PCV13 Vaccination May Reduce Incidence of Acute Chest Syndrome for Children with Sickle-Cell Disease

A potential public health benefit of 13-valent pneumococcal conjugate vaccine is the reduction of acute chest syndrome among children with sickle-cell disease.

The implementation of 13-valent pneumococcal conjugate vaccine (PCV13) was associated with reduction in the incidence of acute chest syndrome (ACS) among children with sickle-cell disease (SCD) in France, according to a study published in JAMA Network Open.

The findings provide evidence for the involvement of Streptococcus pneumoniae (S pneumoniae) in childhood ACS, the study authors noted. ACS is a specific severe complication of SCD with a complex physiopathology. Though S pneumoniae has been estimated to be responsible for 4.5% of ACS, its precise involvement in ACS is difficult to determine.

PCV13 has been used in the general population since 2010 in many countries, including France, and has been shown to have a significant reduction in invasive and non-invasive pneumococcal disease, including lower respiratory tract infections. Despite its use, the public health outcomes of PCV13 implementation concerning ACS are still unknown.

To address this knowledge gap, the researchers conducted a study to assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. Researchers used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. Participants included children younger than 18 years of age with SCD hospitalized in France between January 2007 and December 2019.

Researchers measured the monthly incidence of ACS per 1000 children with SCD. They also calculated control outcomes including the monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period.

Researchers identified 107,694 hospitalizations of children with SCD during the study period (median [IQR] age, 9 [4-13] years; 56,264 [52.2%] boys). Of these, ACS accounted for 4007 (3.7%) cases, pneumonia for 1789 (1.7%), other LRTIs for 1153 (1.1%), asthma crises for 845 (0.8%), acute pyelonephritis for 889 (0.8%), and VOC for 69,920 (64.9%).

Results showed that PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (−0.9% per month; 95% CI, −1.4% to −0.4%; P < .001), with an estimated cumulative change of −41.8% (95% CI, −70.8% to −12.7%) by December 2019. The sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time.

Results were found to be similar among different age groups. No change was found for the 3 control outcomes over the study period.

Overall, PCV13 supplementation was associated with an important reduction in the incidence of ACS in children with SCD. However, the finding that the decrease of ACS incidence following PCV13 implementation suggests an important pneumococcal involvement with this entity contrasts previous research, according to the authors of the current study.

The authors suggest that this new evidence of the key role of S pneumoniae in ACS should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children. They encourage including their potential to reduce ACS in children with SCD in the assessment of potential public health benefits of such next generation PCVs.

The study faced limitations. The diagnosis of ACS relies on nonspecific criteria that allow for possible clinical overlap with pneumonia, meaning there was potential for misclassification. Additionally, the analysis may have been affected by simultaneous cointerventions targeting the same outcome.


Assad Z, Michel M, Valtuille Z, et al. Incidence of acute chest syndrome in children with sickle cell disease following implementation of the 12-valent pneumococcal conjugate vaccine in France.” JAMA Netw Open. 2022;5(8):e2225141. doi:10.1001/jamanetworkopen.2022.25141