Immunization against pertussis in adolescents and adults

Clinical Microbiology and Infection xxx (2016) 1e7

Contents lists available at ScienceDirect

Clinical Microbiology and Infection journal homepage: www.clinicalmicrobiologyandinfection.com

Original Article

Immunization against pertussis in adolescents and adults S. Esposito*, N. Principi, for the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Vaccine Study Group (EVASG)
degli Studi di Milano, Fondazione IRCCS Ca' Granda Pediatric High Intensity Care Unit, Department of Pathophysiology and Transplantation, Universita Ospedale Maggiore Policlinico, Milan, Italy

a r t i c l e i n f o

a b s t r a c t

Article history: Received 29 August 2015 Received in revised form 23 December 2015 Accepted 3 January 2016 Available online xxx

Pertussis is a highly contagious infectious disease caused by Bordetella pertussis that can be extremely serious, particularly in young infants. For many years the efforts of health authorities throughout the world to prevent pertussis had the main goals of reducing the morbidity of infants and children under 5 years of age, maintaining protection for several years during the school-age period and developing a significant herd immunity to directly and indirectly reduce the risk of the spread of the disease among young infants and the risk of transmission of the infection from preschool children to infants. However, the increased risk of B. pertussis infection among adolescents and adults due to the waning immunity to this bacterium induced by vaccines and natural infection seems to be the main reason for the resurgence of pertussis. We discuss the reasons for the administration of pertussis vaccines to individuals for whom they were previously not recommended, the expected results of the administration of additional pertussis vaccine doses and the differences in the administration of pertussis vaccines in different countries. An analysis of the literature revealed several reports indicating the need for the modification of immunization schedules against pertussis, with booster doses among adolescents and the need for the vaccination of pregnant women. However, to monitor the true epidemiology of pertussis, effective programmes to collect pertussis cases, adequate reporting systems and vaccination coverage monitoring should be urgently implemented. S. Esposito, CMI 2016;▪:1 © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Editor: I. Gyssens Keywords: Acellular pertussis vaccine Adolescent vaccination Bordetella pertussis Chronic cough Pertussis Whole cell pertussis vaccine

Introduction Pertussis is a highly contagious infectious disease caused by Bordetella pertussis that can be extremely serious, particularly in young infants (http://www.cdc.gov/pertussis/about/signssymptoms.html). To prevent pertussis effective vaccines have been developed and are included in national immunization schedules worldwide for many years. Initially the vaccines were composed of a suspension of inactivated B. pertussis cells prepared with killed whole microorganisms, called whole-cell pertussis (wP) vaccines. They have been routinely recommended in industrialized countries since the 1940s and were used in throughout the world until the 1990s, when the acellular pertussis (aP)

* Corresponding author: S. Esposito, Pediatric High Intensity Care Unit, Depart
degli Studi di Milano, ment of Pathophysiology and Transplantation, Universita Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122 Milano, Italy E-mail address: [email protected] (S. Esposito).

vaccinesdvaccines composed of components of B. pertussis able to evoke protective immunitydwere licensed [1]. Because these new preparations were found to be significantly less reactogenic than the wP vaccines and were considered similarly effective to the wP vaccines, they progressively substituted the old preparations in most, if not all, countries. Because wP vaccines are less expensive, they remained in the immunization schedules of a number of developing countries, and in those countries they continue to be used today for pertussis prevention (http://www.who.int/ biologicals/vaccines/pertussis/en/). For many years the efforts of health authorities to prevent pertussis throughout the world had the main goals of reducing the morbidity of infants and children under 5 years of age, maintaining the protection for several years in the school-age period and developing significant herd immunity to directly and indirectly reduce the risk of the spread of the disease among young infants and the risk of the transmission of the infection from preschool-age children to infants [2]. This focus of pertussis preventive strategies on infants and young children was due to several epidemiologic

http://dx.doi.org/10.1016/j.cmi.2016.01.003 1198-743X/© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Esposito S, Principi N, Immunization against pertussis in adolescents and adults, Clinical Microbiology and Infection (2016), http://dx.doi.org/10.1016/j.cmi.2016.01.003

2

S. Esposito, N. Principi / Clinical Microbiology and Infection xxx (2016) 1e7

studies that had long shown that pertussis to be mainly a disease of infants and young children. The most severe cases of pertussis occurred in paediatric patients, and children were the greatest cause of the diffusion of B. pertussis throughout the community [3,4]. For many years nearly all health authorities worldwide recommended immunization schedules in which wP or aP vaccines were administered as a primary series of vaccinations in the first semester of life (with two or three consecutive doses) and two subsequent boosters, one in the second year of life and one in the preschool period. Vaccination schedules with two or three doses of vaccines against pertussis in the first semester of life showed similar efficacy, and their use depended on the schedules implemented in different countries for the vaccines combined with pertussis (i.e. the pentavalent and the hexavalent vaccines) [5]. However, even in countries with high pertussis vaccination coverage among infants, the incidence of the disease, which in the first decades of wP use had been significantly reduced, began to grow after the 1980s, particularly among unvaccinated infants and infants too young to have received all of the primary vaccine doses, as well as among adolescents and adults [6e8]. Because the increased risk of mild infection due to B. pertussis among adolescents and adults is considered to be the main reason for the resurgence of pertussis as a disease in infants, a modification to the pertussis immunization schedule with booster doses among adolescents and adults was recommended to reduce the risk of diffusion of B. pertussis among unprotected younger infants. Although available pertussis vaccines are far from being perfect and there is a need for better vaccines, in periodical global and regional meetings several groups of international experts, such as those included in the Global Pertussis Initiative (GPI) [9] and the Consensus on Pertussis Booster Vaccine in Europe (COPE group) [10], attempted to develop evidence-based recommendations for vaccination strategies to reduce disease burden. Initially it was suggested that adolescents and adults should receive booster doses of pertussis vaccine; later other measures were suggested, including: (a) the vaccination of family members and other adults in close contact with the neonate through the so-called cocooning strategy, (b) the administration of pertussis vaccine to pregnant women and (c) the administration of a vaccine dose immediately after birth. However, despite several attempts to reduce the incidence of pertussis beyond the first paediatric years of life and to limit the risk of pertussis in younger children, the actual pertussis incidence remained relevant because the recommendations of experts are only partially accepted by national health authorities (http://vaccine-schedule.ecdc.europa.eu/Pages/Scheduler.aspx) [11]. Here we discuss the reasons for the administration of pertussis vaccines to individuals for whom they were previously not recommended, the expected results of the administration of additional pertussis vaccine doses and the differences in the administration of pertussis vaccines in different countries. Epidemiology of pertussis The true global epidemiology of pertussis has not been precisely defined because the epidemiologic data collection varies between countries, which affects the interpretation of incidence trends. Surveillance of the general population, sentinel systems, voluntary notification by healthcare providers and laboratory notification are used for epidemiologic reporting with varying efficacies. Moreover, based on surveillance, the applied diagnostic methods and the definition of a pertussis case are also largely variable and include the World Health Organization pertussis clinical case definition, laboratory confirmation, local case definition and doctors' clinical diagnosis. Finally, over time, several countries have significantly

