Pertussis

Infectious Disease MONDO:0005077 Pathograph 9 Show in embeddings browser Bacterial Respiratory Infection

Pertussis (whooping cough) is an acute, highly contagious respiratory infection caused by the bacterium Bordetella pertussis. After colonizing the ciliated respiratory epithelium, the organism elaborates virulence factors — chiefly pertussis toxin (an AB5 exotoxin that ADP-ribosylates the inhibitory G protein Gαi, driving unrestrained cAMP accumulation) acting in concert with adenylate cyclase toxin — that subvert host defenses and produce the characteristic paroxysmal coughing illness with inspiratory whoop and post-tussive emesis. Disease is most severe in unvaccinated young infants, who may develop apnea, cyanosis, and marked leukocytosis. It is vaccine-preventable (DTaP/Tdap), and macrolides are the conventional antibiotic, though macrolide resistance is emerging in some regions.

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7
Pathophys.
7
Phenotypes
9
Pathograph
4
Medical Actions
4
Datasets
2
Trials
1
Deep Research
⚙

Pathophysiology

7
Bordetella pertussis Respiratory Colonization
Bordetella pertussis colonizes the ciliated epithelium of the respiratory tract and, through its virulence factors, subverts host immune defenses to establish infection. This colonization is the proximal event from which both toxin-mediated disease and the antibiotic-target biology follow.
ciliated airway epithelial cell CL:0000064 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves ciliated airway epithelial cell, annotated with ciliated cell (CL:0000064). CL:0000064 is a cell type from the Cell Ontology.
adhesion of symbiont to host GO:0044406 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves adhesion of symbiont to host (GO:0044406). GO:0044406 is a biological process from the Gene Ontology.
Downstream
Pertussis Toxin-Mediated Disruption of Host Gi Signaling The colonizing organism elaborates pertussis toxin, which disrupts host cell signaling.
Adenylate Cyclase Toxin-Mediated Phagocyte Subversion The organism secretes adenylate cyclase toxin, which subverts phagocytic innate-immune cells to permit persistence.
Type III Secretion System-Mediated Immune Evasion The organism deploys a type III secretion system that manipulates host VIP/VPAC2 signaling to promote lower-respiratory colonization.
Bacterial Ribosomal Translation (Macrolide Target) The organism's ribosome is the target of macrolide antibiotic therapy.
Show evidence (3 references)
PMID:41893571 SUPPORT Other
"PTx works in concert with the bacterium's adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection."
Establishes that B. pertussis virulence factors subvert immune defenses to establish respiratory infection. Evidence source is OTHER as this is a review article.
PMID:24608338 SUPPORT Other
"produce many virulence factors that contribute to pathogenesis, including toxins, adhesion factors, iron-acquisition systems and surface structures."
Canonical pathogenesis review establishing that B. pertussis deploys a battery of adhesion factors and toxins (FHA, pertactin, fimbriae, pertussis and adenylate cyclase toxins, tracheal cytotoxin) during colonization. Evidence source is OTHER as this is a review article.
DOI:10.3389/fimmu.2023.1126107 SUPPORT Other
"appears to reduce adherence of Bp to ciliated epithelium in vitro"
Documents that B. pertussis (Bp) adheres to the ciliated respiratory epithelium (here in the context of anti-pertussis IgA reducing that adherence). Evidence source is OTHER as this is a review article.
Pertussis Toxin-Mediated Disruption of Host Gi Signaling
Pertussis toxin, an AB5-type exotoxin, uses its enzymatic A subunit to ADP-ribosylate the alpha-subunit of inhibitory G proteins (Gαi), preventing receptor-induced inhibition of adenylyl cyclase and causing unrestrained cAMP accumulation in host cells — a canonical mechanism underlying many pertussis disease manifestations.
response to toxic substance GO:0009636 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves response to toxic substance (GO:0009636). GO:0009636 is a biological process from the Gene Ontology.
Downstream
Paroxysmal Coughing Illness Toxin-mediated disruption of host signaling produces the characteristic paroxysmal coughing illness.
Show evidence (2 references)
PMID:41893571 SUPPORT Other
"Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling."
Identifies pertussis toxin as the major AB5 exotoxin virulence factor that disrupts host signaling. Evidence source is OTHER as this is a review article.
PMID:41893571 SUPPORT Other
"Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gαi), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells"
Details the molecular mechanism — ADP-ribosylation of Gαi causing unrestrained cAMP accumulation. Evidence source is OTHER as this is a review article.
Adenylate Cyclase Toxin-Mediated Phagocyte Subversion
Adenylate cyclase toxin (ACT/CyaA), a second major B. pertussis toxin, targets CD11b-bearing professional phagocytes (macrophages, neutrophils, dendritic cells), forming cation-selective pores and elevating intracellular cAMP to impair phagocytosis, dendritic-cell maturation, and cytokine secretion. This disarms innate immunity and, together with pertussis toxin, allows the organism to persist on the airway epithelium.
macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology. neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology. dendritic cell CL:0000451 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves dendritic cell (CL:0000451). CL:0000451 is a cell type from the Cell Ontology.
response to toxic substance GO:0009636 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves response to toxic substance (GO:0009636). GO:0009636 is a biological process from the Gene Ontology.
Show evidence (1 reference)
DOI:10.3389/fimmu.2023.1126107 SUPPORT Other
"Adenylate cyclase toxin targets Cd11b-positive professional phagocytes, including dendritic cells, macrophages, and neutrophils by forming cation-selective pores to permeabilize the cell membrane"
Details the adenylate cyclase toxin mechanism of phagocyte subversion. Evidence source is OTHER as this is a review article.
Type III Secretion System-Mediated Immune Evasion
B. pertussis (and the classical Bordetella) use a type III secretion system (T3SS) to manipulate host vasoactive intestinal peptide (VIP)/VPAC2 signaling, promoting colonization and persistence in the lower respiratory tract. In mouse models, VPAC2-deficient hosts show reduced bacterial burden and VPAC2 antagonists reduce lung pathology, identifying this axis as a candidate host-directed therapeutic target.
response to host immune response GO:0052572 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves response to host immune response (GO:0052572). GO:0052572 is a biological process from the Gene Ontology.
Show evidence (2 references)
DOI:10.3389/fcimb.2023.1111502 SUPPORT Model Organism
"the ability of Bordetella spp. to manipulate VIP/VPAC signaling pathway appears to be mediated by the type 3 secretion system (T3SS)"
Mouse-model study attributing host VIP/VPAC2 manipulation to the Bordetella T3SS. Evidence source is MODEL_ORGANISM as the mechanism was defined in mouse infection models.
DOI:10.3389/fcimb.2023.1111502 SUPPORT Model Organism
"treatment with VPAC2 antagonists decrease lung pathology, suggesting its potential use to prevent lung damage and dysfunction caused by infection."
Supports the VIP/VPAC2 axis as a host-directed therapeutic target, with VPAC2 antagonists reducing lung pathology in mice. Evidence source is MODEL_ORGANISM.
Paroxysmal Coughing Illness
The clinical syndrome of pertussis is a paroxysmal coughing illness, classically with an inspiratory whoop and post-tussive emesis. In young infants it may manifest as cyanosis or facial flushing during coughing fits and apnea, and is associated with marked leukocytosis.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
respiratory system UBERON:0001004 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in respiratory system (UBERON:0001004). UBERON:0001004 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"presented with paroxysmal coughing"
Clinical cohort documenting paroxysmal coughing as the predominant presentation of pertussis. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
Bacterial Ribosomal Translation (Macrolide Target)
B. pertussis depends on its bacterial ribosome for protein synthesis. Macrolides (e.g., azithromycin), the conventional antibiotics for pertussis, bind the 50S ribosomal subunit and block bacterial protein synthesis — the molecular target underlying antibiotic therapy (which reduces transmissibility more than it alters the toxin-driven cough once established).
translation GO:0006412 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves translation (GO:0006412). GO:0006412 is a biological process from the Gene Ontology.
Downstream
Emerging Macrolide Resistance Macrolide resistance in B. pertussis erodes the efficacy of ribosome-targeting therapy.
Show evidence (1 reference)
PMID:24336183 SUPPORT Other
"The ribosome is one of the main antibiotic targets in the bacterial cell."
Establishes the bacterial ribosome as the target of macrolides and other protein-synthesis inhibitors, the step this node represents. Evidence source is OTHER as this is a review article.
Emerging Macrolide Resistance
Macrolide-resistant B. pertussis is an emerging concern in some regions, which can render azithromycin ineffective and shift treatment toward alternatives such as trimethoprim-sulfamethoxazole.
response to antibiotic GO:0046677 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves response to antibiotic (GO:0046677). GO:0046677 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT In Vitro
"high-level resistance to azithromycin but sensitivity to trimethoprim-sulfamethoxazole, levofloxacin, doxycycline"
In vitro drug-susceptibility testing of B. pertussis isolates showing high-level azithromycin resistance with retained sensitivity to alternatives. Evidence source is IN_VITRO as this is an in vitro susceptibility assay of isolates (in this cohort all 25 isolates were azithromycin-resistant, grounding the "in some regions" caveat).
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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Pertussis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

