2012): 48,277 cases in U.S. (>8.5 cases per 100,000)
- In 2018, there were 15,609 reported cases in U.S.
- Infants: 88.7 per 100,000 in 2012
- Mortality: 18 deaths (mostly infants) in 2012
- General Population
- Pertussis still affects children more than adults
- Infants younger than 6 months represent 38% of U.S. cases
- Children under age 5 years represent 71% of U.S. cases
- Pertussis is a common cause of adult Chronic Cough
- Pertussis is responsible for 20% of adults and teens with severe cough >2 weeks presenting to ED
- Most cases in children occur in over age 10 years
- With waning Immunity, teens and adults are reservoir
- Immunity wanes by as much as 42% per year since last DTaP
- Klein (2012) N Engl J Med 367(11): 1012-9 [PubMed]
- Infants are infected by adults
III. Causes
- 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)
- Contrast with most Viral Infections which incubate for a few days
V. Findings: Signs and Symptoms
-
General Findings
- Variable severity based on age and Immunity
- Pertussis without classic Paroxysmal coughing spasms is common
- Especially in teens and adults with prolonged cough (>30% of Pertussis cases)
- 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)
- Indistinguishable from a Common Cold (but highly contagious)
- Low grade fever or afebrile
- Malaise
- Mild Conjunctivitis
- Mild dry cough
- Pharyngitis
- Rhinorrhea or Rhinitis
- Sneezing
- Lacrimation
-
Paroxysmal cough Stage (2-4 weeks with peak at 2 weeks, may persist up to 10 weeks)
- Infants under age 6 months
- Apnea (mortality risk)
- Cyanosis
- Bradycardia
- Persistent cough (not in spasms, and whooping is uncommon)
- Decreased oral intake
- Choking or gagging
- Gasping
- Face reddened and flailing limbs with coughing spasms
- Older infants, children and adults
- Gradually progressive cough in spasms to severe, Staccato Coughing fits
- Starts as a dry, intermittent cough before progressing to a Paroxysmal cough
- Coughing spasms result from difficult clearing thick mucus in the trachea and Bronchi
- Patient feels as if cannot breath during coughing fit
- Sensation of Strangulation or suffocation can be significantly anxiety provoking
- Post-tussive Emesis may occur
- Typically breathing is unencumbered between Coughing Fits
- May be asymptomatic between coughing episodes
- Inspiratory whoop
- Most common in young children
- Uncommon under age 6 months, and in teens and adults
- High pitched whooping sound triggered by gasping after a severe coughing spell
- Occurs when a deep breath is taken against a closed glottis
- Most common in young children
- Associated secondary conditions (from severe coughing spells)
- Subconjunctival Hemorrhage
- Back Pain
- Post-tussive Emesis
- Mallory Weiss Tear
- Cyanosis
- Cough Syncope
- Cough fracture (Rib Fracture)
- Petechiae (face and trunk)
- Pneuomothorax
- Pneumomediastinum
- Abdominal Hernia or Inguinal Hernia
- Urinary Incontinence
- Rectal Prolapse
- Gradually progressive cough in spasms to severe, Staccato Coughing fits
- Infants under age 6 months
- Convalescent Stage (2-3 weeks, may last months in young infants)
VI. Differential Diagnosis
- Catarrhal stage
- Viral Upper Respiratory Infection (e.g. Adenovirus)
- High fever suggests alternative diagnosis
- Paroxysmal stage
- See Cough Causes
- Mycoplasma pneumoniae
- Chlamydia pneumoniae (TWAR, typically in older adults)
- Neonatal Chlamydia Pneumonia (Chlamydia trachomatis)
- RSV Bronchiolitis (esp. infants)
- Convalescent stage with persistent cough
- See Chronic Cough
- Asthma
- Gastroesophageal Reflux
- Acute Sinusitis with post nasal drainage
VII. Diagnosis
- See Bordetella Pertussis Test
-
Cough for less than one week is typically of viral origin
- Consider Pertussis when cough persists for longer than 2 weeks, especially when worsens over time or
- During local outbreaks or known Pertussis contact
- Clinical suspicion criteria (CDC clinical case definition)
- Major Criteria: Acute cough for 14 days
- Minor criteria (requires one)
- Paroxysmal cough
- Post-tussive Emesis
- Inspiratory Whoop
- Pertussis outbreak
- Precaution
- Requiring minor criteria misses a significant number of Pertussis cases
- Do not rely solely on CDC clinical case definition for Pertussis Diagnosis (esp. minor criteria)
- Cornia (2010) JAMA 304(8): 890-6 [PubMed]
- Requiring minor criteria misses a significant number of Pertussis cases
- Factors most predictive of Pertussis
- Inspiratory Whooping (esp. in children LR+ 2.9 vs adults LR+ 1.2)
