Pertussis

1. Disease Information

Overview

Pertussis, commonly known as whooping cough, is an acute, highly contagious respiratory infection caused by the Gram-negative coccobacillus bacterium Bordetella pertussis (NCBI Taxonomy: NCBITaxon:520) (colak2023bordetellapertussisand pages 1-2, ifill2023lipidamodifications pages 18-25). The disease is characterized by severe paroxysmal coughing episodes followed by a characteristic inspiratory "whoop," which can result in apnea, cyanosis, and post-tussive vomiting (chamorro2023bordetellabronchisepticaand pages 2-3). Pertussis is particularly dangerous in neonates and young infants, in whom it can cause brain damage and death (colak2023bordetellapertussisand pages 1-2). B. pertussis is an obligate human pathogen with no known environmental reservoir (ifill2023lipidamodifications pages 18-25).

Key Identifiers

The following table provides a comprehensive reference for all disease identifiers and ontology terms:

Table: This table compiles key disease identifiers and ontology mappings relevant to pertussis, spanning diagnosis, phenotypes, anatomy, biology, treatments, and drugs. It is useful as a quick reference for disease knowledge base curation and ontology annotation.

Synonyms and Alternative Names

Common synonyms include: whooping cough, 100-day cough, tussis convulsiva, and Bordetella pertussis infection.

Data Source

Information is derived from aggregated disease-level resources including WHO surveillance data, CDC reports, systematic reviews, and peer-reviewed literature, rather than individual patient EHR data.

2. Etiology

Disease Causal Factors

Pertussis is caused exclusively by infection with Bordetella pertussis, a small Gram-negative coccobacillus (0.8 µm × 0.4 µm) that colonizes the ciliated epithelium of the trachea and bronchi (colak2023bordetellapertussisand pages 1-2, ifill2023lipidamodifications pages 18-25). Transmission occurs via respiratory droplets through sneezing and severe coughing, with possible transmission from asymptomatic individuals (chamorro2023bordetellabronchisepticaand pages 2-3). The pathogen produces a variety of antigenic compounds that individually or simultaneously damage host cells (colak2023bordetellapertussisand pages 1-2).

Risk Factors

Age: Infants under one year are at the highest risk of severe disease and mortality, with approximately 3% mortality in neonates (ifill2023lipidamodifications pages 18-25). Among infants under 6 months, 12.9% of pertussis cases required hospital admission, 4.8% required ICU admission, and 1.6% resulted in death in an Australian cohort study (regan2023maternalpertussisvaccination pages 5-6).

Vaccination status: Unvaccinated individuals face the highest risk for infection, hospitalization, and death (wang2025resurgenceofpertussis pages 5-7). Waning vaccine immunity, particularly from acellular pertussis vaccines, leaves adolescents and adults susceptible to infection and capable of transmitting the pathogen to vulnerable infants (wang2025resurgenceofpertussis pages 2-4, caulfield2023generatingenhancedmucosal pages 4-5).

Environmental/behavioral: Household contact with infected individuals, lack of maternal vaccination during pregnancy, and low community vaccine coverage are important risk factors (wang2025resurgenceofpertussis pages 5-7).

Protective Factors

Vaccination: Both whole-cell (wP) and acellular (aP) pertussis vaccines significantly reduce disease incidence and severity. Natural infection provides 4–20 years of immunity (wang2025resurgenceofpertussis pages 4-5).

Maternal vaccination: Maternal Tdap vaccination at approximately 28 weeks' gestation provides 70.4% effectiveness in infants under 2 months and 65.1% effectiveness in infants under 6 months against notified pertussis infection (regan2023maternalpertussisvaccination pages 5-6, regan2023maternalpertussisvaccination pages 1-2).

3. Phenotypes

Clinical Stages and Symptoms

Pertussis progresses through three classic stages spanning up to 12 weeks (ifill2023lipidamodifications pages 18-25):

Catarrhal stage (1–2 weeks): Presents with mild respiratory symptoms resembling a common cold, including rhinorrhea, mild cough, and low-grade fever (HP:0001945). This is the most infectious period (ifill2023lipidamodifications pages 18-25).

Paroxysmal stage (up to 8 weeks): Characterized by intense paroxysmal coughing episodes (HP:0012735) followed by the inspiratory "whoop" (HP:0031247), post-tussive vomiting (HP:0033847), apnea (HP:0002105), and cyanosis (HP:0000961) (chamorro2023bordetellabronchisepticaand pages 2-3, ifill2023lipidamodifications pages 18-25).

Convalescent stage (average 4 weeks): Gradual reduction in cough intensity and frequency, though symptoms may persist for months depending on disease severity and comorbidities (ifill2023lipidamodifications pages 18-25).

Severity by Age

In children, pertussis is typically life-threatening and severe. Teenagers and adults present with milder disease, ranging from asymptomatic carriage to chronic persistent cough (chamorro2023bordetellabronchisepticaand pages 2-3). Severe complications including seizures (HP:0001250), encephalopathy, and pneumonia (HP:0002205) can occur across age groups but are most common in infants (ernst2022novelstrategiesto pages 1-2).