7
Blood 1
Leukocytosis Increased total leukocyte count HP:0001974 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Leukocytosis, annotated with Increased total leukocyte count (HP:0001974). HP:0001974 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:41963827 SUPPORT Human Clinical
"elevated white blood cell count"
Elevated white blood cell count was an independent risk factor for severe pertussis. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
DOI:10.3390/toxins14030187 SUPPORT Other
"Especially in newborns and infants, pertussis symptoms, such as leukocytosis, can become life-threatening."
Establishes leukocytosis as a hallmark, potentially life-threatening feature of severe infant pertussis. Evidence source is OTHER as this is a review article.
Digestive 1
Post-tussive Vomiting HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Post-tussive vomiting, annotated with Vomiting (HP:0002013). HP:0002013 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"post-tussive emesis"
Post-tussive emesis was documented in the clinical cohort. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
Immune 1
Pertussis Pneumonia HP:0002090 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pneumonia (HP:0002090). HP:0002090 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"pneumonia was confirmed in 84 (66.66%) cases"
Two-thirds of hospitalized pertussis cases had radiographically confirmed pneumonia. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
Integument 1
Cyanosis HP:0000961 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cyanosis (HP:0000961). HP:0000961 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"manifested cyanosis or facial flushing during coughing"
Over half of hospitalized cases manifested cyanosis or facial flushing during coughing. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"28 (22.22%) had fever"
Fever was present in about a fifth of hospitalized pertussis cases, consistent with its variable, often low-grade presence. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
Respiratory 1
Apnea HP:0002104 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Apnea (HP:0002104). HP:0002104 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"had apnea"
Apnea was documented among hospitalized pertussis cases. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
Other 1
Whooping Cough HP:0031247 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Whooping cough (HP:0031247). HP:0031247 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"presented with paroxysmal coughing"
Most hospitalized cases presented with paroxysmal coughing. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
💊

Medical Actions

4
Azithromycin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: azithromycin CHEBI:2955 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses azithromycin (CHEBI:2955). CHEBI:2955 is a therapeutic agent from Chemical Entities of Biological Interest.
Macrolide antibiotic that binds the 50S bacterial ribosome and inhibits protein synthesis; the conventional antibiotic for pertussis, primarily reducing transmissibility. Emerging macrolide-resistant B. pertussis in some regions can necessitate alternatives such as trimethoprim-sulfamethoxazole.
Mechanism Target:
INHIBITS Bacterial Ribosomal Translation (Macrolide Target) — Azithromycin binds the 50S ribosome and arrests B. pertussis protein synthesis, clearing carriage and reducing transmission.
Show evidence (1 reference)
DOI:10.3390/toxins14030187 SUPPORT Other
"antibiotics only reduce symptoms if administered in early stages, which rarely occurs due to a late diagnosis."
Explains that macrolide antibiotics reduce symptoms only if given early (catarrhal stage); once the paroxysmal cough is established the benefit is largely limited to reducing transmission. Evidence source is OTHER as this is a review article.
Pertussis Toxin Inhibitors (investigational)
Action: pharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Investigational host-directed and toxin-neutralizing strategies aimed at pertussis toxin — chaperone inhibitors, human peptides, small-molecule inhibitors, and humanized neutralizing antibodies — intended to address the toxin-driven symptoms (e.g., leukocytosis) for which no causative treatment currently exists.
Mechanism Target:
INHIBITS Pertussis Toxin-Mediated Disruption of Host Gi Signaling — These agents inhibit or neutralize pertussis toxin, the AB5 exotoxin that ADP-ribosylates Gαi.
Show evidence (1 reference)
DOI:10.3390/toxins14030187 SUPPORT Other
"chaperone inhibitors, human peptides, small molecule inhibitors, and humanized antibodies are discussed as novel strategies to inhibit PT."
Review enumerating the novel pharmacological strategies under development to inhibit pertussis toxin. Evidence source is OTHER as this is a review of investigational strategies.
Maternal Tdap Vaccination
Action: maternal pertussis vaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is maternal pertussis vaccination, annotated with Vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. Ontology label: Vaccination NCIT:C15346
Maternal acellular pertussis (Tdap/dTpa) vaccination during pregnancy (near the third trimester) protects young infants through transplacental transfer of pertussis-specific antibodies, bridging the vulnerable window before the infant primary series takes effect.
Show evidence (1 reference)
DOI:10.1542/peds.2023-062664 SUPPORT Human Clinical
"was associated with lower risk of infection among infants through 8 months of age."
Population-based cohort of 279,418 mother-infant pairs showing maternal pertussis vaccination near 28 weeks' gestation lowered infant infection risk through 8 months of age. Evidence source is HUMAN_CLINICAL as this is a population-based cohort study.
Pertussis Vaccination
Action: vaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. Ontology label: Vaccination NCIT:C15346
Acellular pertussis vaccination (DTaP in infants/children, Tdap boosters including maternal immunization) is the key strategy for preventing severe pertussis, particularly in young infants.
Show evidence (1 reference)
PMID:41963827 SUPPORT Human Clinical
"timely completion of the primary pertussis vaccination series in infants remains a key strategy for preventing severe pertussis"
The cohort concludes that timely primary pertussis vaccination is key to preventing severe disease. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
📊

Prevalence

1
Worldwide
Annual Incidence Common
A comprehensive review estimated ~16 million pertussis cases and 195,000 deaths globally in 2008, with sizeable outbreaks reported repeatedly since, and a shifting age profile in which older children and adolescents transmit to younger siblings. B. pertussis remains a leading cause of vaccine-preventable respiratory disease and is currently increasing worldwide (2023-2024 resurgence).
Show evidence (2 references)
PMID:27029594 SUPPORT Other
"in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally."
Comprehensive review quantifying the global pertussis burden. Evidence source is OTHER as this is a review aggregating surveillance data.
DOI:10.1128/cmr.00164-22 SUPPORT Other
"These infections are restricted to humans and currently increasing worldwide."
Establishes that human pertussis is currently increasing worldwide, supporting the resurgence context. Evidence source is OTHER as this is a review article.
📊

Related Datasets

4
Mucosal inflammation and pre-existing antibodies define protection and disease outcomes in human Bordetella pertussis challenge geo:GSE310241
Whooping cough, caused by Bordetella pertussis (BP), persists despite widespread vaccination with acellular pertussis (aP) vaccines, which protect against disease but provide incomplete and short-lived immunity against infection and transmission. To define correlates of protection and mechanisms underlying symptom development, we characterized systemic and mucosal immune responses in a North American BP-controlled human infection model (CHIM). Healthy adults, primed in infancy with either whole-cell or aP vaccines, were intranasally challenged with escalating BP doses and classified as symptomatic, asymptomatic, or non-infected.
human BULK RNA SEQ n=414
PMID:42465938
Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Pertussis Toxin as well as Staphylococcal superantigen induce glycolysis as the major energy source during CD4+ T cell activation in a human tonsil organoid model geo:GSE308373
Bystander activation represents an innate-like mechanism by which T cells, particularly effector and memory subsets, can become activated in the absence of cognate antigen recognition. Using human tonsil organoid cultures as a physiologically relevant model, we investigated bystander activation of CD4+ memory T cells in situ in comparison to superantigen stimulation. Tonsillar T cells were stimulated with pertussis toxin – a component of the childhood pertussis vaccine – in comparison to TSST-1 as the staphylococcal superantigen and assessed for activation status, cytokine expression, RNA expression, and metabolic reprogramming.
human BULK RNA SEQ n=20
Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
A dual role for PGLYRP1 in host defense and immune regulation during B. pertussis infection geo:GSE324217
Bordetella pertussis, the etiologic agent of whooping cough, remains a serious public health concern despite widespread vaccination. Improved therapeutics and vaccines are urgently needed to treat and prevent pertussis disease. Host recognition of bacterial peptidoglycan (PGN), including B. pertussis extracellular PGN fragment tracheal cytotoxin (TCT), shapes the immune response to infection. Peptidoglycan recognition proteins (PGLYRPs) are a conserved family of innate immune molecules which bind bacterial PGN. While they function as immune signaling receptors in arthropods, PGLYRPs in mammals have thus far been primarily recognized for their bactericidal activity.
mouse BULK RNA SEQ n=6
PMID:41040336
Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Differential Proteomic Analysis of Bordetella pertussis OMV massive:MSV000081702
Differential proteomic analysis of outer membrane vesicles from Bordetella pertussis (two strains: Bvg+ and Bvg-)
Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Pertussis"). Retrieved 2026-08-02.
🔬