- Posttussive Emesis (LR+ 1.7)
- Paroxysmal cough (adults LR+ 1.2)
VIII. Labs: Specific Bordatella Testing
- See Bordetella Pertussis Test
-
Bordatella PCR (preferred first-line)
- Sample obtained with nasopharyngeal Dacron or nylon swab with results back in 1-2 days
- Efficacy
- Sufficient accuracy alone (Pertussis Culture was previously recommended for confirmation)
- Test Sensitivity: 77 to 97%
- Much better Test Sensitivity than Pertussis Culture
- Test Sensitivity best in first 3-4 weeks (wanes after 3-4 weeks)
- Test Specificity: 88 to 97%
- False Negatives after 4 weeks of cough
- Lower Test Specificity than culture (higher False Positive Rate)
- Bordatella Pertussis Culture
- Indicated during Pertussis outbreaks and for strain identification
- Sample obtained with nasopharyngeal Dacron or nylon swab
- Requires special transport media and culture conditions
- Results are delayed 7-10 days
- Efficacy
- Test Sensitivity: 20 to 80%
- Low Test Sensitivity (best in first two weeks)
- False Negatives occur at >2 weeks from cough onset (esp. if after Antibiotics started)
- Test Specificity: 100%
- Test Sensitivity: 20 to 80%
- Pertussis Serology
- Indicated in late presentation from onset of cough (4-12 weeks)
- Efficacy
- Test Sensitivity: 65%
- Test Specificity: 92%
- False Positives in recently vaccinated patients (within last year)
- False Positives in infants age <6 months (maternal antibodies)
- Avoid unhelpful tests
- Direct fluorescent Antibody assays
- Low Test Sensitivity and Test Specificity
- Direct fluorescent Antibody assays
IX. Labs: Other
-
Complete Blood Count
- Significant Leukocytosis during the paroxysmal stage
- Leukocytosis (esp. Lymphocytosis) from 15,000 to as high as 100,000
- Leukocytosis >20,000 with >50% Lymphocytes is highly suggestive of Pertussis in infants <3 months
- Higher White Blood Cell Counts are associated with worse course (consider hospitalization)
X. Imaging
- Chest XRay
-
Echocardiogram indications
- Pulmonary Hypertension suspected in severely ill children
XI. Management: General
- Pertussis is a clinical diagnosis (see diagnosis above)
- Classic paroxysms of cough and the associated whoop, are often absent in adults
- Consider Pertussis in any patient with Chronic Cough, especially with suspected waning Immunity
- Hospital Admission Indications
- All infants <4 months (and consider ICU admission)
- High risk of apnea and death
- Infants older than 4 months with severe symptoms, apnea, Cyanosis
- Children with serious comorbidity
- Cardiopulmonary disease
- Neurologic or muscular disorders
- Very high White Blood Cell Counts (associated with worse prognosis)
- All infants <4 months (and consider ICU admission)
- Severe Pertussis with Hyperleukocytosis, Pulmonary Hypertension (typically infants and young children)
- Exchange Transfusion
- Improved survival in severe Pertussis and severe Leukocytosis
- Kuperman (2014) Transfusion 54(6): 1630-3 [PubMed]
- Extracorporeal Membrane Oxygenation (ECMO)
- Indicated in severe Pulmonary Hypertension or Critical Illness (but poor outcomes)
- De Barry (2005) Pediatr Surg Int 21(8): 692-4 [PubMed]
- Exchange Transfusion
- Treatment and reporting are based on clinical suspicion
- Test and treat empirically at time of testing if clinically suspect
- Do not delay Antibiotics for test confirmation
- Test will return about the time a 5 day Antibiotic course is completed
- Early treatment within 1-2 weeks has the best efficacy in preventing spread to contacts
- Effective in reducing disease spread if started in the first 21 days of onset
- Antibiotics do not however otherwise alter course, complication rate or mortality
- Antibiotics eradicate B. Pertussis from nasopharynx (hence decreasing spread)
- Altunaiji (2007) Cochrane Database Syst Rev (3): CD004404 [PubMed]
- Do not delay Antibiotics for test confirmation
- Antibiotic indications (for Pertussis treatment)
- Age <12 months: Within 6 weeks of onset of cough
- Age >12 months: Within 3 weeks of onset of cough
- Quarantine at time of diagnosis for 5 full days on Antibiotics
- Or more if longer than three weeks since symptom onset
- Treat close contacts (asymptomic contacts need not be quarantined)
- Report clinically suspected cases before confirmation
- Other measures
- Corticosteroids have not been found effective in reducing cough or hospitalization length of stay
- Test and treat empirically at time of testing if clinically suspect
-
Antibiotic dosing
