**2.1. Loss of immunity**

Neither vaccination nor disease induces long-term protection against pertussis. Loss of protection occurs from 4 to 12 years after the last dose of vaccine and from 7 to 20 years after an episode of disease. The duration of protection of the whole-cell vaccine corresponds to that of the natural infection [3, 25].

observed on overall infant mortality. It also indicates the limited duration of the protection for pertussis in adolescents, pointing to the need for booster vaccination in adolescents who received the aP vaccine compared to those who had at least one dose of wP. There was no resurgence of the disease in Canada, but the periodic cycle had a higher peak in 2012 than in the previous two cycles. An increase in reported cases was limited to certain regions and happened over short periods. In general, the situation in the country is very heterogeneous with multiple causes for increase in pertussis cases (low vaccine coverage, decreasing immunity, previous wP vaccine with low efficacy), but there is no evidence that aP has contributed to the most recent increase in cases. The data suggest that the immunity induced by aP vaccines decreases before the booster dose of adolescence. Therefore, it can be concluded that the timing of adolescent's vaccination is important and that the age in which the third booster is

Clinical Experiences in Pertussis in a Population with High Vaccination Rate

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In Brazil, a country that still uses wP vaccines, national vaccination coverage in infants under 1 year of age with DTP3 (diphtheria-tetanus-pertussis) vaccine was high (>95%) between 2001 and 2011. From 2006 to 2012, the number of municipalities with coverage above 95% decreased from 83 to 55%, resulting in a heterogeneous coverage throughout the country. The causes for the decline were mainly operational issues due to supply and social problems. In Brazil, the number of pertussis cases increased from 2001 to 2012, with a large increase in morbidity and mortality among infants under 1 year old. This increase was attributed in part to improvements in surveillance sensitivity. Between 2007 and 2012, 51% of reported cases of whooping cough in children under 6 months of age did not receive any dose of vaccine, 37% received only one dose against whooping cough, and 12% received 2 or more doses. The majority of deaths, 342 (97%), occurred in children younger than 1 year of age. The increase in fatal cases among children under 6 months of age led the country to introduce the aP vaccine in pregnant women and also to recommend a cocooning strategy. The recurrence of the natural cycle, the drop in vaccination coverage, and the increase in laboratory tests may be responsible for the increase in the number of cases. There is no evidence of diminishing immunity, as cases are predominant in young infants not yet immunized, supported by the fact that the increase is not observed in older age groups, and the change in disease activity

does not exceed what would normally be expected in epidemic cycles [3, 29].

In Chile, the quality of data was improved in 2012, since the laboratory methods were previously not ideal. The resurgence of whooping cough observed in 2011 and 2012 was preceded by a drop in vaccine coverage and thus may be partly linked to this fall [3]. In Cuba, the notification is based only on the clinical definition, without laboratory confirmation. The country's data is therefore not comparable with data from other countries, thereby limiting its usefulness [3]. In Mexico, the data quality has serious limitations, and the sensitivity of the surveillance system is low. The increase in cases may be related to the low and heterogeneous vaccination coverage. The use of a more sensitive laboratory method (PCR) may explain the recent increase in cases, an idea supported by the dissociation of the total infant cases from whooping cough and infant mortality in 2012 [3]. In the European Union (EU), 40,727 cases of whooping cough were notified in 29 countries in 2014. The reporting rate was 9.1 cases per 100,000 inhabitants, higher than in 2013 but lower than in the epidemic year of 2012 [18]. Germany reported 12,339 cases (15.3 cases per 100,000 inhabitants) in 2014. Rates

commonly ministered (14–16 years old) may be too late.

The protection evoked by the vaccine tends to get lost over time. Predicted time of the drop of antibody protective levels after vaccination to pre-vaccine levels varies according to different antigens: 15.3 years for pertactin, 11 years for fimbria types 2 and 3, 5 years for pertussis toxin (PT), and 9.5 years for filamentous hemagglutinin. Adolescent vaccination has a good costbenefit, since it leads to a significant reduction in costs with the disease, but yet not all developed countries provide the booster dose for individuals aged between 10 and 17 years. There is evidence that immunization of adolescents also does not provide long-term protection, which may lead to the risk of adults and elderly people being more affected by infection. This raises the issue that adults should also receive booster doses, since adolescents and adults only have protection for a few years, and should receive booster doses every 10 years [20].

The antibodies to pertactin are correlated to the protection of the disease, but nowadays there is an increase of non-pertactin producing *B. pertussis* strains. In developed countries that use the acellular vaccine (which has pertactin as one of its components), loss of immunity may occur, as well as failure to prevent colonization by pertussis. However, other components of the vaccine (pertussis toxin, filamentous hemagglutinin, or fimbriae) also seem to prevent symptomatic pertussis [26].
