Pertussis (Whooping Cough)

Overview
Epidemiology
Pathophysiology
Etiology and Risk Factors
Three Clinical Stages
Diagnosis
Treatment
Complications
Prognosis
Prevention and Vaccination
Recent Research
Key Research Papers
Connections
Featured Videos

1. Overview

Pertussis — known to most people as whooping cough — is a highly contagious bacterial respiratory infection caused by Bordetella pertussis, a gram-negative coccobacillus that infects only humans. It is one of the few vaccine-preventable diseases that continues to cause substantial illness and death in every region of the world, not because the vaccine fails to work, but because protection wanes over time and leaves teenagers and adults vulnerable without their realizing it.

The disease earns its common name from a single, unforgettable sound: the high-pitched “whoop” that some patients make at the very end of a prolonged coughing fit — a desperate, crowing inhalation after the lungs have been emptied by a sustained barrage of uncontrollable coughs. This paroxysmal stage can persist for six to ten weeks, a duration so remarkable that pertussis is sometimes called the “100-day cough” in Chinese medicine and other traditional systems.

Two details about pertussis are consistently underappreciated by patients and clinicians alike. First, the characteristic whoop is absent in many people who have it — including most infants under six months, who may show only brief pauses in breathing (apnea), and most adults, who typically present with a prolonged, nagging cough that is mistaken for bronchitis or a lingering cold. Second, it is these unrecognized adult and adolescent cases that fuel the majority of infant deaths: a parent or sibling who does not know they have pertussis keeps going to work and holding the baby, with tragic results. Pertussis remains the leading cause of vaccine-preventable infant death in the United States.

2. Epidemiology

Before widespread vaccination, pertussis was one of the great killers of infancy: in the United States alone, more than 200,000 cases and roughly 9,000 deaths were reported annually in the early 1900s. Introduction of whole-cell pertussis vaccine in the 1940s and ’50s drove cases down by over 99%, reaching a historical low of about 1,010 cases reported in 1976. Since then, case counts have risen steadily. Large epidemic years — 2012 (48,000 cases, highest since 1955), 2014, 2022 — have reaffirmed that pertussis is not under control despite high childhood vaccination rates.

The resurgence has two widely accepted drivers. First, the shift in the 1990s from the reactogenic whole-cell pertussis vaccine (wP) to the acellular pertussis vaccine (aP, now used in DTaP and Tdap) improved safety but reduced the durability of immune protection. Studies show that aP-immunized children can lose significant protection within 3–5 years of their last dose, far faster than wP-immunized children. Second, B. pertussis has evolved mutations in the pertactin antigen — a target of acellular vaccine antibodies — that help it escape vaccine-induced immunity; pertactin-deficient strains now predominate in many high-income countries.

The disease causes approximately 160,000 deaths per year globally, almost all in infants in low-income countries. In high-income countries, deaths are concentrated in babies under three months, before the primary vaccination series is complete. The incidence follows cyclical patterns with outbreaks every 3–5 years, corresponding to accumulation of susceptible individuals. Seasonal peaks occur in summer and autumn in temperate climates.

3. Pathophysiology

Bordetella pertussis is an obligate human pathogen that colonizes the ciliated epithelium of the upper and lower respiratory tract. It does not invade tissues or enter the bloodstream in typical disease; instead, it produces a sophisticated arsenal of toxins and adhesins that disable the respiratory defenses and trigger systemic effects.

