Study Adds New Rationale for Pneumococcal Vaccination in At-Risk Adults

Adults hospitalized with invasive pneumococcal disease (IPD) frequently harbor previously undiagnosed monoclonal immunoglobulins and antibody deficiencies, according to a prospective multicenter study published in Scientific Reports. Investigators from multiple hospitals in Sweden's Region Västra Götaland followed 156 adult patients with IPD, drawing blood during acute infection and again 2 to 4 months later in convalescence, and compared the results with samples from 64 age- and sex-matched controls without IPD.¹

The findings suggest that a single episode of IPD may be the first clinical clue to an underlying, previously undiagnosed B-cell malignancy or antibody deficiency.¹

M Protein Detection Reveals Hidden Malignancies

Among patients without a previously known hematological malignancy, M protein—an abnormal, non-functional immunoglobulin produced by a clonal population of plasma cells—was detected in 22% of IPD patients during acute infection, compared with 5% of controls. After statistical adjustment for age, sex, and predisposing conditions, patients with IPD had roughly 8-fold higher odds of M protein detection than non-hospitalized controls.¹

Follow-up testing resolved the M protein in 7 patients by the convalescent phase, but among those with persistent M protein, 7 were subsequently diagnosed with a hematological malignancy, including multiple myeloma, Waldenstrom macroglobulinemia, and mantle cell lymphoma, while another 12 were diagnosed with monoclonal gammopathy of undetermined significance (MGUS), a precursor condition that is usually asymptomatic and often goes undetected.¹

Patients newly diagnosed with MGUS or a B-cell malignancy had a median age of 76 years and most presented with pneumonia. None of the patients with newly diagnosed MGUS died during follow-up, though 1 patient with a new B-cell malignancy diagnosis died within a year of the IPD episode.¹

Immunoglobulin Deficiencies Often Went Unrecognized

Beyond M protein, the study also examined overall immunoglobulin (Ig) levels. IgG2 concentrations were significantly lower in patients than in controls during both the acute and convalescent phases, and minor but significant differences in IgG4 levels were also observed. Overall, 44% of patients sampled during acute infection and 34% in convalescence had at least 1 Ig or IgG subclass below the lower limit of the reference interval, compared with 16% of controls.¹

Follow-up evaluation of patients with persistently low Ig levels led to a diagnosis of primary immunodeficiency in 3 patients, including 2 with a history of repeated bacterial respiratory infections, and secondary immunodeficiency in 4 additional patients tied to a known hematological malignancy or prior rituximab treatment. In total, 7 patients started immunoglobulin replacement therapy following the investigation. The study also found that circulating B-cell counts remained significantly lower in patients than in controls during convalescence, pointing to a lingering effect on the adaptive immune system even after recovery from the acute infection.¹

The authors noted that because M protein, Ig, and IgG subclass levels are not part of routine care for a single IPD episode, most of these patients would otherwise go undiagnosed in current clinical practice. They concluded that assessment of M protein and Ig levels could be considered in adult patients following an episode of IPD, while acknowledging that larger, more comprehensive studies are needed to confirm which patient subgroups would benefit most from such investigation.¹

A Shifting Pneumococcal Vaccine Landscape

The Swedish findings arrive as pneumococcal disease overall is drawing renewed attention. Culture-confirmed pneumococcal disease declined during COVID-19 restrictions but has since rebounded, with a particularly sharp post-pandemic rise among children under 5 years, and international data indicate that IPD incidence nearly doubled between 2012 and 2024. Serotype replacement—the emergence of strains not covered by earlier vaccines—has also intensified, with nonPCV13 serotypes now accounting for roughly three-quarters of culture-confirmed cases in some surveillance data.²

For pharmacists, this evolving picture adds another layer to an already complex vaccination landscape. Pneumococcal conjugate vaccines PCV15, PCV20, and PCV21, along with the polysaccharide vaccine PPSV23, each carry different serotype coverage and administration recommendations, and the choice of product can depend on a patient's age, prior vaccination history, and even geography. For example, PCV20 covers serotype 4, a strain more prevalent in unhoused populations in the Western United States, while PCV21 does not.^3,4

Paul Licciardi, PhD, group leader of vaccine immunology at the Murdoch Children's Research Institute, said the growth in vaccine options reflects the bacterium's ability to evolve under vaccine pressure.

“The bacteria have ways of evolving under vaccine pressure,” Licciardi told Drug Topics.⁴ He added that while all currently available conjugate vaccines are highly effective, higher-valency options provide additional benefit as new serotypes emerge.

What This Means for Pharmacists

Taken together, the Swedish study and the broader pneumococcal vaccine landscape underscore 2 distinct but related roles for pharmacists. First, as frontline immunizers, pharmacists must stay current on shifting vaccine recommendations and serotype coverage to match the right product to each patient's age, risk factors, and local epidemiology.^3,4

Second, the new data on M protein and immunoglobulin deficiencies highlight that an IPD diagnosis itself carries clinical significance beyond the acute infection, since it may be the first sign of a previously unrecognized B-cell malignancy, MGUS, or antibody deficiency requiring further workup.¹

Pharmacists counseling patients recovering from IPD, particularly older adults, may want to be aware that clinicians are increasingly considering additional immunologic workup following a pneumococcal infection and can reinforce the importance of follow-up care and continued vaccination given the ongoing shifts in circulating serotypes.^1-4

REFERENCES

1. Härnqvist T, Bergman K, Mellgren Å, et al. Invasive pneumococcal disease unmasks monoclonal immunoglobulins and antibody deficiencies: a multicenter prospective study in adults. Sci Rep. 2026;16:23203. doi:10.1038/s41598-026-61992-8

2. Nowosielski B. Pneumococcal disease is rebounding, requiring broader vaccine distribution. Drug Topics. June 7, 2026. Accessed July 27, 2026. https://www.drugtopics.com/view/pneumococcal-disease-is-rebounding-requiring-broader-vaccine-distribution

3. Nowosielski B, Garofoli GK. FAQ: how a variety of pneumococcal vaccines protect patient populations. Drug Topics. May 12, 2026. Accessed July 27, 2026. https://www.drugtopics.com/view/how-a-variety-of-pneumococcal-vaccines-protect-patient-populations

4. Nowosielski B, Licciardi P. Q&A: pharmacists help patients navigate pneumococcal vaccine options. Drug Topics. July 20, 2026. Accessed July 27, 2026. https://www.drugtopics.com/view/pharmacists-help-patients-navigate-pneumococcal-vaccine-options