Protocol for fever control using external cooling in mechanically ventilated patients with septic shock: SEPSISCOOL II randomised controlled trial.

INTRODUCTION: Fever treatment is commonly applied in patients with sepsis but its impact on survival remains undetermined. Patients with respiratory and haemodynamic failure are at the highest risk for not tolerating the metabolic cost of fever. However, fever can help to control infection. Treating fever with paracetamol has been shown to be less effective than cooling. In the SEPSISCOOL pilot study, active fever control by external cooling improved organ failure recovery and early survival. The main objective of this confirmatory trial is to assess whether fever control at normothermia can improve the evolution of organ failure and mortality at day 60 of febrile patients with septic shock. This study will compare two strategies within the first 48 hours of septic shock: treatment of fever with cooling or no treatment of fever. METHODS AND ANALYSIS: SEPSISCOOL II is a pragmatic, investigator-initiated, adaptive, multicentre, open-label, randomised controlled, superiority trial in patients admitted to the intensive care unit with febrile septic shock. After stratification based on the acute respiratory distress syndrome status, patients will be randomised between two arms: (1) cooling and (2) no cooling. The primary endpoint is mortality at day 60 after randomisation. The secondary endpoints include the evolution of organ failure, early mortality and tolerance. The target sample size is 820 patients. ETHICS AND DISSEMINATION: The study is funded by the French health ministry and was approved by the ethics committee CPP Nord Ouest II (Amiens, France). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04494074.

Use of Rapid Antigen Triple Test Nasal Swabs (COVID-VIRO ALL-IN TRIPLEX: Severe Acute Respiratory Syndrome Coronavirus 2, Respiratory Syncytial Virus, and Influenza) in Children With Respiratory Symptoms: A Real-life Prospective Study.

Background: In autumn 2022, the epidemics due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), and influenza overlapped, and these diseases can present with the same symptomatology. The use of a triple antigen test (SARS-CoV-2 + influenza A/B + RSV) seems crucial for accurate viral diagnosis in the context of implementing long-acting monoclonal antibody vaccination against RSV in the upcoming RSV season. Methods: We assessed the usefulness of the triple test in real life in this prospective study performed from October 2022 to May 2023 and involving 116 pediatricians (2 emergency department pediatricians and 114 ambulatory pediatricians). Children <15 years old with flu-like illness (with fever), bronchiolitis (dyspnea ± wheezing), otitis, and croup were enrolled and sampled with a nasal triple test. Results: For 8329 children with flu-like illness (65.3%), bronchiolitis (17.9%), otitis (8.8%), and croup (6.3%), the use of the triple test led to a viral diagnosis in 47.9% of cases. The highest RSV positivity occurred in children with bronchiolitis (32.9%). The highest influenza A and B positivity (24.6% and 19.6%) occurred in children with flu-like illness. A succession of 3 epidemics (RSV and influenza A and B) occurred over time with several overlap periods. Conclusions: The triple test allowed for a viral diagnosis in half of our cases. The upcoming introduction of RSV prevention will emphasize the need for active surveillance with viral results both in ambulatory settings and hospitals. Clinical Trials Registration. NCT0441231.

Vaccine-preventable Pediatric Acute Bacterial Meningitis in France: A Time Series Analysis of a 19-Year Prospective National Surveillance Network.