modified the pertussis surveillance system, and a comparison of the current actual epidemiology with those of previous years is difficult as a result of the different methods used for pertussis diagnosis (http://ecdc.europa.eu/en/publications/Publications/AER-2014VPD-FINAL.pdf). However, it is highly likely that the real incidence of pertussis in Europe is significantly higher than that derived from the surveillance systems due to underconsulting, underrecognition, misdiagnosis and underreporting of the disease. A study carried out in the United Kingdom reported that only 69.6% of the 1239 pertussis cases diagnosed in the North West Region between 1 April 1994 and 31 December 1996 were reported [12]. The notification rate was even lower for cases diagnosed at hospitals (29.6%) and laboratory-reported cases (45.6%). The rate of notification was estimated to be 35.7% (863/2420) using the captureerecapture method. Similarly, an evaluation of pertussis incidence carried out in Italy in 2000 through a paediatric sentinel network showed that despite wide variations among geographic areas the total number of diagnosed cases was 6e9 times higher than that collected by statutory notifications [13]. Underrecognition and misdiagnosis seem particularly important among adolescents and adults because in these subjects atypical presentation of pertussis is common. Persistent cough is frequently the only sign of the disease, and because this symptom can be attributed to a number of more common underlying causes, including Mycoplasma pneumoniae infection, rhinosinusitis and upper respiratory tract infection, pertussis is often not considered and specific laboratory tests for pertussis diagnosis are not performed [14]. On the other hand, in patients with chronic cough, nasopharyngeal samples are frequently negative, and only serology can identify pertussis cases. Serum collection and saliva sampling for the detection of specific antibodies are considered valid methods for pertussis diagnosis [15], although the cutoff levels of antibodies against different pertussis antigens, mainly pertussis toxin, that are considered indicative of recent or active infection are not definitively established [16]. Despite all these limitations, and considering that in different studies the epidemiology may differ whether the research is conducted during the epidemic peaks or in between the peaks, official data indicate that in the last 20 years in Europe a resurgence of pertussis has occurred, with an increase in the incidence of disease in younger infants, adolescents and adults. The data collected by the European-wide programme (EUVAC-NET), a project funded by the European Community for the surveillance of vaccinepreventable diseases in the European Union in 1998, clearly indicate that the total number of pertussis cases reported in Europe in subjects greater than 15 years of age more than doubled from 1998 to the period 2003e2007 (http://www.euvac.net/graphics/euvac/ pdf/pertussis1.pdf). A relevant increase was also found in patients 10e14 years of age. Moreover, regarding children <1 year of age, the incidence of pertussis, which was reduced from 1998 to 2001, was shown to have increased in 2002 and to have remained substantially unmodified in 2003e2007 (http://www.euvac.net/graphics/ euvac/pdf/pertussis1.pdf and http://www.euvac.net/graphics/ euvac/pdf/pertussis2.pdf). However, the greatest recorded increase in the pertussis incidence rate in Europe was in 2012, the last year for which official data are available. During this year the notification rate of pertussis cases was more than twice as high as in the previous year. The overall rate of confirmed cases in 2012 was 10.93 cases per 100 000 individuals (http://ecdc.europa.eu/en/ publications/Publications/AER-2014-VPD-FINAL.pdf), whereas during the period 2003e2007 the rate was 4.1/100 000 individuals (http://www.euvac.net/graphics/euvac/pdf/pertussis2.pdf). Young children and adolescents were the most commonly affected age groups, but a relevant number of cases were also diagnosed in adults (http://ecdc.europa.eu/en/publications/Publications/AER-

Please cite this article in press as: Esposito S, Principi N, Immunization against pertussis in adolescents and adults, Clinical Microbiology and Infection (2016), http://dx.doi.org/10.1016/j.cmi.2016.01.003