Laboratory Abnormalities

Leukocytosis (HP:0001974) is a hallmark laboratory finding, particularly in severe infant disease, and is strongly associated with pertussis toxin activity and poor outcomes (ernst2022novelstrategiesto pages 1-2).

Quality of Life Impact

Pertussis causes significant functional impairment during the paroxysmal stage, with prolonged nocturnal coughing causing sleep disturbance (HP:0002360), exhaustion, rib fractures in adults, and inability to perform daily activities for weeks.

4. Genetic/Molecular Information

Pathogen Genomics (Not Host Genetics)

Pertussis is an infectious disease; causal human genetic variants are not applicable. However, pathogen evolution plays a critical role in disease dynamics.

Pathogen genetic evolution: The transition from ptxP1 to ptxP3 allele in the pertussis toxin promoter has been identified as a major evolutionary event, resulting in increased toxin production and enhanced respiratory tract colonization (wang2025resurgenceofpertussis pages 2-4). Pertactin (PRN) deletions and variations, as well as filamentous hemagglutinin (FHA) loss, represent vaccine-driven selection events in circulating strains (wang2025resurgenceofpertussis pages 2-4, chamorro2023bordetellabronchisepticaand pages 33-33). Additionally, fimbriae 2 (FIM2)-negative and pertactin-negative strains have been identified in France and other countries (chamorro2023bordetellabronchisepticaand pages 2-3).

Macrolide resistance: Macrolide-resistant B. pertussis (MRBp) strains have emerged globally, with prevalence exceeding 95% of isolates in China and up to 50% in Chinese hospital settings (jiang2024theeffectof pages 8-10, chamorro2023bordetellabronchisepticaand pages 2-3). Resistance rates remain negligible in the USA, UK, and Finland (chamorro2023bordetellabronchisepticaand pages 2-3).

5. Environmental Information

Infectious Agent

Bordetella pertussis is the sole causative agent. It belongs to the genus Bordetella, which comprises 16 species. Related species include B. parapertussis (can cause milder whooping cough) and B. bronchiseptica (primarily a veterinary pathogen) (chamorro2023bordetellabronchisepticaand pages 2-3).

Transmission Dynamics

Pertussis is transmitted via airborne respiratory droplets from sneezing and coughing. It is highly contagious, with secondary attack rates of up to 80–90% in susceptible household contacts. Adults and adolescents with waning immunity serve as the primary reservoir for transmission to vulnerable infants (ifill2023lipidamodifications pages 18-25, chamorro2023bordetellabronchisepticaand pages 2-3).

6. Mechanism / Pathophysiology

Virulence Factors

The following table summarizes the major virulence determinants of B. pertussis:

Table: This table summarizes the major Bordetella pertussis virulence determinants, their known mechanisms, roles in disease, and relevance to current or emerging vaccine strategies. It is useful for linking pathogenesis to diagnostics, therapeutic targeting, and vaccine design.

BvgAS Two-Component Regulatory System

All major virulence factors are regulated by the BvgAS two-component system, comprising the sensor kinase BvgS and response regulator BvgA. This system functions as a molecular rheostat controlling virulence gene expression across three phenotypic phases: Bvg+ (virulent, virulence-activated genes expressed), Bvg- (avirulent), and Bvgi (intermediate) (chamorro2023bordetellabronchisepticaand pages 13-15, colak2023bordetellapertussisand pages 2-3). Phosphorylated BvgA activates transcription of genes encoding adhesins (FHA, FIM, PRN), toxins (PT, ACT, DNT), and the T3SS (colak2023bordetellapertussisand pages 2-3).

Pertussis Toxin (PT) – Central Virulence Factor

PT is a 117-kDa AB-type exotoxin with unique importance in pertussis pathogenesis. The S1 subunit ADP-ribosylates inhibitory Gαi subunits of G-protein coupled receptors, disrupting cAMP signaling in target cells (ernst2022novelstrategiesto pages 1-2). PT inhibits chemokine release and neutrophil recruitment, delays antibody-mediated bacterial clearance, enables intracellular macrophage infection, and produces systemic effects including leukocytosis, hyperinsulinemia, and histamine sensitivity (chamorro2023bordetellabronchisepticaand pages 16-18, chamorro2023bordetellabronchisepticaand pages 15-16). PT is uniquely expressed in B. pertussis; related species carry the gene but cannot transcribe it due to promoter mutations (chamorro2023bordetellabronchisepticaand pages 15-16).

Adenylate Cyclase Toxin (ACT/CyaA)

ACT enters phagocytes and elevates intracellular cAMP, inhibiting phagocytosis and opsonization, inducing macrophage apoptosis, and disrupting epithelial tight junctions (chamorro2023bordetellabronchisepticaand pages 16-18, ernst2022novelstrategiesto pages 1-2).

Type III Secretion System (T3SS)

The T3SS injects effector proteins (including BteA) into host cells and modulates VIP/VPAC2 signaling pathways, promoting lower respiratory tract colonization and persistence (first2023bordetellaspp.utilize pages 1-2). VPAC2-deficient mice showed decreased bacterial burden, and VPAC2 antagonists decreased lung pathology in mouse models, suggesting this pathway as a potential therapeutic target (first2023bordetellaspp.utilize pages 1-2).

