Understanding the Epidemiology of Pertussis in Denmark

Vaccination against pertussis was introduced in Denmark in 1961 and quickly had a profound effect on the number of reported cases. Most importantly, the vaccine had a major effect on the number of infant deaths caused by pertussis. Where previous epidemics in the 1950s reached staggering incidences of around 1800 per 100 000 (annual, 1952), the first vaccine-era epidemic in 1964 had an annual incidence of approx. 490 per 100 000 [1]. Although 152 infants died from pertussis in the period from 1950 to 1959, only 20 died in the period from 1962 to 1986 [1]. Infant deaths from pertussis are now very rare, and only seven deaths have been registered in the period from 1995 to 2024 [2]. The two latest occurred in 2023 and 2010, and both were infants too young to be vaccinated. In Denmark, the current system for surveillance of pertussis is mandatory and is based on automatically collected data from laboratories. This has been in place for all age groups since 2007 [3]. There is moreover a mandatory clinical notification of cases in children less than 6 years of age. All cases of laboratory-confirmed pertussis can be monitored near real time, and the surveillance of pertussis can therefore be followed accurately without any lag. Denmark has experienced three substantial epidemics of pertussis during the last decade. These took place in 2016, 2019 and 2023. Before that, the latest epidemic had occurred in 2002. Common for all three recent epidemics was, that signs of increased incidence started to show in May or June, a rapid increase was observed around August (at the end of school summer holidays) and the highest incidence was in the period from October to February. So, although the highest incidence occurred in the winter months, the epidemics started half a year earlier. Many still tend to place pertussis in the ‘winter respiratory infections’ group, but pertussis occurs all year round. As for many other countries, pertussis almost disappeared in Denmark during and just after the COVID-19 period [4]. The vaccine introduced in 1961 for infants was a locally produced whole-cell vaccine and was initially given at 5 + 6 + 7 + 15 months of age, and from 1969 at 5 + 9 weeks and 10 months of age. This vaccine was later replaced by an acellular vaccine in 1997 along with a change in schedule to 3 + 5 + 12 months of age which is still recommended today. In 2003, an acellular pre-school booster at 5 years of age was included as well. In November 2019, a maternal vaccination during pregnancy was introduced, first as a temporary measure but it has now been made a permanent part of the vaccination schedule. This maternal vaccine is recommended at 24–32 weeks of gestation and at each pregnancy. In contrast to most other European countries, additional boosters for children, adolescents or adults are not included in the recommended schedule for pertussis vaccines in Denmark, as the primary intention is to prevent infant morbidity and mortality and not to avoid all cases. Additionally, a system of reminders for childhood vaccinations is in place. From 1997 to 2014, the acellular vaccines in use were locally produced (SSI, later AJ Vaccines) monocomponent DTaP or TdaP with a high dose (40 and 20 μg) of detoxified pertussis toxin as the only pertussis component (DiTeKiPol, DiTeKiPol/Act-Hib, diTekiBooster). Since 2014, various vaccine brands have been used, and the monocomponent childhood DTaP/TdaP were replaced in 2019. The current vaccines in 2025 are Pentavac for the infant series, Boostrix Polio for the 5 years booster and Triaxis or Boostrix for the maternal vaccination (deTekiBooster until Aug 2023). Pertussis vaccination in Denmark has had a high coverage since its introduction with more than 85% uptake of the infant series and more than 81% for the pre-school booster throughout all years with known data (96% and 92% in 2024) [2]. No significant changes in coverage were observed, neither increase nor decrease, during the COVID-19 years. Coverage of the maternal programme is currently estimated to be around 52%. Trying to compare old surveillance data to new is risky at best: changes in available diagnostic methods, the actual use of such methods, improved treatments, better knowledge, and changes in vaccine schedules have all had a massive impact on the epidemiology of pertussis. As an example, a new vaccine and vaccine schedule was introduced in 1997, and in 1999 there was suddenly a massive increase in cases. The primary reason for the increase was, however, that PCR was introduced as a diagnostic method in 1998; previous to that only culturing was available. All laboratory-confirmed cases are registered automatically; however, the system remains dependent on whether practitioners actually choose to make use of diagnostic tests. During epidemics, the higher focus on pertussis leads to a higher focus on diagnostic tests compared to non-epidemic periods. Moreover, there are also differences in the regional guidelines for testing. The 2023 epidemic was exceptionally high, with an incidence of 102 per 100 000. The previous two and a half years had shown extremely low incidences (Table 1), and the general population immunity to pertussis in 2023 was likely unusually low and driving the epidemic. The introduction of multiplex diagnostic tests including pertussis along with influenza and SARS-CoV-2, as well as the public being more used to having diagnostic tests done for respiratory infections, have likely also enhanced the proportion of laboratory-confirmed pertussis cases in 2023. Previously, the main age group for confirmed pertussis in Denmark was young children, but this was from a time when textbooks mainly mentioned pertussis as a ‘childhood disease’. From 2000 to 2004, children under 1 year old represented 16% of all cases, in the years 2015 to 2019 it was 7% and in the years from 2020 to 2024, where the maternal vaccination has been in place most of the time, this age group represented just 3% of all confirmed cases. Conversely, adults aged 30 years and older represented 13% from 2000 to 2004, 39% from 2015 to 2019 and 42% from 2020 to 2024. This is in keeping with heightened awareness amongst clinicians that pertussis infection is not just limited to children, and more adults are being referred for testing. Serology as a diagnostic method was introduced in Denmark in 2010, and this is particularly suitable for laboratory diagnosis of adults who are likely to wait some time before seeking medical advice. PCR is unsuitable if used after 3–4 weeks of illness due to low sensitivity, and the sensitivity of culture is even lower after this time [5]. Although PCR is currently the main method used in Denmark, laboratory confirmation of adult cases by serology has likely had an impact on the awareness of adult pertussis. As for the future for pertussis in Denmark, time will show. The protection conferred by pertussis vaccines is not lifelong, and eradication of pertussis is therefore unrealistic. Future changes to the Danish vaccination schedule will depend on thorough evaluations from the Danish National Immunisation Technical Advisory group. But no matter the changes, epidemics will likely continue to occur 4–5 years apart, as has been the case with pertussis both before and after widespread vaccinations were introduced around the world. T.D. compiled the data and background and was the main writer. P.H.A. and A.R. contributed knowledge on epidemiology and laboratory diagnostics and contributed to the writing of the main manuscript. We are very grateful for the work done at the departments of clinical microbiology in Denmark, as the surveillance of pertussis is based on laboratory data. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.