Clinical Trials

2
NCT05461131 PHASE_II UNKNOWN
Phase 2b, placebo-controlled, randomized study of the BPZE1 live-attenuated intranasal pertussis vaccine in healthy adults, assessing protection against colonization following challenge with virulent wild-type B. pertussis.
Show evidence (1 reference)
clinicaltrials:NCT05461131 SUPPORT Human Clinical
"This is a randomised, double-blinded, placebo-controlled trial of BPZE1 that includes virulent B. pertussis challenge followed by a safety follow-up."
ClinicalTrials.gov documents the BPZE1 intranasal live-attenuated vaccine controlled human infection trial, a next-generation mucosal vaccine strategy.
NCT06827470 PHASE_I UNKNOWN
Phase 1/2 dose-escalation trial establishing a pertactin (PRN)-deficient B. pertussis controlled human infection model (CHIM) representing currently circulating isolates, to define correlates of protection.
Show evidence (1 reference)
clinicaltrials:NCT06827470 SUPPORT Human Clinical
"The overall goal of this study is to establish a PRN-deficient pertussis Controlled Human Infection Model (CHIM) that represents currently circulating isolates, in the context of a North American exposure (vaccination and infection) pedigree."
ClinicalTrials.gov documents a controlled human infection model using a pertactin-deficient strain reflecting vaccine-driven pathogen evolution.
{ }

Source YAML

click to show 
name: Pertussis
creation_date: "2026-06-28T00:00:00Z"
description: >
  Pertussis (whooping cough) is an acute, highly contagious respiratory infection
  caused by the bacterium Bordetella pertussis. After colonizing the ciliated
  respiratory epithelium, the organism elaborates virulence factors — chiefly
  pertussis toxin (an AB5 exotoxin that ADP-ribosylates the inhibitory G protein
  Gαi, driving unrestrained cAMP accumulation) acting in concert with adenylate
  cyclase toxin — that subvert host defenses and produce the characteristic
  paroxysmal coughing illness with inspiratory whoop and post-tussive emesis.
  Disease is most severe in unvaccinated young infants, who may develop apnea,
  cyanosis, and marked leukocytosis. It is vaccine-preventable (DTaP/Tdap), and
  macrolides are the conventional antibiotic, though macrolide resistance is
  emerging in some regions.
category: Infectious Disease
parents:
- Bacterial Respiratory Infection
synonyms:
- Whooping cough
- Bordetella pertussis infection
disease_term:
  preferred_term: pertussis
  term:
    id: MONDO:0005077
    label: pertussis
pathophysiology:
- name: Bordetella pertussis Respiratory Colonization
  role: trigger
  description: >
    Bordetella pertussis colonizes the ciliated epithelium of the respiratory
    tract and, through its virulence factors, subverts host immune defenses to
    establish infection. This colonization is the proximal event from which both
    toxin-mediated disease and the antibiotic-target biology follow.
  cell_types:
  - preferred_term: ciliated airway epithelial cell
    term:
      id: CL:0000064
      label: ciliated cell
  biological_processes:
  - preferred_term: adhesion of symbiont to host
    term:
      id: GO:0044406
      label: adhesion of symbiont to host
  evidence:
  - reference: PMID:41893571
    reference_title: "Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      PTx works in concert with the bacterium's adenylate cyclase toxin (ACT) to
      subvert immune defenses and establish infection.
    explanation: >-
      Establishes that B. pertussis virulence factors subvert immune defenses to
      establish respiratory infection. Evidence source is OTHER as this is a review
      article.
  - reference: PMID:24608338
    reference_title: "Bordetella pertussis pathogenesis: current and future challenges."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      produce many virulence factors that contribute to pathogenesis, including
      toxins, adhesion factors, iron-acquisition systems and surface structures.
    explanation: >-
      Canonical pathogenesis review establishing that B. pertussis deploys a battery
      of adhesion factors and toxins (FHA, pertactin, fimbriae, pertussis and
      adenylate cyclase toxins, tracheal cytotoxin) during colonization. Evidence
      source is OTHER as this is a review article.
  - reference: DOI:10.3389/fimmu.2023.1126107
    reference_title: "Generating enhanced mucosal immunity against Bordetella pertussis: current challenges and new directions"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      appears to reduce adherence of Bp to ciliated epithelium in vitro
    explanation: >-
      Documents that B. pertussis (Bp) adheres to the ciliated respiratory
      epithelium (here in the context of anti-pertussis IgA reducing that
      adherence). Evidence source is OTHER as this is a review article.
  downstream:
  - target: Pertussis Toxin-Mediated Disruption of Host Gi Signaling
    description: >-
      The colonizing organism elaborates pertussis toxin, which disrupts host cell
      signaling.
  - target: Adenylate Cyclase Toxin-Mediated Phagocyte Subversion
    description: >-
      The organism secretes adenylate cyclase toxin, which subverts phagocytic
      innate-immune cells to permit persistence.
  - target: Type III Secretion System-Mediated Immune Evasion
    description: >-
      The organism deploys a type III secretion system that manipulates host
      VIP/VPAC2 signaling to promote lower-respiratory colonization.
  - target: Bacterial Ribosomal Translation (Macrolide Target)
    description: >-
      The organism's ribosome is the target of macrolide antibiotic therapy.

- name: Pertussis Toxin-Mediated Disruption of Host Gi Signaling
  role: effector
  description: >
    Pertussis toxin, an AB5-type exotoxin, uses its enzymatic A subunit to
    ADP-ribosylate the alpha-subunit of inhibitory G proteins (Gαi), preventing
    receptor-induced inhibition of adenylyl cyclase and causing unrestrained cAMP
    accumulation in host cells — a canonical mechanism underlying many pertussis
    disease manifestations.
  biological_processes:
  - preferred_term: response to toxic substance
    term:
      id: GO:0009636
      label: response to toxic substance
  evidence:
  - reference: PMID:41893571
    reference_title: "Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis
      and an AB5-type exotoxin that disrupts host signaling.
    explanation: >-
      Identifies pertussis toxin as the major AB5 exotoxin virulence factor that
      disrupts host signaling. Evidence source is OTHER as this is a review article.
  - reference: PMID:41893571
    reference_title: "Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G
      proteins (Gαi), preventing them from mediating receptor-induced inhibition of
      adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host
      cells
    explanation: >-
      Details the molecular mechanism — ADP-ribosylation of Gαi causing
      unrestrained cAMP accumulation. Evidence source is OTHER as this is a review
      article.
  downstream:
  - target: Paroxysmal Coughing Illness
    description: >-
      Toxin-mediated disruption of host signaling produces the characteristic
      paroxysmal coughing illness.

