Shift in Clinical Profile of Hospitalized Pneumonia in Children in the Non-pharmaceutical Interventions Period During the COVID-19 Pandemic: A Prospective Multicenter Study.

Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 were implemented in March 2020. These measures were followed by a major impact on viral and non-viral diseases. We aimed to assess the impact of NPI implementation in France on hospitalized community-acquired pneumonia (hCAP) frequency and the clinical and biological characteristics of the remaining cases in children. We performed a quasi-experimental interrupted time-series analysis. Between June 2014 and December 2020, eight pediatric emergency departments throughout France reported prospectively all cases of hCAP in children from age 1 month to 15 years. We estimated the impact on the monthly number of hCAP using segmented linear regression with autoregressive error model. We included 2,972 hCAP cases; 115 occurred during the NPI implementation period. We observed a sharp decrease in the monthly number of hCAP after NPI implementation [-63.0% (95 confidence interval, -86.8 to -39.2%); p < 0.001]. Children with hCAP were significantly older during than before the NPI period (median age, 3.9 vs. 2.3 years; p < 0.0001), and we observed a higher proportion of low inflammatory marker status (43.5 vs. 33.1%; p = 0.02). Furthermore, we observed a trend with a decrease in the proportion of cases with pleural effusion (5.3% during the NPI period vs. 10.9% before the NPI; p = 0.06). NPI implementation during the COVID-19 (coronavirus disease 2019) pandemic led not only to a strong decrease in the number of hCAP cases but also a modification in the clinical profile of children affected, which may reflect a change in pathogens involved.

Diagnostic Accuracy of Routinely Available Biomarkers to Predict Bacteremia in Children With Community-Acquired Pneumonia: A Secondary Analysis of the GPIP/ACTIV Pneumonia Study in France, 2009-2018.

Objective(s): Blood cultures (BC), when performed in children seen in the emergency department with community-acquired pneumonia (CAP), are most of the time sterile. We described the diagnostic accuracy of white blood cells (WBC), absolute neutrophils count (ANC), C-reactive protein (CRP), and procalcitonin (PCT) to predict blood culture (BC) result in childhood CAP. Study Design: Secondary analysis of a prospective study carried out in eight pediatric emergency departments (France, 2009-2018), including children (≤15 years) with CAP. Analyses involved univariate comparisons and ROC curves. Results: We included 13,752 children with CAP. BC was positive in 137 (3.6%) of the 3,829 children (mean age 3.7 years) in whom it was performed, mostly with Streptococcus pneumoniae (n = 107). In children with bacteremia, ANC, CRP and PCT levels were higher (median 12,256 vs. 9,251/mm3, 223 vs. 72 mg/L and 8.6 vs. 1.0 ng/mL, respectively; p ≤ 0.002), but WBC levels were not. The area under the ROC curve of PCT (0.73 [95%CI 0.64-0.82]) was significantly higher (p ≤ 0.01) than that of WBC (0.51 [0.43-0.60]) and of ANC (0.55 [0.46-0.64]), but not than that of CRP (0.66 [0.56-0.76]; p = 0.21). CRP and PCT thresholds that provided a sensitivity of at least 90% were 30 mg/L and 0.25 ng/mL, respectively, for a specificity of 25.4 and 23.4%, respectively. CRP and PCT thresholds that provided a specificity of at least 90% were 300 mg/L and 20 ng/mL, respectively, for a sensitivity of 31.3 and 28.9%, respectively. Conclusions: PCT and CRP are the best routinely available predictive biomarkers of bacteremia in childhood CAP.

Long-term Association of 13-Valent Pneumococcal Conjugate Vaccine Implementation With Rates of Community-Acquired Pneumonia in Children.

Importance: In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. Objective: To assess the long-term outcome of PCV13 implementation on CAP in children. Design, Setting, and Participants: This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography-confirmed CAP were included. Exposures: Community-acquired pneumonia. Main Outcomes and Measures: The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed using a segmented regression model, adjusted for influenza-like illness syndromes. Results: We enrolled 12 587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (-0.8% per month [95% CI, -1.0% to -0.5% per month]), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month [95% CI, 0.4%-1.4% per month]), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (-48% [95% CI, -84% to -12%]), CAP requiring hospitalization (-30% [95% CI, -56% to -5%]), and CAP with high inflammatory biomarkers (-30% [95% CI, -54% to -6%]), without any rebound thereafter. Conclusions and Relevance: The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.

Change in Bacterial Causes of Community-Acquired Parapneumonic Effusion and Pleural Empyema in Children 6 Years After 13-Valent Pneumococcal Conjugate Vaccine Implementation.

We describe here changes in the bacterial causes of pleural empyema before and after implementation of the 13-valent pneumococcal conjugate vaccine (PCV13) program in France (2009-2017). For 220 (39.3%) of 560 children, a bacterial cause was found. The frequency of pneumococcal infection decreased during the study from 79.1% in 2009 to 36.4% in 2017 (P < .001). Group A streptococcus is now the leading cause of documented empyema (45.5%).

Impact of PCV13 on community-acquired pneumonia by C-reactive protein and procalcitonin levels in children.

BACKGROUND: Many countries have observed an early and strong impact of implementation of the 13-valent pneumococcal conjugate vaccine (PCV13) on community-acquired pneumonia (CAP). High levels of C-reactive protein (CRP) and procalcitonin (PCT) are considered biomarkers of bacterial infection (particularly infection due to pneumococcus); therefore, PCV13 implementation should have different effectiveness on CAP depending on the levels of these two biomarkers. To demonstrate this assumption, we analyzed the evolution of number of CAP cases seen in pediatric emergency departments in France after PCV13 implementation (in 2010) by levels of these two biomarkers. METHODS: From June 2009 to May 2015, 8 pediatric emergency units prospectively enrolled all children (1month to 15years) with radiologically confirmed CAP. RESULTS: A cohort of 9586 children with CAP was enrolled (median age 3years). CAP with pleural effusion (PE-CAP) and proven pneumococcal pneumonia (PP-CAP) accounted for 5.5% and 2.0% of cases. During the study period, the number of cases of overall CAP decreased by 25.4%, hospitalized CAP by 30.5%, PE-CAP by 63.4%, CAP with CRP level≥100mg/L by 50.9%, CAP with PCT level≥4ng/L by 60.4% and PP-CAP by 86.4%. We found no change in number of cases of CAP with low levels of CRP (<20 or <40mg/L) or PCT (<0.5ng/mL). The number of cases of CAP overall increased (20.0%) in the last year of the study as compared with the preceeding year but not cases with CRP level≥100mg/L and/or PCT level≥4ng/mL. CONCLUSION: PCV13 implementation has had a strong impact on number of CAP cases with high levels of CRP and/or PCT in children but no impact on that with low levels of these two biomarkers. Five years after PCV13 implementation, a sustained reduction in CAP cases is observed.