Immune Response and Evasion

B. pertussis initially induces IL-10 production and suppresses IFN-γ responses, creating an immunosuppressive state (chamorro2023bordetellabronchisepticaand pages 13-15). Optimal protective immunity requires coordinated Th1 (IFN-γ) and Th17 (IL-17) cellular responses (chamorro2023bordetellabronchisepticaand pages 23-25, chamorro2023bordetellabronchisepticaand pages 11-13). Tissue-resident memory (TRM) CD4+ T cells in nasal tissue expand IL-17+ responses upon secondary infection, recruiting Siglec F+ neutrophils for pathogen clearance (caulfield2023generatingenhancedmucosal pages 3-4). IgA antibodies produced during natural infection can reduce bacterial adherence to ciliated epithelium (caulfield2023generatingenhancedmucosal pages 3-4). B. pertussis-specific IgG antibodies appear 4–6 weeks post-infection when bacteria are nearly cleared (chamorro2023bordetellabronchisepticaand pages 11-13).

7. Anatomical Structures Affected

Primary organ: Respiratory system (UBERON:0001004), specifically the trachea (UBERON:0003126) and bronchi (UBERON:0002185), where B. pertussis attaches to ciliated epithelium (colak2023bordetellapertussisand pages 1-2).

Upper respiratory tract: Nasopharynx (UBERON:0001706) and nasal cavity (UBERON:0001728) are important colonization and transmission sites (chamorro2023bordetellabronchisepticaand pages 23-25).

Secondary involvement: Lungs (UBERON:0002048) in cases complicated by pneumonia; central nervous system in cases of encephalopathy.

Cell types targeted: Ciliated respiratory epithelial cells (primary colonization target), macrophages (CL:0000895; targeted by ACT and FHA), neutrophils (CL:0000775; recruitment impaired by PT), dendritic cells (CL:0000451; targeted by ACT), and CD4+ T cells (CL:0000624; critical for Th1/Th17 protective responses) (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 16-18).

8. Temporal Development

Onset

Pertussis can occur at any age but is most severe in neonates and infants under 6 months. The incubation period is 7–10 days. Onset is typically insidious, with the catarrhal stage mimicking a common cold (ifill2023lipidamodifications pages 18-25).

Progression

The disease follows a predictable three-stage course over up to 12 weeks: catarrhal (1–2 weeks) → paroxysmal (up to 8 weeks) → convalescent (average 4 weeks) (ifill2023lipidamodifications pages 18-25). The disease is self-limited but may last several months in severe cases.

Patterns

Pertussis exhibits an endemic pattern with epidemic peaks every 3–5 years (colak2023bordetellapertussisand pages 1-2). The 2023–2024 global resurgence has been particularly dramatic, with Europe experiencing an increase from 4.7 to 104.4 cases per million between 2022 and 2023 (wang2025resurgenceofpertussis pages 1-2).

9. Inheritance and Population

Epidemiology

Global burden: Approximately 24.1 million pertussis cases and 160,700 deaths occur annually worldwide in children younger than 5 years (ifill2023lipidamodifications pages 18-25, ernst2022novelstrategiesto pages 1-2). The WHO recorded 151,074 notified cases in 2018 despite 86% global vaccination coverage, making pertussis the worst-controlled childhood vaccine-preventable disease (chamorro2023bordetellabronchisepticaand pages 2-3). The global incidence rate was approximately 23.6 cases per million in 2023 (wang2025resurgenceofpertussis pages 2-4).

2023–2024 resurgence: Large-scale global outbreaks have been reported since 2023, with significant increases in the United Kingdom, France, Denmark, the United States, Australia, and multiple low- and middle-income countries including China, Afghanistan, and Indonesia (wang2025resurgenceofpertussis pages 1-2). Contributing factors include genetic mutations in B. pertussis, waning vaccine immunity, COVID-19 pandemic disruptions to vaccination programs, disease cyclicity, and improved diagnostic awareness (wang2025resurgenceofpertussis pages 1-2, wang2025resurgenceofpertussis pages 8-9).

Age distribution: The age profile has shifted from predominantly infants and young children to now including significant disease burden in adolescents and adults, with patients aged ≥14 years accounting for 67% of total incidence in some surveys (colak2023bordetellapertussisand pages 1-2). Adolescents aged 10–19 years showed the highest incidence in six European countries during the 2023–2024 resurgence (wang2025resurgenceofpertussis pages 2-4).

Inheritance: Not applicable (infectious disease, not a genetic disorder).

10. Diagnostics

Clinical Criteria

Clinical diagnosis is the starting point, based on characteristic paroxysmal cough lasting ≥2 weeks, post-tussive vomiting, and inspiratory whoop. Pertussis is commonly underdiagnosed in adults due to milder or atypical clinical presentations (chamorro2023bordetellabronchisepticaand pages 2-3, wang2025resurgenceofpertussis pages 8-9).