BACKGROUND: In France, vaccination has been implemented against Hi serotype b (Hib), pneumococcus with pneumococcal conjugate vaccines (PCV), and Neisseria meningitidis serogroup C (MenC). These interventions with different coverage and uptake have disrupted the epidemiology of vaccine-preventable acute bacterial meningitis (ABM). METHODS: We analyzed data from a French prospective surveillance network of ABM in children ≤15 years old enrolled by 259 pediatric wards (estimated national coverage: 61%). From 2001 to 2020, the effect of vaccine implementation was estimated with segmented linear regression. RESULTS: We analyzed 7,186 cases, mainly due to meningococcus (35.0%), pneumococcus (29.8%), and Hi (3.7%). MenC ABM incidence decreased (-0.12%/month, 95% CI: -0.17 to -0.07, P < 0.001) with no change for the overall meningococcal ABM when comparing the pre-MenC vaccination and the post-MenC vaccination trends. Despite a decreasing MenB ABM incidence without a vaccination program (-0.43%/month, 95% CI: -0.53 to -0.34, P < 0.001), 68.3% of meningococcal ABM involved MenB. No change in pneumococcal ABM incidence was observed after the PCV7 recommendation. By contrast, this incidence significantly decreased after the switch to PCV13 (-0.9%/month, 95% CI: -1.6 to -0.2%, P = 0.01). After May 2014, a rebound occurred (0.5%/month, 95% CI: 0.3-0.8%, P < 0.001), with 89.5% of non-PCV13 vaccine serotypes. Hib ABM incidence increased after June 2017. CONCLUSIONS: PCV7 and MenC vaccine introduction in France, with slow vaccine uptake and low coverage, had no to little impact as compared to the switch from PCV7 to PCV13, which occurred when coverage was optimal. Our data suggest that MenB and next-generation PCVs could prevent a large part of the ABM incidence in France.

Age-specific resurgence in invasive pneumococcal disease incidence in the COVID-19 pandemic era and its association with respiratory virus and pneumococcal carriage dynamics: a time series analysis.

Using multiple national surveillance systems, we found an increase in invasive pneumococcal disease (IPD) incidence in the early post-COVID-19 pandemic period that strongly varied by age. Age-groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in IPD incidence, with no change in pneumococcal carriage.

Antibiotic Resistance of Haemophilus influenzae in Nasopharyngeal Carriage of Children with Acute Otitis Media and in Middle Ear Fluid from Otorrhea.

Haemophilus influenzae (Hi) is one of the leading bacteria implicated in childhood acute otitis media (AOM). Recent concerns have been raised about the emergence of Hi-resistant strains. We aimed to analyze the evolution of ß-lactam resistance to Hi among strains isolated from nasopharyngeal carriage in children with AOM and in mild ear fluid (MEF) after the spontaneous perforation of the tympanic membrane (SPTM) in France. In this national ambulatory-based cohort study over 16 years, we analyzed the rate of Hi nasopharyngeal carriage and the proportion of ß-lactam-resistant Hi strains over time using a segmented linear regression model. Among the 13,865 children (median [IQR] age, 12.7 [9.3-17.3] months; 7400 [53.4%] male) with AOM included from November 2006 to July 2022, Hi was isolated in 7311 (52.7%) children by nasopharyngeal sampling. The proportion of ß-lactamase-producing and ß-lactamase-negative, ampicillin-resistant (BLNAR) Hi strains in nasopharyngeal carriage remained stable during the study period. Among the 783 children (median [IQR] age, 20 [12.3-37.8] months; 409 [52.2%] male) with SPTM included from October 2015 to July 2022, Hi was isolated in 177 (22.6%) cases by MEF sampling. The proportions of ß-lactamase-producing and BLNAR Hi strains did not significantly differ between nasopharyngeal (17.6% and 8.8%, respectively) and MEF (12.6% and 7.4%) samples. Accordingly, amoxicillin remains a valid recommendation as the first-line drug for AOM in France.

Respiratory Syncytial Virus in Outpatient Children with Bronchiolitis: Continuous Virus Circulation During the Nonepidemic Period.

We aimed to estimate the respiratory syncytial virus positivity rate among ambulatory children with bronchiolitis according to the bronchiolitis epidemic period as defined by the French Public Health Institute. The positivity rate was 28.9% during the nonepidemic period and 50.6% during the epidemic period, which suggests continuous virus circulation between bronchiolitis annual peaks.

Diagnostic accuracy of a rapid antigen triple test (SARS-CoV-2, respiratory syncytial virus, and influenza) using anterior nasal swabs versus multiplex RT-PCR in children in an emergency department.

