Pertussis and Other Bordetella Infections¶

Chapter 165 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 165

Key Clinical Points¶

Pertussis is an acute respiratory infection caused by Bordetella pertussis, characterized by a 'violent cough' (whoop).
Infants <1 year are at the highest risk for severe disease and death; 84% of US deaths occur in infants <2 months.
Clinical course typically involves three phases: catarrhal, paroxysmal, and convalescent.
Lymphocytosis (>10^8–10^9/L) is a hallmark in children but is uncommon in other infections and absent in adults.
Macrolides (azithromycin, erythromycin, clarithromycin) are first-line treatments; early administration in the catarrhal phase is most effective.
Pertactin-negative strains have emerged since 2010 due to immune pressure from acellular vaccines.
Chemoprophylaxis is required for household contacts within 21 days of cough onset in the index case.
Fever is uncommon (<5%) and suggests a bacterial superinfection.
Vaccination: Tdap at 27–36 weeks in pregnancy provides 90–93% protection for infants <2 months.
Diagnosis relies on nasopharyngeal culture (gold standard) or real-time PCR (preferred).

DEFINITION & CLASSIFICATION¶

• Definition (Harrison's 22e): Pertussis means 'violent cough,' describing the hallmark paroxysmal coughing episodes. • Clinical Presentation: ◦ Characterized by a "whoop" (inspiratory sound at end of spasm); absent in infants ≤6 months, more common in children. ◦ Known as "the 100-day cough" due to its prolonged clinical course. • Pathogen: Bordetella pertussis (gram-negative pleomorphic bacillus). ◦ Highly contagious: 80–100% attack rate among unimmunized contacts.

Bordetella Species¶

• Clinically Significant Species: ◦ B. pertussis (human-specific) ◦ B. parapertussis (milder disease; lacks pertussis toxin gene but shares antigenic similarity) ◦ B. bronchiseptica (zoonotic infections in animals) ◦ B. holmesii (emergent cause of bacteremia)

EPIDEMIOLOGY¶

• Global Burden: ~40 million annual cases; 400,000 deaths (90% in infants). • Demographics: ◦ Unimmunized populations: Peaks in preschool children. ◦ Highly immunized regions: Shifts to infants <1 year. • Trends: ◦ Increased incidence in high-income countries since late 1990s. ◦ Adolescents and adults serve as reservoirs for transmission. • Transmission: 56% of household contacts are asymptomatic carriers.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Virulence Factors: ◦ Pertussis toxin: ADP-ribosylates G proteins; mediates lymphocyte circulation and adhesion. ◦ Filamentous hemagglutinin & Pertactin: Major antigens for serotyping. ◦ Tracheal cytotoxin: Causes mucosal damage. ◦ Adenylate cyclase-hemolysin: Impairs phagocytosis. ◦ Dermonecrotic toxin: Contributes to respiratory injury. • Evolutionary Shift: ◦ Pertactin-negative strains (>80% in some regions) emerged since 2010 due to acellular vaccine pressure.

Clinical Features by Age¶

• Infants (<6 months): Atypical presentation (apnea, cyanosis, poor feeding); no whoop; 50% have pneumonia. • Children (preschool/school-age): Classic triad: catarrhal phase (coryza), paroxysmal phase (whooping cough, post-tussive vomiting), and convalescent phase (prolonged cough). • Adolescents/Adults: Atypical symptoms (persistent cough, night sweats); 41% have worse cough at night; 69–92% may have a whoop.

Table 165-1 highlights specific percentages for these groups: • Cough: 70–99% in adolescents/adults. • Worse at night: 61–87% (adolescents/adults) vs. 41% (infants/children). • Whoop: 8–82% (adolescents/adults) vs. 69–92% (infants/children). • Post-tussive vomiting: 17–65% (adolescents/adults) vs. 48–60% (infants/children).

CLINICAL FEATURES¶

• Clinical Phases: 1. Catarrhal phase (1–2 weeks): Mild symptoms (coryza, low-grade fever, malaise) resembling common cold. 2. Paroxysmal phase (2–4 weeks): Severe coughing spasms (5–10 coughs per episode), post-tussive vomiting, and audible whoop; worse at night. 3. Convalescent phase: Gradual resolution over 1–3 months; recrudescence possible for 6–12 months with viral infections. • Key Clinical Indicators: ◦ Fever: Uncommon (<5%); presence suggests bacterial superinfection. ◦ Complications (Infants): Pneumothorax, pneumomediastinum, pulmonary hypertension (50% of those with pneumonia), apnea, and encephalopathy. ◦ Complications (Children/Adults): Rib fractures, carotid artery aneurysm, cough syncope, and weight loss. • Laboratory Hallmark: Lymphocytosis (>10^8–10^9/L) in children.

Complications¶

• Respiratory: Pneumothorax, pneumomediastinum, pulmonary hypertension. • Neurologic: Seizures, encephalopathy (rare), apnea. • Metabolic/Other: Weight loss, dehydration, urinary incontinence, carotid artery aneurysm.

DIFFERENTIAL DIAGNOSIS¶

• Infants/Children: Viral infections (RSV, adenovirus), Mycoplasma pneumoniae, Chlamydia pneumoniae. • Adolescents/Adults: Chronic cough syndromes (ACE inhibitor use, GERD, asthma), tuberculosis, foreign body aspiration. • Key Differentiators: ◦ Lymphocytosis >10^8–10^9/L → supports B. pertussis over other pathogens. ◦ Whoop and post-tussive vomiting → more specific in adults with prolonged cough. ◦ Suspect if: Cough lasts >14 days OR after exposure to confirmed case.

