Bordetella pertussis

Bordetella pertussis

A bacterium that causes whooping cough and is host-restricted to humans.

Genome Size of Bordetella species

Environmental bacteria: ~6 Mbp, Opportunistic pathobionts: ~5 Mbp, Host-restricted pathogens: ~4 Mbp (B. pertussis smallest).

B. pertussis Disease

Causes whooping cough (pertussis) in humans.

B. bronchiseptica

A Bordetella species that infects pigs, dogs, rabbits, and birds, causing atrophic rhinitis and kennel cough.

B. parapertussis

A Bordetella species that infects humans and sheep, causing mild whooping cough and pneumonia.

FHA (Filamentous Hemagglutinin)

A major surface adhesin that binds to sulphated carbohydrates and is crucial for colonization and immune modulation.

Fimbriae (Fim2/Fim3)

Hair-like appendages that strengthen attachment and facilitate persistent colonization.

Pertactin (Prn)

An outer membrane autotransporter that plays a role in epithelial adhesion/invasion and is a target of neutralizing antibodies.

OtbAB (BP1251/BP1252)

Novel 'orphan' B-subunit adhesins that are emerging vaccine targets and are highly immunogenic.

BvgAS Regulatory System

The master switch for gene expression in Bordetella species.

Bvg+ Phase

The virulent phase at 37°C in the host, expressing Class 1 genes (fhaB, fim, ptx, prn, cyaA) for adhesion and toxins.

Bvgi Phase

The intermediate phase during transition, expressing Class 2 & 3 genes (vrg-6, bipA) with an unclear function.

Bvg- Phase

The avirulent phase at low temperature ex vivo, expressing Class 4 genes related to motility/flagella for environmental survival.

Flagella Expression

Flagella are expressed ONLY in the Bvg- phase.

Pathogenesis Pathway

The step-by-step process of Bordetella pertussis infection.

Exposure

Infection begins with exposure to respiratory droplets.

Adherence

FHA/Fim bind to ciliated epithelial cells.

Invasion

Penetration through the epithelium occurs.

Infection

Involves toxin production, including pertussis toxin and adenylate cyclase.

Toxicity

Local and systemic effects caused by the toxins.

Invasiveness

The ability of the pathogen to spread to distant sites.

Tissue Damage

Results in cough and lung damage.

Pro-inflammatory phase

Phase 1 of immune response where Th1 cells produce IFN-γ, Th17 cells produce IL-17, macrophages are activated, and neutrophil recruitment occurs.

Regulatory phase

Phase 2 of immune response where Treg cells suppress inflammation, IL-10 and TGF-β are produced, dendritic cell modulation occurs, and CPS promotes phagocytosis.

Incubation period

Lasts 5-10 days, with a maximum of 21 days before symptoms appear.

Catarrhal stage

Onset stage of pertussis occurring in week 0, lasting 1-2 weeks.

Paroxysmal stage

Stage of pertussis occurring in week 2, lasting 1-6 weeks, characterized by 'whooping' cough.

Convalescent stage

Stage of pertussis occurring in week 8, lasting weeks to months, leading to recovery.

Communicable period

The time from onset to 3 weeks after the start of paroxysmal cough.

Challenged animal study

CFU peaks around day 7 and is cleared by day 35.

Unchallenged cage mate study

Delayed peak around day 21 and is cleared by day 42.

Contact transmission

Highly efficient method of spreading infection.

Pre-DTP Era cases

150,000-250,000 cases/year in the US before the 1940s.

Post-DTP Era cases

Dramatic decline to less than 5,000 cases/year from the 1950s to 1980s.

Resurgence of cases

Increase in cases since the 1990s despite vaccination, shifting to older age groups.

Reasons for resurgence

Waning vaccine immunity, strain evolution, and better diagnostic detection.

DTP3 coverage

Increased from approximately 20% to 90% from 1980 to 2019.

Annual pertussis cases

Fluctuate between 10-40 million globally despite high vaccination coverage.