S. Esposito, N. Principi / Clinical Microbiology and Infection xxx (2016) 1e7

2014-VPD-FINAL.pdf). As reported by the Annual Epidemiological Report of the European Centre for Disease Control (http://ecdc. europa.eu/en/publications/Publications/AER-2014-VPD-FINAL.pdf) the increase in the incidence of pertussis was not uniform across all European countries. The Netherlands reported the highest number of cases in 2012, which was more than twice that detected in 2011. The United Kingdom reported nearly ten times more cases in 2012 than in 2011, but significant increases were also evidenced in Denmark, Latvia, Czech Republic, Austria, Lithuania, Ireland, Poland and Portugal. In Estonia and Italy no increase was reported [17]. The greater incidence of pertussis in groups of subjects previously considered at lower risk of infection and the impact of these infections on the youngest children, those not yet vaccinated or not completely vaccinated, were confirmed by several national studies performed in recent years, some of which used methods adequate to collect most, if not all, pertussis cases. A study carried out in France showed that 32% of adults with persistent cough lacking an evident cause had pertussis [18]. Similarly, a second regional French study showed that the annual incidence of pertussis in all patients with chronic cough was 145 cases per 100 000 individuals, a value several times higher than that reported in the official documents for subjects of the same age (Lasserre et al., paper presented at 28th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), 2010). Finally, Wendelboe et al. [19] performed a prospective international multicentre study in France and Germany to evaluate the source of 95 pertussis cases that occurred in infants 6 months of age and examined 404 individuals among household and nonhousehold contacts of infected infants. A comprehensive diagnostic evaluation (including PCR and serology) was performed on all participants independent of their symptoms. The source of pertussis was identified for 48% of the infants. Parents were the most common source of pertussis (55%), followed by siblings (16%), aunts/uncles (10%), friends/cousins (10%), grandparents (6%) and part-time caretakers (2%). Reasons for resurgence of pertussis When the increase in pertussis incidence was discovered, most experts did not think that it was due to any real change in pertussis epidemiology; rather, they believed that the development of new definitions of the disease, greater physician awareness of its clinical importance and above all the frequent use of molecular methods to identify the pathogen had improved the ability of clinicians to diagnose pertussis cases, including atypical cases [20,21]. Later the increase was thought to possibly also be due to the emergence of genetically modified B. pertussis strains that reduced the efficacy of pertussis vaccines [22]. However, the analysis of the age distribution of pertussis cases, with unexpected cases of pertussis occurring in adolescents, adults and very young infants, indicated that if all of the above-mentioned factors played a role in the resurgence of pertussis, it must have mainly been due to waning of the immune protection conferred by the vaccines administered to children. Several studies have shown that pertussis immunization is effective in the short term but that the protection evoked by all of the pertussis vaccines tends to wane with time [23e25]. A description of this problem was provided by Esposito et al. [26], who studied 38 children 5e6 years of age who had received the combined tetanus, diphtheria, aP and hepatitis B (TdaP-HBV) vaccine when they were 3, 5 and 11 months old and 21 subjects of similar age and gender who developed pertussis in the first year of life. Serum immunoglobulin G (IgG) antibody titres against P antigens included in the vaccine (P toxin, filamentous hemagglutinin and pertactin), peripheral blood mononuclear cellespecific proliferation in the presence of these P antigens and the secretion of the cytokines gamma interferon, interleukin (IL) 2, IL-4 and IL-5 by

3

those cells were measured 5 years after vaccination or infection. Only a small proportion of the children were found to have significant serum concentrations of specific IgG antibodies against all three B. pertussis antigens. Additionally, a minority of the children had persistent T-cell responses, indicating that the immune response induced by primary pertussis vaccination was not greatly qualitatively or quantitatively different from those observed in children with natural infection and that protection had rapidly declined in both groups. Subsequent studies showed that the primary vaccination series and the booster dose in the second year of life conferred protection persisting for approximately 7e10 years and that the second booster dose in the preschool period protracted protection for a similar period of time, although there were great differences among the subjects [27e30]. However, the speed at which the protection wanes depends on various factors, including the vaccination schedule and the type of vaccine. The aP vaccine seems to provide shorter-lasting protection than the wP vaccine: Clark et al. [31] found that children who received the entire series of aP vaccinations at the correct time were protected for a few years but became more likely to develop pertussis at 7e10 years of age, whereas those previously vaccinated with the wP vaccine were only at risk of developing pertussis during adolescence. Moreover, pertussis vaccines include different antigens, among which P toxin (PT) and pertactin (PTC) have a major role for pertussis prevention [5]. However, PT immunity is shorter than PTC immunity, but unfortunately PTC-deficient B. pertussis strains are emerging fast, and thus the benefits of PTC immunity might decrease [32,33]. Administration of booster doses to adolescents and adults Several vaccines are available to protect adolescents who have no immunity against pertussis even though they were previously vaccinated. Generally a combination of tetanusediphtheria and aP vaccines is used. In Europe three different preparations are on the market. In two vaccines the pertussis component includes five antigens (PTC, fimbriae types 2 and 3 (F2 and F3), PT and filamentous hemagglutinin (FH)), whereas in the third vaccine only three antigens (PTC, PT and FH) are included. Moreover, to limit the reactogenicity of the vaccines, which tends to increase with age, the content of the pertussis antigens was reduced (dTap) in comparison to other pertussis vaccines [10]. This does not alter the immunogenicity or the incidence of adverse events [34e36] (Mertsola et al., paper presented at 6th World Congress of the World Society for Pediatric Infectious Diseases, 2009). It was shown that a few weeks after dTap administration more than 90% of subjects who were previously vaccinated against pertussis during infancy and the preschool period were seropositive for pertussis antigens [34,35]. Moreover, similar data were collected in a nonvaccinated adolescent population, although estimation of the protective effect of pertussis vaccines is hampered by the lack of serologic correlates predictive of protection against pertussis infection [37e39]. The incidence of adverse events after dTap was found to not be substantially different from that reported in children who had received the full dose of the aP vaccine in the second year of life or in the preschool period [34]. Furthermore, the administration of a booster dose of dTap vaccine to adolescents was reported to result in the maintenance of antibody concentrations against all pertussis antigens included in the vaccine for at least 5 years at a significantly higher level than those measured before administration of the booster dose [40]. However, on the basis of the antibody concentrations measured beyond 5 years after the booster dose, Bailleux et al. [41] developed several mathematical models specifically designed to predict

Please cite this article in press as: Esposito S, Principi N, Immunization against pertussis in adolescents and adults, Clinical Microbiology and Infection (2016), http://dx.doi.org/10.1016/j.cmi.2016.01.003