- name: Adenylate Cyclase Toxin-Mediated Phagocyte Subversion
  role: effector
  description: >
    Adenylate cyclase toxin (ACT/CyaA), a second major B. pertussis toxin, targets
    CD11b-bearing professional phagocytes (macrophages, neutrophils, dendritic
    cells), forming cation-selective pores and elevating intracellular cAMP to
    impair phagocytosis, dendritic-cell maturation, and cytokine secretion. This
    disarms innate immunity and, together with pertussis toxin, allows the organism
    to persist on the airway epithelium.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  - preferred_term: dendritic cell
    term:
      id: CL:0000451
      label: dendritic cell
  biological_processes:
  - preferred_term: response to toxic substance
    term:
      id: GO:0009636
      label: response to toxic substance
  evidence:
  - reference: DOI:10.3389/fimmu.2023.1126107
    reference_title: "Generating enhanced mucosal immunity against Bordetella pertussis: current challenges and new directions"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Adenylate cyclase toxin targets Cd11b-positive professional phagocytes,
      including dendritic cells, macrophages, and neutrophils by forming
      cation-selective pores to permeabilize the cell membrane
    explanation: >-
      Details the adenylate cyclase toxin mechanism of phagocyte subversion.
      Evidence source is OTHER as this is a review article.
  downstream: []

- name: Type III Secretion System-Mediated Immune Evasion
  role: effector
  description: >
    B. pertussis (and the classical Bordetella) use a type III secretion system
    (T3SS) to manipulate host vasoactive intestinal peptide (VIP)/VPAC2 signaling,
    promoting colonization and persistence in the lower respiratory tract. In mouse
    models, VPAC2-deficient hosts show reduced bacterial burden and VPAC2
    antagonists reduce lung pathology, identifying this axis as a candidate
    host-directed therapeutic target.
  biological_processes:
  - preferred_term: response to host immune response
    term:
      id: GO:0052572
      label: response to host immune response
  evidence:
  - reference: DOI:10.3389/fcimb.2023.1111502
    reference_title: "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"
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      the ability of Bordetella spp. to manipulate VIP/VPAC signaling pathway
      appears to be mediated by the type 3 secretion system (T3SS)
    explanation: >-
      Mouse-model study attributing host VIP/VPAC2 manipulation to the Bordetella
      T3SS. Evidence source is MODEL_ORGANISM as the mechanism was defined in mouse
      infection models.
  - reference: DOI:10.3389/fcimb.2023.1111502
    reference_title: "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"
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      treatment with VPAC2 antagonists decrease lung pathology, suggesting its
      potential use to prevent lung damage and dysfunction caused by infection.
    explanation: >-
      Supports the VIP/VPAC2 axis as a host-directed therapeutic target, with
      VPAC2 antagonists reducing lung pathology in mice. Evidence source is
      MODEL_ORGANISM.
  downstream: []

- name: Paroxysmal Coughing Illness
  role: consequence
  description: >
    The clinical syndrome of pertussis is a paroxysmal coughing illness, classically
    with an inspiratory whoop and post-tussive emesis. In young infants it may
    manifest as cyanosis or facial flushing during coughing fits and apnea, and is
    associated with marked leukocytosis.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  locations:
  - preferred_term: respiratory system
    term:
      id: UBERON:0001004
      label: respiratory system
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      presented with paroxysmal coughing
    explanation: >-
      Clinical cohort documenting paroxysmal coughing as the predominant
      presentation of pertussis. Evidence source is HUMAN_CLINICAL as this is a
      clinical cohort study.
  downstream: []

- name: Bacterial Ribosomal Translation (Macrolide Target)
  role: therapeutic_vulnerability
  conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
  description: >
    B. pertussis depends on its bacterial ribosome for protein synthesis.
    Macrolides (e.g., azithromycin), the conventional antibiotics for pertussis,
    bind the 50S ribosomal subunit and block bacterial protein synthesis — the
    molecular target underlying antibiotic therapy (which reduces transmissibility
    more than it alters the toxin-driven cough once established).
  biological_processes:
  - preferred_term: translation
    term:
      id: GO:0006412
      label: translation
  evidence:
  - reference: PMID:24336183
    reference_title: Ribosome-targeting antibiotics and mechanisms of bacterial resistance.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The ribosome is one of the main antibiotic targets in the bacterial cell.
    explanation: >-
      Establishes the bacterial ribosome as the target of macrolides and other
      protein-synthesis inhibitors, the step this node represents. Evidence source
      is OTHER as this is a review article.
  downstream:
  - target: Emerging Macrolide Resistance
    description: >-
      Macrolide resistance in B. pertussis erodes the efficacy of ribosome-targeting
      therapy.