Laboratory Tests

PCR assays: The fastest and most sensitive method for laboratory confirmation. Various target genes are used to differentiate Bordetella species, including IS481, IS1001, hIS1001, IS1002, ptxS1, ptxA-Pr, fla, and BP3385 (chamorro2023bordetellabronchisepticaand pages 5-7).

Microbiological culture: Highly specific but lower sensitivity and time-consuming. Allows colony subtyping and antimicrobial susceptibility testing (chamorro2023bordetellabronchisepticaand pages 5-7).

Serology: Detects specific antibodies (anti-PT IgG, anti-FHA) with high sensitivity and specificity, but appears positive late in infection. Useful for retrospective diagnosis in adults (chamorro2023bordetellabronchisepticaand pages 5-7).

Laboratory Abnormalities

Marked leukocytosis (white blood cell count >20,000/µL) with lymphocyte predominance is a characteristic finding in severe infant pertussis and is directly attributable to pertussis toxin effects on leukocyte trafficking (ernst2022novelstrategiesto pages 1-2).

11. Outcome/Prognosis

Mortality

Neonates experience the most severe disease with approximately 3% mortality (ifill2023lipidamodifications pages 18-25). Globally, approximately 160,700 pertussis-related deaths occur annually in children under 5 years (ifill2023lipidamodifications pages 18-25, ernst2022novelstrategiesto pages 1-2). Mortality rates are substantially lower in adolescents and adults. In an Australian cohort, 1.6% of pertussis cases in infants under 6 months resulted in death (regan2023maternalpertussisvaccination pages 5-6).

Complications

Severe complications include pneumonia (HP:0002205), encephalopathy, seizures (HP:0001250), apnea (HP:0002105), and pulmonary hypertension, particularly in infants (ernst2022novelstrategiesto pages 1-2). Hyperleukocytosis is a prognostic marker for severe disease and poor outcomes (ernst2022novelstrategiesto pages 1-2).

Prognostic Factors

Age (younger age = worse prognosis), vaccination status, pertussis toxin levels (PT is strongly associated with severe symptoms and poor outcomes; strains lacking PT cause only mild symptoms), and degree of leukocytosis are key prognostic indicators (ernst2022novelstrategiesto pages 1-2).

12. Treatment

Pharmacotherapy

Macrolide antibiotics are the first-line treatment (MAXO:0001001): azithromycin (CHEBI:2955), clarithromycin, and erythromycin. However, antibiotics only reduce symptoms if administered within the first two weeks of infection (during the catarrhal stage), which rarely occurs due to late diagnosis. Antibiotics eliminate B. pertussis and prevent transmission but have limited therapeutic benefit after the paroxysmal stage begins (ernst2022novelstrategiesto pages 2-5, chamorro2023bordetellabronchisepticaand pages 2-3).

Macrolide resistance is an emerging concern: over 95% of prevailing B. pertussis isolates in China are macrolide-resistant, though rates remain negligible in Western countries (jiang2024theeffectof pages 8-10, chamorro2023bordetellabronchisepticaand pages 2-3). Sub-inhibitory concentrations of erythromycin may still reduce virulence of MRBp by affecting the BvgAS regulatory system, biofilm formation, and virulence factor expression (jiang2024theeffectof pages 1-5, jiang2024theeffectof pages 8-10).

Alternative agents: Trimethoprim-sulfamethoxazole (TMP-SMX) when macrolides are contraindicated.

Supportive Care

Supportive care (MAXO:0000127) includes hydration, oxygen supplementation for hypoxemia, and monitoring. Severe infant cases may require intensive care (MAXO:0000058) and mechanical ventilation (MAXO:0000014) (chamorro2023bordetellabronchisepticaand pages 2-3).

Novel Therapeutic Approaches

Pertussis toxin inhibitors: Multiple pharmacological strategies are under investigation, including chaperone inhibitors, human peptides (defensins), small molecule inhibitors, and humanized neutralizing antibodies targeting PT (ernst2022novelstrategiesto pages 2-5).

VPAC2 antagonists: Preclinical research demonstrates that VPAC2 antagonists decrease lung pathology in mouse models, targeting the VIP/VPAC2 signaling pathway exploited by Bordetella through the T3SS (first2023bordetellaspp.utilize pages 1-2).

Intravenous pertussis immune globulin: Evaluated in a Phase 3 trial (NCT00004422) for severe childhood pertussis infection.

13. Prevention

Primary Prevention – Vaccination

Vaccination (MAXO:0000474) remains the cornerstone of pertussis prevention. Two main vaccine types are in use:

Table: This table compares established and emerging pertussis vaccine platforms across composition, immune profile, durability, strengths, and limitations. It is useful for understanding why current acellular vaccines reduce severe disease yet incompletely prevent transmission, and why mucosal and live-attenuated approaches are being pursued.