4

S. Esposito, N. Principi / Clinical Microbiology and Infection xxx (2016) 1e7

further antibody decay for pertussis antigens. The predicted times for sufficient antibody decay to reach prevaccination levels were 15.3 years (95% confidence interval (CI) 7.0e28.0) for PTC, 11.0 years (95% CI 5.7e18.9) for F2 and F3, 10.5 years (95% CI 3.6e24.7) for PT and 9.5 years (95% CI 4.2e24.6) for FH. For at least 87% of the subjects the 10-year predicted antibody concentration was higher than the limit of quantitation for each pertussis antigen measured. Although there are no definitive data indicating that these antibody concentrations are adequate to significantly reduce or avoid the risk of pertussis, they support the effectiveness of pertussis vaccination with the administration of a booster dose with dTap in all adolescents, at least until the beginning of the adulthood. Furthermore, dTap administration to adolescents has been found able to reduce not only the incidence of pertussis in vaccinated individuals but also the transmission of the disease in the general population [42]. A retrospective analysis of pertussis cases reported in the United States between 1990 and 2009 showed that the introduction of dTap for adolescents in 2005 was associated with a considerable decrease in the number of cases involving subjects of 11e18 years of age [43]. In Western Australia, where dTap was administered to all high school students during the 2008e2009 epidemic, there was a decrease in pertussis case reports involving adolescents and infants of <6 months of age [44]. Moreover, at the end of a pertussis outbreak that occurred at a nursery through 12th grade school in St. Croix, US Virgin Islands, 18% of unvaccinated students were reported to have confirmed or probable pertussis compared to 6% of the vaccinated individuals, with a relative risk between unvaccinated and vaccinated subjects of 2.9 [45]. Finally, adolescent booster vaccination may be cost-effective. Purdy et al. [46] reported that in the United States, immunization of adolescents 10e19 years of age would prevent 0.7e1.8 million pertussis cases and save $0.6e$1.6 billion over a decade. Despite these premises, very few countries in Europe have included pertussis vaccination of adolescents in their systematically recommended vaccination schedules. Recognizing the need for pan-European guidance, a European group of experts (the COPE Group) met in 2008 and 2009 to develop a series of recommendations to rationalize the use of pertussis vaccines in all age groups and all subjects at risk. They proposed that adolescents 10e17 years of age should receive a combined dTap vaccine instead of a Td vaccine, regardless of the complete primary vaccination schedule or the type of previous pertussis booster received. Unfortunately the suggestions of that group and other experts worldwide [2] had only a partial effect because in actuality only 18 European countries have included a booster dose of the pertussis vaccine in their national immunization schedules for adolescents. Bulgaria, Croatia, Cyprus, Denmark, Lithuania, Latvia, Malta, Netherlands, Poland, Portugal, Romania, Slovenia and Spain do not recommend the P vaccine for adolescents (http://vaccine-schedule.ecdc.europa.eu/ Pages/Scheduler.aspx). On the other hand, one pertussis vaccine dose has an effect in protection of hospitalization and most severe disease. The immunologic evidence that administration of a booster dose of the pertussis vaccine to adolescents does not offer lifelong protection, which would generate the risk of adults and the elderly becoming the source of infection among unvaccinated or incompletely vaccinated children, suggested that further doses of the vaccine need to be given after adolescence. On the other hand, the vaccine was found to be immunogenic and effective in adolescents and adults. When administered to adults the dTap vaccine was found to be able to induce antibody levels not substantially different from those evoked in adolescents, with similar safety and tolerability [47e50]. Moreover, in a multicentre prospective study dTap administered to subjects aged 15e65 years was shown to have a protective effect of 95% against pertussis diagnosed by culture,

serology or PCR [51,52]. However, as for adolescents, for adults immunologic data suggested that the protection given by a single booster dose does not offer long-term protection and that periodic administration of the dTap vaccine would probably be needed to obtain this objective [53e55]. Interestingly, one study showed that among adolescents who received a dTap vaccine pertussis protection waned within 2 to 4 years [56]. The COPE Group and the GPI recommended that adults receive a single dose of dTap instead of dT, particularly for healthcare workers who can easily transmit the disease to unprotected subjects at high risk of developing severe pertussis [57]. However, even without considering periodical administration of dTap every 10 years to all adults, the proposal of a single dTap dose was poorly followed by the health authorities of European countries. Presently only Austria, Belgium, Czech Republic, France, Germany, Greece and Liechtenstein have included at least one booster dose of dTap in the adult immunization schedule, and among these countries only Austria, Belgium and Liechtenstein recommend multiple doses (http://vaccine-schedule.ecdc.europa.eu/Pages/Scheduler.aspx). Considering the data overall, despite the limitations due to epidemiologic changes, effectiveness of pertussis vaccines and waning immunity, we are in favour of a policy of receiving a dTap vaccination booster every 10 years without age limits to improve community protection against P. After the implementation of these booster programmes among adolescents and adults, it will be extremely important to evaluate their cost-effectiveness with adequate surveillance systems. Cocoon vaccination strategy and administration of pertussis vaccine in pregnant women The most recently developed strategies to reduce the risk of severe pertussis infection in younger infants are the cocoon strategy, which consists of vaccination of the family members and close contacts of the neonate, and vaccination of pregnant woman. As previously mentioned, because a great number of pertussis cases that occur in young infants are due to pertussis transmitted from parents or individuals who come into close contact with the infant and who, although previously vaccinated during childhood, have lost their immunity, it was hypothesized that the administration of a dTap dose to these subjects could significantly reduce the risk of pertussis in the first months of life [58]. Most of the data presently available regarding the effectiveness of cocooning are derived from studies based on computer simulation and statistical analysis. Some of those studies have shown that a cocoon strategy that is limited to the administration of a dTap dose to parents is not efficient [59e61]. However, Coudeville et al. [62] reported that combining the cocooning of parents with a systematic adolescent and adult booster can maintain a low incidence of pertussis. Conflicting data were also reported by two other studies carried out in humans. One study found that postpartum vaccination targeting only the mother was not associated with a reduction in the incidence of pertussis in young infants [63]. In a second study, the vaccination status of both parents of children <4 months of age who had pertussis was evaluated [64], and confirmed pertussis was significantly more common among children born to mothers and fathers who were not given the vaccine 4 weeks before the onset of pertussis symptoms. Although mathematical models have shown that cocooning can be cost-effective because it reduces the costs associated with pertussis [65], it seems clear that the potential efficacy of this pertussis preventive strategy is dependent on the number of adults who are vaccinated and on their previous immunization against the disease. Moreover, cocooning has some problems from an immunologic point of view because even if the dTap dose is given immediately after birth, it takes at least 2 weeks

Please cite this article in press as: Esposito S, Principi N, Immunization against pertussis in adolescents and adults, Clinical Microbiology and Infection (2016), http://dx.doi.org/10.1016/j.cmi.2016.01.003

