Recurrent Invasive Pneumococcal Disease Carries Elevated Risk for Nearly Two Decades, Canadian Cohort Finds

Adults who survive a first episode of invasive pneumococcal disease (IPD) remain at substantially higher risk of a second episode than the general population for years afterward, according to a population-based cohort study published in JAMA Network Open. The findings also point to a persistent, largely unaddressed opportunity for pneumococcal vaccination in this high-risk group.¹

Nearly 2 Decades of Population-Based Surveillance

Investigators tracked 7006 adults who survived a primary IPD episode across Calgary and the Toronto-Peel region of Canada between 2004 and 2022. Of this cohort, 274 patients (3.9%) developed recurrent IPD (rIPD), collectively experiencing 334 recurrent episodes. The incidence of rIPD was highest in the year immediately following a primary episode, at 1468 cases per 100,000 person-years, compared with a baseline rate of just 9.7 cases per 100,000 person-years in the general adult population under surveillance—an incidence rate ratio (IRR) of 152 (95% CI, 124-185).

Although risk declined over time, it remained markedly elevated: from study years 5 through 17, the rIPD rate stabilized at 149 cases per 100,000 person-years—15 times the general population rate (IRR, 15; 95% CI, 11-20). This magnitude of risk elevation is consistent with earlier international data; a 25-year Australian surveillance study similarly found recurrent IPD incidence to be approximately 27-fold greater than that of primary disease in the general population.^1,2

Immunocompromising and Social Risk Factors Drive Recurrence

In adjusted analysis, the strongest predictors of rIPD were a history of hematopoietic stem cell transplant or hematologic cancer (adjusted OR, 5.17; 95% CI, 3.35-7.98) and HIV infection (adjusted OR, 4.47; 95% CI, 2.84-7.04). Experiencing homelessness (adjusted OR, 1.87; 95% CI, 1.30-2.69) and alcohol use disorder (adjusted OR, 1.50; 95% CI, 1.07-2.11) were also independently associated with increased odds of recurrence.

Conversely, patients 65 years or older had lower odds of rIPD than younger adults (adjusted OR, 0.55; 95% CI, 0.34-0.90), and primary infection with serotype 3 (adjusted OR, 0.33; 95% CI, 0.16-0.67) or serotype 7F (adjusted OR, 0.42; 95% CI, 0.21-0.87) was associated with reduced recurrence risk relative to other serotypes.

Notably, the proportion of recurrences caused by the same serotype as the primary episode declined sharply with time, from 68.6% when recurrence occurred within 89 days to just 6.3% when it occurred more than 2 years later.¹

Vaccination Rates Remained Low Despite High Eligibility

At the time of the primary IPD episode, 88% of patients with a known vaccination history were eligible for the pneumococcal vaccine, yet only 27.9% received a dose. Among patients with known vaccination status between their first and second episodes, 72.9% were eligible, but only 22.2% received a dose before recurrence.

Serotype coverage data suggest meaningful potential benefit from current-generation vaccines: among isolates from first recurrences, 63.1% were of serotypes included in the 20-valent pneumococcal conjugate vaccine (PCV20; Prevnar 20) and 70.8% in the 21-valent pneumococcal conjugate vaccine (PCV21; Capvaxive), with 89.6% covered by at least one of the two.¹

Implications for Pharmacists

The study authors note that current Canadian guidance does not formally recognize a prior IPD episode itself as an indication for vaccination, despite the markedly elevated recurrence risk it confers. In the US, the CDC's Advisory Committee on Immunization Practices recommends a single dose of a pneumococcal conjugate vaccine (PCV15, PCV20, or PCV21) for all adults 50 years and older, as well as younger adults with qualifying risk conditions and no or unknown vaccination history.

Because many patients at risk of recurrence—including those experiencing homelessness, alcohol use disorder, or immunocompromise—may face additional barriers to routine outpatient care, the authors suggest vaccination be offered during the index hospitalization itself. This finding dovetails with prior research from the same Calgary-based investigators showing that comorbidity burden and disease severity, not age alone, drive both early and late mortality in IPD, reinforcing the stakes of closing this vaccination gap before a recurrence occurs.

Pharmacists in inpatient, transitions-of-care, and ambulatory settings are well positioned to flag eligible but unvaccinated patients at IPD-related encounters and to help translate eligibility into completed doses.^1,3,4

REFERENCES

1. Ricketson LJ, Shigayeva A, Rajakumar I, et al. Incidence of recurrent invasive pneumococcal disease in Canada. JAMA Netw Open. 2026;9(7):e2621797.

2. Malo JA, Ware RS, Lambert SB. Estimating the risk of recurrent invasive pneumococcal disease in Australia, 1991-2016. Vaccine. 2021;39(40):5748-5756.

3. Centers for Disease Control and Prevention. Pneumococcal vaccine recommendations. Accessed August 28, 2026. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html

4. Ricketson LJ, Nettel-Aguirre A, Vanderkooi OG, Laupland KB, Kellner JD. Factors influencing early and late mortality in adults with invasive pneumococcal disease in Calgary, Canada: a prospective surveillance study. PLoS One. 2013;8(10):e71924.