Vaccination Schedule

The WHO recommends primary DTaP/DTwP vaccination starting at 6 weeks of age, with subsequent doses at 10–14 weeks and 14–18 weeks, followed by a booster dose in the second year of life. Tdap boosters are recommended for adolescents. Maternal Tdap vaccination (MAXO:0000260) during the third trimester (optimal at 28–32 weeks' gestation) is recommended by the WHO since 2015 to protect newborns through transplacental antibody transfer (wang2025resurgenceofpertussis pages 5-7).

Maternal Vaccination Effectiveness

In a population-based cohort study of 279,418 mother–infant pairs in Australia, maternal dTpa vaccination near 28 weeks' gestation provided 70.4% effectiveness (95% CI: 50.5–82.3) among infants under 2 months, declining to 43.3% (95% CI: 6.8–65.6) at 7–8 months, with protection becoming non-significant after 8 months of age (regan2023maternalpertussisvaccination pages 1-2, regan2023maternalpertussisvaccination pages 6-7).

Waning Immunity Challenge

Acellular pertussis vaccine efficacy is approximately 85% after 6 doses but decreases by approximately 11.7% annually, with protection lasting 4–12 years compared to 7–20 years for natural infection (chamorro2023bordetellabronchisepticaand pages 20-22). The COVID-19 pandemic further disrupted vaccination coverage, contributing to the 2023–2024 global resurgence (wang2025resurgenceofpertussis pages 1-2).

Next-Generation Vaccine Strategies

BPZE1 live attenuated vaccine: Attenuated by inactivating genes encoding PT, TCT, and DNT. A single nasal dose provides complete protection in mice. In humans, it induces specific IgG, IgA, and memory B cells with a Th1 phenotype. Currently in Phase 2b clinical trials (NCT05461131) using a controlled human infection model (chamorro2023bordetellabronchisepticaand pages 23-25).

OMV-based vaccines: Outer membrane vesicles carry native immunogenic structures and trigger both innate and adaptive immune responses. They show promising results in animal models with broader IgG subclass responses than acellular vaccines (colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 9-10).

Intranasal mucosal vaccines: Designed to induce local IgA, IL-17, and tissue-resident memory CD4+ T cells at the site of infection, potentially preventing both colonization and transmission (chamorro2023bordetellabronchisepticaand pages 23-25, caulfield2023generatingenhancedmucosal pages 3-4).

Post-Exposure Prophylaxis

Macrolide antibiotics (particularly azithromycin) are recommended for close contacts of confirmed cases, regardless of vaccination status.

14. Other Species / Natural Disease

Comparative Biology

B. pertussis is exclusively a human pathogen with no known natural animal reservoir (ifill2023lipidamodifications pages 18-25). However, the closely related B. bronchiseptica (NCBITaxon:518) causes respiratory infections across a wide range of mammals, including the canine infectious respiratory disease complex (CIRDC) in dogs (chamorro2023bordetellabronchisepticaand pages 2-3). B. bronchiseptica is increasingly implicated in zoonotic human infections and serves as an important comparative model for understanding Bordetella pathogenesis (chamorro2023bordetellabronchisepticaand pages 2-3).

Cross-Species Considerations

While B. pertussis infection is restricted to humans, the genus Bordetella includes species with zoonotic potential. B. bronchiseptica can be transmitted from animals to humans, particularly immunocompromised individuals (chamorro2023bordetellabronchisepticaand pages 2-3).

15. Model Organisms

Mouse Models

Mouse models (Mus musculus, NCBITaxon:10090) are widely used for pertussis research, though B. pertussis requires much higher bacterial doses to establish infection in mice compared to natural human infection, representing a major limitation (chamorro2023bordetellabronchisepticaand pages 11-13). Mouse models have been valuable for studying nasal cavity infection, catarrhal-stage upper respiratory tract dynamics, neonatal disease with PT-mediated pathology, and vaccine-induced immune responses (caulfield2023generatingenhancedmucosal pages 5-6, caulfield2023generatingenhancedmucosal pages 6-7). VPAC2-knockout mice have been used to demonstrate the role of VIP/VPAC2 signaling in Bordetella colonization (first2023bordetellaspp.utilize pages 1-2).

Baboon (Nonhuman Primate) Models

The baboon model (Papio sp.) provides superior recapitulation of human disease, exhibiting many similarities to human infection in terms of pathogenesis and immune responses (chamorro2023bordetellabronchisepticaand pages 11-13). In baboons, B. pertussis infection induces IL-17 secretion and generates long-lasting Th17 and Th1 immune responses persisting at least 24 months (chamorro2023bordetellabronchisepticaand pages 11-13). Baboon studies have been critical for demonstrating that injectable vaccines prevent disease but fail to prevent nasal colonization and transmission, whereas intranasal vaccines can prevent both (chamorro2023bordetellabronchisepticaand pages 25-27).

B. bronchiseptica as Comparative Model

B. bronchiseptica naturally colonizes multiple mammalian hosts including mice, rats, swine, and dogs, and serves as a comparative model for understanding Bordetella pathogenesis when B. pertussis host restriction limits experimentation (chamorro2023bordetellabronchisepticaand pages 11-13).