Filamentous hemagglutinin (FHA) and pertactin mediate attachment to ciliated cells. Once attached, the bacterium secretes several key virulence factors:

Pertussis toxin (PT): The signature virulence factor and primary immunogen. PT is an AB5 toxin that ADP-ribosylates Gi proteins in host cells, disrupting intracellular signaling. In the airway, PT paralyzes ciliated cells and impairs macrophage function. Systemically, PT blocks lymphocyte trafficking from lymph nodes, producing the characteristic extreme lymphocytosis (absolute lymphocyte count exceeding 10,000–100,000 cells/µL in infants) that predicts disease severity. PT also sensitizes the respiratory center to histamine (histamine-sensitizing factor), contributing to coughing paroxysms and potentially to apnea.
Tracheal cytotoxin (TCT): A fragment of peptidoglycan that directly kills ciliated epithelial cells, halting the mucociliary escalator that normally clears mucus and debris from the airway. TCT also triggers IL-1 release, contributing to fever. The destruction of cilia creates a viscous mucus accumulation that the now-immobilized airway cannot clear — the biological substrate for the violent coughing paroxysms.
Adenylate cyclase toxin (ACT): Enters host immune cells and elevates cAMP, blunting the oxidative burst of neutrophils and macrophages and facilitating immune evasion.
Dermonecrotic toxin: Contributes to local tissue damage in the airway.

The incubation period from exposure to first symptoms is typically 7–10 days, with a range of 4–21 days. Unlike many respiratory pathogens, B. pertussis is most contagious during the earliest, mildest stage of illness, before the diagnosis is even suspected — a feature that makes outbreak control exceptionally difficult.

4. Etiology and Risk Factors

The overwhelming cause of pertussis is Bordetella pertussis. A closely related species, Bordetella parapertussis, causes a similar but generally milder illness (“parapertussis”) and is not covered by pertussis vaccines. Bordetella holmesii has occasionally been identified in pertussis-like illness, particularly in immunocompromised patients.

Transmission occurs via respiratory droplets generated by coughing, sneezing, or breathing in close proximity to an infected person. The attack rate in susceptible household contacts approaches 80–100% — among the highest of any bacterial respiratory infection. The basic reproduction number (R0) in an unvaccinated population is estimated at 12–17, similar to measles in its transmissibility.

Risk factors for infection and severe disease include:

Infants under 12 months — highest mortality risk; those under three months have not yet completed the primary DTaP series and have no vaccine-induced protection.
Adolescents and adults whose vaccine-induced immunity has waned, who may be unaware they are infectious.
Unvaccinated or under-vaccinated individuals of any age.
Household contacts of a confirmed case — the most important proximal risk factor for infant cases.
Pregnancy — third-trimester maternal Tdap is now recommended specifically to transfer passive antibody protection to the newborn.
Immunocompromised patients who may have an attenuated or absent vaccine response.

5. Three Clinical Stages

Classic pertussis in an unvaccinated child progresses through three distinct stages. Vaccinated individuals and adults often have attenuated or atypical presentations that do not follow this progression clearly.

Stage 1: Catarrhal Stage (1–2 weeks)

The catarrhal stage is clinically indistinguishable from a common upper respiratory infection: runny nose (coryza), low-grade fever, mild conjunctival injection, and a slight, non-specific cough. Parents and clinicians almost never suspect pertussis at this stage. This is the most consequential stage epidemiologically: bacterial density on the respiratory mucosa is at its peak, the person is maximally contagious, and the opportunity to start antibiotics in the early, effective window is slipping away. The catarrhal stage lasts 1–2 weeks and transitions almost imperceptibly into the next stage.

Stage 2: Paroxysmal Stage (2–6 weeks, sometimes longer)

The paroxysmal stage is defined by the abrupt onset of paroxysmal coughing — episodes of 5–20 rapid, forceful coughs in a single expiratory burst, during which the person cannot breathe in. The forced exhalation exhausts the functional residual capacity of the lungs, and when the airway finally opens, air rushes in against a partially closed glottis, producing the high-pitched inspiratory “whoop.”

A single paroxysm can last 1–2 minutes, and patients may have 15–25 paroxysms per day. Paroxysms are often triggered by eating, drinking, physical activity, or being held. They may end in post-tussive emesis (vomiting after a coughing fit) — a classic feature that suggests pertussis in a patient with prolonged cough. Cyanosis during paroxysms is common, particularly in infants; subconjunctival hemorrhages and facial petechiae from the Valsalva-like pressure of sustained coughing are seen in severe cases.

