Unique Changes in the Incidence of Acute Chest Syndrome in Children with Sickle-Cell Disease Unravel the Role of Respiratory Pathogens: A Time-Series Analysis

International audienceBackground: Acute chest syndrome (ACS) is a life-threatening complication of sickle-cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that ACS incidence followed the unprecedented population-level changes in respiratory pathogens dynamics following the COVID-19-related non-pharmaceutical interventions (NPIs).Research question: What is the respective role of respiratory pathogens in ACS epidemiology?Study design: AND METHODS. We performed an interrupted time-series analysis of patient records from a national hospital-based surveillance system. All children < 18 years of age with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1000 children with SCD over time was analyzed using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen.Results: Among the 55,941 hospitalizations of children with SCD, 2306 episodes of ACS were included (median [IQR] age, 9 [5-13] years). We observed a significant decrease in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8% to -12.2%; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2% to 41.6%; P = .007). Using population-level incidence of several respiratory pathogens, we found that Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9% to 56.9%; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3% to 11.3%; P = .004), whereas other respiratory pathogens had only a minor role.Interpretation: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiological situation allowed to unravel the contribution of these respiratory pathogens, in particular S. pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population

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

International audienceImportance: Acute 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 measures: Monthly 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 [4-12] 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