DIAGNOSTIC APPROACH¶

Nasopharyngeal Culture: Gold standard; 100% specificity; limited by sensitivity and time.
Multitarget Real-time PCR: Preferred method; detects B. pertussis, B. parapertussis, and B. holmesii; remains positive longer than culture.
Specimen Collection: Nasopharyngeal aspiration → immediate inoculation on Bordet-Gengou or Regan-Lowe agar; use phosphate-buffered saline for transport.
Serology (Atypical cases): IgA/IgG detection to pertussis toxin, filamentous hemagglutinin, and fimbriae; 4-fold increase in titers supports diagnosis.

MANAGEMENT & TREATMENT¶

Antimicrobial Selection: Macrolides (azithromycin, erythromycin, clarithromycin) are first-line to eradicate B. pertussis from nasopharynx.
Chemoprophylaxis: Recommended for household contacts within 21 days of cough onset in the index case; also for high-risk individuals (infants <1 year, pregnant women).
Vaccination Strategy: ◦ Infants: 3-dose primary series (2, 4, 6 months); boosters at 15–18 months and 4–6 years. ◦ Adolescents/Adults: Tdap vaccine (adolescent dose 11–18 years; adult catch-up). ◦ Pregnancy: Tdap at 27–36 weeks → 90–93% effective in preventing infant disease.

Table 165-2 details specific antimicrobial regimens: • <1 month: ◦ Azithromycin (AZ): 10 mg/kg/day single dose for 5 days (preferred). ◦ Erythromycin (ER): 40–50 mg/kg/day in 4 divided doses for 14 days (not preferred, use only if AZ unavailable). ◦ Clarithromycin: Not recommended. ◦ TMP-SMZ: Contraindicated in infants <2 months. • Infants (≥6 months) and children: ◦ Azithromycin (AZ): 10 mg/kg on day 1; 5 mg/kg (max 500 mg) on days 2–5. ◦ Erythromycin (ER): 40–50 mg/kg/day (max 2 g/d) in 4 divided doses for 14 days. ◦ Clarithromycin: 15 mg/kg/day (max 1 g/d) in 2 divided doses for 7 days. ◦ TMP-SMZ: TMP 8 mg/kg, SMZ 40 mg/kg in 2 divided doses for 14 days (for patients allergic to macrolides; data limited).

Chemoprophylaxis Details¶

• Erythromycin estolate: 50 mg/kg/day reduced confirmed cases by 67% in trials. • Preferred Agents: Newer macrolides preferred due to better tolerability.

COMPLICATIONS & PROGNOSIS¶

• Prognosis: Generally good with treatment; severe in infants <1 year (mortality 0.2–0.5%). • Infant Complications: Pneumothorax (1%), pulmonary hypertension (50% of those with pneumonia), apnea, encephalopathy. • Child/Adult Complications: Rib fractures, carotid artery aneurysm, cough syncope, weight loss. • Long-term: Bronchiectasis possible in severe cases.

SPECIAL POPULATIONS¶

• Pregnancy: Tdap at 27–36 weeks → provides passive immunity to neonates <2 months; no increased risk of adverse outcomes. • Immunocompromised Hosts: Higher morbidity and prolonged carriage (e.g., HIV, transplant recipients). ◦ Warning: Vaccination may be contraindicated in those with CD4 <15% or on immunosuppressive therapy.

KEY PEARLS & HIGH-YIELD POINTS¶

• Lymphocytosis: >10^8–10^9/L is a hallmark in children; absent in adults. • Vaccine Impact: Pertactin-negative strains are common due to acellular vaccine use. • Transmission: 56% of household contacts are asymptomatic carriers. • Clinical Trap: Fever suggests bacterial superinfection, not pertussis itself. • Clinical Trap: Atypical presentation in adults (persistent cough, no whoop) may delay diagnosis.

Reference Tables¶

TABLE 165-1 Clinical Features of Pertussis, by Age Group and Diagnostic Status¶

Harrison's 22e, p.1278

FEATURE	PERCENTAGE OF PATIENTS
	ADOLESCENTS AND ADULTS	INFANTS AND CHILDREN
Cough
	70–99
Worse at night	61–87	41
	8–82
Post-tussive vomiting	17–65	48–60

TABLE 165-2 Antimicrobial Therapy for Pertussis¶

Harrison's 22e, p.1280

PATIENT AGE GROUP	PRIMARY AGENTS			ALTERNATE AGENT
	AZITHROMYCIN (AZ)	ERYTHROMYCIN (ER)	CLARITHROMYCIN	TRIMETHOPRIM (TMP)- SULFAMETHOXAZOLE (SMZ)a
<1 month	AZ is the recommended agent for this age group, at 10 mg/kg per day in a single dose for 5 days	ER is not preferred, only use if AZ unavailable; 40–50 mg/kg per day in 4 divided doses for 14 days	Not recommended in this age group	Contraindicated in infants <2 months
	10 mg/kg per day in a single dose for 5 days	40–50 mg/kg per day in 4 divided doses for 14 days	15 mg/kg per day in 2 divided doses for 7 days
Infants (≥6 months) and children	10 mg/kg on day 1, 5 mg/kg mg per day (maximum 500 mg) on days 2–5	40–50 mg/kg per day (maximum 2 g/d) in 4 divided doses for 14 days	15 mg/kg per day (maximum 1 g/d) in 2 divided doses for 7 days	TMP 8 mg/kg per day, SMZ 40 mg/kg per day in 2 divided doses for 14 days
	500 mg on day 1, 250 mg/d on days 2–5	2 g/d in 4 divided doses for 14 days	1 g/d in 2 divided doses for 7 days
Comments	Abdominal discomfort, prescribed with caution to cardiac patients	Frequent gastrointestinal side effects, hypersensitivity reactions	Epigastric distress and cramps	For patients allergic to macrolides, data on effectiveness are limited