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Summary Table

Domain	Key Points
Risk Factors	Unvaccinated or incompletely vaccinated infants (<6 months), waning immunity in adolescents/adults, close household contacts of an infected individual, lack of maternal Tdap vaccination during pregnancy
Etiology	Bordetella pertussis, a gram-negative coccobacillus; transmitted via respiratory droplets; highly contagious (attack rate >80% in susceptible household contacts)
Patient Presentation	Prolonged paroxysmal cough lasting weeks, post-tussive emesis, inspiratory "whoop," cough worse at night; infants may present with apnea rather than classic whoop
Classic Physical Exam	Patient appears well between coughing episodes; subconjunctival hemorrhage from forceful coughing; in young infants: cyanosis, apnea episodes
Key Diagnostic Results	Marked lymphocytosis (WBC 20,000 to >100,000 with lymphocyte predominance); nasopharyngeal PCR (test of choice); culture on Regan-Lowe or Bordet-Gengou agar (gold standard but low sensitivity)
Management	Azithromycin is the preferred macrolide for treatment and post-exposure prophylaxis; supportive care for infants (hospitalization, oxygen, suctioning); same regimen for close contacts regardless of vaccination status
Keywords	"Staccato cough," "paroxysmal cough with whoop," "post-tussive vomiting," "100-day cough," "lymphocytosis in a child with cough," "apneic episodes in a young infant"

1. Pathophysiology

Bordetella pertussis colonizes the ciliated respiratory epithelium of the upper airways. The organism does not invade the bloodstream; instead, it produces a series of toxins and adhesins that cause localized damage and systemic immune dysregulation.

Pertussis toxin (PT) is the most important virulence factor. It is an ADP-ribosylating toxin that inactivates the inhibitory G-protein ($G_i$) of host cells. This leads to two testable consequences. First, in pancreatic islet cells, loss of $G_i$ signaling causes unopposed insulin secretion, which can produce hypoglycemia, particularly in neonates. Second, PT causes lymphocytosis by preventing lymphocyte migration from the bloodstream into lymph nodes, a phenomenon called "lymphocyte trapping." This is why the CBC classically shows a striking leukocytosis with lymphocyte predominance, not neutrophilia.

Filamentous hemagglutinin (FHA) and fimbriae mediate attachment to ciliated epithelial cells. Once attached, the organism releases tracheal cytotoxin, which directly destroys ciliated cells and paralyzes the mucociliary escalator. The loss of cilia results in mucus accumulation and impaired clearance, which is the direct cause of the prolonged, violent cough. Because the damage is structural and takes weeks to regenerate, the cough persists long after the bacteria are eradicated by antibiotics. This explains why macrolide therapy shortens infectivity but does not necessarily shorten the duration of cough if started late.

Adenylate cyclase toxin (ACT) impairs neutrophil and macrophage function, allowing the organism to evade early innate immunity. This is why the infection establishes itself during the catarrhal phase when it clinically resembles a benign upper respiratory infection, making early diagnosis difficult.

In young infants (under 6 months), the immune response to pertussis toxin can trigger severe pulmonary hypertension driven by leukocyte aggregation in the pulmonary vasculature. This is the mechanism behind fulminant or "malignant" pertussis, which carries a high mortality rate and may require exchange transfusion to reduce the white cell burden.

2. Clinical Manifestation and Classification

Pertussis follows a three-stage clinical course. Recognizing the stage at presentation determines both the diagnostic approach and the expected benefit of antibiotic therapy.

Stage	Duration	Clinical Features	Contagiousness	Notes
Catarrhal	1 to 2 weeks	Rhinorrhea, mild cough, low-grade fever; clinically indistinguishable from a viral URI	Highest	Most contagious period; antibiotics given here may shorten illness duration
Paroxysmal	2 to 8 weeks	Sudden bursts (paroxysms) of rapid, forceful coughs followed by an inspiratory "whoop"; post-tussive emesis; patient appears well between episodes	Moderate, decreasing	Classic presentation; antibiotics at this stage reduce transmission but do not significantly shorten symptoms
Convalescent	Weeks to months	Gradual decrease in cough frequency and severity; intercurrent viral URIs can trigger recurrence of paroxysms	Minimal to none	Known as the "100-day cough"; supportive care only

Atypical Presentations

Population	Distinguishing Feature
Neonates and young infants (<6 months)	May NOT whoop; present instead with apnea, cyanosis, or seizures; highest morbidity and mortality group
Adolescents and adults (waned immunity)	Prolonged cough (>2 weeks) without classic whoop; often misdiagnosed as bronchitis or reactive airway disease; these patients serve as the primary reservoir transmitting to unvaccinated infants
Partially vaccinated children	Milder paroxysms, shorter duration; diagnosis requires high clinical suspicion