BACKGROUND: In children, respiratory infections such as SARS-CoV-2, respiratory syncytial virus (RSV), and influenza share similar clinical signs and symptoms. Here we compared the performance of a rapid antigen diagnostic test using a self-collected anterior nasal swab (COVID-VIRO ALL IN TRIPLEX) and multiplex RT-PCR. METHODS: From October to December 2022, in the emergency pediatrics unit of Orleans Hospital, France, we evaluated the diagnostic accuracy of the triplex test. RESULTS: For the 263 children, sensitivity of the test was 88.9% (95%CI 51.8-99.7), 79.1% (95%CI 64.0-90.0), and 91.6% (95%CI 84.1-96.3), for SARS-CoV-2, RSV, and influenza, respectively. Specificity was 100% for each virus. For RT-PCR with cycle threshold < 32, sensitivity was 100.0% [95%CI 59.0-100.0], 87.2% [95%CI 72.6-95.7] and 92.3% [95%CI 84.896.9] for SARS-CoV-2, RSV, and influenza respectively. CONCLUSIONS: This easy-to-perform triplex test is a considerable advance, allowing clinicians to obtain an accurate diagnosis in most cases of respiratory infection. More data are needed to validate this test in different contexts and across several seasons.

Diagnostic Accuracy of Group A Streptococcus Rapid Antigen Detection Test on Middle Ear Fluid in Children With Acute Otitis Media With Spontaneous Perforation: A Prospective Multicenter Evaluation.

Group A Streptococcus is one of the leading causes of otorrhea. The performance of rapid antigen tests in 256 children with otorrhea showed excellent sensitivity, 97.3% (95% confidence interval: 90.7%-99.7%), and specificity, 100% (95% confidence interval: 98.0%-100%). In a period of increasing invasive and noninvasive group A Streptococcus infections, an early diagnosis could be useful.

Otorrhea bacterial profile, epidemiology before widespread use of the third-generation pneumococcal conjugate vaccine in French children, a prospective study from 2015 to 2023.

OBJECTIVES: The aim of this study was to describe the bacterial profile of middle ear fluid from spontaneous perforation of the tympanic membrane (SPTM) prior to widespread utilization of third- generation pneumococcal conjugate vaccines (PCVs). PATIENTS AND METHODS: From October 2015 to January 2023, children with SPTM were prospectively enrolled by pediatricians. RESULTS: Among the 852 children with SPTM, 73.2% were less than 3 years old; more frequently than older children, they were and suffering from complex acute otitis media (AOM) (27.9%) and conjunctivitis (13.1%). In children under 3 years of age, NT Haemophilus influenzae (49.7%) was the main otopathogen isolated, particularly in those with complex AOM (57.1%). In children over 3 years of age, Group A Streptococcus accounted for 57%. In pneumococcal cases (25.1%), serotype 3 was the main serotype isolated (16.2%), followed by 23B (15.2%). CONCLUSION: Our data from 2015 to 2023 represent a robust baseline preceding the widespread utilization of next-generation PCVs.

Dynamics of Antibiotic Resistance of Streptococcus pneumoniae in France: A Pediatric Prospective Nasopharyngeal Carriage Study from 2001 to 2022.

Epidemiological surveillance of nasopharyngeal pneumococcal carriage is important for monitoring serotype distribution and antibiotic resistance, particularly before and after the implementation of pneumococcal conjugate vaccines (PCVs). With a prospective surveillance study in France, we aimed to analyze the dynamics of pneumococcal carriage, antibiotic susceptibility and serotype distribution in children aged 6 to 24 months who had acute otitis media between 2001 and 2022 with a focus on the late PCV13 period from May 2014 to July 2022. Trends were analyzed with segmented linear regression with autoregressive error. For the 17,136 children enrolled, overall pneumococcal carriage was stable during the study. During the late PCV13 period, the five most frequent serotypes were all non-PCV13 serotypes: 15B/C (14.3%), 23B (11.0%), 11A (9.6%), 15A (7.4%) and 35B (6.5%). During the same period, we observed a rebound of penicillin non-susceptibility (+0.15% per month, 95% confidence interval, +0.08 to 0.22, p < 0.001). Five serotypes accounted for 64.4% of the penicillin non-susceptible strains: 11A (17.5%), 35B (14.9%), 15A (13.9%), 15B/C (9.9%) and 19F (8.2%); non-PCV13/PCV15 accounted for <1%, and non-PCV15/PCV20 accounted for 28%. The next generation PCVs, particularly PCV20, may disrupt nasopharyngeal carriage and contribute to decreasing the rate of antibiotic resistance among pneumococci.