Critical exceptions to the classic picture:

Infants under 6 months often do not produce a whoop. Instead they may show apnea (cessation of breathing) with or without cyanosis, sometimes so severe it requires resuscitation. The cough may sound weak or barely audible, belying the life-threatening nature of the illness.
Vaccinated adolescents and adults often have no whoop and no post-tussive emesis. The presentation is a persistent, exhausting cough lasting weeks that is routinely misattributed to bronchitis, asthma, GERD, or “a cold that won’t go away.” This missed diagnosis in adults is the source of most infant exposures.

Stage 3: Convalescent Stage (weeks to months)

The convalescent stage is characterized by gradual resolution of paroxysms, but the cough does not disappear quickly. A declining but persistent cough may continue for 3–6 months — hence “100-day cough.” Patients are no longer infectious in the convalescent stage (bacteria have been cleared from the airway), but they remain functionally impaired. For months, any subsequent respiratory illness — even a minor cold — can trigger a recurrence of paroxysmal coughing that mimics the original illness.

6. Diagnosis

Clinical diagnosis alone is unreliable: the presentation mimics many respiratory conditions, and the classic whoop is absent in many patients. Laboratory confirmation is essential for guiding treatment decisions, informing public health response, and identifying cases in non-classical presentations.

Nasopharyngeal PCR (most sensitive and practical)

Real-time PCR on a nasopharyngeal swab or aspirate is the recommended first-line diagnostic test. It is highly sensitive and specific, returns results within hours, and detects both B. pertussis and B. parapertussis. PCR is most sensitive in the first 3–4 weeks of illness. Proper specimen collection requires a nasopharyngeal swab (not a nasal swab — the posterior nasopharynx must be sampled) or nasopharyngeal aspirate. Dacron or rayon swabs are preferred; calcium alginate swabs inhibit PCR.

Bacterial Culture (gold standard, slower)

Nasopharyngeal culture on Regan-Lowe charcoal agar (or Bordet-Gengou medium) is the definitive test for isolating viable organisms, essential for antibiotic susceptibility testing and epidemiological strain typing. Culture is most productive in the first 2 weeks of illness when bacterial density is highest. Sensitivity declines sharply after antibiotic treatment is started. Culture takes 7–14 days to result, making it impractical for clinical management decisions, but it remains the gold standard for public health surveillance purposes.

Serology (anti-pertussis toxin IgG)

A single-serum anti-pertussis toxin IgG (anti-PT IgG) antibody above a laboratory-defined threshold (typically ≥100 IU/mL in the absence of recent vaccination) is useful for diagnosing pertussis weeks into illness when PCR and culture are no longer sensitive. This test is most valuable in adolescents and adults presenting in the paroxysmal or convalescent stage. It requires that the patient has not been vaccinated in the previous year, as vaccination itself raises anti-PT IgG. Not available as a standard rapid test in many US laboratories.

Complete Blood Count Findings

A CBC showing marked absolute lymphocytosis — particularly an absolute lymphocyte count above 10,000 cells/µL in an infant, or above 20,000 cells/µL — is a classic laboratory clue to pertussis. In severely ill hospitalized infants, extreme lymphocytosis exceeding 50,000 or even 100,000 cells/µL is associated with pulmonary hypertension and fatal outcome. The lymphocytosis is mechanistically driven by pertussis toxin, which prevents lymphocytes from leaving lymph nodes and re-entering tissues, causing them to accumulate in the bloodstream.

7. Treatment

Treatment with antibiotics serves two purposes: eradicating the bacteria from the respiratory tract (which reduces contagiousness and, if started early enough, may attenuate the clinical course) and shortening the infectious period to prevent spread to contacts. Antibiotics started after 3–4 weeks of illness have essentially no impact on symptom duration — the damage to ciliated cells from tracheal cytotoxin is done, and the prolonged cough will continue until cilia regenerate.

