Children With Sickle Cell Disease Have Higher Rates of Invasive Pneumococcal Disease Despite Vaccination

Pediatric patients with sickle cell disease (SCD) have higher rates of invasive pneumococcal disease (IPD), in part due to reduced vaccine effectiveness against included serotypes and a heightened incidence of IPD due to serotypes not included in traditional pneumococcal conjugate vaccines (PCVs), according to results garnered by investigators and published in Vaccine.¹

Children with sickle cell disease may need multiple doses of pneumococcal conjugate vaccine to be better protected against invasive pneumococcal disease. | Image Credit: © Alexey Novikov - stock.adobe.com

Children With Sickle Cell Disease Face Heightened Risk of Severe IPD

Pneumococcal vaccination campaigns have been widely successful in increasing coverage across key populations, including those at high risk for severe IPD. The disease is highly variable in nature, with serotypes most prevalent in transmission differing across age and risk groups. Despite successful immunization campaigns and targeted surveillance strategies around the globe, IPD coverage remains concerningly lacking. Many countries around the world lack immunization policies specifically tailored for high-risk children, and there is substantial variation in which risk conditions are recognized, vaccine timing, and proper dosing.^2,3

Immunologic effects related to SCD, including a skewed T-helper immune response and impaired complement activation, make pediatric patients with this condition at heightened risk for IPD. Those with SCD are recommended to receive an additional dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) following a routine vaccination series, according to the Advisory Committee on Immunization Practices. However, even with vaccination, children with SCD are at a significantly higher risk of developing IPD and do not generate as robust a response to PCV vaccines as compared with healthy children.^1,4

Investigators Find Lack of Protection, Even With Vaccination

In the current trial, the investigators aimed to evaluate the impact of existing and future conjugated vaccines against IPD in children with and without SCD. The trial analyzed patients in a high-income setting with high vaccine coverage that utilized a 3 + 1 dosing schedule. A total of 1302 IPD cases occurred during the study period among patients 18 years or younger that were eligible for inclusion.¹

Among these IPD cases, 299 (23%) occurred in children with at least 1 underlying condition, while 24 were among children with SCD. In the cohort of children with SCD, there were higher incidence rates of IPD observed during both pre- and post-pneumococcal conjugate vaccine 13 (PCV13) availability compared with otherwise healthy children.¹

The investigators sought to determine the reduction in IPD incidence following the implementation of PCV13. They observed that, despite high coverage with pneumococcal conjugate vaccine 7 (PCV7) and PCV13 in the pediatric population, there was only a modest reduction of 28.1% (95% CI, 25.9-37.2%) in the incidence of overall IPD during the post-PCV13 period in children diagnosed with SCD. This, compared with a more significant 59.5% reduction in children without any underlying health conditions, indicates major disparities in IPD protection between healthy children and those with SCD.¹

Of note, the investigators found that around 61% of the remaining IPD among children with SCD were caused by serotypes not included in the PCV13 vaccine. Additionally, the authors determined that vaccine failure of PCV13 was observed to be more than twice that of PCV7. These data indicate that future PCV vaccines should be modified to include a greater number of serotypes, with particular focus on the serotypes that most often impact patients at higher risk of severe disease.¹

“This finding highlights the importance of maintaining immunogenicity and subsequent vaccine effectiveness while increasing valency in pneumococcal vaccines, especially in vulnerable populations with high risk of disease burden,” the investigators concluded.¹

REFERENCES

1. Zhang Z, Yildirim M, Keskinocak P, et al. Serotype specific pneumococcal vaccine effectiveness in children with sickle cell disease: A two-decade analysis. Vaccine. 2025;56:127193. doi:10.1016/j.vaccine.2025.127193

2. Halpern L. Surveillance, targeted interventions critical to combat variable nature of invasive pneumococcal disease. Pharmacy Times. Published April 22, 2025. Accessed May 13, 2025. https://www.pharmacytimes.com/view/surveillance-targeted-interventions-critical-to-combat-variable-nature-of-invasive-pneumococcal-disease

3. Gerlach A. Global review finds gaps in pneumococcal vaccine policies for high-risk children. Pharmacy Times. Published May 10, 2025. Accessed May 13, 2025. https://www.pharmacytimes.com/view/global-review-finds-gaps-in-pneumococcal-vaccine-policies-for-high-risk-children

4. Ildirim I, Lapidot R, Shaik-Dasthagirisaheb YB, et al. Invasive pneumococcal disease after 2 decades of pneumococcal conjugate vaccine use. Pediatrics. 2024;153(1):e2023063039. doi:10.1542/peds.2023-063039