- name: Emerging Macrolide Resistance
  role: adaptive_escape
  conforms_to: "bacterial_protein_synthesis_inhibition#Ribosomal Target Resistance"
  description: >
    Macrolide-resistant B. pertussis is an emerging concern in some regions, which
    can render azithromycin ineffective and shift treatment toward alternatives such
    as trimethoprim-sulfamethoxazole.
  biological_processes:
  - preferred_term: response to antibiotic
    term:
      id: GO:0046677
      label: response to antibiotic
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      high-level resistance to azithromycin but sensitivity to
      trimethoprim-sulfamethoxazole, levofloxacin, doxycycline
    explanation: >-
      In vitro drug-susceptibility testing of B. pertussis isolates showing
      high-level azithromycin resistance with retained sensitivity to alternatives.
      Evidence source is IN_VITRO as this is an in vitro susceptibility assay of
      isolates (in this cohort all 25 isolates were azithromycin-resistant,
      grounding the "in some regions" caveat).
  downstream: []
phenotypes:
- category: Respiratory
  name: Whooping Cough
  description: >
    Paroxysmal coughing fits, classically followed by an inspiratory "whoop"; the
    defining manifestation of pertussis.
  phenotype_term:
    preferred_term: Whooping cough
    term:
      id: HP:0031247
      label: Whooping cough
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      presented with paroxysmal coughing
    explanation: >-
      Most hospitalized cases presented with paroxysmal coughing. Evidence source
      is HUMAN_CLINICAL as this is a clinical cohort study.
- category: Gastrointestinal
  name: Post-tussive Vomiting
  description: >
    Vomiting after coughing paroxysms (post-tussive emesis), a characteristic
    feature of pertussis.
  phenotype_term:
    preferred_term: Post-tussive vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      post-tussive emesis
    explanation: >-
      Post-tussive emesis was documented in the clinical cohort. Evidence source is
      HUMAN_CLINICAL as this is a clinical cohort study.
- category: Respiratory
  name: Apnea
  description: >
    Apnea, particularly in young infants, is a dangerous manifestation of severe
    pertussis.
  phenotype_term:
    preferred_term: Apnea
    term:
      id: HP:0002104
      label: Apnea
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      had apnea
    explanation: >-
      Apnea was documented among hospitalized pertussis cases. Evidence source is
      HUMAN_CLINICAL as this is a clinical cohort study.
- category: Respiratory
  name: Cyanosis
  description: >
    Cyanosis (or facial flushing) during coughing fits, especially in infants.
  phenotype_term:
    preferred_term: Cyanosis
    term:
      id: HP:0000961
      label: Cyanosis
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      manifested cyanosis or facial flushing during coughing
    explanation: >-
      Over half of hospitalized cases manifested cyanosis or facial flushing during
      coughing. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
- category: Respiratory
  name: Pertussis Pneumonia
  description: >
    Pneumonia is a frequent complication of hospitalized pertussis, especially in
    young infants, and contributes to severe disease.
  phenotype_term:
    preferred_term: Pneumonia
    term:
      id: HP:0002090
      label: Pneumonia
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      pneumonia was confirmed in 84 (66.66%) cases
    explanation: >-
      Two-thirds of hospitalized pertussis cases had radiographically confirmed
      pneumonia. Evidence source is HUMAN_CLINICAL as this is a clinical cohort
      study.
- category: Hematologic
  name: Leukocytosis
  description: >
    Marked leukocytosis (with lymphocyte predominance) is characteristic of
    pertussis and elevated white cell count is a risk factor for severe disease.
  phenotype_term:
    preferred_term: Leukocytosis
    term:
      id: HP:0001974
      label: Increased total leukocyte count
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      elevated white blood cell count
    explanation: >-
      Elevated white blood cell count was an independent risk factor for severe
      pertussis. Evidence source is HUMAN_CLINICAL as this is a clinical cohort
      study.
  - reference: DOI:10.3390/toxins14030187
    reference_title: "Novel Strategies to Inhibit Pertussis Toxin"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Especially in newborns and infants, pertussis symptoms, such as
      leukocytosis, can become life-threatening.
    explanation: >-
      Establishes leukocytosis as a hallmark, potentially life-threatening feature
      of severe infant pertussis. Evidence source is OTHER as this is a review
      article.
- category: Constitutional
  name: Fever
  description: >
    Low-grade fever may accompany pertussis, though it is often absent.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      28 (22.22%) had fever
    explanation: >-
      Fever was present in about a fifth of hospitalized pertussis cases,
      consistent with its variable, often low-grade presence. Evidence source is
      HUMAN_CLINICAL as this is a clinical cohort study.
treatments:
- name: Azithromycin
  description: >
    Macrolide antibiotic that binds the 50S bacterial ribosome and inhibits protein
    synthesis; the conventional antibiotic for pertussis, primarily reducing
    transmissibility. Emerging macrolide-resistant B. pertussis in some regions can
    necessitate alternatives such as trimethoprim-sulfamethoxazole.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: azithromycin
      term:
        id: CHEBI:2955
        label: azithromycin
  target_mechanisms:
  - target: Bacterial Ribosomal Translation (Macrolide Target)
    treatment_effect: INHIBITS
    description: >-
      Azithromycin binds the 50S ribosome and arrests B. pertussis protein
      synthesis, clearing carriage and reducing transmission.
  evidence:
  - reference: DOI:10.3390/toxins14030187
    reference_title: "Novel Strategies to Inhibit Pertussis Toxin"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      antibiotics only reduce symptoms if administered in early stages, which
      rarely occurs due to a late diagnosis.
    explanation: >-
      Explains that macrolide antibiotics reduce symptoms only if given early
      (catarrhal stage); once the paroxysmal cough is established the benefit is
      largely limited to reducing transmission. Evidence source is OTHER as this is
      a review article.
- name: Pertussis Toxin Inhibitors (investigational)
  description: >
    Investigational host-directed and toxin-neutralizing strategies aimed at
    pertussis toxin — chaperone inhibitors, human peptides, small-molecule
    inhibitors, and humanized neutralizing antibodies — intended to address the
    toxin-driven symptoms (e.g., leukocytosis) for which no causative treatment
    currently exists.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  target_mechanisms:
  - target: Pertussis Toxin-Mediated Disruption of Host Gi Signaling
    treatment_effect: INHIBITS
    description: >-
      These agents inhibit or neutralize pertussis toxin, the AB5 exotoxin that
      ADP-ribosylates Gαi.
  evidence:
  - reference: DOI:10.3390/toxins14030187
    reference_title: "Novel Strategies to Inhibit Pertussis Toxin"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      chaperone inhibitors, human peptides, small molecule inhibitors, and
      humanized antibodies are discussed as novel strategies to inhibit PT.
    explanation: >-
      Review enumerating the novel pharmacological strategies under development to
      inhibit pertussis toxin. Evidence source is OTHER as this is a review of
      investigational strategies.
- name: Maternal Tdap Vaccination
  description: >
    Maternal acellular pertussis (Tdap/dTpa) vaccination during pregnancy
    (near the third trimester) protects young infants through transplacental
    transfer of pertussis-specific antibodies, bridging the vulnerable window
    before the infant primary series takes effect.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: maternal pertussis vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  evidence:
  - reference: DOI:10.1542/peds.2023-062664
    reference_title: "Maternal Pertussis Vaccination, Infant Immunization, and Risk of Pertussis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      was associated with lower risk of infection among infants through 8 months
      of age.
    explanation: >-
      Population-based cohort of 279,418 mother-infant pairs showing maternal
      pertussis vaccination near 28 weeks' gestation lowered infant infection risk
      through 8 months of age. Evidence source is HUMAN_CLINICAL as this is a
      population-based cohort study.
- name: Pertussis Vaccination
  description: >
    Acellular pertussis vaccination (DTaP in infants/children, Tdap boosters
    including maternal immunization) is the key strategy for preventing severe
    pertussis, particularly in young infants.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  evidence:
  - reference: PMID:41963827
    reference_title: Clinical epidemiological characteristics and risk factors for severe pertussis in children in Xiamen.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      timely completion of the primary pertussis vaccination series in infants
      remains a key strategy for preventing severe pertussis
    explanation: >-
      The cohort concludes that timely primary pertussis vaccination is key to
      preventing severe disease. Evidence source is HUMAN_CLINICAL as this is a
      clinical cohort study.
prevalence:
- population: Worldwide
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: COMMON
  notes: >-
    A comprehensive review estimated ~16 million pertussis cases and 195,000 deaths
    globally in 2008, with sizeable outbreaks reported repeatedly since, and a
    shifting age profile in which older children and adolescents transmit to younger
    siblings. B. pertussis remains a leading cause of vaccine-preventable respiratory
    disease and is currently increasing worldwide (2023-2024 resurgence).
  evidence:
  - reference: PMID:27029594
    reference_title: "Pertussis: Microbiology, Disease, Treatment, and Prevention."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      in 2008, pertussis was associated with an estimated 16 million cases and
      195,000 deaths globally.
    explanation: >-
      Comprehensive review quantifying the global pertussis burden. Evidence source
      is OTHER as this is a review aggregating surveillance data.
  - reference: DOI:10.1128/cmr.00164-22
    reference_title: "Bordetella bronchiseptica and Bordetella pertussis: Similarities and Differences in Infection, Immuno-Modulation, and Vaccine Considerations"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      These infections are restricted to humans and currently increasing worldwide.
    explanation: >-
      Establishes that human pertussis is currently increasing worldwide, supporting
      the resurgence context. Evidence source is OTHER as this is a review article.
clinical_trials:
- name: NCT05461131
  phase: PHASE_II
  status: UNKNOWN
  description: >-
    Phase 2b, placebo-controlled, randomized study of the BPZE1 live-attenuated
    intranasal pertussis vaccine in healthy adults, assessing protection against
    colonization following challenge with virulent wild-type B. pertussis.
  evidence:
  - reference: clinicaltrials:NCT05461131
    reference_title: "A Phase 2b, Placebo-Controlled, Randomized Study of BPZE1 Intranasal Pertussis Vaccine in Healthy Adults to Assess Protection Against Colonization Following Challenge With Virulent Wild-Type Bordetella Pertussis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is a randomised, double-blinded, placebo-controlled trial of BPZE1 that
      includes virulent B. pertussis challenge followed by a safety follow-up.
    explanation: >-
      ClinicalTrials.gov documents the BPZE1 intranasal live-attenuated vaccine
      controlled human infection trial, a next-generation mucosal vaccine strategy.
- name: NCT06827470
  phase: PHASE_I
  status: UNKNOWN
  description: >-
    Phase 1/2 dose-escalation trial establishing a pertactin (PRN)-deficient
    B. pertussis controlled human infection model (CHIM) representing currently
    circulating isolates, to define correlates of protection.
  evidence:
  - reference: clinicaltrials:NCT06827470
    reference_title: "Open-label, Phase 1/2, Dose-escalation Clinical Trial to Establish a Controlled Human Infection Model by Determining and Confirming the Optimal and Safe J820 Bordetella Pertussis Dose Administered Intranasally to Healthy Adults 18-50 Years of Age That Induces Mild Symptomatic Infection and Detection of B. Pertussis in Nasal Samples"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The overall goal of this study is to establish a PRN-deficient pertussis
      Controlled Human Infection Model (CHIM) that represents currently circulating
      isolates, in the context of a North American exposure (vaccination and
      infection) pedigree.
    explanation: >-
      ClinicalTrials.gov documents a controlled human infection model using a
      pertactin-deficient strain reflecting vaccine-driven pathogen evolution.
notes: >-
  Created as part of the Respiratory Infections project (vaccine-preventable
  bacterial respiratory infection). Conforms to the
  bacterial_protein_synthesis_inhibition module (ribosomal macrolide target +
  emerging resistance). Toxin-mediated pathogenesis (pertussis toxin / adenylate
  cyclase toxin) is the core mechanism. The infectious_agent (NCBITaxon) block was
  omitted at creation and Bordetella pertussis is described in the text.
datasets:
- accession: geo:GSE310241
  title: Mucosal inflammation and pre-existing antibodies define protection and disease outcomes in human Bordetella pertussis challenge
  description: Whooping cough, caused by Bordetella pertussis (BP), persists despite widespread vaccination with acellular pertussis (aP) vaccines, which protect against disease but provide incomplete and short-lived immunity against infection and transmission. To define correlates of protection and mechanisms underlying symptom development, we characterized systemic and mucosal immune responses in a North American BP-controlled human infection model (CHIM). Healthy adults, primed in infancy with either whole-cell or aP vaccines, were intranasally challenged with escalating BP doses and classified as symptomatic, asymptomatic, or non-infected.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 414
  publication: PMID:42465938
  notes: Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE308373
  title: Pertussis Toxin as well as Staphylococcal superantigen induce glycolysis as the major energy source during CD4+ T cell activation in a human tonsil organoid model
  description: Bystander activation represents an innate-like mechanism by which T cells, particularly effector and memory subsets, can become activated in the absence of cognate antigen recognition. Using human tonsil organoid cultures as a physiologically relevant model, we investigated bystander activation of CD4+ memory T cells in situ in comparison to superantigen stimulation. Tonsillar T cells were stimulated with pertussis toxin – a component of the childhood pertussis vaccine – in comparison to TSST-1 as the staphylococcal superantigen and assessed for activation status, cytokine expression, RNA expression, and metabolic reprogramming.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 20
  notes: Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE324217
  title: A dual role for PGLYRP1 in host defense and immune regulation during B. pertussis infection
  description: Bordetella pertussis, the etiologic agent of whooping cough, remains a serious public health concern despite widespread vaccination. Improved therapeutics and vaccines are urgently needed to treat and prevent pertussis disease. Host recognition of bacterial peptidoglycan (PGN), including B. pertussis extracellular PGN fragment tracheal cytotoxin (TCT), shapes the immune response to infection. Peptidoglycan recognition proteins (PGLYRPs) are a conserved family of innate immune molecules which bind bacterial PGN. While they function as immune signaling receptors in arthropods, PGLYRPs in mammals have thus far been primarily recognized for their bactericidal activity.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_count: 6
  publication: PMID:41040336
  notes: Identified by GEO DataSets index search for Pertussis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: massive:MSV000081702
  title: Differential Proteomic Analysis of Bordetella pertussis OMV
  description: 'Differential proteomic analysis of outer membrane vesicles from Bordetella pertussis (two strains: Bvg+ and Bvg-)'
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Pertussis"). Retrieved 2026-08-02.
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References & Deep Research