Antibiotic Regimens

Azithromycin (first-line for all ages): 5-day course. For infants under 1 month: 10 mg/kg/day once daily for 5 days. For all others: 500 mg on day 1, then 250 mg days 2–5 (or 500 mg/day for 3 days as an alternative). Preferred in pregnancy and in infants because of excellent safety profile and convenient dosing.
Clarithromycin (alternative, not used in infants <1 month): 15 mg/kg/day divided twice daily for 7 days in children; 500 mg twice daily for 7 days in adults.
Erythromycin (alternative): 40–50 mg/kg/day divided four times daily for 14 days. Effective but poorly tolerated due to GI side effects; associated with hypertrophic pyloric stenosis in neonates — use only when azithromycin is unavailable in infants under 1 month.
Trimethoprim-sulfamethoxazole (TMP-SMX) (alternative for macrolide-intolerant patients ≥2 months): TMP 8 mg/kg/day + SMX 40 mg/kg/day divided twice daily for 14 days. Not safe in infants under 2 months or in pregnancy near term.

Post-Exposure Prophylaxis

All household and close contacts should receive antibiotic post-exposure prophylaxis (same regimens as treatment) regardless of vaccination status, because vaccination does not provide complete protection and the attack rate in household contacts is very high. Priority contacts include all household members and anyone with face-to-face contact within 3 feet for ≥1 hour, or direct contact with respiratory secretions. Prophylaxis is most effective when given within 21 days of onset in the index case.

Supportive Care

For mild to moderate cases, supportive care at home includes rest, adequate hydration, small frequent meals (large meals can trigger paroxysms), humidified air, and avoiding cough triggers where possible. Cough suppressants, expectorants, bronchodilators, corticosteroids, and antihistamines have not been shown to reduce severity or duration of pertussis cough and are not recommended. Hospitalized infants require continuous cardiorespiratory monitoring, supplemental oxygen, nasogastric feeding if oral intake is impaired, and suction of secretions.

8. Complications

Most older children, adolescents, and adults with pertussis recover fully with supportive care and experience no lasting complications beyond the prolonged cough. The complication profile in infants under 6 months is dramatically more serious.

Complications in Infants (<6 months)

Apnea: The most common serious complication in very young infants, particularly under 2 months. Episodes of breathing cessation can be prolonged and require bag-valve-mask ventilation or intubation. Central apnea from pertussis toxin effects on the brainstem respiratory center distinguishes this from obstructive apnea.
Pulmonary hypertension: Extreme lymphocytosis from pertussis toxin causes pulmonary capillary plugging and mechanical obstruction of pulmonary blood flow, leading to acute pulmonary arterial hypertension. This is the mechanism behind sudden deterioration and death in severely ill infants. Absolute lymphocyte counts above 50,000 cells/µL are an independent predictor of fatal pulmonary hypertension.
Pneumonia: Secondary bacterial pneumonia (from Staphylococcus aureus, Streptococcus pneumoniae, or gram-negative organisms) is the most common cause of pertussis-related death. Primary B. pertussis pneumonia also occurs. Pulmonary infiltrates develop in 12–20% of hospitalized infants.
Encephalopathy: Hypoxic brain injury from apnea and cyanosis, or from direct toxin effects. Seizures during the illness may reflect hypoxic brain injury, hypoglycemia (from vomiting), or direct CNS effects of pertussis toxin. Permanent neurological sequelae occur in a small but real proportion of severely affected infants.

Complications in Older Patients

Rib fractures: The mechanical force of sustained paroxysmal coughing can fracture ribs, most commonly the posterior ribs. Rib fractures have been reported even in previously healthy adults.
Urinary incontinence: Stress incontinence from the repeated Valsalva-like pressure of coughing fits is particularly common in women and can persist for weeks after the acute illness.
Subconjunctival hemorrhage: Small hemorrhages visible on the white of the eye from elevated venous pressure during coughing; alarming in appearance but harmless.
Syncope: Post-tussive syncope from vagally mediated vasodilation or reduced cerebral perfusion during prolonged paroxysms.
Pneumothorax and pneumomediastinum: Rare but reported complications from alveolar rupture during extreme coughing efforts.
Otitis media in young children from Eustachian tube dysfunction associated with prolonged coughing and mucosal inflammation.