S. Esposito, N. Principi / Clinical Microbiology and Infection xxx (2016) 1e7

for the vaccine to evoke protective antibody levels, and during this period the neonate remains exposed to the risk of B. pertussis transmission [66]. Finally, cocooning is costly and resource intensive to implement, and it requires full acceptance by parents and close contacts to truly effective. This last requirement cannot easily be met because although a high percentage of mothers accept dTap (75e86%), fathers are significantly more resistant (58%), and aunts (19%) and grandparents (12%) are even more resistant [67]. Vaccination of pregnant women is based on the fact that pertussis antibodies are transferred from the mother to foetus after vaccination or after natural infection. In a double-blind, placebocontrolled trial, vaccination in the third trimester of pregnancy produced sufficient concentrations of pertussis antibodies in neonates and infants of 2 months of age to assure theoretical protection in a great number of children [68]. Moreover, that trial [68] and two retrospective studies [69,70] showed that administration of the pertussis vaccine to pregnant woman was well tolerated, without any safety issues for the mother or the foetus. One study found a small but statistically significant increased risk of chorioamnionitis in vaccinated pregnant women [70]; however, because the risk was small and above all there was no increased risk of preterm birth, one of the most common complications of chorioamnionitis was observed; the authors stressed that this finding should be considered with great caution and suggested that the risk of chorioamnionitis may have been due to residual confounding variables. Finally, dTap administration during pregnancy does not interfere with the immune response to pertussis vaccine given during infancy according to the national immunization schedule [68,71]. Several trials have shown the clinical benefits associated with dTap vaccination during pregnancy. A study carried out in the United Kingdom, where pertussis vaccination for pregnant women has been recommended since 1 October 2012 (http://www.dh.gov. uk/health/2012/09/whooping-cough/), determined the vaccine's effectiveness by reviewing data of 26 684 women who experienced a live birth from 1 October 2012 to 3 September 2013 [72]. In the first 9 months of 2013, the total number of confirmed pertussis cases decreased in all age groups, but the decrease in infants of <3 months of age was the greatest proportionally, with a reduction of 78% compared to the first 9 months of 2012. Moreover, compared to 2011, the period of time during which a steep increase in pertussis activity occurred that disproportionally affected infants (https://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/338567/PHE_pertussis_in_pregnancy_ information_for_HP_2014_doc_V3.pdf), infants of <3 months of age were the only age group of infants that had fewer cases. The pertussis vaccine was found to have maximal efficacy when it was administered 28 days before birth, presumably because this permits significant antibody amounts to be transferred to the foetus and reduces the probability of the mother transferring the pathogen to the neonate [73]. A second study carried out in the United Kingdom showed that during the 10 months after pertussis vaccination during pregnancy became recommended, the laboratory confirmed that pertussis cases in infants <8 weeks of age were significantly more common (71%) among subjects born to unvaccinated mothers than among those born to women who received the vaccine at the proper time during pregnancy [74]. The estimated vaccine efficacy was 91%. Despite these favourable findings and the recommendations of all experts [10,58], in Europe presently only the United Kingdom, Ireland and Belgium have included pertussis vaccine for pregnant women in the national immunization schedule (http://vaccineschedule.ecdc.europa.eu/Pages/Scheduler.aspx), and in those countries the estimated coverage seems suboptimal. In the United Kingdom, where a strong campaign in favour of pertussis vaccine use in pregnancy involving general practitioners was implemented

5

from January to August 2014, P coverage in pregnant women was only slightly higher than 50% (https://www.gov.uk/government/ publications/pertussis-immunisation-in-pregnancy-vaccinecoverage-estimates-in-england-october-2013-to-march-2014/ pertussis-vaccination-programme-for-pregnant-women-vaccinecoverage-estimates-in-england-april-to-august-2014). In Belgium it was lower than 50%, although it showed a slight increase over time [75]. It is important to highlight that when wP vaccines are used during pregnancy, maternal antibodies could interfere with the immune response of the infant, and thus immunization in pregnancy does not seem to be a good strategy in resource-poor countries where the wP vaccines are still used [76]. All these data explain why only one country (i.e. Belgium) officially included cocooning among the methods of preventing pertussis in only young infants and why the GPI recommends maternal immunization during pregnancy as the primary strategy to protect young infants and only suggests cocooning when administration of dTap to pregnant women is not possible [58]. Administration of pertussis vaccine to neonates Some attempts have been made to verify whether administration of a dose of pertussis vaccine immediately after birth is effective at protecting neonates and infants. In some cases it was reported that this measure provided a greater antibody response to subsequent doses of the pertussis vaccine [77e80]. However, the available data are not sufficient to allow firm conclusions to be drawn. Moreover, a possible interference of the pertussis vaccine given during the neonatal period in the development of antibodies against Haemophilus influenzae type b and hepatitis vaccines found in the study by Knuf et al. [78] suggests that caution should be taken in regards to this measure and indicates the need for further studies to clarify the value of this measure in clinical practice. Conclusions In Europe, as in other parts of the world, the issue of waning protection offered by the paediatric schedule of pertussis vaccine administration, which has been implemented for a long time, and the need for further doses later in life and in selected subjects has been raised by multiple groups of experts. Several documents have reported the reasons for the need to modify immunization schedules. The recommendations have been only partially followed by the health authorities of various European countries. This is not surprising for the implementation of the cocooning strategy and the vaccination of neonates because the available data on the efficacy of these measures are not convincing. However, the lack of compliance to the recommendations for immunization of adolescents and adults is unacceptable, at least for those at high risk of transmission of the infection. Inclusion of a booster in the national immunization schedule requires the solution of a great number of organizational and economic problems. To be definitively convinced that the addition of a booster has to be made, health authorities require evidence that pertussis is truly a problem in their country. The response in the United Kingdom after the sharp increase of pertussis cases in young infants in 2011 clearly supports this fact. After evidence of the sharp increase in pertussis cases, the British Department of Health recommended that all women should be vaccinated against pertussis during every pregnancy (https://www.gov.uk/ government/uploads/system/uploads/attachment_data/file/ 338567/PHE_pertussis_in_pregnancy_information_for_HP_2014_ doc_V3.pdf). Determination of the true epidemiology of pertussis is not possible if effective programmes of collection of pertussis cases with adequate diagnostic facilities are not implemented in every

Please cite this article in press as: Esposito S, Principi N, Immunization against pertussis in adolescents and adults, Clinical Microbiology and Infection (2016), http://dx.doi.org/10.1016/j.cmi.2016.01.003

6

S. Esposito, N. Principi / Clinical Microbiology and Infection xxx (2016) 1e7

country. Moreover, reporting systems have to be maximally efficient. Finally, when new doses of pertussis vaccine are recommended, coverage has to be strictly monitored, and efficient strategies to assure compliance have to be planned. Unfortunately, in a great number of European countries one or more of these fundamental measures have not yet been implemented, and this explains the differences in the incidence of pertussis, vaccine use and vaccination coverage between countries. As suggested by the experts at the meeting in Barcelona, Spain, on 20 November 2012 (http://ecdc.europa.eu/en/publications/Publications/pertussismeeting-2012.pdf), the implementation of comprehensive studies specifically aimed at evaluating all issues associated with pertussis in all European countries is desirable in order to obtain common plans of action against this disease.