16. Active Clinical Trials

Several clinical trials are currently recruiting or active:

• NCT06827470: Establishing a Controlled Human Infection Model (CHIM) of pertactin-deficient B. pertussis at Dalhousie University, Canada (Phase 1, recruiting, n=60) (NCT06827470 chunk 2)
• NCT06803524: 10-year follow-up after single-dose acellular pertussis vaccination at Mahidol University, Thailand (Phase 4, recruiting, n=126) (NCT06803524 chunk 3)
• NCT05897879: Impact of bacterial expression and immune response in severity of pertussis at Institut Pasteur (recruiting, n=210)
• NCT07097012: Concurrent versus sequential administration of Tdap and RSV vaccines in pregnancy, Canadian Immunization Research Network (Phase 4, recruiting, n=60)
• NCT06946499: Phase II/III study of a fully liquid hexavalent DTwP-HepB-IPV-Hib vaccine by LG Chem (recruiting, n=1186)
• NCT07112144: Phase III clinical trial of a cell-free DPT combined vaccine by Changchun BCHT Biotechnology (recruiting, n=1650)

Summary

Pertussis remains one of the least controlled vaccine-preventable diseases worldwide despite decades of immunization efforts (chamorro2023bordetellabronchisepticaand pages 2-3). The 2023–2024 global resurgence, driven by waning acellular vaccine immunity, pathogen evolution (ptxP3 allele expansion, pertactin-deficient strains), COVID-19-related vaccination disruptions, and natural disease cyclicity, underscores the urgent need for improved vaccination strategies (wang2025resurgenceofpertussis pages 2-4, wang2025resurgenceofpertussis pages 1-2). Current research priorities include development of mucosal vaccines that can prevent both disease and transmission, controlled human infection models to define correlates of protection, and novel therapeutics targeting pertussis toxin and host-pathogen signaling pathways (chamorro2023bordetellabronchisepticaand pages 23-25, ernst2022novelstrategiesto pages 2-5, first2023bordetellaspp.utilize pages 1-2, NCT06827470 chunk 2).

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8. (ernst2022novelstrategiesto pages 12-13): Katharina Ernst. Novel strategies to inhibit pertussis toxin. Toxins, 14:187, Mar 2022. URL: https://doi.org/10.3390/toxins14030187, doi:10.3390/toxins14030187. This article has 29 citations.

9. (chamorro2023bordetellabronchisepticaand pages 13-15): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

10. (chamorro2023bordetellabronchisepticaand pages 18-20): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

11. (chamorro2023bordetellabronchisepticaand pages 23-25): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

12. (chamorro2023bordetellabronchisepticaand pages 11-13): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

13. (caulfield2023generatingenhancedmucosal pages 3-4): Amanda D. Caulfield, Maiya Callender, and Eric T. Harvill. Generating enhanced mucosal immunity against bordetella pertussis: current challenges and new directions. Frontiers in Immunology, Feb 2023. URL: https://doi.org/10.3389/fimmu.2023.1126107, doi:10.3389/fimmu.2023.1126107. This article has 13 citations and is from a peer-reviewed journal.

14. (church2025nasalimmunizationwith pages 14-15): Alison Hofmann Church, Soman N. Abraham, Herman F. Staats, and Brandi T. Johnson-Weaver. Nasal immunization with compound 48/80-adjuvanted acellular pertussis vaccines is an effective strategy to induce pertussis-specific systemic and mucosal immunity. Clinical and Experimental Vaccine Research, 14:246-260, Apr 2025. URL: https://doi.org/10.7774/cevr.2025.14.e23, doi:10.7774/cevr.2025.14.e23. This article has 1 citations.

15. (rudi2024useofmucosally pages 10-13): E. Rudi, E. Gaillard, D. Bottero, and D. Hozbor. Use of mucosally administered outer membrane vesicles derived from bordetella pertussis to diminish nasal bacterial colonization. bioRxiv, Mar 2024. URL: https://doi.org/10.1101/2024.03.11.584448, doi:10.1101/2024.03.11.584448. This article has 0 citations.

16. (regan2023maternalpertussisvaccination pages 1-2): Annette K. Regan, Hannah C. Moore, Michael J. Binks, Lisa McHugh, Christopher C. Blyth, Gavin Pereira, Karin Lust, Mohinder Sarna, Ross Andrews, Damien Foo, Paul V. Effler, Stephen Lambert, and Paul Van Buynder. Maternal pertussis vaccination, infant immunization, and risk of pertussis. Pediatrics, Oct 2023. URL: https://doi.org/10.1542/peds.2023-062664, doi:10.1542/peds.2023-062664. This article has 56 citations and is from a highest quality peer-reviewed journal.

17. (regan2023maternalpertussisvaccination pages 7-8): Annette K. Regan, Hannah C. Moore, Michael J. Binks, Lisa McHugh, Christopher C. Blyth, Gavin Pereira, Karin Lust, Mohinder Sarna, Ross Andrews, Damien Foo, Paul V. Effler, Stephen Lambert, and Paul Van Buynder. Maternal pertussis vaccination, infant immunization, and risk of pertussis. Pediatrics, Oct 2023. URL: https://doi.org/10.1542/peds.2023-062664, doi:10.1542/peds.2023-062664. This article has 56 citations and is from a highest quality peer-reviewed journal.