9. Prognosis

Prognosis varies dramatically by age. In the United States, the case fatality rate in infants under 2 months approaches 1–2% even with modern intensive care; in infants 2–11 months it falls to roughly 0.5%. In children over 1 year and adults, mortality is extremely rare. Globally, pertussis accounts for approximately 160,000 deaths per year, predominantly in infants in low-resource settings without access to intensive care.

The prolonged cough of the paroxysmal and convalescent stages is functionally debilitating but leaves no permanent pulmonary damage in the vast majority of patients. Lung function testing returns to normal after recovery. The major long-term concern is neurological: infants who sustained significant hypoxic injury or encephalopathy during the acute illness may have persistent developmental delay, seizure disorders, or cognitive impairment.

Natural infection does not confer lifelong immunity. Both vaccine-induced and infection-induced immunity wane over time, and reinfection — typically producing a milder illness — is documented and common.

10. Prevention and Vaccination

Vaccination is the cornerstone of pertussis prevention. The childhood DTaP series (diphtheria, tetanus, acellular pertussis) and adult Tdap booster are the tools that, when used at high coverage rates, dramatically reduce infant mortality from pertussis.

DTaP: Primary Childhood Series

The primary series consists of five DTaP doses at ages 2 months, 4 months, 6 months, 15–18 months, and 4–6 years. The acellular pertussis component contains 2–5 purified B. pertussis antigens (pertussis toxoid, FHA, pertactin, fimbriae) rather than the whole inactivated organism used in older whole-cell vaccines. Efficacy of the complete 5-dose series is approximately 80–85% in the first few years after the last dose, declining to perhaps 30–50% a decade later.

Tdap: Adolescent and Adult Booster

A single Tdap dose (lower antigen content than DTaP) is recommended for all adolescents at the 11–12-year well visit if they have not previously received Tdap. Adults who have not previously received Tdap should receive one dose. Thereafter, the standard recommendation is a Td (tetanus-diphtheria, no pertussis) booster every 10 years, though some experts advocate for Tdap at every 10-year booster given the resurgence.

Maternal Tdap: The Cocooning Strategy

The most critical pertussis vaccination recommendation for infant protection is maternal Tdap during the third trimester of every pregnancy, ideally between 27 and 36 weeks gestation. Maternal vaccination generates high levels of anti-pertussis antibodies that cross the placenta and provide the newborn with passive protection for the first 1–2 months of life — the most vulnerable window before the infant can complete their own primary series. Studies show maternal vaccination is approximately 90% effective at preventing pertussis-related hospitalization and death in infants under 2 months.

The broader “cocooning” strategy — vaccinating all household members and close caregivers of a newborn — was the original approach to protecting infants but has been largely supplanted by direct maternal vaccination as the evidence base grew showing the latter to be more effective and more efficiently targeted. Both approaches are complementary.

Healthcare Worker Vaccination

All healthcare personnel who have not previously received Tdap should receive a single dose. Healthcare workers are a significant source of pertussis exposure for hospitalized infants and immunocompromised patients.

11. Recent Research

Pertussis research has been energized by the resurgence of disease since the 1990s and by the recognition that current acellular vaccines, while safe, may not provide the durable population-level protection that whole-cell vaccines once achieved. Three areas dominate the current research agenda.

The first is understanding why aP immunity wanes faster than wP immunity. Animal models and human immunological studies suggest that whole-cell vaccines induced a mixed Th1/Th17 mucosal immune response in the airway, while acellular vaccines primarily induce systemic Th2 and antibody responses. Th17-driven responses, particularly secretory IgA in the respiratory mucosa, appear to be the mechanism that clears colonization before disease develops. Current acellular vaccines may not generate sufficient mucosal immunity. Efforts to develop next-generation pertussis vaccines that better mimic the mucosal immunity of wP vaccines — including live attenuated strains, outer membrane vesicle vaccines, and intranasal delivery platforms — are in clinical trials.

