Pertussis – an old disease, new challenges

Over the last two decades, most European countries have reported a resurgence of whooping cough (pertussis) in child populations, despite high vaccination coverage (1). These follow ever earlier resurgences in the United States, Canada and Australia (2). The highest rates, and the most severe illnesses, occur in unvaccinated infants under the age of 3 months. This means that the main problem we face is how to ensure immunity against pertussis among young infants. In this issue of the journal, Berti et al. (3) publish recent data on the incidence of pertussis over a 13-year period (January 2000 to December 2012) in a highly vaccinated Italian population. Pertussis immunisation has been recommended in Italy since the 1960s, and for the first 30 years, the whole-cell pertussis vaccine was used. Since the 1990s, the acellular pertussis vaccine has been given to Italian children at three, five and 11 months and five to six years old, and in 2003, this was extended to children aged 12–14. In 2012, vaccination coverage in children under the age of 24 months was 95.1%. After the vaccinations were extended from infants to preschool children and then to school-aged children, the annual incidence of pertussis hospitalisations fell in oneto nine-year-old children, but not in infants or adolescents (3). In 2012, the incidence of pertussis hospitalisations was 46.2 per 100 000 (95%CI 22.8–69.6) children of all ages. Pertussis vaccinations are currently started at two months of age in most European countries (4). However, in a small number of countries, including Finland and Sweden, the first vaccination with acellular vaccine is given at three months of age, followed by booster vaccinations at 5 and 11–12 months and at 4–6 and 12 to 15 years of age (1,5). In Nordic countries, the coverage of the basic three-vaccination series has been very high, reaching 98 to 99% in Sweden (5). During the years 2007–2012, an average of 16 unvaccinated Finnish infants aged <3 months were hospitalised each year for microbiologically verified Bordetella pertussis infection (Infection Register, National Institute for Health and Welfare, Finland), providing an age-specific incidence of about 106 per 100 000. In Sweden, about 20 infants aged < 2.5 months were hospitalised for pertussis each year from 2008 to 2011 (5), which provides an agespecific incidence of about 100 per 100 000. A resurgence of pertussis in infants and a shift of cases from preschool children to adolescents, and even young adults, has been documented in most western countries (1,2). The shift is due to booster vaccinations given at preschool and school ages. Possible reasons for the reemergence of pertussis in well-vaccinated populations include increased awareness of the disease, activated surveillance, use of the highly sensitive polymerase chain reaction (PCR) for diagnosis and genetic changes in circulating B. pertussis strains under the selective vaccination pressure (1,4). Although booster vaccinations are currently offered after infancy, coverage at preschool age, and especially at school age, is less than coverage of the primary series in infancy. In addition, the waning of immunity may be faster in those vaccinated with the acellular vaccine, which contains fewer antigens than the previous whole-cell vaccine. Recent animal experiments even suggest that although acellular pertussis vaccine protects against the disease, it fails to prevent infection and transmission (6). The risk of an increasing occurrence of pertussis in young adults, including mothers and fathers of newborns babies, has been recognised in many countries and pertussis vaccinations are currently offered to pregnant women in parts of the United States and in the United Kingdom and the Netherlands and to all adults in France and Canada (4). We have known for some time that other household members are a common source of pertussis infections and that mothers, in particular, are responsible for transmitting pertussis to infants in more than 75% of cases (4,5). The most beneficial time to vaccinate pregnant women is the second half of pregnancy, because the immunoglobulin G transport through the placenta is most efficient during the third trimester. Safety data on vaccinating pregnant women are limited, but the registers have not revealed any alarming safety signals (4). Starting vaccinations at two months of age instead of the current 3 months in some countries would decrease the susceptible infant population by a third. However, vaccinating newborns may interfere with the responses to other vaccines given in infancy and, therefore, it is currently not recommended (1). An important adult target group who is insufficiently vaccinated is staff working with newborns and unvaccinated infants. Recent Finnish studies have documented that about 10% of unvaccinated or partially vaccinated infants hospitalised for bronchiolitis at less than six months of age with no clinical suspicion of pertussis had mixed respiratory syncytial virus (RSV) and B. pertussis infection (7,8). When hospital records were analysed retrospectively, the clinical pictures did not differ substantially between B. pertussis positive and negative bronchiolitis cases. A study of 126 English children under the age of 5 months, who were treated in the paediatric intensive care unit for respiratory infection, found that 20% of them had B. pertussis. In addition, retrospective analyses showed that pertussis positive infants presented more often with apnoeas and coughing spells than pertussis-negative infants (9).