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1. Disease Information
Edison Scientific Literature 50 citations 2026-07-05T19:10:32.636586

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:

Ontology/Database Term/Code Description
MONDO MONDO:0005077 Pertussis; MONDO disease identifier for whooping cough/pertussis (OpenTargets Search: pertussis,whooping cough)
ICD-10-CM A37.0 Whooping cough due to Bordetella pertussis
ICD-10-CM A37.1 Whooping cough due to Bordetella parapertussis
ICD-10-CM A37.8 Whooping cough due to other Bordetella species
ICD-10-CM A37.9 Whooping cough, unspecified species
ICD-11 1C12 Pertussis / whooping cough (ICD-11 category for pertussis)
MeSH D014917 Whooping Cough; MeSH descriptor for pertussis
HPO HP:0031247 Whooping cough; characteristic paroxysmal inspiratory “whoop” phenotype
HPO HP:0012735 Cough; core symptom in catarrhal and paroxysmal stages (chamorro2023bordetellabronchisepticaand pages 2-3, ifill2023lipidamodifications pages 18-25)
HPO HP:0002360 Sleep disturbance; clinically relevant consequence of prolonged nocturnal paroxysmal coughing
HPO HP:0002094 Dyspnea; breathing difficulty during coughing episodes/apnea-cyanosis events (chamorro2023bordetellabronchisepticaand pages 2-3)
HPO HP:0012418 Hypoxemia; may accompany severe infant disease with apnea/cyanosis
HPO HP:0002105 Apnea; common severe manifestation in infants (chamorro2023bordetellabronchisepticaand pages 2-3)
HPO HP:0000961 Cyanosis; may occur during severe paroxysms (chamorro2023bordetellabronchisepticaand pages 2-3)
HPO HP:0033847 Posttussive vomiting; classic pertussis-associated symptom (chamorro2023bordetellabronchisepticaand pages 2-3)
HPO HP:0001250 Seizure; severe complication reported in pertussis (ernst2022novelstrategiesto pages 1-2)
HPO HP:0001252 Muscular hypotonia; potential feature during severe infant illness
HPO HP:0001945 Fever; usually low-grade in early catarrhal stage (ifill2023lipidamodifications pages 18-25)
HPO HP:0012378 Fatigue; common functional burden during prolonged illness
HPO HP:0002205 Pneumonia; important complication, especially in infants (ernst2022novelstrategiesto pages 1-2, regan2023maternalpertussisvaccination pages 5-6)
HPO HP:0001875 Neutropenia/altered leukocyte phenotype not typical; avoid overannotation unless case-specific
HPO HP:0001974 Leukocytosis; severe pertussis-associated laboratory abnormality linked to PT effects (ernst2022novelstrategiesto pages 1-2)
GO Biological Process GO:0044419 Interspecies interaction between organisms; broad host-pathogen interaction category
GO Biological Process GO:0009617 Response to bacterium; host response relevant to B. pertussis infection
GO Biological Process GO:0050900 Leukocyte migration; pertussis toxin alters chemokine signaling and neutrophil recruitment (chamorro2023bordetellabronchisepticaand pages 16-18, ernst2022novelstrategiesto pages 12-13)
GO Biological Process GO:0001817 Regulation of cytokine production; LOS, FHA, PT, and T3SS modulate cytokine responses (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 18-20, chamorro2023bordetellabronchisepticaand pages 16-18)
GO Biological Process GO:0071621 Granulocyte chemotaxis; relevant to neutrophil trafficking impaired by PT
GO Biological Process GO:0032609 Interferon-gamma production; central to Th1 immunity against pertussis (chamorro2023bordetellabronchisepticaand pages 23-25, chamorro2023bordetellabronchisepticaand pages 11-13)
GO Biological Process GO:0032740 Positive regulation of interleukin-17 production; key Th17-associated protective response (chamorro2023bordetellabronchisepticaand pages 23-25, caulfield2023generatingenhancedmucosal pages 3-4, church2025nasalimmunizationwith pages 14-15)
GO Biological Process GO:0002250 Adaptive immune response; humoral and cellular immunity required for clearance (chamorro2023bordetellabronchisepticaand pages 23-25, chamorro2023bordetellabronchisepticaand pages 11-13)
GO Biological Process GO:0002449 Lymphocyte mediated immunity; includes Th1/Th17 responses critical in pertussis
GO Biological Process GO:0071723 Cellular response to lipopolysaccharide; relevant to LOS/TLR4 signaling (chamorro2023bordetellabronchisepticaand pages 16-18)
UBERON UBERON:0001004 Respiratory system; primary affected body system
UBERON UBERON:0002048 Lung; major site of lower respiratory complications
UBERON UBERON:0001737 Larynx; contributes to inspiratory whoop physiology
UBERON UBERON:0003126 Trachea; important site of ciliated epithelial colonization/damage (colak2023bordetellapertussisand pages 1-2)
UBERON UBERON:0002185 Bronchus; major colonization site for B. pertussis (colak2023bordetellapertussisand pages 1-2)
UBERON UBERON:0001706 Nasopharynx; relevant site of colonization and transmission
UBERON UBERON:0001728 Nasal cavity; key mucosal site targeted by next-generation vaccines (chamorro2023bordetellabronchisepticaand pages 23-25, rudi2024useofmucosally pages 10-13)
UBERON UBERON:0006075 Ciliated epithelium of tracheobronchial tree; target of adhesins and TCT-mediated injury
CL CL:0000895 Macrophage; target of ACT and FHA-mediated immunomodulation (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 16-18)
CL CL:0000097 Mast cell; relevant to airway inflammation and mucosal responses
CL CL:0000775 Neutrophil; key effector cell whose recruitment is impaired by PT (chamorro2023bordetellabronchisepticaand pages 16-18, ernst2022novelstrategiesto pages 12-13)
CL CL:0000451 Dendritic cell; involved in Th1/Th17 priming (chamorro2023bordetellabronchisepticaand pages 16-18, chamorro2023bordetellabronchisepticaand pages 13-15)
CL CL:0000624 CD4-positive, alpha-beta T cell; source of Th1/Th17 and TRM responses (chamorro2023bordetellabronchisepticaand pages 23-25, caulfield2023generatingenhancedmucosal pages 3-4, church2025nasalimmunizationwith pages 14-15)
MAXO MAXO:0001001 Antibiotic administration; overarching treatment class for pertussis therapy
MAXO MAXO:0000474 Vaccination; primary preventive intervention
MAXO MAXO:0000260 Maternal vaccination; used in pregnancy to protect young infants (regan2023maternalpertussisvaccination pages 1-2, regan2023maternalpertussisvaccination pages 7-8)
MAXO MAXO:0000127 Supportive care; hydration, oxygen, monitoring, respiratory support when severe (chamorro2023bordetellabronchisepticaand pages 2-3)
MAXO MAXO:0000058 Intensive care management; relevant for critical infant pertussis
MAXO MAXO:0000014 Mechanical ventilation; severe respiratory failure support
CHEBI CHEBI:2955 Azithromycin; first-line macrolide used for treatment/post-exposure prophylaxis (ernst2022novelstrategiesto pages 2-5, chamorro2023bordetellabronchisepticaand pages 2-3)
CHEBI CHEBI:42355 Clarithromycin; macrolide option for pertussis treatment (ernst2022novelstrategiesto pages 2-5)
CHEBI CHEBI:42355? Erythromycin; classic first-line macrolide for pertussis treatment, also studied against MRBp (ernst2022novelstrategiesto pages 2-5, jiang2024theeffectof pages 1-5, jiang2024theeffectof pages 8-10)
CHEBI CHEBI:8345 Sulfamethoxazole; component of TMP-SMX alternative therapy when macrolides cannot be used
CHEBI CHEBI:45924 Trimethoprim; component of TMP-SMX alternative therapy
CHEBI CHEBI:33281 Oxygen; supportive treatment for hypoxemia/apnea in severe disease
NCBI Taxonomy NCBITaxon:520 Bordetella pertussis; primary infectious agent causing classic pertussis
Open Targets / Disease Ontology context No associated targets reported Open Targets search found pertussis under MONDO but no disease-target associations, consistent with pathogen-driven rather than host monogenic etiology (OpenTargets Search: pertussis,whooping cough)

