Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France

Abstract

IMPORTANCEAcute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. OBJECTIVE To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. DESIGN, SETTING, AND PARTICIPANTS This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. EXPOSURES PCV13 implementation. MAIN OUTCOMES AND MEASURESMonthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. RESULTS Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age,[8][9][10][11][12] years; 2228 [55.6%] boys). 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 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period.CONCLUSIONS AND RELEVANCE PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

Oxidative reactions catalyzed by hydrogen peroxide produced byStreptococcus pneumoniaeand other Streptococci Cause the Release and Degradation of Heme from Hemoglobin

“…Acute chest syndrome is an important cause of hospitalization and mortality in children with SCD and Spn is a leading etiologic agent of acute chest syndrome. While the precise role of Spn is still unclear, SCD children are ~100-fold more susceptible to pneumococcal infection (71). Studies of the oxidation of hemoglobin by Spn-H 2 O 2 , however, have been neglected.…”

Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens

“…1,2 More than 5000 children with SCD lived in France in 2019. 3 Acute chest syndrome (ACS) is a potentially life-threatening complication of SCD, affecting more than half of patients with SCD in the first decade of life.…”

Cardiopulmonary Complications of Sickle Cell Disease in Children

“…Identification of exact infectious etiology in children varies and can be identified in over two-thirds of cases, with viruses predominating [7]. Of note, since the initiation of pneumococcal vaccination with PCV-13 (13-valent pneumococcal conjugate vaccine), one cohort in France demonstrated a 41.8% decrease in ACS over time [8]. Diagnosis is clinical, and criteria are the following: new infiltrate on chest X-ray, hypoxemia, and respiratory signs/symptoms [1].…”