Pertussis re-emergence in the post-vaccination era

Elena Chiappini 0 1 Alessia Stival 0 1 Luisa Galli 0 1 Maurizio de Martino 0 1 0 Anna Meyer University Hospital, Department of Health Sciences, University of Florence , Florence , Italy 1 Background: Resurgence of pertussis in the post-vaccination era has been reported in Western countries. A shift of cases from school-age children to adolescents, adults and children under 1 year of age has been described in the last decade, and mortality rates in infants are still sustained. We aimed to review and discuss the possible vaccination strategies which can be adopted in order to improve the pertussis control, by searches of Pubmed, and websites of US and European Centers for Disease Control and Prevention , between 1st January 2002, and 1st March 2013 Discussion: The following vaccination strategies have been retrieved and analysed: the cocooning strategy, the immunization of pregnant women and newborns, vaccination programs for preschool children, adolescents, adults and health-care workers. Cost-effectiveness studies provide some contrasting data, mainly supporting both maternal vaccination and cocooning. Adolescent and/or adult vaccination seems to be cost-effective, however data from observational studies suggest that this vaccination strategy, used alone, leads to a reduced pertussis burden globally, but does not affect the disease incidence in infants. Moreover, substantial logistical and economic difficulties have to be overcome to vaccinate the largest number of individuals. Summary: The simultaneous use of more than one strategy, including cocooning strategy plus vaccination of adolescents and adults, seems to be the most reasonable preventive measure. The development of new highly immunogenic and efficacious pertussis vaccines continues to be a primary objective for the control of pertussis. - Background Pertussis is still a major public health concern in Western countries where, despite high vaccination coverage, yearly incidence continues to increase and mortality in children under 6 months of age reaches 0.2% [1]. This trend has been reported in Canada, the United States and Australia since the 1980s and in Europe some years later [2]. Large outbreaks recently occurred in the United States, reporting impressive figures. As an example, during the 2010 Californian epidemic, over 9,000 cases have been recorded, for a rate of 23.4 per 100,000, the highest number in 60 years [3-5]. Similarly, in the UK in 2012 the highest mortality rate was registered since 1982, with 10 deaths, all occurred in infants under 12 months old [6]. In Europe, 27 countries currently provide national surveillance data for pertussis under vaccine-preventable diseases): 17,596 confirmed cases were reported in 2009, corresponding to an incidence of 4.9 per 100,000 [7]. Data were heterogeneous among countries, ranging from 0.02 to 115 per 100,000. Pertussis rates were higher in Northern European countries, probably because some of them, including Sweden, Norway and Germany, achieved a high immunization coverage and introduced a booster dose after a primary immunization only recently. However, different rates may have been influenced not only by differences in vaccination policies, but also by differences in reporting procedures and surveillance systems, case definitions, and laboratory methods [2,7,8]. Possible reasons for the re-emergence of pertussis include the increased awareness of the disease, the development of new clinical definitions, and the spread use of polymerase chain reaction assays for laboratory confirmation, improving the diagnostic ability even in cases with atypical presentation [3,4,7,9]. Genetic changes in circulating strains of Bordetella pertussis, occurring under selective vaccination pressure, should also be considered [4,10]. Finally, protection from pertussis is not life-long, but restricted to a period of 58 years, after natural infection, as well as after vaccination [11]. This waning of immunity explains the shift of the incidence peak from school-age to adolescents/ adults, and the spread from these subjects to infants and young children, still unvaccinated or not-fully vaccinated (Figure 1) [4,7,8,12-17]. Children under 6 months of age have a 20-fold higher rate of infection than the total population and 90% of pertussis deaths occur in this age class [18]. Aim of the present study is to review and discuss the possible vaccination strategies which can be adopted in Western countries in order to improve the pertussis control. Discussion Literature search Data for this review were retrieved by searches of Pubmed, references from relevant articles and openaccess websites of US Centers for Disease Control and Prevention (CDC) and European Centre for Disease Prevention and Control (ECDC). In order to verify the completeness of the PubMed database, we also performed the same key word searches with other databases (Web of Science, Embase, Pascal), but the results were virtually overlapping with regard to the subjects of interest, or supplied supplemental articles out of the scope of this review. The search was limited to English-language publications involving humans. The search has been performed in order to identify articles published between 1st Janury, 2002 and 1st March, 2013. In particular the search strategy used in the PubMed database was the following: pertussis [Title] AND vaccine [Title]) AND (schedule [Title] OR strategy [Title] OR booster [Title] OR (cost [Title] AND effectives [Title]) OR efficacy [Title] OR pregnancy [Title] OR pregnant [Title] OR infants [Title] OR newborn [Title] OR adolescents [Title] OR (health-care [Title] AND worker [Title])) AND (hasabstract [text] AND 2003/02/ 16 [PDat] : 2013/02/12 [PDat] AND humans [MeSH Terms] AND English [lang]). This search resulted in 132 articles which were reduced to 94 on the basis of titles and abstracts. Types of pertussis vaccines currently available in Western countries In developed countries whole cell pertussis vaccines (wP) are not used anymore, due to the high rates of reported adverse events. In the 1970s and 1980s acellular pertussis (aP) vaccines were demonstrated to be effective, but less reactogenic than wP vaccines. As a consequence aP are now adopted in Western countries [19]. No preparation containing pertussis antigens alone is licensed in the United States or Europe to date [20]. Several pertussis vaccines are available combined with diphtheria and tetanus toxoids plus, eventually hepatitis B virus and/ or Haemophilus influenza type B and/or poliovirus antigens (i.e. Infarix, InfarixHepB, Infarix-hexa, Infarix-penta, Tetravac, Pentavac, Triacelluvax, Daptacel, Pentacel). They may include three antigens from purified Bartonella pertussis bacteria: pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) (i.e.: Infarix, Triacelluvax), or may be five-component vaccines additionally containing fimbrial antigen 2 (Fim2) and fimbrial antigen 3 (Fim3) (i.e. Daptacel (...truncated)