Surveillance of noninvasive group A Streptococcus infections in French ambulatory pediatrics before and during the COVID-19 pandemic: a prospective multicenter study from 2018-2022.

OBJECTIVES: We evaluated the burden of noninvasive group A Streptococcus (GAS) infections in ambulatory pediatrics before and during the COVID-19 pandemic in France. METHODS: We analyzed data from a national network of ambulatory pediatricians between 2018 and 2022. Clinicians evaluating children ≤15 years old for tonsillopharyngitis, perianal infections, paronychia/blistering dactylitis, and scarlet fever were invited to perform a rapid antigen detection test (RADT) for GAS. Monthly incidence of noninvasive GAS infections per 10,000 visits was modeled using time series analysis, considering two breakpoints: March 2020 (first national lockdown) and March 2022 (end of mandatory mask-wearing in schools). RESULTS: Over the study period, 125 pediatricians recorded 271,084 infectious episodes. GAS-related illnesses represented 4.3% of all infections. In March 2020, the incidence of GAS diseases decreased by 84.5% (P <0.001), with no significant trend until March 2022. After March 2022, the incidence significantly increased (+23.8% per month, P <0.001), with similar patterns across all monitored GAS-related diseases. CONCLUSION: By using routine clinical data and RADTs, we have monitored changes in the incidence of noninvasive GAS infections in ambulatory pediatrics. COVID-19 mitigation measures have had a major impact on the epidemiology of noninvasive GAS infections, but their relaxation was followed by a surge above baseline levels.

Meningitis caused by extended-spectrum ß-lactamase-producing Escherichia coli in infants in France: a case series.

Objectives: We report the first case series focusing on clinical and biological characteristics of meningitis caused by ESBL-producing Escherichia coli in infants. Methods: Between 2001 and 2020, data on all cases of E. coli meningitis were prospectively collected from a network of 259 paediatric wards and 168 microbiology laboratories in France. We analysed the clinical and biological characteristics, short-term complications and long-term sequelae of ESBL-producing E. coli meningitis cases in patients <6 months old. Results: In total, 548 cases of E. coli paediatric meningitis were reported. ESBL-producing E. coli represented 12 (2.2%) cases. We included 10 patients aged <6 months old. Eight (80%) patients presented at least one sign of clinical severity: six needed mechanical ventilation, three presented signs of shock and one was in a coma. The overall short-term prognosis was good, with only one meningitis-attributed death in the first hours of care. All surviving children received carbapenems for a median of 21 days (range 9-28). Two relapses occurred, including one in a patient who received only 14 days of imipenem. We reported no long-term sequelae at a median follow-up of 20 months. Conclusions: Meropenem seems to be the treatment of choice for ESBL-producing E. coli meningitis in children and needs to be given as early as possible (<48 h) and for at least 21 days. Maternal colonization or infection with ESBL-producing Enterobacteriaceae needs to be reported to the neonatal or paediatric ICU team, in order to adapt the empirical antibiotic therapy.

Diagnostic accuracy of SARS-CoV-2 rapid antigen test from self-collected anterior nasal swabs in children compared to rapid antigen test and RT-PCR from nasopharyngeal swabs collected by healthcare workers: A multicentric prospective study.

