**Fundings**

The major causative agent of pertussis, *Bordetella pertussis*, was first isolated in 1906 by Bordet and Gengou [3], and throughout that century, endemic and epidemic episodes of the disease

In 1933, a vaccine which conferred a certain degree of protection was described, a suspension of killed *B. pertussis* cells [5]. In that decade and in the next, several whole cell pertussis preparations have been described and used in both prevention and treatment of the disease, with some efficacy [6]. In 1947, the Kendrick protection test was described, with intracerebral challenge in mice that is until now recommended by the WHO as an assay of potency of whole cell pertussis vaccines and the only one that showed correlation with protection in children [7]. Immunization against pertussis is part of the childhood immunization schedule and in some countries it is also recommended in booster doses for adolescents and adults [8]. Whole cell pertussis vaccines (wP), composed of inactivated suspensions of partially detoxified *B. pertussis*, have been used in vaccination programs for 60 years with proven efficacy, combined with tetanus and diphtheria toxoids adsorbed on aluminum salts as adjuvants [9]. The introduction of these vaccines in the 1950s–1960s led to a dramatic reduction of more than 90% in the

incidence and mortality caused by the disease in the industrialized world [10].

age, making the resurgence of the disease a worldwide problem [17–19].

faster loss of immunity could certainly contribute to this scenario [20].

immunity for a period of 8.5 years after the last dose [22].

Adverse reactions related to them led to development of acellular pertussis vaccines (aP), containing purified antigenic components of *B. pertussis*. These preparations are effective and less reactogenic [11], and they have replaced the (wP) in several countries in the last two decades. However, their cost of production is much higher, making prohibitive their introduction in developing countries. Preliminary clinical trials in the 1990s comparing bacterial triple vaccines formulated with diphtheria (D) and tetanus (T) toxoids combined with whole cell pertussis component (DTwP) or acellular pertussis component (DTaP), suggested similar efficacy and immunogenicity [12–16]. More recent data showed that pertussis is not adequately controlled, and epidemic outbreaks are occurring even in countries with high vaccination cover-

This increase in the incidence is certainly related to multiple factors. The improved diagnostic testing, which would lead to an increase in reported cases; the decrease in vaccine efficacy and

Besides that, the introduction of the aP vaccines which appear to require earlier and more frequent booster doses for disease control, suggest a shorter period of effective immunity [21]. A recent study in a systematic review and meta-analysis of published studies comparing the efficacy of wP and aP within 3 years after the 3-dose primary series concluded that the protection against the disease was lower for aP vaccines than for the wP, with efficacy of 84% and 94%, respectively [22]. The study, comparing the duration of immunity conferred by childhood vaccination scheme using 3–5 doses of DTaP, suggested that for each year after the last dose of DTaP, the disease probability would be increased 1.33 times. Assuming 85% of vaccine efficacy it was estimated that only 10% of the vaccinated children had persistence of pertussis

Broadly speaking, aP vaccines are considered safer, but there is a currently consensus that they also require more frequent booster doses, given that they confer protective immunity for a shorter

were recorded [4].

4 Pertussis - Disease, Control and Challenges

This work was funded by the Brazilian National Bank for Economic and Social Development (BNDES), National Council for Scientific and Technological Development (CNPq) and Butantan Foundation.