18. (ernst2022novelstrategiesto pages 2-5): Katharina Ernst. Novel strategies to inhibit pertussis toxin. Toxins, 14:187, Mar 2022. URL: https://doi.org/10.3390/toxins14030187, doi:10.3390/toxins14030187. This article has 29 citations.

19. (jiang2024theeffectof pages 1-5): Kaichong Jiang, Yang Luan, Wei Wang, Da Xue, Shuyue Tang, Xiaokang Peng, Xiaoguai Liu, and Zengguo Wang. The effect of erythromycin in macrolide-resistant bordetella pertussis: inhibitory on growth, toxin expression, and virulence. Unknown journal, Feb 2024. URL: https://doi.org/10.21203/rs.3.rs-3933379/v1, doi:10.21203/rs.3.rs-3933379/v1.

20. (jiang2024theeffectof pages 8-10): Kaichong Jiang, Yang Luan, Wei Wang, Da Xue, Shuyue Tang, Xiaokang Peng, Xiaoguai Liu, and Zengguo Wang. The effect of erythromycin in macrolide-resistant bordetella pertussis: inhibitory on growth, toxin expression, and virulence. Unknown journal, Feb 2024. URL: https://doi.org/10.21203/rs.3.rs-3933379/v1, doi:10.21203/rs.3.rs-3933379/v1.

21. (wang2025resurgenceofpertussis pages 5-7): Sijia Wang, Shimo Zhang, and Jue Liu. Resurgence of pertussis: epidemiological trends, contributing factors, challenges, and recommendations for vaccination and surveillance. Human Vaccines & Immunotherapeutics, Jun 2025. URL: https://doi.org/10.1080/21645515.2025.2513729, doi:10.1080/21645515.2025.2513729. This article has 56 citations and is from a peer-reviewed journal.

22. (wang2025resurgenceofpertussis pages 2-4): Sijia Wang, Shimo Zhang, and Jue Liu. Resurgence of pertussis: epidemiological trends, contributing factors, challenges, and recommendations for vaccination and surveillance. Human Vaccines & Immunotherapeutics, Jun 2025. URL: https://doi.org/10.1080/21645515.2025.2513729, doi:10.1080/21645515.2025.2513729. This article has 56 citations and is from a peer-reviewed journal.

23. (caulfield2023generatingenhancedmucosal pages 4-5): Amanda D. Caulfield, Maiya Callender, and Eric T. Harvill. Generating enhanced mucosal immunity against bordetella pertussis: current challenges and new directions. Frontiers in Immunology, Feb 2023. URL: https://doi.org/10.3389/fimmu.2023.1126107, doi:10.3389/fimmu.2023.1126107. This article has 13 citations and is from a peer-reviewed journal.

24. (wang2025resurgenceofpertussis pages 4-5): Sijia Wang, Shimo Zhang, and Jue Liu. Resurgence of pertussis: epidemiological trends, contributing factors, challenges, and recommendations for vaccination and surveillance. Human Vaccines & Immunotherapeutics, Jun 2025. URL: https://doi.org/10.1080/21645515.2025.2513729, doi:10.1080/21645515.2025.2513729. This article has 56 citations and is from a peer-reviewed journal.

25. (chamorro2023bordetellabronchisepticaand pages 33-33): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

26. (colak2023bordetellapertussisand pages 2-3): Çiğdem Yılmaz Çolak and Burcu Emine Tefon Öztürk. Bordetella pertussis and outer membrane vesicles. Pathogens and Global Health, 117:342-355, Sep 2023. URL: https://doi.org/10.1080/20477724.2022.2117937, doi:10.1080/20477724.2022.2117937. This article has 13 citations and is from a peer-reviewed journal.

27. (chamorro2023bordetellabronchisepticaand pages 15-16): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

28. (chamorro2023bordetellabronchisepticaand pages 20-22): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

29. (colak2023bordetellapertussisand pages 3-5): Çiğdem Yılmaz Çolak and Burcu Emine Tefon Öztürk. Bordetella pertussis and outer membrane vesicles. Pathogens and Global Health, 117:342-355, Sep 2023. URL: https://doi.org/10.1080/20477724.2022.2117937, doi:10.1080/20477724.2022.2117937. This article has 13 citations and is from a peer-reviewed journal.

30. (wang2025resurgenceofpertussis pages 10-11): Sijia Wang, Shimo Zhang, and Jue Liu. Resurgence of pertussis: epidemiological trends, contributing factors, challenges, and recommendations for vaccination and surveillance. Human Vaccines & Immunotherapeutics, Jun 2025. URL: https://doi.org/10.1080/21645515.2025.2513729, doi:10.1080/21645515.2025.2513729. This article has 56 citations and is from a peer-reviewed journal.

31. (ifill2023lipidamodifications pages 225-228): Gyles Anderson Ifill. Lipid a modifications in bordetella pertussis : regulation and function of the lgm locus. Text, Jan 2023. URL: https://doi.org/10.14288/1.0406206, doi:10.14288/1.0406206. This article has 0 citations and is from a peer-reviewed journal.