3. Diagnostic Workup

Test	Role	Timing	Key Details
Nasopharyngeal PCR	Best initial test / Test of choice	Optimal in first 3 to 4 weeks of cough (catarrhal and early paroxysmal stage)	High sensitivity and rapid turnaround; most widely recommended diagnostic modality
Nasopharyngeal culture (Regan-Lowe or Bordet-Gengou agar)	Gold standard / Most accurate test	Best yield in first 2 weeks (catarrhal stage)	Very high specificity but low sensitivity (organism is fastidious and slow-growing); takes 7 to 12 days
CBC with differential	Supportive evidence	Any stage	Leukocytosis with lymphocyte predominance is a classic clue; WBC can exceed 100,000 in severe infant cases
Serology (anti-PT IgG)	Retrospective / Late diagnosis	After 2 to 8 weeks of cough	Useful when PCR/culture window has passed; a single elevated anti-PT IgG in an unvaccinated individual or a fourfold rise in paired sera supports diagnosis
Chest X-ray	Supportive, not diagnostic	When complications suspected	Classic finding is a "shaggy heart" sign (perihilar infiltrates and atelectasis creating an indistinct cardiac border); may also show pneumothorax or subcutaneous emphysema from forceful coughing
DFA (Direct Fluorescent Antibody)	Largely abandoned	N/A	Poor sensitivity and specificity; no longer recommended by CDC

The diagnostic approach to pertussis depends heavily on how many weeks the patient has been coughing.

For patients presenting within the first 3 weeks of cough onset, nasopharyngeal PCR is the first-line test. The swab must be obtained from the posterior nasopharynx (not the throat or anterior nares) using a Dacron or calcium alginate swab. PCR has high sensitivity during this window because bacterial load in the nasopharynx is still significant. Culture can be obtained simultaneously from the same swab, but because B. pertussis is extremely fastidious and growth takes over a week, culture alone should not delay clinical decision-making.

For patients presenting after 3 to 4 weeks of cough, the organism is largely cleared from the nasopharynx, and both PCR and culture sensitivity drop substantially. In this window, serology becomes the most useful tool. A single elevated anti-pertussis toxin IgG level in a patient who has not received a pertussis-containing vaccine in the prior 12 months is considered diagnostic. This scenario is commonly tested: a teenager or adult with a cough lasting 6 or more weeks, negative PCR, but elevated anti-PT IgG.

The CBC finding of lymphocytosis is not diagnostic on its own but is a powerful clue, particularly in infants. If you see a vignette describing a young infant with paroxysmal cough, apnea, and a WBC of 60,000 with 80% lymphocytes, pertussis should be at the top of your differential. Notably, this lymphocytosis is composed of mature, normal-appearing small lymphocytes (not blasts), which distinguishes it from leukemia.

4. Management and Treatment

Clinical Scenario	Treatment	Dose and Duration	Notes
First-line treatment (all ages >1 month)	Azithromycin	10 mg/kg on Day 1, then 5 mg/kg on Days 2 through 5 (5-day course)	Preferred macrolide due to short course, fewer GI side effects, and fewest drug interactions
Alternative (age >1 month)	Clarithromycin	15 mg/kg/day divided BID for 7 days	Acceptable alternative if azithromycin unavailable
Alternative (age >1 month)	Erythromycin	40 to 50 mg/kg/day divided QID for 14 days	Longer course, more GI side effects; associated with infantile hypertrophic pyloric stenosis (IHPS) in infants <1 month
Macrolide allergy or intolerance (age >2 months)	TMP-SMX	TMP 8 mg/kg/day divided BID for 14 days	Not recommended for infants <2 months; not effective as first-line
Infants <1 month	Azithromycin	10 mg/kg/day for 5 days	Preferred over erythromycin in this age group because erythromycin carries a risk of IHPS
Post-exposure prophylaxis	Same macrolide regimens as treatment	Same doses as above	Given to all close contacts regardless of age or vaccination status; initiated within 21 days of exposure
Severe infant pertussis	ICU admission, respiratory support	Mechanical ventilation, ECMO if needed	Exchange transfusion or leukapheresis considered for WBC >100,000 with pulmonary hypertension

Acute management centers on two goals: reducing transmission and preventing complications.

Antibiotics are most effective when started during the catarrhal stage, where they can shorten the duration and severity of symptoms. Once the paroxysmal stage is well established, antibiotics still reduce contagiousness (the patient is considered non-infectious after 5 days of appropriate therapy) but have minimal impact on symptom duration because the cough is driven by epithelial damage, not ongoing infection.

Azithromycin is universally preferred across all age groups, including neonates. The critical teaching point is why erythromycin is avoided in infants under 1 month old: it is associated with infantile hypertrophic pyloric stenosis. This is a commonly tested association. If a vignette describes a 2-week-old infant with pertussis exposure, the correct prophylactic agent is azithromycin, not erythromycin.

Post-exposure prophylaxis (PEP) is given to all close contacts (household members, childcare contacts, healthcare workers who had unprotected face-to-face exposure). The regimen is identical to treatment. PEP is given regardless of vaccination status because vaccine-induced immunity wanes over time and does not guarantee protection against colonization.

