**3. Epidemiology**

of infection to older age groups, with often unspecific and unrecognized clinical features. Adult subjects with atypical pertussis, often asymptomatic or paucisymptomatic, can become a source of infection for younger children, especially those younger than 2 months of age, who have not

A possible solution to limit the likelihood that an infant can be infected during the first months

Two important results could be achieved through this approach: the first is placental transmission of immunity induced by vaccination; the second is to prevent the mother from being

In the light of the positive experiences of some countries that have recently introduced vaccination in pregnancy, such as USA, Canada, Australia, and UK, vaccination in the third trimester of pregnancy appears to be one of the cornerstones for the prevention of this infection in infants [3].

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

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 pro-

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,

yet started the vaccination programs for infants [2] .

64 Pertussis - Disease, Control and Challenges

of life is mother's immunization during pregnancy.

**2. Etiopathogenic and immunological aspects**

toxins (TCT excluded) are highly immunogenic [5].

despite the spreading of these new variants of *B. pertussis* [7, 9].

duction [5].

a potential source of infection for the infant.

Before the availability of the pertussis vaccine (introduced in the 1950s), about 80% of cases occurred in children <5 years and less than 3% of cases in subjects ≥15 years of age [2].

In 1974, vaccination was included in the "Expanded Programme on immunization" by World Health Organization (WHO), which allowed a gradual increase in vaccine coverage (CV); in 2008, 82% of newborns had received three doses of pertussis vaccine (avoiding 687,000 deaths) and in 2014, the CV was estimated almost equal to 86% [2, 3].

Despite the excellent results related to the worldwide extensive vaccination, WHO data estimated 16 million cases of pertussis in 2010 (95% of which in developing countries), and 195,000 deaths in the pediatric population. In 2013, pertussis caused about 63,000 deaths in children under the age of 5 years [10].

In the USA, the latest CDC estimates reported 15,737 cases in 2016, with a 86% vaccine coverage with three doses. In particular, an incidence rate of 85.5/100,000 and a percentage of hospitalizations of 44% has been registered in children <6 months of age. In children between 6 and 11 months, incidence rate was 27.1/100,000, and 11.9% of them were hospitalized. In the same year, 7 deaths were registered; 6 of them involved <1 year old subjects [11].

With the introduction of vaccination programs, pertussis spreading has shifted to older age groups, thus involving adolescents and adults.

Accordingly to WHO data, this shift may be related to several factors, such as the increased recognition of less frequent manifestations of pathology in older adults, the use of more sensitive lab tests, a more accurate surveillance system that covers the entire life span, and the progressive decay of protective immunity related to a reduction in natural boosters [2].

However, the highest rates of morbidity and mortality attributable to pertussis are reported in children <1 year of age, especially in infants younger than 2 months of age [12]. Infants usually start immunization generally not before 2 months of age and this involves a time frame during which the risk of acquiring pertussis infection transmitted by family members and caregivers (mother, older siblings, grandparents, etc.) is very high [13].
