**6. Available vaccines**

major symptoms with severe complications [15]. The prognosis between the first and second year of life is particularly severe, with a high incidence as well as a high number of hospital admissions and deaths (0.2% and 4% lethality rates in developed and developing countries,

The pertussis incubation period generally lasts 7–10 days, with a range between 4 and 21 days; rarely, it can last up to 42 days. The typical course of the disease is divided into three phases. The first one, called "catarrhal stage," is characterized by the onset of rhinitis, sneezing, fever, and occasional mild coughing. The cough gradually becomes stiffer, and after 1–2 weeks, the second phase, called "paroxysmal stage" begins. Fever is generally low throughout the duration of the disease. It is during the paroxysmal stage that the diagnosis of pertussis can be suspected. Coughing is typical, generally violent, with sudden and paroxysmal attacks, frequently followed by vomiting. It is generally an expression of the difficulty of ejecting the mucus from the tracheobronchial tract. At the end of the paroxysmal attack, a long high-pitched whoop

Paroxysmal episodes are often followed by physical prostration. In the period between an episode and the other, the subject does not look ill. Paroxysmal attacks occur more frequently at night, with an average of 15 attacks in 24 hours. During the first 1 or 2 weeks of the paroxysmal phase, the attacks increase in frequency, remain stable for another 2–3 weeks and then gradually decrease. The paroxysmal stage usually lasts from 1 to 6 weeks, but can persist up to 10 weeks. In the third phase, "convalescence stage," there is a gradual recovery; paroxysmal cough attacks are less common and tend to disappear in 2 or 3 weeks. However, paroxysmal attacks can occur again, for many months after the onset of pertussis, in the case of concomitant respiratory infections.

The abovementioned description refers to pertussis in its typical form and without therapeutic intervention. Antibiotics significantly improve the clinical picture. The classic presentation

Adolescents, adults, and partially immunized children may have a milder course of disease than babies and infants; the infection can be asymptomatic or can present with symptoms ranging from mild cough to a classical pertussis with persistent cough. Although the disease may be milder in elderly people, such subjects may transmit the infection to other susceptible

The most common complication and cause of death related to pertussis is secondary bacterial pneumonia (about 10% of cases). Neurological complications, such as seizures and encephalopathy, are more common among newborns and may occur as a result of hypoxia or toxin-induced damage. Other less severe complications include otitis media, anorexia, and dehydration. Complications due to paroxysmal attacks include pneumothorax, epistaxis, conjunctival hem-

After natural infection, anti-PT antibodies (the only *B. pertussis* specific antigen) are found in 80–85% of patients [2]. Antibodies to different *B. pertussis* antigens are believed to play a

respectively) [16].

66 Pertussis - Disease, Control and Challenges

sound or gasp occurs (except in newborns) [17].

of pertussis occurs less frequently even after vaccination [18].

subjects, including unimmunized or not completely vaccinated infants [19].

orrhage, subdural hematomas, hernias, and rectal prolapse [17, 20].

**5. Immunological aspects**

The WHO, in the "position paper" on pertussis vaccination published in 2015 [2], points out that the primary goal of immunization should be to reduce the risk of severe forms in childhood, when morbidity and mortality are particularly high, and indicates 90% as the minimum level of coverage to be achieved with three doses in infants, starting vaccination at 6 weeks of age.

Historically, vaccination is carried out using two types of vaccine: whole or old generation vaccine and acellular or new generation vaccine. Both are mainly used as components of combined products (along with diphtheria and tetanus toxoid) in a 3-dose vaccine schedule.

The whole cell vaccine, consisting of inactivated bacteria, showed a highly variable efficacy (36–96%) and a relatively high reactogenicity in several clinical trials, and for this reason, its wide-scale use was limited [25–27]. The use of the whole cell vaccine may correlate with relatively frequent adverse reactions (AE) (26–40% of doses) such as fever, irritability, reactions at the inoculation site, or more rare AE, such as hypotonia-hyporesponsiveness (1/1500–2000 doses) [28, 29]. The proportion of local reactions tends to increase with the increase of age and of the number of administered doses; for these reasons, whole cell vaccines are not recommended in adolescents and adults [29].