- Azithromycin (preferred first line option)
- Avoid shorter 3 day courses due to lack of supporting evidence
- Child: 10 mg/kg orally on day 1 and then 5 mg/kg daily for days 2-5
- Adult: 500 mg orally on day 1 and then 250 mg daily for days 2-5
- Other Macrolides
- Clarithromycin
- Child: 7.5 mg/kg twice daily for 7 days
- Adult: 500 mg orally twice daily for 7 days
- Erythromycin delayed release tablet
- Child: 40-60 mg/kg/day divided three to four times daily orally for 14 days
- Use with caution in young infants (risk of Hypertrophic Pyloric Stenosis)
- Adults: 666 mg orally three times daily orally for 14 days
- Child: 40-60 mg/kg/day divided three to four times daily orally for 14 days
- Clarithromycin
- Other agents with some efficacy against Pertussis (not as effective as Macrolides)
- Trimethoprim/sulfamethoxazole (Bactrim, Septra)
- Clindamycin
- Azithromycin (preferred first line option)
XII. Management: Prevention of spread
- Quarantine
- Pertussis patients are off work and out of school
- May return after 5 days on Antibiotics or sooner if 3 weeks after paroxysmal stage ends
- Post-exposure Prophyaxis
- Indications: Exposure to source patient within 21 days of cough onset
- Household exposures
- Other close contacts (including healthcare workers who did not wear masks)
- Infants under 6 months, pregnant women in third trimester or Immunocompromised
- Protocol
- Contacts are typically asymptomatic and need not be quarantined
- Use same Antibiotic course as above
- Monitor contacts for 3 weeks for onset of symptoms
- Post-exposure Vaccination indications
- Indications: Exposure to source patient within 21 days of cough onset
XIII. Prevention
- Precautions
- Adults are often the vector of Pertussis transmission to unimmunized or underimmunized children
- Adults tend to have subclinical persentations that are often missed
- VaccineAntigen deficient strains (escape mutants) have become more common
- VaccineAntigens include Pertussis toxin, fimbriae 2, 3, filamentous hemagglutinin, Pertussis toxin
- Pertactin (a key Immunization component) is absent in some U.S. Pertussis strains as of 2013
- May result in decreased Immunization efficacy if pertactin-negative strains become more common
- Queenan (2013) N Engl J Med 368(6): 583-4 [PubMed]
- Immunity wanes 2-4 years (even as early as 1 year) after each acellular Pertussis Vaccine
- Repeated pertussis Vaccination in adults has poor efficacy in preventing childhood Pertussis
- Vaccinated patients have reduced severity of illness, but may still become infected and the transmit the infection
- Infants too young to vaccinate are responsible for 85% of Pertussis deaths
- Resulted in recommendation as of 2012 to repeat pertussis Vaccination in third trimester of all pregnancies
- Passive Immunity in the first 3 months of life is a key current strategy for young infant protection
- Adults are often the vector of Pertussis transmission to unimmunized or underimmunized children
-
Diphtheria Tetanus Acellular Pertussis Vaccine (DTaP)
- Primary Series for 5 doses by age 5 years
-
Tdap (Boostrix, Adacel)
- Age 7-10 years old for single catch-up dose if Primary Series with <5 DTaP doses or unknown status
- Age 11-18 years old: Single dose pimary series booster
- Age 18-64 years old: Single Tdap to replace any of the every 10 year Tetanus boosters
- Pregnant women in third trimester between 27 and 36 weeks (repeat with each pregnancy)
XIV. Complications
- Infants
- Hospitalization
- Apnea (50% of infants)
- Superimposed Bacterial Pneumonia (20% of infants, with high mortality rate)
- Dehydration
- Encephalopathy (may present with Seizures)
- Death (rate has been rising for infants)
- Teens and adults
- See Findings
- Prolonged cough (up to 6 weeks)
- Weight loss (33%)
- Urinary Incontinence (28%)
- Syncope (6%)
- Severe coughing spasm complications
- Cough fracture (4%, Rib Fracture associated with severe coughing spells)
- Pneumothorax
- Subdural Hemorrhage
- Epistaxis
- Subconjunctival Hemorrhage
- Hernia
- Rectal Prolapse
- Infectious complications
- Otitis Media (most common infectious complication)
- Secondary Bacterial Pneumonia (2-4%)
XV. Resources
- CDC Pertussis
XVI. 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
- Harrison and Ruttan (2023) Crit Dec Emerg Med 38(2): 23-31
- 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]
- Kline (2021) Am Fam Physician 104(2): 186-92 [PubMed]
- Tiwari (2005) MMWR Recomm Rep 54(RR-14): 1-16 [PubMed]