Pertussis
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pertussis whooping cough
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I now have extensive information to compile a comprehensive answer. Let me synthesize everything from Harrison's, Rosen's Emergency Medicine, and Goldman-Cecil Medicine.
Pertussis (Whooping Cough)
Overview
Pertussis is an acute respiratory infection caused by Bordetella pertussis, a gram-negative pleomorphic aerobic bacillus. The name means "violent cough," and the Chinese call it "the 100-day cough" - both accurately describe the clinical picture. The inspiratory whoop at the end of paroxysmal coughing gives rise to the common name "whooping cough," though this finding is variable and often absent in infants and adults.
- Harrison's Principles of Internal Medicine 22E, p. 1320
Microbiology
The genus Bordetella has 10 species; 4 are clinically significant:
| Species | Clinical Significance |
|---|---|
| B. pertussis | Classic whooping cough (humans only) |
| B. parapertussis | Milder pertussis-like illness; does NOT express pertussis toxin gene |
| B. holmesii | Up to 20% of pertussis-like syndrome cases by PCR; formerly thought to cause only bacteremia |
| B. bronchiseptica | Animal pathogen (kennel cough in dogs, rhinitis in pigs); occasional human opportunistic infection |
B. pertussis is a slow-growing, fastidious organism requiring selective media, forming small glistening bifurcated colonies. It is identified by direct fluorescent antibody testing or species-specific agglutination.
Virulence Factors
Most virulence factors are co-regulated by a single genetic locus enabling antigenic modulation and phase variation:
- Pertussis toxin (PT) - the most important virulence factor; composed of a B oligomer-binding subunit and an A protomer that ADP-ribosylates G proteins in target cells. It:
- Causes leukocytosis-lymphocytosis
- Enhances glucose-stimulated insulin secretion
- Has immunomodulatory effects - early in disease it downregulates immune responses (inhibits alveolar macrophages, blocks neutrophil recruitment), perpetuating infection; later it upregulates inflammation to enhance shedding
- Adenylate cyclase toxin - binds CR3 to enter cells, raises cAMP supraphysiologically, impairing macrophage and neutrophil antibacterial function
- Filamentous hemagglutinin (FHA) - adhesin; component of most acellular vaccines
- Pertactin (PRN) - adhesin; vaccine component
- Fimbriae - adhesins; in some vaccine formulations
- Tracheal cytotoxin - causes ciliary damage and respiratory epithelial cell loss
The pathogenesis of the paroxysmal cough is not fully understood but bradykinin-induced inflammation and pertussis toxin-mediated interference with sphingosine-1-phosphate anti-inflammatory signaling are thought to contribute.
- Goldman-Cecil Medicine, Pathobiology
Epidemiology
- Pertussis remains endemic worldwide, including in countries with vaccination programs
- Highly contagious; spread by aerosol droplets from both symptomatic and asymptomatic individuals
- Asymptomatically infected adults are thought to drive a substantial fraction of overall transmission
- Incidence rose in the 1980s-1990s (particularly adolescents and adults) due to waning immunity from childhood DTaP vaccination
- Recent epidemics linked to inconsistent immunization in vulnerable populations
- Immunization is only ~80% effective after 3 doses
Clinical Stages
Incubation period: 7-10 days (range up to ~3 weeks).