[19]

[20] [21]

[22] [23]

[24] [25]

Acknowledgement Supported in part by a grant from the Italian Ministry of Health (Bando Giovani Ricercatori 2009) GR-2009-1596786. Transparency declaration

[26]

[27]

All authors report no conflicts of interest relevant to this article. References [1] Cherry JD. Historical review of pertussis and the classical vaccine. J Infect Dis 1996;174(Suppl. 3):8259e63. € nig CH, Caro JJ, Plotkin S. Potential strategies to reduce [2] Forsyth K, Tan T, von Ko the burden of pertussis. Pediatr Infect Dis J 2005;24(Suppl. 5):S69e74. [3] Roush SW, Murphy TV. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA 2007;298:2155e63. [4] Centers for Disease Control and Prevention. PertussisdUnited States, 1997e2000. MMWR Morb Mortal Wkly Rep 2002;51:73e6. [5] Esposito S, Tagliabue C, Bosis S, Ierardi V, Gambino M, Principi N. Hexavalent vaccines for immunization in paediatric age. Clin Microbiol Infect 2014;20(Suppl. 5):76e85. [6] Centers for Disease Control and Prevention. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. MMWR Morb Mortal Wkly Rep 2011;60:13e5. [7] Cornia PB, Hersh AL, Lipsky BA, Newman TB, Gonzales R. Does this coughing adolescent or adult have pertussis? JAMA 2010;304:890e6. [8] Celentano LP, Massari M, Paramatti D, Salmaso S, Tozzi AE, EUVAC-NET Group. Resurgence of pertussis in Europe. Pediatr Infect Dis J 2005;24:761e5. [9] Campins-Martí M, Cheng HK, Forsyth K, Guiso N, Halperin S, Huang LM, et al., International Consensus Group on Pertussis Immunisation. Recommendations are needed for adolescent and adult pertussis immunization: rationale and strategies for consideration. International Consensus Group on Pertussis Immunisation. Vaccine 2001;20:641e6. [10] Zepp F, Heininger U, Mertsola J, Bernatowska E, Guiso N, Roord J, et al. Rationale for pertussis booster vaccination throughout life in Europe. Lancet Infect Dis 2011;11:557e70. [11] Centers for Disease Control and Prevention. National and state vaccination coverage among adolescents aged 13e17 yearsdUnited States, 2012. MMWR Morb Mortal Wkly Rep 2013;62:685e93. [12] Devine MJ, Bellis MA, Tocque K, Syed Q. Whooping cough surveillance in the north west of England. Commun Dis Public Health 1998;1:121e5. [13] Ciofi Degli Atti ML, Salmaso S, Bella A, Arigliani R, Gangemi M, Chiamenti G, et al., Pediatric Sentinel Surveillance Study Group. Pediatric sentinel surveillance of vaccine-preventable diseases in Italy. Pediatr Infect Dis J 2002;21: 763e8. [14] Terasaki G, Paauw DS. Evaluation and treatment of chronic cough. Med Clin North Am 2014;98:391e403. [15] Campbell H, Amirthalingam G, Fry NK, Litt D, Harrison TG, Wagner K, et al. Oral fluid testing for pertussis, England and Wales, June 2007eAugust 2009. Emerg Infect Dis 2014;20:968e75. [16] Mertens PL, Stals FS, Steyerberg EW, Richardus JH. Sensitivity and specificity of single IgA and IgG antibody concentrations for early diagnosis of pertussis in adults: an evaluation for outbreak management in public health practice. BMC Infect Dis 2007;7:53. [17] Gonfiantini MV, Carloni E, Gesualdo F, Pandolfi E, Agricola E, Rizzuto E, et al. Epidemiology of pertussis in Italy: disease trends over the last century. Euro Surveill 2014;19:20921. [18] Gilberg S, Njamkepo E, Du Chatelet IP, Partouche H, Gueirard P, Ghasarossian C, et al. Evidence of Bordetella pertussis infection in adults

[28]

[29]

[30] [31] [32]

[33]

[34]

[35]

[36]

[37]

[38] [39]

[40]

[41]

[42]

[43]