2024 England outbreak cases

12,200 confirmed cases by the end of July 2024.

Infant deaths in outbreak

9 infant deaths reported in the 2024 England outbreak.

Maternal vaccination rate

Decreased from 74.7% in 2017 to 58.9% in 2024.

Childhood vaccination rates

12 months: 91%, 24 months: 92.5%, 5 years: 92.8% (WHO target: 95%).

Pre-vaccination era transmission

Infants were susceptible to natural infection, leading to immune adolescents/adults.

Vaccination era transmission

Infants are vaccinated early but immunity wanes, leading to adults transmitting to infants.

B. pertussis

Human-specific bacterium with a streamlined genome.

BvgAS master regulator

Controls the expression of virulence versus survival genes in B. pertussis.

Multiple adhesins

Proteins like FHA, Fim, Prn, and OtbAB that mediate attachment of B. pertussis.

Highly contagious

B. pertussis is transmitted via respiratory droplets.

Vaccine immunity

Current acellular vaccines provide shorter protection than whole-cell vaccines.

What bacterium is primarily responsible for whooping cough?

Bordetella pertussis

What are the two other Bordetella species that cause pertussis-like disease?

Bordetella parapertussis and Bordetella holmesii

Who identified Bordetella pertussis as the cause of whooping cough?

Jules Bordet and Octave Gengou in 1906

What was the death rate from whooping cough in the USA in the 1920s?

1 in 500

What is the global annual death toll from pertussis?

Approximately 100,000 deaths in children

What is the primary mode of transmission for Bordetella pertussis?

Through water droplets; it cannot survive outside the host.

What is the basic reproduction number (R0) for Bordetella pertussis?

15-17

What are the three clinical stages of whooping cough?

1. Catarrhal, 2. Paroxysmal, 3. Convalescent

What symptoms characterize the catarrhal stage of whooping cough?

Coryza, low-grade fever, and mild occasional cough lasting 7 to 10 days.

What occurs during the paroxysmal stage of whooping cough?

Sudden, intense coughing fits, difficulty expelling mucus, and a high-pitched whoop.

What is the role of filamentous hemagglutinin (FHA) in Bordetella pertussis?

It aids in adherence to the respiratory epithelium and modulates immune responses.

What is the function of pertactin in Bordetella pertussis?

It contributes to stable adhesion and may assist in epithelial cell invasion.

What are the effects of pertussis toxin (PT) on the immune system?

It inhibits chemokine production and leukocyte recruitment, leading to lymphocytosis.

What is the function of adenylate cyclase toxin (ACT)?

It elevates intracellular cAMP, blocking phagocytosis and disarming immune cells.

How does Bordetella pertussis evade the immune system?

By manipulating immune cell responses and delaying clearance through various toxins.

What is the significance of the BvgAS system in Bordetella species?

It regulates virulence gene expression based on environmental signals.

What is the role of the mucociliary escalator in the respiratory system?

It traps and removes inhaled particles and pathogens through coordinated ciliary movement.

What is the impact of vaccination on immunity to Bordetella pertussis?

Vaccination induces strong Th1 and Th17 responses, promoting effective clearance.

What are the limitations of current pertussis vaccines?

Immunity wanes within 4-7 years, and they do not protect against B. parapertussis or B. holmesii.

What is the treatment for Bordetella pertussis infection?

Antibiotics like erythromycin and supportive care; antibiotics are less effective during the paroxysmal phase.

What is the role of IgA and IgG in the immune response to Bordetella pertussis?

IgA neutralizes toxins and blocks adhesion, while IgG provides long-term protection.

What are the key components of the acellular pertussis vaccine?

Includes pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (Prn).

How does Bordetella pertussis adapt to different host microenvironments?

By altering gene expression in response to local signals, prioritizing adhesins in the upper respiratory tract.

What is the consequence of Prn-deficient Bordetella pertussis strains?

They can evade antibody-mediated clearance and are increasingly prevalent due to vaccine selection pressure.