Acellular vaccines are less reactogenic [30] and, thanks to their better safety and tolerability profile, their introduction has led to a gradual increase in coverage rates in most Western countries and, consequently, to a significant reduction in the incidence of the disease.

However, several studies have shown that the effectiveness of acellular vaccines decreases over time, leading to an increase in pertussis incidence after 8–12 years, even in areas with high vaccine coverage; this disadvantage has been reduced but not eliminated by using booster doses of reduced antigenic vaccine (ap) [31–33]. The duration of protection, however, tends to decrease, regardless of the administration of whole or acellular vaccine [34].

**8. Immunization in pregnancy**

given during pregnancy or lactation [45].

to be vaccinated.

Vaccination of pregnant women with dTpa vaccine is nowadays considered the best strategy for the protection of <2 months of age infants, which are a high-risk cohort being too young

Pertussis Immunization in Pregnancy: A Review http://dx.doi.org/10.5772/intechopen.72085 69

However, vaccination during pregnancy has been considered for a long time a negligible

The rationale for vaccination in pregnancy with a single dose of dTap is to provide protection against pertussis to the baby in his first months of life through the transplacental passage of maternal antibodies. One of the concerns firstly considered was the possible interference of maternal antibodies on the child's ability to mount an adequate immune response to pediatric DTaP or to other conjugated vaccines containing tetanus or diphtheria toxoids. Other concerns were related to the lack of data on safety and potential teratogenicity. However, now it is well known that there are no potentially serious adverse events in either the mother or the fetus following vaccination during pregnancy [43, 44]. One of the issues for the development of recommendations addressed to immunization of women during pregnancy and lactation is the lack of studies to make evidence-based decisions. Most of the available data on vaccine safety are derived from passive surveillance records. According to the CDC, the risk of a fetus following mother's vaccination during pregnancy is only theoretical. However, when considering vaccination, it is important to distinguish between live and inactivated vaccines. In particular, there is no theoretical reason to suspect that inactivated, bacterial or toxoid vaccines (pertussis one included), are associated with an increased risk of adverse events when

As of 2008 [46], the Advisory Committee on Immunization Practices (ACIP) recommended that pregnant women not previously vaccinated with dTap should receive a dose in the immediate postpartum period prior to hospital discharge; could receive dTap even a 2-year interval after a previous dose of dT vaccine; should receive dT during pregnancy as protection against tetanus and diphtheria when indicated; could postpone dT vaccine during pregnancy and replace it with dTap vaccine in the immediate postpartum period, if sufficient protection against tetanus and diphtheria was already available. In conclusion, although there were no contraindications for the administration of dTap vaccine during pregnancy, healthcare professionals had to eval-

Subsequently, an analysis was performed comparing immunization in pregnancy to postpartum vaccination in terms of impact, effectiveness, and costs [47]. Vaccination during pregnancy turned out to allow to prevent more cases of disease, hospitalization, and death than the postpartum approach for two reasons: first, because protection is achieved for both the mother and the child at birth; second, because vaccination, when performed during the third trimester of gestation, optimizes the transplacental transfer of maternal antibodies to the

Based on this evidence, ACIP [48] recommended in 2011 the use of dTpa to all pregnant women who had not previously received the vaccine. The vaccine has to be administered between the

uate risks and benefits before deciding to administer dTap to a pregnant woman.

fetus, ensuring protection for the newborn during his first months of life.

option because of the difficulty to assess its effectiveness and safety.

The introduction of pertussis vaccines, especially acellular ones, has certainly resulted in a strong containment of the incidence of disease, as a result of a gradual increase in vaccine coverage in most Western countries.

However, the illusion of having found a suitable tool to solve a relevant public health problem such as pertussis was short-lived. Since the early 2000s, a rise in pertussis incidence has been observed in several geographic areas, even where high vaccine coverage has been achieved for a long time [35]. This scenario underlines the need to identify a vaccine strategy that prevents the circulation of infection in all age groups and that, above all, helps to prevent illness in infants who have the highest risk of severe and even deadly complications.
