**2. Etiopathogenic and immunological aspects**

The transmission of *B. pertussis*, which is an exclusively human and airborne pathogen, occurs through Flügge droplets. The pathogen is characterized by a high basic reproduction number (R0), and for this, it is highly contagious. The infection predominantly affects children and still represents one of the most important causes of death in subjects younger than 1 year of age [4].

Once introduced into the respiratory tract, the pathogen adheres to the ciliary cells of the epithelium by means of adhesins (FHA: filamentous hemagglutinin, FIM1, 2 and 3: fimbriae, PRN: pertactin) and exerts its pathogenic action through the production of some toxins (PT: pertussis toxin PT, AC: adenylated cyclase, DNT: dermonecrotic toxin, TCT: cytotoxin). Adhesins and toxins (TCT excluded) are highly immunogenic [5].

During the incubation period, *B. pertussis* replication, colonization of the respiratory tract, and production of large amounts of toxins occur, causing damage to the epithelium. The toxicity caused by *B. pertussis* stimulates the production of proinflammatory cytokines (IL-1, INF-α, and IL-6) in host cells, responsible for the clinical picture together with the nitric oxide production [5].

Published data show that *B. pertussis* strains evolved over time, with different isolates in pre- and post-immunization ages. Changes in genomic sequences of virulence factors such as PT, FIM, and PRN have been observed in circulating strains. So far, there is no evidence that the effectiveness of whole-cell vaccines decreases due to a continued selection of less susceptible clones to vaccines [6]. In regions where acellular vaccines are in use, the circulation of PRN-negative bacteria, in which the antigen contained in the vaccine is unexpressed, has recently been detected [7]. Very recently, a strain which does not express either PRN or PT has also been described [8].

However, no significant changes in the efficacy of acellular vaccines have been documented, despite the spreading of these new variants of *B. pertussis* [7, 9].