The second area is pertactin-deficient (PRN-negative) strains. Pertactin, one of the antigens in acellular vaccines, has been subject to selection pressure from vaccination: strains that have deleted or downregulated pertactin avoid a key antibody target while losing nothing essential for their own biology. PRN-negative strains have expanded dramatically since 2010 and now represent more than 80% of US isolates. The clinical significance remains debated — available evidence suggests these strains do not cause more severe disease but may be more adept at infecting vaccinated individuals.

The third is optimizing maternal vaccination across different healthcare systems and populations. Research in the United Kingdom, the United States, and Argentina has confirmed the effectiveness of maternal Tdap, but uptake remains below 50% in many countries due to hesitancy and access barriers. Implementation science research is identifying strategies to improve uptake, particularly among communities with historically lower antenatal care engagement.

12. Key Research Papers

Cherry JD. Epidemic pertussis in 2012 — the resurgence of a vaccine-preventable disease. New England Journal of Medicine. 2012;367(9):785–787. doi:10.1056/NEJMp1209051. PMID: 22931279.
Witt MA, Katz PH, Witt DJ. Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak. Clinical Infectious Diseases. 2012;54(12):1730–1735. doi:10.1093/cid/cis287. PMID: 22423127.
Leuridan E, Hens N, Peeters N, de Witte L, Van Damme P, Desombere I. Maternal pertussis antibody decay and effect on infant response to primary pertussis vaccination. Vaccine. 2011;29(11):2225–2231. doi:10.1016/j.vaccine.2010.12.055. PMID: 21238570.
Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model. Proceedings of the National Academy of Sciences. 2014;111(2):787–792. doi:10.1073/pnas.1314688110. PMID: 24277828.
Skoff TH, Blain AE, Watt J, et al. Impact of the US maternal tetanus, diphtheria, and acellular pertussis vaccination program on preventing pertussis in infants <2 months of age: a case-control evaluation. Clinical Infectious Diseases. 2017;65(12):1977–1983. doi:10.1093/cid/cix724. PMID: 29048520.
Paddock CD, Sanden GN, Cherry JD, et al. Pathology and pathogenesis of fatal Bordetella pertussis infection in infants. Clinical Infectious Diseases. 2008;47(3):328–338. doi:10.1086/589753. PMID: 18558873.
Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clinical Microbiology Reviews. 2005;18(2):326–382. doi:10.1128/CMR.18.2.326-382.2005. PMID: 15831828.
Olin P, Gustafsson L, Barreto L, et al. Declining pertussis incidence in Sweden following the introduction of acellular pertussis vaccine. Vaccine. 2003;21(17–18):2015–2021. doi:10.1016/s0264-410x(02)00777-3. PMID: 12706693.
Berbers GA, de Rond LG, Habermehl P, et al. Seroprevalence of pertussis toxin-specific antibodies and their protective level among unvaccinated and vaccinated persons in Europe and the USA: a systematic review and meta-analysis. Lancet Infectious Diseases. 2021;21(3):389–400. doi:10.1016/S1473-3099(20)30312-1. PMID: 32822605.
Hellenbrand W, Beier D, Jensen E, et al. The epidemiology of pertussis in Germany: past and present. BMC Infectious Diseases. 2009;9:22. doi:10.1186/1471-2334-9-22. PMID: 19236706.
Halperin SA. The control of pertussis — 2007 and beyond. New England Journal of Medicine. 2007;356(2):110–113. doi:10.1056/NEJMp068218. PMID: 17215530.
Liang JL, Tiwari T, Moro P, et al. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports. 2018;67(2):1–44. doi:10.15585/mmwr.rr6702a1. PMID: 29702631.

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