Invasive pneumococcal disease in the 2020-2023 period
Occurrence of invasive pneumococcal disease, 2020-2023
During the COVID-19 pandemic in 2020 and 2021, the occurrence of invasive pneumococcal disease (IPD) was historically low, with 369 and 353 cases, respectively, corresponding to incidences of 6.3 and 6.0 per 100,000, Figure 1. For comparison, 2019 brought 639 cases; the lowest number of cases recorded to date, corresponding to an incidence of 11.0 per 100,000. Similar decreases were recorded during the COVID-19 pandemic for many of the infectious diseases that are monitored, which may likely be attributed to the interventions implemented to reduce COVID-19 transmission. Since the introduction of pneumococcal vaccination in the childhood vaccination programme in 2007, a steady decline in incidence has been observed. However, the decline in 2020 and 2021 was more pronounced than the previous decline and coincided with restrictions against COVID-19 as well as the introduction of a temporary pneumococcal vaccination programme for individuals aged 65 years or more and for certain risk groups under 65 years of age. Most of this considerable decline is probably due to restrictions as the incidence of IPD increased once again in 2022 and 2023 to 553 and 622 cases, corresponding to incidences of 9.4 and 10.5, respectively. In 2023, IPD incidence was therefore nearly in line with that recorded in 2019.
The incidence of IPD is highest in very young children under two years of age and in individuals aged 65 years and older, Figure 2. The decrease in IPD incidence in 2020 and 2021 was particularly pronounced among individuals aged 65 years and older, where the incidence dropped from 35.6 per 100,000 in 2019 to 17.8 in 2020 and 16.2 in 2021. In 2022 and 2023, the number of cases in this age group increased again, corresponding to incidences of 27.5 and 30.7, respectively. Among children below two years of age, the incidence decreased significantly following the introduction of a seven-valent pneumococcal vaccine (PCV7) in 2007 and decreased further after the vaccination programme switched to the 13-valent pneumococcal vaccine (PCV13) in 2010. However, no clear decrease was observed in incidence in 2020 and 2021, but as only few cases are recorded in this age group (12-20 annual cases in 2020-2023), it is difficult to draw any definite conclusions.
Pneumococci may be present in the nasopharynx without causing disease (known as carriage). In addition to IPD, pneumococci may cause non-invasive diseases such as pneumonia and acute otitis media. The IPD diagnosis can be made by detecting pneumococci in blood, cerebrospinal fluid and other normally sterile sites, such as pleural and joint fluid; and it can be detected by culture or PCR. If IPD is diagnosed using PCR only, it is often impossible to identify the serotype. The IPD diagnosis is most commonly based on findings in blood, whereas the proportion of IPD cases with findings in cerebrospinal fluid ranged from 9% to 13% in the 2020-2023 period, Table 1.
Temporary vaccination programme for adults in 2020-2023 and new vaccines
In April 2020, a temporary vaccination programme with a 23-valent polysaccharide pneumococcal vaccine (PPV23) was introduced. This programme concluded in January 2023. Initially, the vaccine was offered to people at particularly high risk of developing IPD and people aged 65 years and older with certain chronic conditions. Subsequently, the programme was extended first to include all people aged 65 years and older, and then to also include individuals under 65 years with certain chronic conditions. In the period during which the vaccine was provided free of charge (2020-2023), approximately 75% of the people aged 65 years and older who were offered the vaccine opted for vaccination. A study based on Danish data has shown that in this target group and from 15 June to 18 September, the vaccine was 58% (95 % CI: 21-78%) effective against IPD caused by the serotypes it covers.
In 2022, two new conjugated pneumococcal vaccines obtained marketing authorisation in Denmark for individuals aged 18 years and older. Both vaccines were subsequently approved for children from the age of 6 weeks. The vaccines are a 15-valent vaccine (PCV15) and a 20-valent vaccine (PCV20).
Although this temporary vaccination programme is no longer in place, conditional subsidies are still provided for certain vaccines for specific groups, as described on the website of the Danish Health Authority. Additionally, the website of the SSI on vaccination against pneumococci has been updated with guidance on the available vaccination options.
Serotype trends
More than 100 different serotypes of pneumococci exist that may cause infections in humans with varying frequencies. Following the introduction of PCV7 and subsequently PCV13 in the childhood vaccination programme, the incidence of IPD caused by the serotypes included in these vaccines has decreased significantly. However, an increase has been observed in the share of cases caused by serotypes included in the PCV13 in 2021 and 2022. This increase may, in particular, be attributed to an increase in serotype 3; see below for more information.
While the incidence of IPD caused by serotypes included in PCV13 has decreased since the implementation of the PCV13 in the childhood vaccination programme, the number of IPD cases caused by serotypes not included in the vaccine has increased. This phenomenon, known as "serotype replacement," involves that other serotypes than those targeted by vaccines start to dominate. Figure 3 presents the number of cases caused by serotypes included in various vaccines.
The serotypes most frequently causing IPD in the 2020-2023 period were serotypes 8, 3, 22F, 9N and 24F, Figure 4. Among these, serotype 3 is included in all available vaccines; 22F is included in PCV15, PCV20, and PPV23; serotype 8 is included in PCV20 and PPV23; and 9N is included in PPV23. Currently, serotype 24F is not covered by any vaccine.
In the 2013-2021 period, serotype 8 was the most common cause of invasive IPD, but the number of cases recorded declined sharply in 2020 and has remained stable in the 2020-2023 period. This reduction coincided with the introduction of a vaccine for adults that covers serotype 8. The number of IPD cases caused by serotype 3, which is covered by all available vaccines, also showed a decrease in 2020-2021, but has subsequently increased again. Serotype 3 is now the most commonly occurring serotype; and in 2022 and 2023, it caused more cases than before the COVID-19 pandemic. Despite vaccination, efforts to curb the incidence of serotype 3 have been unsuccessful, and the effectiveness of the currently available vaccines against this particular serotype remains unclear.
This annual report is also described in EPI-NEWS 18/2024.
General information about invasive pneumococcal disease
Invasive pneumococcal disease (IPD) is defined as a disease episode for which pneumococci (Streptococcus pneumoniae) have been detected in blood, cerebrospinal fluid or another normally sterile sampling material. Vaccination against pneumococcal disease forms part of the Danish childhood vaccination programme and is also recommended for special risk groups. You can read more about IPD and pneumococcal vaccination on the SSI website.
In 2007, a 7-valent conjugate pneumococcal vaccine (PCV7) was introduced for the first time in the Danish childhood vaccination programme. In relation to this, from October 2007, it became mandatory for laboratories to report findings of invasive pneumococci and to submit a bacterial isolate to the SSI for serotype determination, among others. This annual report is based on data from isolates submitted to SSI and also on data from the Danish Microbiology Database, MiBa.
Previously, pneumococcal meningitis cases and all cases of IPD in children below five years of age were notifiable in writing to the SSI. However, since the new Executive Order on the Notification of Infectious Diseases (Executive Order no. 1260 of 27/10/2023) came into force on 1 November 2023, IPD has been exclusively subject to mandatory laboratory reporting regardless of clinical manifestations and age. However, the duty to notify remains in place for cases that occur in an unusual manner that raises concerns, and in cases with suspicion of clustering of pneumococcal cases.