32. (colak2023bordetellapertussisand pages 9-10): Çiğdem Yılmaz Çolak and Burcu Emine Tefon Öztürk. Bordetella pertussis and outer membrane vesicles. Pathogens and Global Health, 117:342-355, Sep 2023. URL: https://doi.org/10.1080/20477724.2022.2117937, doi:10.1080/20477724.2022.2117937. This article has 13 citations and is from a peer-reviewed journal.

33. (first2023bordetellaspp.utilize pages 1-2): Nicholas J. First, Jose Pedreira-Lopez, Manuel R. F. San-Silvestre, Katelyn M. Parrish, Xiao-Hong Lu, and Monica C. Gestal. Bordetella spp. utilize the type 3 secretion system to manipulate the vip/vpac2 signaling and promote colonization and persistence of the three classical bordetella in the lower respiratory tract. Frontiers in Cellular and Infection Microbiology, Mar 2023. URL: https://doi.org/10.3389/fcimb.2023.1111502, doi:10.3389/fcimb.2023.1111502. This article has 9 citations.

34. (wang2025resurgenceofpertussis pages 1-2): Sijia Wang, Shimo Zhang, and Jue Liu. Resurgence of pertussis: epidemiological trends, contributing factors, challenges, and recommendations for vaccination and surveillance. Human Vaccines & Immunotherapeutics, Jun 2025. URL: https://doi.org/10.1080/21645515.2025.2513729, doi:10.1080/21645515.2025.2513729. This article has 56 citations and is from a peer-reviewed journal.

35. (wang2025resurgenceofpertussis pages 8-9): Sijia Wang, Shimo Zhang, and Jue Liu. Resurgence of pertussis: epidemiological trends, contributing factors, challenges, and recommendations for vaccination and surveillance. Human Vaccines & Immunotherapeutics, Jun 2025. URL: https://doi.org/10.1080/21645515.2025.2513729, doi:10.1080/21645515.2025.2513729. This article has 56 citations and is from a peer-reviewed journal.

36. (chamorro2023bordetellabronchisepticaand pages 5-7): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

37. (regan2023maternalpertussisvaccination pages 6-7): Annette K. Regan, Hannah C. Moore, Michael J. Binks, Lisa McHugh, Christopher C. Blyth, Gavin Pereira, Karin Lust, Mohinder Sarna, Ross Andrews, Damien Foo, Paul V. Effler, Stephen Lambert, and Paul Van Buynder. Maternal pertussis vaccination, infant immunization, and risk of pertussis. Pediatrics, Oct 2023. URL: https://doi.org/10.1542/peds.2023-062664, doi:10.1542/peds.2023-062664. This article has 56 citations and is from a highest quality peer-reviewed journal.

38. (colak2023bordetellapertussisand pages 11-12): Çiğdem Yılmaz Çolak and Burcu Emine Tefon Öztürk. Bordetella pertussis and outer membrane vesicles. Pathogens and Global Health, 117:342-355, Sep 2023. URL: https://doi.org/10.1080/20477724.2022.2117937, doi:10.1080/20477724.2022.2117937. This article has 13 citations and is from a peer-reviewed journal.

39. (chamorro2023bordetellabronchisepticaand pages 25-27): Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Stéphanie Longet, Egbert Mundt, and Stéphane Paul. Bordetella bronchiseptica and bordetella pertussis: similarities and differences in infection, immuno-modulation, and vaccine considerations. Clinical Microbiology Reviews, Sep 2023. URL: https://doi.org/10.1128/cmr.00164-22, doi:10.1128/cmr.00164-22. This article has 72 citations and is from a highest quality peer-reviewed journal.

40. (caulfield2023generatingenhancedmucosal pages 5-6): Amanda D. Caulfield, Maiya Callender, and Eric T. Harvill. Generating enhanced mucosal immunity against bordetella pertussis: current challenges and new directions. Frontiers in Immunology, Feb 2023. URL: https://doi.org/10.3389/fimmu.2023.1126107, doi:10.3389/fimmu.2023.1126107. This article has 13 citations and is from a peer-reviewed journal.

41. (caulfield2023generatingenhancedmucosal pages 6-7): Amanda D. Caulfield, Maiya Callender, and Eric T. Harvill. Generating enhanced mucosal immunity against bordetella pertussis: current challenges and new directions. Frontiers in Immunology, Feb 2023. URL: https://doi.org/10.3389/fimmu.2023.1126107, doi:10.3389/fimmu.2023.1126107. This article has 13 citations and is from a peer-reviewed journal.

42. (NCT06827470 chunk 2): Establishing a Controlled Human Infection Model of Pertactin-deficient Bordetella Pertussis. Dalhousie University. 2025. ClinicalTrials.gov Identifier: NCT06827470

43. (NCT06803524 chunk 3): Punnee Pitisuttithum. 10-year Follow-up After a Single Dose Acellular Pertussis Vaccination. Mahidol University. 2025. ClinicalTrials.gov Identifier: NCT06803524

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