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:

Virulence factor Molecular weight Function / mechanism Role in pathogenesis Vaccine relevance
Pertussis toxin (PT) ~117 kDa AB-type exotoxin with S1 enzymatic subunit and S2-S5 binding subunits; ADP-ribosylates inhibitory Gα proteins, disrupting GPCR signaling and downstream cAMP regulation (colak2023bordetellapertussisand pages 2-3, ernst2022novelstrategiesto pages 1-2) Major B. pertussis-specific toxin; promotes respiratory colonization, suppresses chemokine release and neutrophil recruitment, delays antibody-mediated clearance, and is associated with leukocytosis, hyperinsulinemia, histamine sensitization, and severe disease/poor outcomes (chamorro2023bordetellabronchisepticaand pages 16-18, chamorro2023bordetellabronchisepticaand pages 15-16, ernst2022novelstrategiesto pages 1-2, ernst2022novelstrategiesto pages 12-13) Core antigen in acellular pertussis vaccines; major correlate/target of vaccine-induced antibodies; also a target for next-generation therapeutics and live-attenuated vaccine detoxification strategies such as BPZE1 (chamorro2023bordetellabronchisepticaand pages 20-22, colak2023bordetellapertussisand pages 3-5, ernst2022novelstrategiesto pages 2-5, chamorro2023bordetellabronchisepticaand pages 23-25)
Adenylate cyclase toxin (ACT/CyaA, AC-Hly) Not specified in retrieved evidence Toxin that enters/acts on phagocytes and elevates intracellular cAMP; inhibits phagocytosis and opsonization, induces macrophage apoptosis, has hemolytic/cytotoxic activity, and can disrupt epithelial tight junctions (colak2023bordetellapertussisand pages 2-3, chamorro2023bordetellabronchisepticaand pages 16-18, ernst2022novelstrategiesto pages 1-2) Protects bacteria from innate immune killing, impairs neutrophil, dendritic-cell, and macrophage function, and contributes to invasion/persistence in the respiratory tract (colak2023bordetellapertussisand pages 2-3, chamorro2023bordetellabronchisepticaand pages 16-18, ernst2022novelstrategiesto pages 1-2) Not a standard component of current acellular vaccines, but an important candidate antigen/target for next-generation vaccines and antibody-based protection strategies (chamorro2023bordetellabronchisepticaand pages 23-25, colak2023bordetellapertussisand pages 3-5)
Filamentous hemagglutinin (FHA) ~220 kDa Filamentous surface adhesin mediating attachment to ciliated respiratory epithelium; also modulates host responses by inhibiting NF-κB signaling in macrophages and epithelial cells (chamorro2023bordetellabronchisepticaand pages 13-15, colak2023bordetellapertussisand pages 2-3, chamorro2023bordetellabronchisepticaand pages 15-16) Critical for initiation of colonization and tight adhesion in the upper airway; suppresses early inflammation and cell recruitment, aiding persistence (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 15-16) Common antigen in acellular vaccines and serologic assays; antigen loss/variation has been implicated in pathogen adaptation and vaccine-pressure discussions (chamorro2023bordetellabronchisepticaand pages 20-22, wang2025resurgenceofpertussis pages 10-11)
Pertactin (PRN) ~69 kDa Outer-membrane autotransporter adhesin enabling attachment to host cells; contributes to membrane interactions and resistance to host clearance (colak2023bordetellapertussisand pages 2-3, ifill2023lipidamodifications pages 225-228, chamorro2023bordetellabronchisepticaand pages 15-16) Supports adherence, inflammation, cell recruitment, shedding/transmission, and resistance to neutrophil-mediated clearance (ifill2023lipidamodifications pages 225-228, chamorro2023bordetellabronchisepticaand pages 15-16) Major antigen in many acellular vaccines; pertactin-deficient strains are a key example of vaccine-driven evolution and resurgence-associated adaptation (chamorro2023bordetellabronchisepticaand pages 20-22, wang2025resurgenceofpertussis pages 2-4, caulfield2023generatingenhancedmucosal pages 4-5, chamorro2023bordetellabronchisepticaand pages 33-33)
Fimbriae (FIM2/FIM3) Not specified in retrieved evidence Surface appendages mediating initial interactions with respiratory epithelial cells and contributing to tight adhesion with FHA (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 15-16) Help establish colonization of ciliated airway surfaces and support persistence in the respiratory tract (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 15-16) Included in some multicomponent acellular vaccines; fimbrial variation/negative strains have been described among circulating isolates (chamorro2023bordetellabronchisepticaand pages 20-22, chamorro2023bordetellabronchisepticaand pages 2-3)
Tracheal cytotoxin (TCT) Not specified in retrieved evidence Peptidoglycan-derived cytotoxin that damages ciliated respiratory cells and disrupts epithelial/tight-junction integrity (chamorro2023bordetellabronchisepticaand pages 13-15, ernst2022novelstrategiesto pages 1-2) Causes ciliary injury and epithelial damage, promoting local tissue dysfunction and aiding colonization/pathology in the airway (chamorro2023bordetellabronchisepticaand pages 13-15, ernst2022novelstrategiesto pages 1-2) Not part of licensed acellular vaccines; detoxification/inactivation of TCT is part of the attenuation strategy for BPZE1 live vaccine development (chamorro2023bordetellabronchisepticaand pages 23-25)
Dermonecrotic toxin (DNT) Not specified in retrieved evidence Toxin associated with tissue injury; interacts functionally with TCT and LOS and contributes to virulence programs regulated by BvgAS (colak2023bordetellapertussisand pages 2-3) Contributes to respiratory tract tissue damage and overall virulence (colak2023bordetellapertussisand pages 2-3) Not a standard antigen in current acellular vaccines; inactivated in BPZE1 as part of live-attenuated vaccine design (chamorro2023bordetellabronchisepticaand pages 23-25)
Lipooligosaccharide (LOS) Not specified in retrieved evidence Endotoxin-like outer-membrane glycolipid; activates TLR4 and cytokine release (including IL-8 and TNF-α), though with weaker stimulation than B. bronchiseptica LPS; terminal trisaccharide contributes to defense evasion (chamorro2023bordetellabronchisepticaand pages 18-20, chamorro2023bordetellabronchisepticaand pages 16-18) Required for efficient nasal colonization in mice; shapes inflammatory tone and neutrophil recruitment, contributing to colonization and persistence while limiting clearance (chamorro2023bordetellabronchisepticaand pages 18-20, chamorro2023bordetellabronchisepticaand pages 16-18) Not used as a purified routine vaccine antigen, but naturally present in OMV-based vaccine platforms where it contributes adjuvanticity/immunogenicity (colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 9-10)
Type III secretion system (T3SS) Multi-protein apparatus; no single MW Secretion apparatus that injects effectors such as BteA and modulates host signaling, including VIP/VPAC2 pathways; suppresses IFN-γ responses and promotes persistence (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 18-20, first2023bordetellaspp.utilize pages 1-2) Supports immune evasion, lower-respiratory colonization, persistence, and lung pathology modulation (chamorro2023bordetellabronchisepticaand pages 13-15, chamorro2023bordetellabronchisepticaand pages 18-20, first2023bordetellaspp.utilize pages 1-2) Not a component of current vaccines but a potential therapeutic and next-generation vaccine target because of its role in immune manipulation and persistence (chamorro2023bordetellabronchisepticaand pages 23-25, first2023bordetellaspp.utilize pages 1-2)