Testing for SARS-CoV-2 is central to COVID-19 management. Rapid antigen test from self-collected anterior nasal swabs (SCANS-RAT) are often used in children but their performance have not been assessed in real-life. We aimed to compare this testing method to the two methods usually used: reverse transcription polymerase chain reaction from nasopharyngeal swabs collected by healthcare workers (HCW-PCR) and rapid antigen test from nasopharyngeal swabs collected by healthcare workers (HCW-RAT), estimating the accuracy and acceptance, in a pediatric real-life study. From September 2021 to January 2022, we performed a manufacturer-independent cross-sectional, prospective, multicenter study involving 74 pediatric ambulatory centers and 5 emergency units throughout France. Children ≥6 months to 15 years old with suggestive symptoms of COVID-19 or children in contact with a COVID-19-positive patient were prospectively enrolled. We included 836 children (median 4 years), 774 (92.6%) were symptomatic. The comparators were HCW-PCR for 267 children, and HCW-RAT for 593 children. The sensitivity of the SCANS-RAT test compared to HCW-RAT was 91.3% (95%CI 82.8; 96.4). Sensitivity was 70.4% (95%CI 59.2; 80.0) compared to all HCW-PCR and 84.6% (95%CI 71.9; 93.1) when considering cycle threshold <33. The specificity was always >97%. Among children aged ≥6 years, 90.9% of SCANS-RAT were self-collected without adult intervention. On appreciation rating (from 1, very pleasant, to 10, very unpleasant), 77.9% of children chose a score ≤3. SCANS-RAT have good sensitivity and specificity and are well accepted by children. A repeated screening strategy using these tests can play a major role in controlling the pandemic.

Trends in pediatric ambulatory community acquired infections before and during COVID-19 pandemic: A prospective multicentric surveillance study in France.

Background: Covid-19 pandemic control has imposed several non-pharmaceutical interventions (NPIs). Strict application of these measures has had a dramatic reduction on the epidemiology of several infectious diseases. As the pandemic is ongoing for more than 2 years, some of these measures have been removed, mitigated, or less well applied. The aim of this study is to investigate the trends of pediatric ambulatory infectious diseases before and up to two years after the onset of the pandemic. Methods: We conducted a prospective surveillance study in France with 107 pediatricians specifically trained in pediatric infectious diseases. From January 2018 to April 2022, the electronic medical records of children with an infectious disease were automatically extracted. The annual number of infectious diseases in 2020 and 2021 was compared to 2018-2019 and their frequency was compared by logistic regression. Findings: From 2018 to 2021, 185,368 infectious diseases were recorded. Compared to 2018 (n=47,116) and 2019 (n=51,667), the annual number of cases decreased in 2020 (n=35,432) by about a third. Frequency of scarlet fever, tonsillopharyngitis, enteroviral infections, bronchiolitis, and gastroenteritis decreased with OR varying from 0·6 (CI95% [0·5;0·7]) to 0·9 (CI95% [0·8;0·9]), p<0·001. In 2021, among the 52,153 infectious diagnoses, an off-season rebound was observed with increased frequency of enteroviral infections, bronchiolitis, gastroenteritis and otitis with OR varying from 1·1 (CI95% [1·0;1·1]) to 1·5 (CI95% [1·4;1·5]), p<0·001. Interpretation: While during NPIs strict application, the overall frequency of community-acquired infections was reduced, after relaxation of these measures, a rebound of some of them (enteroviral infections, bronchiolitis, gastroenteritis, otitis) occurred beyond the pre-pandemic level. These findings highlight the need for continuous surveillance of infectious diseases, especially insofar as future epidemics are largely unpredictable. Funding: ACTIV, AFPA, GSK, MSD, Pfizer and Sanofi.

Association between the COVID-19 pandemic and pertussis derived from multiple nationwide data sources, France, 2013 to 2020.

BackgroundInterventions to mitigate the COVID-19 pandemic may impact other respiratory diseases.AimsWe aimed to study the course of pertussis in France over an 8-year period including the beginning of the COVID-19 pandemic and its association with COVID-19 mitigation strategies, using multiple nationwide data sources and regression models.MethodsWe analysed the number of French pertussis cases between 2013 and 2020, using PCR test results from nationwide outpatient laboratories (Source 1) and a network of the paediatric wards from 41 hospitals (Source 2). We also used reports of a national primary care paediatric network (Source 3). We conducted a quasi-experimental interrupted time series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles and secular trend, and included a binary variable for the first national lockdown (start 16 March 2020).ResultsWe identified 19,039 pertussis cases from these data sources. Pertussis cases decreased significantly following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.10 (95% CI: 0.04-0.26) and 0.22 (95% CI: 0.07-0.66) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 with a median of, respectively, one (IQR: 0-2) and 0 cases (IQR: 0-0) per month before and after lockdown (p = 0.0048).ConclusionsThe strong reduction in outpatient and hospitalised pertussis cases suggests an impact of COVID-19 mitigation measures on pertussis epidemiology. Pertussis vaccination recommendations should be followed carefully, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.

Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France.

Importance: An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. Objective: To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. Design, Setting, and Participants: This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Exposures: Implementation of NPIs during the COVID-19 pandemic. Main Outcomes and Measures: The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. Results: During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. Conclusions and Relevance: In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.

Long-term impact of invasive meningococcal disease in children: SEINE study protocol.

INTRODUCTION: Invasive meningococcal disease (IMD) is still an important cause of mortality in children and survivors can have significant long-term disabling sequelae. There are few prospective studies looking at the long term neuropsychological and developmental consequences of IMD in surviving children, and the rate of sequelae may be underestimated. The SEINE study aims to have a more reliable estimate of the real rate of sequelae by assessing the long-term physical, neuropsychological, learning disorders and sensory sequelae of IMD in children and adolescents and by assessing the post-traumatic stress in parents. METHODS AND ANALYSIS: The SEINE study is a multicentre, prospective, non-randomized, interventional study based on the French bacterial meningitis surveillance network. The study will include 100 children aged from birth to 15 years old, hospitalized in a Paris area paediatric ward for a meningococcal meningitis or a purpura fulminans between 2010 and 2019. The first outcome will assess long-term sequelae (physical, neurological, or sensory) measured by a general clinical and neurological examination, a neurocognitive assessment, learning development, a pure tone audiometry and an ophthalmic examination. The second outcome will assess the long-term post-traumatic stress in parents measured by the Impact of Event Scare Revised questionnaire. PERSPECTIVES: By providing a better estimation of the rate of sequelae in children and offering an adapted follow-up of these children, we believe that the SEINE study will help to improve the management of patients surviving IMD. TRIAL REGISTRATION NUMBER: NCT04685850.

Comparative genomic analysis of ESBL-producing Escherichia coli from faecal carriage and febrile urinary tract infection in children: a prospective multicentre study.

Background: The reliability of ESBL-producing Escherichia coli (ESBL-Ec) faecal carriage monitoring to guide probabilistic treatment of febrile urinary tract infection (FUTI) in children remains unclear. Objectives: To compare the genomic characteristics of ESBL-Ec isolates from faecal carriage and FUTI to assess their correlation and identify a FUTI-associated virulence profile. Methods: We conducted a prospective multicentre hospital and ambulatory-based study. We analysed the genotypes and virulence factors of both faecal and FUTI ESBL-Ec by whole genome sequencing. Correlations were assessed by non-parametric Spearman coefficient and virulence factors were assessed by chi-squared tests with Bonferroni correction. Results: We included 218 ESBL-Ec causing FUTI and 154 ESBL-Ec faecal carriage isolates. The most frequent ST was ST131 (44%) in both collections. We found high correlation between carriage and ESBL-Ec FUTI regarding genes/alleles (rho = 0.88, P < 0.0001) and combinations of virulence genes, MLST and serotypes (rho = 0.90, P < 0.0001, rho = 0.99, P = 0.0003, rho = 0.97, P = 0.005 respectively). Beside this strong correlation, we found five genes that were significantly associated with FUTI (papC, papGII, hlyC, hek and traJ). The strongest association with FUTI was found with adhesin gene allele papGII (54% in FUTI versus 16% in carriage) and for papGII and gene traJ alone or in combination (63% versus 24%). Conclusions: The genomic profile of ESBL-Ec causing FUTI in children strongly correlates with faecal carriage isolates except for a few genes. The presence of papGII and/or traJ in a previously identified carriage strain could be used as a marker of uropathogenicity and may guide the empirical antimicrobial choice in subsequent FUTI.

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.