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. 2025 May 22:56:127193.
doi: 10.1016/j.vaccine.2025.127193. Epub 2025 May 2.

Serotype specific pneumococcal vaccine effectiveness in children with sickle cell disease: A two-decade analysis

Ziyu Zhang  1 , Melike Yildirim  2 , Pinar Keskinocak  1 , Yazdani Basha Shaik Dasthagirisaheb  3 , Sarah Hinderstein  4 , Khang Tran  5 , Molly Crockett  6 , Meagan Burns  6 , Hillary Johnson  6 , Marija Popstefanija  6 , Lawrence C Madoff  6 , Stephen I Pelton  3 , Inci Yildirim  7
Affiliations

Serotype specific pneumococcal vaccine effectiveness in children with sickle cell disease: A two-decade analysis

Ziyu Zhang et al. Vaccine. .

Abstract

Objectives: Sickle cell disease (SCD) is the most common genetic hematologic disease globally and children with SCD are at increased risk for pneumococcal disease.

Methods: We utilized data from population-based enhanced surveillance for invasive pneumococcal disease (IPD) in children <18 years of age in Massachusetts from 2002 to 2020. We calculated incidence rates (IR) among children with SCD using bootstrapping resampling and incidence rate ratios (IRR) for pre- and post-PCV13 periods. Vaccine effectiveness (VE) was calculated as 100*(1-IRR), and PCV13 vaccine failure probability was predicted using a random forest model.

Results: Children with SCD had higher IR during both pre-/post-PCV13 periods compared with otherwise healthy children 240.0/100,000 versus 4.6/100,000 in pre-PCV13 period (2002-2009); 172.7/100,000 versus 1.9/100,000 in post-PCV13 period (2011-2020), respectively. After widespread use of PCV7 for a decade, a modest reduction of 28.1 % (95% CI 25.9-37.2%) in the incidence of overall IPD during the post-PCV13 period was observed in children with SCD, whereas a more substantial 59.5% (96% CI 57.8-61.4%) reduction was observed in otherwise healthy children. There was a 60.8% (95% CI 55.2%-NA) reduction in the incidence of VST13 IPD in children with SCD and an 83.0% (95% CI 80.67-85.63%) reduction in children without underlying health condition. Overall, 61.1% of the remaining IPD among children with SCD were due to non-PCV13 serotypes (8, 10A, 15A,15B, 22F, 23B), many of which are included in expanded valency vaccines.

Conclusion: Children with SCD continue to have higher rates of IPD compared with otherwise healthy children despite vaccination. Majority of the remaining disease is due to serotypes not included in vaccine formulations that have been used for the last two decades. Our study highlights the potential value of expanded valency vaccines and importance of risk-based vaccination strategies tailored for this vulnerable population.

Keywords: Incidence rate (IR); Incidence rate ratio (IRR); Invasive pneumococcal disease (IPD); Risk-based vaccination; Sickle cell disease (SCD); Vaccine effectiveness (VE).

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pinar Keskinocak reports financial support was provided by Georgia Institute of Technology. Stephan Pelton reports was provided by Seelig Charitable Foundation Trust and Pfizer. Inci Yildirim and Pinar Keskinocak reports a relationship with Centers for Disease Control and Prevention that includes: funding grants. Inci Yildirim reports a relationship with National Institutes of Health that includes: funding grants. Inci Yildirim reports a relationship with Gates Foundation that includes: funding grants. Inci Yildirim reports a relationship with Merck & Co Inc. that includes: board membership. Inci Yildirim reports a relationship with Sanofi Pasteur Inc. that includes: board membership. Stephen Pelton reports a relationship with Pfizer that includes: board membership, consulting or advisory, and funding grants. Stephen Pelton reports a relationship with Merck & Co Inc. that includes: board membership, consulting or advisory, and funding grants. Stephen Pelton reports a relationship with Seqirus Inc. that includes: board membership and consulting or advisory. Stephen Pelton reports a relationship with Sanofi Pasteur Inc. that includes: board membership and consulting or advisory. Pinar Keskinocak reports a relationship with National Science Foundation that includes: funding grants. Pinar Keskinocak reports a relationship with The Carter Center that includes: funding grants. Funding statement: This research has been supported in part by the Center for Health and Humanitarian Systems, the William W. George endowment, and the following benefactors at Georgia Tech: Andrea Laliberte, Richard Rick E. and Charlene Zalesky, and Claudia and Paul Raines. Funded in part by a research grant from BMC from the Seelig Charitable Foundation Trust and Pfizer to Boston Medical Center. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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