presenting with persistent cough in a French area with very high whole-cell vaccine coverage. J Infect Dis 2002;186:415e8. Wendelboe AM, Njamkepo E, Bourillon A, Floret DD, Gaudelus J, Gerber M, et al., Infant Pertussis Study Group. Transmission of Bordetella pertussis to young infants. Pediatr Infect Dis J 2007;26:293e9. Cherry JD. Epidemic pertussis in 2012dthe resurgence of a vaccine preventable disease. N Engl J Med 2012;367:785e7. Cherry JD, Tan T, Wirsing von Konig CH, Forsyth KD, Thisyakorn U, Greenber D, et al. Clinical definitions of pertussis: summary of a global pertussis initiative roundtable meeting, February 2011. Clin Infect Dis 2012;54:1756e64. Kallonen T, He Q. Bordetella pertussis strain variation and evolution postvaccination. Expert Rev Vaccines 2009;8:863e75. Blumberg DA, Mink CM, Cherry JD, Johnson C, Garber R, Plotkin SA, et al. Comparison of acellular and whole-cell pertussis-component diphtheriaetetanusepertussis vaccines in infants. The APDT Vaccine Study Group. J Pediatr 1991;119:194e204. Plotkin SA. The effectiveness of whole-cell pertussis vaccines. Dev Biol Stand 1997;89:171e4. Sheridan SL, Frith K, Snelling TL, Grimwood K, McIntyre PB, Lambert SB. Waning vaccine immunity in teenagers primed with whole cell and acellular pertussis vaccine: recent epidemiology. Expert Rev Vaccines 2014;13: 1081e106. Esposito S, Agliardi T, Giammanco A, Faldella G, Cascio A, Bosis S, et al. Longterm pertussis-specific immunity after primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine in comparison with that after natural infection. Infect Immun 2001;69: 4516e20. Gustafsson L, Hessel L, Storsaeter J, Olin P. Long-term follow-up of Swedish children vaccinated with acellular pertussis vaccines at 3, 5, and 12 months of age indicates the need for a booster dose at 5 to 7 years of age. Pediatrics 2006;118:978e84. Klein NP, Bartlett J, Rowhani-Rahbar A, Fireman B, Baxter R. Waning protection after fifth dose of acellular pertussis vaccine in children. N Engl J Med 2012;367:1012e9. Witt MA, Arias L, Katz PH, Truong ET, Witt DJ. Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort. Clin Infect Dis 2013;56:1248e54. Tartof SY, Lewis M, Kenyon C, White K, Osborn A, Liko J. Waning immunity to pertussis following 5 doses of DTaP. Pediatrics 2013;131:e1047e52. Clark TA, Messonnier NE, Hadler SC. Pertussis control: time for something new. Trends Microbiol 2012;20:211e3. Martin SW, Pawloski L, Williams M, Weening K, DeBolt C, Qin X, et al. Pertactin-negative Bordetella pertussis strains: evidence for a possible selective advantage. Clin Infect Dis 2015;60:223e37. Zeddeman A, van Gent M, Heuvelman CJ, van der Heide HG, Bart MJ, Advani A, et al. Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012. Euro Surveill 2014;19. pii 20881. Zepp F, Knuf M, Habermehl P, Mannhardt-Laakmann W, Howe B, Friedland LR. Safety of reduced-antigen-content tetanusediphtheriaeacellular pertussis vaccine in adolescents as a sixth consecutive dose of acellular pertussiscontaining vaccine. J Pediatr 2006;149:603e10. Pichichero ME, Blatter MM, Kennedy WA, Hedrick J, Descamps D, Friedland LR. Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents. Pediatrics 2006;117:1084e93. Halperin SA, Smith B, Russell M, Scheifele D, Mills E, Hasselback P, et al. An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults. Vaccine 2000;18:1312e9. Knuf M, Zepp F, Meyer C, Grzegowski E, Wolter J, Riffelmann M. Immunogenicity of a single dose of reduced-antigen acellular pertussis vaccine in a non-vaccinated adolescent population. Vaccine 2006;24:2043e8. Plotkin SA. Complex correlates of protection after vaccination. Clin Infect Dis 2013;56:1458e65. Xing D, Asokanathan C, Xu YH, Bolgiano B, Douglas-Bardsley A, Zhang S, et al. Relationship of immunogenicity to protective potency in acellular pertussis vaccines. Hum Vaccin Immunother 2014;10:2066e73. Barreto L, Gasparini R, Meekison W, Noya F, Young L, Mills E. Humoral immunity 5 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine. Vaccine 2007;25:8172e9.  P. Bailleux F, Coudeville L, Kolenc-Saban A, Bevilacqua J, Barreto L, Andre Predicted long-term persistence of pertussis antibodies in adolescents after an adolescent and adult formulation combined tetanus, diphtheria, and 5component acellular pertussis vaccine, based on mathematical modeling and 5-year observed data. Vaccine 2008;26:3903e8. Kandola K, Lea A, White W, Santos M. A comparison of pertussis rates in the Northwest Territories: pre-and post-acellular pertussis vaccine introduction in children and adolescents. Can J Infect Dis Med Microbiol 2005;16: 271e4. Skoff TH, Cohn AC, Clark TA, Messonnier NE, Martin SW. Early impact of the US Tdap vaccination program on pertussis trends. Arch Pediatr Adolesc Med 2012;166:344e9.

Please cite this article in press as: Esposito S, Principi N, Immunization against pertussis in adolescents and adults, Clinical Microbiology and Infection (2016), http://dx.doi.org/10.1016/j.cmi.2016.01.003