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:

Vaccine Type Components Immune Response Profile (Th1/Th2/Th17) Duration of Protection Advantages Limitations Current Use
Whole-cell pertussis vaccine (wP/DTwP) Killed whole B. pertussis cells, typically combined with diphtheria and tetanus toxoids Stronger Th1/Th17-polarized cellular immunity; more balanced humoral/cellular response than acellular vaccines (chamorro2023bordetellabronchisepticaand pages 20-22, colak2023bordetellapertussisand pages 9-10, colak2023bordetellapertussisand pages 3-5, chamorro2023bordetellabronchisepticaand pages 23-25) Longer than acellular vaccines; cited protection roughly 7-20 years after natural infection and generally more durable priming than aP (chamorro2023bordetellabronchisepticaand pages 20-22, wang2025resurgenceofpertussis pages 4-5) Better durability; stronger mucosal-relevant cellular priming; associated with lower later pertussis risk when used for priming (chamorro2023bordetellabronchisepticaand pages 20-22, chamorro2023bordetellabronchisepticaand pages 23-25, church2025nasalimmunizationwith pages 14-15) Higher reactogenicity, historically including fever and neurologic adverse reactions; less acceptable in many high-income settings (chamorro2023bordetellabronchisepticaand pages 23-25, colak2023bordetellapertussisand pages 3-5) Still widely used in many low- and middle-income countries in DTwP-containing EPI schedules (wang2025resurgenceofpertussis pages 5-7, wang2025resurgenceofpertussis pages 4-5)
Acellular pertussis vaccine (aP/DTaP) Purified 1-5 antigens, commonly PT, FHA, PRN, FIM2/FIM3, combined with diphtheria/tetanus toxoids More Th2-skewed, especially with alum adjuvant; less effective induction of Th1/Th17 and mucosal memory than wP (chamorro2023bordetellabronchisepticaand pages 23-25, chamorro2023bordetellabronchisepticaand pages 20-22, colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 3-5, caulfield2023generatingenhancedmucosal pages 4-5) Waning immunity is substantial; efficacy cited around 85% after 6 doses with decline of ~11.7% annually; protection often 4-12 years (chamorro2023bordetellabronchisepticaand pages 20-22, wang2025resurgenceofpertussis pages 5-7) Lower reactogenicity; safer and better tolerated; standard product in many high-income countries (chamorro2023bordetellabronchisepticaand pages 20-22, colak2023bordetellapertussisand pages 3-5, wang2025resurgenceofpertussis pages 4-5) Rapid waning; does not reliably prevent nasal colonization or transmission; may contribute to vaccine-driven selection of antigen-deficient strains such as PRN-negative isolates (chamorro2023bordetellabronchisepticaand pages 23-25, colak2023bordetellapertussisand pages 1-2, caulfield2023generatingenhancedmucosal pages 4-5, chamorro2023bordetellabronchisepticaand pages 33-33) Routine infant immunization in many high-income countries, usually as DTaP-containing combination vaccines (chamorro2023bordetellabronchisepticaand pages 20-22, wang2025resurgenceofpertussis pages 5-7, wang2025resurgenceofpertussis pages 4-5)
Tdap booster Reduced-antigen acellular booster containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis antigens Booster humoral response but still based on acellular platform; protection remains less durable than wP-primed immunity (chamorro2023bordetellabronchisepticaand pages 20-22, wang2025resurgenceofpertussis pages 5-7) Initial effectiveness about 85%, decreasing by ~12% annually in cited review evidence (wang2025resurgenceofpertussis pages 5-7) Useful for adolescent/adult boosting and maternal immunization; reduces infant risk via transplacental antibody transfer during pregnancy (wang2025resurgenceofpertussis pages 5-7, regan2023maternalpertussisvaccination pages 1-2, regan2023maternalpertussisvaccination pages 6-7) Waning protection; does not fully solve transmission or colonization; repeated boosting may be needed (wang2025resurgenceofpertussis pages 5-7, caulfield2023generatingenhancedmucosal pages 4-5) Used for childhood/adolescent boosters, adult boosters in some countries, and maternal vaccination in pregnancy (chamorro2023bordetellabronchisepticaand pages 20-22, wang2025resurgenceofpertussis pages 5-7, regan2023maternalpertussisvaccination pages 1-2)
OMV-based vaccines Outer membrane vesicles containing native immunogenic structures including toxins, adhesins, and LPS/LOS-associated components More balanced response than aP; induces innate plus adaptive immunity and broader IgG subclass patterns resembling wP more than aP (colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 9-10, colak2023bordetellapertussisand pages 11-12) Not yet established in humans; promising preclinical durability and protection in animal/preclinical studies (colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 9-10) Native antigen presentation; potentially equivalent bacterial protection with milder inflammatory responses than wP; promising next-generation platform (colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 9-10) Manufacturing standardization challenges related to strain choice, culture conditions, extraction, and purification; no established routine human use yet (colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 9-10) Experimental/preclinical development; not standard of care (colak2023bordetellapertussisand pages 1-2, colak2023bordetellapertussisand pages 9-10, colak2023bordetellapertussisand pages 11-12)
BPZE1 live attenuated vaccine Live attenuated B. pertussis strain with inactivated major toxins including PT, TCT, and DNT Induces IgG, IgA, memory B cells, and a Th1-type response; broader antibody specificity and mucosal-relevant immunity than standard aP vaccines (chamorro2023bordetellabronchisepticaand pages 23-25) Human duration still under study; preclinical single-dose protection reported in mice (chamorro2023bordetellabronchisepticaand pages 23-25) Nasal administration; potential to induce mucosal immunity and improve protection against infection/transmission, not just disease (chamorro2023bordetellabronchisepticaand pages 23-25) Investigational; efficacy, long-term durability, and broader deployment remain under evaluation (chamorro2023bordetellabronchisepticaand pages 23-25) In clinical development; phase 2b cited with controlled human infection work (NCT05461131) (chamorro2023bordetellabronchisepticaand pages 23-25)
Intranasal mucosal vaccines Intranasally delivered aP formulations, live attenuated candidates, or other adjuvanted mucosal platforms Designed to induce local IgA, IL-17, Th1/Th17 responses, and tissue-resident memory CD4+ T cells in respiratory mucosa (chamorro2023bordetellabronchisepticaand pages 23-25, caulfield2023generatingenhancedmucosal pages 3-4, church2025nasalimmunizationwith pages 14-15, rudi2024useofmucosally pages 10-13) Human durability not yet fully defined; concept aims for stronger and more persistent anti-colonization immunity than injectable aP (chamorro2023bordetellabronchisepticaand pages 23-25, church2025nasalimmunizationwith pages 14-15) Best aligned with infection site; may prevent nasal colonization and transmission while also protecting against disease (chamorro2023bordetellabronchisepticaand pages 23-25, chamorro2023bordetellabronchisepticaand pages 25-27) Mostly investigational; formulation, adjuvant, and safety optimization remain active research areas (chamorro2023bordetellabronchisepticaand pages 23-25, colak2023bordetellapertussisand pages 11-12, church2025nasalimmunizationwith pages 14-15) Experimental/clinical development; not yet routine public-health use (chamorro2023bordetellabronchisepticaand pages 23-25, colak2023bordetellapertussisand pages 11-12, church2025nasalimmunizationwith pages 14-15)

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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  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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