1. Catarrhal Stage (1-2 weeks)
Indistinguishable from the common cold:
- Coryza, lacrimation, mild cough, low-grade fever, malaise
- Most contagious during this stage
- Patient appears "normal" between episodes
2. Paroxysmal Stage (2-4 weeks)
The hallmark stage:
- Paroxysmal cough: bursts of 5-10 coughs within a single expiration
- Inspiratory whoop: rapid inspiration against a closed glottis at the end of a paroxysm - occurs in 69-92% of children but only 8-82% of adults; uncommon in infants <6 months
- Post-tussive vomiting: 48-60% of children; 17-65% of adults
- Cyanosis and apnea: especially in infants <6 months
- Paroxysms triggered by noise, eating, or physical contact
- Episodes often worse at night
- Fever is uncommon - if present, suggests bacterial superinfection
- Examination findings are remarkably normal between paroxysms
3. Convalescent Stage (1-3 months)
- Coughing episodes become less frequent and less severe
- For 6-12 months, intercurrent viral infections can trigger recrudescence of paroxysmal cough
Atypical Presentation (Adolescents and Adults)
Classic stages are often absent. Features are:
- Severe, prolonged, paroxysmal cough (lasting 3+ weeks)
- Cough worse at night, sweating episodes
- Whoop and post-tussive vomiting are uncommon but more specific when present
- Exposure history to prolonged coughing illness in contacts
Complications
More common in infants:
| Complication | Infants (<2 years, hospitalized) |
|---|---|
| Apnea | 27.1% |
| Pneumonia | 9.4% |
| Seizures | 2.6% |
| Encephalopathy | 0.4% |
| Death | 0.9% |
Other complications from increased intrathoracic pressure:
- Subconjunctival hemorrhages
- Abdominal and inguinal hernias
- Pneumothorax
- Facial and truncal petechiae
- Rib fractures, cough syncope, carotid artery aneurysm (adolescents/adults)
- Weight loss from decreased caloric intake during paroxysms
Pneumonia in infants tends to be primary B. pertussis pneumonia; in older patients it is usually secondary bacterial superinfection.
Diagnosis
Laboratory Findings
- WBC: Markedly elevated with lymphocytosis (a classic finding)
- Chest X-ray: "Shaggy" right-sided heart border, or clear lung fields; perihilar infiltrates or atelectasis in complicated cases
Microbiological Diagnosis
| Method | Notes |
|---|---|
| Culture | Gold standard but B. pertussis is fastidious; needs Bordet-Gengou or Regan-Lowe media; best in catarrhal/early paroxysmal stage; negative after 4th week or after antibiotics |
| PCR | Higher sensitivity; faster turnaround; increasingly preferred; best in first 3-4 weeks |
| DFA (direct fluorescent antibody) | Lower sensitivity/specificity; used as presumptive ID |
| Serology (anti-PT IgG) | Useful for retrospective diagnosis in older children and adults (single elevated level or 2-4x rise in convalescent serum); not useful acutely |
Treatment
| Agent | Notes |
|---|---|
| Azithromycin | Preferred; 5-day course |
| Erythromycin | Effective but 14-day course; GI side effects; risk of pyloric stenosis in neonates <1 month |
| Clarithromycin | 7-day alternative |
| TMP-SMX | Alternative for macrolide-intolerant patients |
Key principle: Antibiotics eliminate the organism from the nasopharynx and limit spread, but after the paroxysmal stage begins, they do not alter clinical course.
Infants <3-6 months with presumed pertussis should be hospitalized for monitoring and supportive care due to risk of apnea.
- Rosen's Emergency Medicine, p. 700
Note on antimicrobial resistance: A 2026 systematic review (PMID 41645470) found emerging macrolide resistance in B. pertussis, which may have implications for first-line treatment choices in some regions.
Prevention & Vaccination
Childhood Schedule
- DTaP (diphtheria, tetanus, acellular pertussis): 5-dose series at 2, 4, 6, 15-18 months, and 4-6 years
Booster Vaccines (Tdap)
Two formulations are licensed:
- Boostrix (GSK): licensed ≥10 years; contains PT, FHA, PRN (3 antigens)
- Adacel (Sanofi Pasteur): licensed 10-64 years; contains PT, FHA, PRN + 2 fimbriae (5 antigens)
Tdap indications:
-
Single dose for all adolescents at 11-12 years
-
All adults who have never received Tdap (regardless of interval since last Td)
-
All pregnant persons: one dose per pregnancy, optimally at 27-36 weeks gestation - maximizes maternal antibody transfer to the infant, bridging the vulnerable first 3 months before the infant's own vaccine series begins
-
All healthcare workers
-
Goldman-Cecil Medicine, Immunization section
Summary Table
| Feature | Infants (<6 mo) | Children (>2 yr) | Adolescents/Adults |
|---|---|---|---|
| Whoop | Rare | Common | Variable (often absent) |
| Apnea | Common | Less common | Rare |
| Classic 3 stages | Yes | Yes | Often atypical |
| Duration | 6-10 weeks | 6-10 weeks | 3+ weeks (often prolonged) |
| Post-tussive emesis | Common | Common | Less common |
Recent evidence to be aware of (from recent systematic reviews):
- A 2026 global seroepidemiology meta-analysis (PMID 42317980) highlights that serologic evidence of pertussis exposure is widespread globally, underscoring that underdiagnosis is a major issue.
