The increase in invasive pneumococcal disease across Europe is driven by Streptococcus pneumoniae, which also causes pneumonia and acute otitis media that can progress to invasive infections. Nearly 100 serotypes are known; however, only a few account for most cases.

Age is the strongest risk factor for severe pneumococcal infection, particularly in children younger than 2 years and older adults; therefore, conjugate vaccination is recommended for both groups. Several additional risk factors increase the likelihood of developing inflammatory pneumococcal disease (IPD).

Identifying High-Risk Adults

In clinical practice, it is crucial to identify patients at a particularly high risk for IPD in a timely manner. Which individual characteristics truly elevate risk? Are research gaps hindering the identification of at-risk populations?

A research team led by Kim Ditzel, MD, from the Department of Pulmonary Medicine, Rijnstate Hospital, Arnhem, Netherlands, examined whether diverse risk profiles hinder the identification of at-risk populations. The investigators conducted a systematic review and meta-analysis of 58 cohort and case-control studies that reported risk estimates for IPD in adults with specific risk factors compared with the general population. Most studies published before March 24, 2025, were eligible for meta-analysis.

The outcome was the risk for IPD, expressed as an incidence rate ratio (IRR), relative risk, hazard ratio, or odds ratio for each condition. More than 50 individual risk factors were consolidated into 22 broad risk domains. Differences in vaccination status among high-risk adults were incorporated into the bias assessment.

The primary outcomes were pooled in terms of incidence rates and odds ratios for adults of all ages, those aged 65 years or older, and those younger than 65 years. All studies were conducted in middle- or high-income countries, with cohorts beginning as early as 1983. IPD was defined as the detection of S pneumoniae in a normally sterile culture.

Key Risk Factors

The analysis identified the highest pooled risk estimates for IPD in adults in several domains, each with an IRR > 10.

Immunosuppressive conditions, including hematologic malignancies, HIV infection, transplant recipient status, and asplenia, showed IRRs of 19.63 (95% CI, 11.10-34.71), 21.87 (95% CI, 15.72-30.43), 30.75 (95% CI, 17.64-53.6), and 24.29 (95% CI, 18.63-31.65), respectively. Elevated IRRs were also reported for cerebrospinal fluid barrier dysfunction (IRR, 16.97; 95% CI, 2.77-103.89) and trisomy 21 (IRR, 47.48; 95% CI, 22.49-100.22).

Chronic diseases are associated with an increased risk for IPD. The highest risk was seen in adults younger than 65 years with kidney disease (IRR, 18.40; 95% CI, 11.38-29.74). The lowest pooled estimate across all risk domains was observed in men of any age (IRR, 1.89; 95% CI, 1.29-2.79).

The authors concluded that age itself, after correcting for other risk factors, represented a relatively low direct risk for IPD. The risk associated with a given condition is generally higher in people younger than 65 years than in the older population. Significant risk increases were confirmed for individuals with diabetes, African American ethnicity, and chronic liver disease.

Individual studies have identified additional risk factors, including homelessness, low income, nursing home residence, obstructive sleep apnea, prior bacterial pneumonia, and indigenous ancestry in North America and Australia. Immunostimulants, such as hematopoietic growth factors and interferons, in addition to immunosuppressants, were associated with a higher risk for IPD.

Four studies examined whether the accumulation of multiple risk factors increased overall individual risk. Adults with multimorbidity consistently showed higher IRR values than those with only one risk factor.

Implications for Practice and Vaccine Coverage

How can these risk probabilities be applied in clinical practice? The most pronounced risk factors align with the current pneumococcal vaccination recommendations for adults. Patients with these risks, especially those with multimorbidity, should be specifically targeted for immunization.

Relevant but often overlooked risk factors include low socioeconomic status, homelessness, and ethnicity. This information is often inaccessible to physicians during treatment, making it more practical to reach these groups through targeted vaccination campaigns at care facilities.

Although the researchers excluded studies that reported risk factors for recurrent IPD, one study reported that preceding pneumonia conferred a significantly increased risk for IPD (IRR, 5.5 and 2.9 for bacterial and influenza pneumonia, respectively).

The authors also excluded studies in which more than 10% of the population was younger than 14 years, and the risk factors for that age group were not identified.

However, pneumococcal infections in children and adolescents are epidemiologically important as they are frequent transmitters to older or vulnerable family members.

A multinational study, including researchers from Belgium and Italy, conducted a systematic literature review to assess the serotype distribution of invasive and noninvasive pneumococcal diseases in children aged 5 years or younger after the introduction of 10-valent pneumococcal conjugate vaccine (PCV) and PCV13 into national immunization programs. The authors reported that the widespread use of these vaccines led to a reduction in pneumococcal diseases in children, including IPD, acute otitis media, and community-acquired pneumonia.

Although the introduction of conjugate vaccines (starting with a PCV7 in 2006) reduced disease rates, it also altered circulating serotypes.

A review of 86 observational studies published from 2006 to 2020, 47 of which reported infectious disease propensity data, was conducted. Studies published after 2020 were excluded to avoid bias associated with the COVID pandemic, which disrupted vaccination uptake, infection surveillance, and healthcare access.

A key focus of this study was to assess the changes in IPD serotype distribution before and after the widespread introduction of PCV13. Even after integration into national immunization schedules, vaccine serotypes persisted in IPD cases, although at a reduced prevalence, with serotypes 3 and 19A among the most common residuals and serotype 1 prominent in some regions.

German surveillance data from 2015 to 2021, extending through the recent 2025 seasons in aligned reports, showed similar persistence, particularly of serotype 3.

The authors concluded that current vaccines provide incomplete protection against severe pneumococcal infections due to residual vaccine serotypes and emerging non-vaccine types. Vaccine- and antibiotic-driven genetic adaptations can facilitate serotype replacement and immune evasion. The impacts of the recently introduced PCV15 and PCV20 require ongoing evaluation alongside the development of next-generation platforms for broader immunogenicity.

This study represents part of a more comprehensive reviewexamining serotypes in IPD and community-acquired pneumonia across age groups, including adults aged 65 years or older, where vaccine serotypes 3 and 19A predominated alongside non-PCV13 serotypes 12F, 15A, and 22F.

Current Recommendations and Gaps

Current recommendations in Germany advise immunization with PCV20 for all infants from 2 months of age and for adults aged 65 years or older.

Adults previously vaccinated with the 23-valent polysaccharide vaccine should receive additional PCV20 immunization after a minimum interval of 6 years.

Vaccination is recommended for children, adolescents, and adults at elevated risk due to congenital or acquired immunodeficiencies and chronic diseases, as outlined in Table 2 of the 2025 STIKO recommendations.

Basic information on pneumococcal infections is available on the Robert Koch Institute in Germany information pages.

Because the effectiveness of polyvalent vaccines is not equal for all serotypes, achieving high vaccination coverage in children, vulnerable adults, and older adults is critical.

Significant immunization gaps persist, particularly in older adults.

A recent study by the Central Research Institute of Ambulatory Health Care in Germany showed large regional disparities in vaccine uptake among individuals aged 65 years or older. Beyond personal consultation with treating physicians, targeted and regionally adapted vaccination campaigns are needed to increase coverage rates.

This story was translated from Univadis Germany, part of the Medscape Professional Network.