For hospitalized infants, supportive care is paramount. This includes continuous cardiorespiratory monitoring, gentle nasopharyngeal suctioning, supplemental oxygen, and IV fluids if post-tussive emesis impairs oral intake. In fulminant cases with hyperleukocytosis (WBC >100,000) and evolving pulmonary hypertension, exchange transfusion or leukapheresis may be life-saving by reducing the leukocyte burden in the pulmonary vasculature.

Vaccination is the cornerstone of long-term prevention. The DTaP series is given at 2, 4, 6, and 15 to 18 months, with a booster at 4 to 6 years. Tdap is given as a single booster at age 11 to 12 and is recommended for all pregnant women during each pregnancy (optimally between 27 and 36 weeks of gestation) to allow passive transfer of maternal antibodies to the newborn. This maternal vaccination strategy is the primary method of protecting infants too young to be vaccinated.

5. Differential Diagnosis and Distractors

Differential	Why It Is Similar	Key Discriminator
Viral URI / Bronchiolitis (RSV)	Both cause cough and rhinorrhea in young children	Pertussis cough is paroxysmal with post-tussive emesis and whooping; viral bronchiolitis presents with wheezing, tachypnea, and diffuse crackles; RSV rapid antigen test is positive
Mycoplasma pneumoniae	Prolonged cough in school-age children and adolescents	Mycoplasma causes a dry, non-paroxysmal cough; often associated with bullous myringitis, rash, or cold agglutinins; chest X-ray shows patchy infiltrates rather than perihilar haziness
Chlamydia trachomatis pneumonia	Staccato cough in young infants (1 to 3 months)	Chlamydial pneumonia is afebrile with a staccato cough (not paroxysmal), accompanied by conjunctivitis and eosinophilia (not lymphocytosis); infant was born via vaginal delivery to a mother with untreated chlamydia
Foreign body aspiration	Sudden-onset cough in a toddler; can become chronic	History of acute choking episode; cough is persistent and unilateral; chest X-ray shows unilateral hyperinflation or atelectasis; no lymphocytosis
Croup (parainfluenza)	Barking cough in a young child	Croup has a "seal-bark" cough with inspiratory stridor (not a whoop); associated with steeple sign on neck X-ray; no post-tussive emesis or lymphocytosis
Reactive airway disease / Asthma	Recurrent or prolonged cough, especially nocturnal	Asthma has expiratory wheezing with reversibility on bronchodilators; no paroxysms, no post-tussive vomiting, and no lymphocytosis; personal or family history of atopy
Tuberculosis	Chronic cough in a child; can persist for weeks	TB has systemic symptoms (weight loss, night sweats, fever); chest X-ray shows hilar lymphadenopathy or Ghon complex; positive PPD/IGRA; no lymphocytosis pattern
Leukemia (ALL)	Extreme leukocytosis in a young child	Leukemia presents with blasts on peripheral smear, anemia, thrombocytopenia, bone pain, and hepatosplenomegaly; pertussis lymphocytosis shows mature, normal small lymphocytes

6. Traps and High-Yield Pearls

The single most common trap on pertussis questions involves age-dependent presentation. Students are conditioned to look for the classic triad of paroxysmal cough, inspiratory whoop, and post-tussive vomiting. However, the highest-risk group (infants under 6 months) often does not whoop. Instead, they present with apnea, cyanosis, or feeding difficulty. If a vignette describes a 6-week-old infant with episodic apnea, cyanosis, and a WBC of 50,000 with lymphocyte predominance, the answer is pertussis, not sepsis or seizure disorder.

A second trap involves antibiotic selection in neonates. Erythromycin is a correct treatment for pertussis in older patients, but it is the wrong answer for infants under 1 month because of the pyloric stenosis risk. The correct choice is azithromycin. Expect a question where erythromycin is listed as a distractor for a newborn with pertussis exposure.

A third testing angle involves the timing of antibiotic benefit. A common vignette presents an adolescent who has been coughing for 4 weeks. Students may think antibiotics are no longer indicated. However, antibiotics are still given to reduce transmission to vulnerable contacts, even though they will not shorten the patient's own symptoms at this stage. The question tests whether you understand the public health rationale for treatment.

Finally, be prepared to distinguish pertussis lymphocytosis from leukemia. Both can produce WBC counts above 50,000. The discriminator is that pertussis produces mature, morphologically normal lymphocytes on the peripheral smear, whereas ALL produces immature lymphoblasts with associated cytopenias (anemia and thrombocytopenia). If the vignette includes a normal hemoglobin and platelet count with mature lymphocytes, the answer is pertussis.

The core competency being tested across pertussis questions is your ability to recognize atypical presentations in high-risk populations, sequence the correct diagnostic test based on duration of illness, and select the appropriate antibiotic based on age.

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