Serotype 4 IPD Threat for Young Adults, Unvaccinated Men

A new study in Vaccine of invasive pneumococcal disease (IPD) cases reveals that serotype 4 is emerging as a distinct threat among young and middle-aged unvaccinated men, raising urgent questions about whether current adult vaccination strategies are reaching the people who need them most.¹

“If you’re going to try and explain the concept of serotype replacement, you could say something like, with the bacteria, there are more than 100 different types,” Paul Licciardi, PhD, group leader of vaccine immunology at the Murdoch Children’s Research Institute, told Drug Topics®.² “Not all of them cause serious disease, but a fair majority do. As you introduce a vaccine, you’re going to get emergence of new types that we call replacement types.”

The landmark Vaccine study, which analyzed 1359 confirmed IPD cases, found that serotype 4 was the third most frequent strain, responsible for over 10% of infections. Crucially, over 83% of these serotype 4 infections occurred in individuals under age 65. This stands in stark contrast with other serotypes, which primarily affect older adults.¹

READ MORE: Vaccine Serotypes Reemerge in Community-Acquired Pneumonia

Shifting Demographics of a Vaccine-Preventable Threat

According to the multivariable analysis, the odds of contracting serotype 4 were significantly higher in males and individuals aged 15 to 64. Lifestyle factors also played a prominent role. A history of psychoactive drug use was associated with 2.5 times higher odds of infection.

Active tobacco smoking, heavy alcohol use, and homelessness were also frequently reported in clinical notes. Clinically, serotype 4 presented a 3-fold increased risk of pneumonia but lower odds of meningitis. Although crude in-hospital mortality was lower for serotype 4, adjusting for age revealed that this was entirely driven by the younger, healthier baseline of the affected population.¹

A Consistent Global Signature of Urban Frailty

This epidemiological pattern is echoed in other nations. In Belgium, a rapid resurgence of serotype 4 IPD occurred between 2020 and 2024, peaking in 2023. This upsurge was heavily concentrated among young adult males living in large cities. A detailed subanalysis of these cases revealed severe socioeconomic vulnerabilities, including high rates of unemployment, homelessness, and heavy alcohol and tobacco use.³

Similarly, CDC surveillance across several sites in the US documented an increase in serotype 4 IPD. The incidence among adults experiencing homelessness was up to 300 times higher than in the general population.⁴

Genetic analysis of these US isolates identified closely related lineages, suggesting rapid transmission within crowded urban environments. These international studies demonstrate that crowded living conditions, inadequate hygiene, and substance use create localized reservoirs for this specific strain.^3,4

Navigating Vaccine Selection, Pharmacist Outreach

As these highly vulnerable groups rarely access traditional primary care, community pharmacies represent a crucial gateway for clinical intervention. A randomized study in Alberta, Canada, demonstrated that providing pharmacists with targeted educational toolkits significantly improved the efficiency of pneumococcal vaccine counseling.^1,4,5

Post-intervention vaccine discussions became faster, and fewer patients refused vaccination due to a perceived lack of benefit. However, refusals due to out-of-pocket cost concerns rose, highlighting the importance of public funding programs. Indeed, when local policies were updated to cover newer pneumococcal conjugate vaccines (PCVs), accessibility dramatically improved.⁵

Pharmacists must also understand how to navigate the complex adult vaccine market, choosing between options like PCV15, PCV20, and the newly approved PCV21. Selecting the right vaccine is a critical clinical decision because PCV21 excludes serotype 4, whereas PCV15 and PCV20 cover it.^1,2,6

To assist with these complex decisions, clinical tools like the CDC's PneumoRecs VaxAdvisor recommend that, in areas with high circulating serotype 4, vaccines containing this serotype, such as PCV20 alone or PCV15 in series with PPSV23, should be preferred over PCV21 alone.⁶

By remaining vigilant to local epidemiological shifts and addressing vaccine hesitancy head-on, community pharmacists can steer vulnerable patients toward the most protective vaccination options. These findings highlight how pharmacist-led education can successfully bridge immunization gaps in under-vaccinated populations.^2,5

“This study identified vulnerable young adults at risk of IPD caused by emerging serotype 4 vs. other serotypes and described factors potentially associated with this serotype,” concluded the authors of the current study.¹ “We also presented the theoretical coverage of currently accepted vaccines to inform future decisions for optimizing regional prevention strategies for IPD.”

READ MORE: Pneumococcal Resource Center

REFERENCES

1. Marín-Caba E, Lorusso N, Sempere J, et al. Young adults at risk of emerging serotype 4 invasive pneumococcal disease vs. other serotypes in Andalusia (Spain), 2022 to 2024: optimising conjugated vaccines strategies. Vaccine. 2026;88:128790. doi:10.1016/j.vaccine.2026.128790

2. Nowosielski B, Licciardi P. Q&A: Pharmacists help patients navigate pneumococcal vaccine options. Drug Topics. July 20, 2026. Accessed August 18, 2026. https://www.drugtopics.com/view/pharmacists-help-patients-navigate-pneumococcal-vaccine-options

3. Cuypers L, Sanchez GJ, Avila JPH, et al. Rapid increase in serotype 4 invasive pneumococcal disease among vulnerable young male adults in Belgium (2020-2024). Int J Infect Dis. 2025;163:108216. doi:10.1016/j.ijid.2025.108216

4. Beall B, Walker H, Tran T, et al. Upsurge of conjugate vaccine serotype 4 invasive pneumococcal disease clusters among adults experiencing homelessness in California, Colorado, and New Mexico. J Infect Dis. 2021 Apr 8;223(7):1241-1249. doi: 10.1093/infdis/jiaa501

5. Ramrattan D, Nagy D, Eurich D, et al. Changing the conversation: empowering community pharmacists to address pneumococcal vaccine hesitancy. JAPhA. 2024;64(6):102202. doi:10.1016/j.japh.2024.102202

6. Pneumococcal vaccine recommendations. CDC. December 11, 2024. Accessed August 18, 2026. https://www2a.cdc.gov/vaccines/m/pneumo/over50yr.asp?ages=%E2%89%A550%20years