Risk conditions for invasive pneumococcal disease in adults: a systematic review and meta-analysis

The burden of invasive pneumococcal disease (IPD) in adults remains high despite vaccination programs. Age is currently the prime criterion used to define target groups for prevention. To support effective intervention programs, we investigated the relative importance of risk conditions associated with adult IPD.

We conducted a systematic search in PubMed and Embase and included all original studies published before March 24th 2025 that reported risk estimates for adult IPD in individuals with risk conditions, compared to the general population (PROSPERO ID 417980). Risk estimates were extracted and meta-analyses were performed for conditions supported by more than one study. Pooled incidence rate ratios with 95% confidence intervals (IRRs (95% CIs)) were calculated as the primary outcome using random-effects models. The risk of bias and the certainty of the evidence were assessed using the ROBINS-E tool and GRADE system respectively.

Of the 2983 reports screened, 58 were included in the systematic review, and 46 supported the meta-analyses. More than 50 different risk conditions for adult IPD were identified, which we synthesized in 22 risk domains for meta-analyses. The highest IRRs (95% CIs) for adult IPD were reported in immunocompromising conditions: transplant recipients 30.75 (17.64-53.60), asplenia 24.29 (18.63-31.65), people living with human immunodeficiency virus (PLWH) 21.87 (15.72-30.43), and haematological malignancy 19.63 (11.10-34.71). Increasing age itself mediated minor risk sizes. At lower age the risk conditions conferred relatively higher risk ratios. Chronic kidney disease in adults <65 years old posed an IRR (95% CI) of 18.40 (11.38-29.74), compared to 5.12 (2.08-12.63) among those over 65. IRRs >10 were also observed for compromised cerebrospinal fluid barrier and Down syndrome. The overall quality of evidence was very low, mainly due to high risk of bias and considerable between-study heterogeneity. Several studies suggested cumulative risk in individuals with multimorbidity, although data on interactions between conditions were limited.

This systematic review and meta-analysis quantify the relative importance of risk conditions for adult IPD. Understanding how these risk conditions interact in cases of multimorbidity remains an important area for future research.

Radboudumc Community for Infectious Diseases encouragement Grant.