- A 2026 systematic review (PMID 42309234) found that asthma and COPD are associated with increased pertussis risk - patients with these conditions warrant extra attention to vaccination status.
- Emerging macrolide resistance in B. pertussis has been documented in a 2026 meta-analysis (PMID 41645470), warranting surveillance of local resistance patterns before defaulting to azithromycin.
Drug dose?
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Harrison's Table 165-2 has everything needed. Here is the complete drug dosing reference:
Pertussis - Antimicrobial Drug Doses
(Harrison's Table 165-2; Harrison's Principles of Internal Medicine 22E, p. 1323)
Azithromycin (Preferred First-Line)
| Age Group | Dose | Duration |
|---|---|---|
| < 1 month | 10 mg/kg/day as a single daily dose | 5 days |
| 1-5 months | 10 mg/kg/day as a single daily dose | 5 days |
| ≥ 6 months (children) | 10 mg/kg on day 1, then 5 mg/kg/day (max 500 mg/day) on days 2-5 | 5 days |
| Adults | 500 mg on day 1, then 250 mg/day on days 2-5 | 5 days |
Caution: Azithromycin is the recommended agent for infants <1 month (erythromycin is associated with infantile hypertrophic pyloric stenosis in neonates). Use with caution in cardiac patients (QT prolongation risk).
Erythromycin (Alternative - less preferred)
| Age Group | Dose | Duration |
|---|---|---|
| < 1 month | Only if azithromycin unavailable; 40-50 mg/kg/day in 4 divided doses | 14 days |
| 1-5 months | 40-50 mg/kg/day in 4 divided doses | 14 days |
| ≥ 6 months (children) | 40-50 mg/kg/day (max 2 g/day) in 4 divided doses | 14 days |
| Adults | 2 g/day in 4 divided doses | 14 days |
Frequent GI side effects; 14-day course is poorly tolerated. Avoid in neonates <1 month due to pyloric stenosis risk.
Clarithromycin (Alternative)
| Age Group | Dose | Duration |
|---|---|---|
| < 1 month | Not recommended | - |
| 1-5 months | 15 mg/kg/day in 2 divided doses | 7 days |
| ≥ 6 months (children) | 15 mg/kg/day (max 1 g/day) in 2 divided doses | 7 days |
| Adults | 1 g/day in 2 divided doses | 7 days |
TMP-SMX (Use only if macrolide-intolerant or macrolide-resistant strain)
| Age Group | Dose | Duration |
|---|---|---|
| < 2 months | Contraindicated | - |
| 2 months - 5 months | TMP 8 mg/kg/day + SMZ 40 mg/kg/day in 2 divided doses | 14 days |
| ≥ 6 months (children) | TMP 8 mg/kg/day + SMZ 40 mg/kg/day in 2 divided doses | 14 days |
| Adults | TMP 320 mg/day + SMZ 1600 mg/day in 2 divided doses | 14 days |
Key Clinical Points
- Same doses apply for post-exposure prophylaxis (chemoprophylaxis for close contacts)
- Antibiotics do not alter clinical course once the paroxysmal stage has begun - they only eliminate the organism and limit spread
- Infants < 3-6 months should be admitted for monitoring (apnea risk)
- Cough suppressants are not effective and have no role
- Beta-agonists and glucocorticoids have been advocated but are not proven effective
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