S. Esposito, N. Principi / Clinical Microbiology and Infection xxx (2016) 1e7 [44] Quinn HE, McIntyre PB. The impact of adolescent pertussis immunization, 2004e2009: lessons from Australia. Bull World Health Organ 2011;89: 666e74. [45] Wei SC, Tatti K, Cushing K, Rosen J, Brown K, Cassiday P, et al. Effectiveness of adolescent and adult tetanus, reduced-dose diphtheria, and acellular pertussis vaccine against pertussis. Clin Infect Dis 2010;51:315e21. [46] Purdy KW, Hay JW, Botteman MF, Ward JI. Evaluation of strategies for use of acellular pertussis vaccine in adolescents and adults: a cost-benefit analysis. Clin Infect Dis 2004;39:20e8. [47] Grimprel E, von Sonnenburg F, Sanger R, Abitbol V, Wolter JM, Schuerman LM. Combined reduced-antigen-content diphtheriaetetanuseacellular pertussis and polio vaccine (dTpa-IPV) for booster vaccination of adults. Vaccine 2005;23:3657e67. [48] Blatter M, Friedland LR, Weston WM, Li P, Howe B. Immunogenicity and safety of a tetanus toxoid, reduced diphtheria toxoid and three-component acellular pertussis vaccine in adults 19e64 years of age. Vaccine 2009;27:765e72. [49] Van der Wielen M, Van Damme P, Joossens E, Francois G, Meurice F, Ramalho A. A randomised controlled trial with a diphtheriaetetanuseacellular pertussis (dTpa) vaccine in adults. Vaccine 2000;18: 2075e82. [50] Van Damme P, Burgess M. Immunogenicity of a combined diphtheriaetetanuseacellular pertussis vaccine in adults. Vaccine 2004;22:305e8. [51] Ward JI, Cherry JD, Chang SJ, Partridge S, Keitel W, Edwards K, et al., APERT Study Group. Bordetella pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized acellular pertussis vaccine trial (APERT). Clin Infect Dis 2006;43:151e7. [52] Ward JI, Cherry JD, Chang SJ, Partridge S, Lee H, Treanor J, et al., APERT Study Group. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med 2005;353:1555e63. € nig CH. Antibody decay after [53] Riffelmann M, Littmann M, Hülsse C, von Ko immunisation of health-care workers with an acellular pertussis vaccine. Eur J Clin Microbiol Infect Dis 2009;28:275e9. €nig CH. Long-term immunoge[54] Littmann M, Hülsse C, Riffelmann M, von Ko nicity of a single dose of acellular pertussis vaccine in paediatric health-care workers. Vaccine 2008;26:2344e9. [55] Christie CDC, Garisson KM, Kiely L, Gupta RK, Heubi J, Marchant CD. A trial of acellular pertussis vaccine in hospital workers during the Cincinnati pertussis epidemic of 1993. Clin Infect Dis 2001;33:997e1003. [56] Acosta AM, DeBolt C, Tasslimi A, Lewis M, Stewart LK, Misegades LK, et al. Tdap vaccine effectiveness in adolescents during the 2012 Washington State pertussis epidemic. Pediatrics 2015;135:981e9. [57] Heininger U. Vaccination of health care workers against pertussis: meeting the need for safety within hospitals. Vaccine 2014;32:4840e3. €nig CH. Strategies to decrease [58] Forsyth K, Plotkin S, Tan T, Wirsing von Ko pertussis transmission to infants. Pediatrics 2015;135:e1475e82. [59] Meregaglia M, Ferrara L, Melegaro A, Demicheli V. Parent “cocoon” immunization to prevent pertussis-related hospitalization in infants: the case of Piemonte in Italy. Vaccine 2013;31:1135e7. [60] Lim GH, Deeks SL, Crowcroft NS. A cocoon immunisation strategy against pertussis for infants: does it make sense for Ontario? Euro Surveill 2014;19. pii:20688. [61] Skowronski DM, Janjua NZ, Tsafack EP, Ouakki M, Hoang L, De Serres G. The number needed to vaccinate to prevent infant pertussis hospitalization and death through parent cocoon immunization. Clin Infect Dis 2012;54:318e27. [62] Coudeville L, van Rie A, Andre P. Adult pertussis vaccination strategies and their impact on pertussis in the United States: evaluation of routine and targeted (cocoon) strategies. Epidemiol Infect 2008;136:604e20.

7

[63] Healy CM, Rench MA, Wootton SH, Castagnini LA. Evaluation of the impact of a pertussis cocooning program on infant pertussis infection. Pediatr Infect Dis J 2015;34:22e6. [64] Quinn HE, Snelling TL, Habig A, Chiu C, Spokes PJ, McIntyre PB. Parental Tdap boosters and infant pertussis: a case-control study. Pediatrics 2014;134: 713e20. pey P, Nguyen VH. Adult [65] Coudeville L, Van Rie A, Getsios D, Caro JJ, Cre vaccination strategies for the control of pertussis in the United States: an economic evaluation including the dynamic population effects. PLoS One 2009;4:e6284. [66] Halperin BA, Morris A, Mackinnon-Cameron D, Mutch J, Langley JM, McNeil SA, et al. Kinetics of the antibody response to tetanus-diphtheriaacellular pertussis vaccine in women of childbearing age and postpartum women. Clin Infect Dis 2011;53:885e92. [67] Rossmann Beel E, Rench MA, Montesinos DP, Healy CM. Acceptability of immunization in adult contacts of infants: possibility of expanding platforms to increase adult vaccine uptake. Vaccine 2014;32:2540e5. [68] Munoz FM, Bond NH, Maccato M, Pinell P, Hammill HA, Swamy GK, et al. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial. JAMA 2014;311:1760e9. [69] Donegan K, King B, Bryan P. Safety of pertussis vaccination in pregnant women in UK: observational study. BMJ 2014;349:g4219. [70] Kharbanda EO, Vazquez-Benitez G, Lipkind HS, Klein NP, Cheetham TC, Naleway A, et al. Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outcomes. JAMA 2014;312:1897e904. [71] Hardy-Fairbanks AJ, Pan SJ, Decker MD, Johnson DR, Greenberg DP, Kirkland KB, et al. Immune responses in infants whose mothers received Tdap vaccine during pregnancy. Pediatr Infect Dis J 2013;32:1257e60. [72] Amirthalingam G, Andrews N, Campbell H, Ribeiro S, Kara E, Donegan K, et al. Effectiveness of maternal pertussis vaccination in England: an observational study. Lancet 2014;384:1521e8. [73] Healy CM, Baker CJ. Prospects for prevention of childhood infections by maternal immunization. Curr Opin Infect Dis 2006;19:271e6. [74] Dabrera G, Amirthalingam G, Andrews N, Campbell H, Ribeiro S, Kara E, et al. A caseecontrol study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012e2013. Clin Infect Dis 2015;60:333e7. [75] Englund JA, Anderson EL, Reed GF, Decker MD, Edwards KM, Pichichero ME, et al. The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids. Pediatrics 1995;96:580e4. [76] Laenen J, Roelants M, Devlieger R, Vandermeulen C. Influenza and pertussis vaccination coverage in pregnant women. Vaccine 2015;33:2125e31. [77] Halasa NB, O’Shea A, Shi JE, LaFleur BJ, Edwards KM. Poor immune responses to a birth dose of diphtheria, tetanus, and acellular pertussis vaccine. J Pediatr 2008;153:327e32. [78] Knuf M, Schmitt HJ, Wolter J, Schuerman L, Jacquet JM, Kieninger D, et al. Neonatal vaccination with an acellular pertussis vaccine accelerates the acquisition of pertussis antibodies in infants. J Pediatr 2008;152:655e60. [79] Knuf M, Schmitt HJ, Jacquet JM, Collard A, Kieninger D, Meyer CU, et al. Booster vaccination after neonatal priming with acellular pertussis vaccine. J Pediatr 2010;156:675e8. [80] Wood N, McIntyre P, Marshall H, Roberton D. Acellular pertussis vaccine at birth and one month induces antibody responses by two months of age. Pediatr Infect Dis J 2010;29:209e15.

Please cite this article in press as: Esposito S, Principi N, Immunization against pertussis in adolescents and adults, Clinical Microbiology and Infection (2016), http://dx.doi.org/10.1016/j.cmi.2016.01.003