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 the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage.

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.

BACKGROUND: 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 the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs). RESEARCH QUESTION: What is the respective role of respiratory pathogens in ACS epidemiology? STUDY DESIGN AND METHODS: This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All children aged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by 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, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed 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, 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); 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 epidemiologic situation allowed determination of 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.

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.

Early formative objective structured clinical examinations for students in the pre-clinical years of medical education: A non-randomized controlled prospective pilot study.

BACKGROUND: The value of formative objective structured clinical examinations (OSCEs) during the pre-clinical years of medical education remains unclear. We aimed to assess the effectiveness of a formative OSCE program for medical students in their pre-clinical years on subsequent performance in summative OSCE. METHODS: We conducted a non-randomized controlled prospective pilot study that included all medical students from the last year of the pre-clinical cycle of the Université Paris-Cité Medical School, France, in 2021. The intervention group received the formative OSCE program, which consisted of four OSCE sessions, followed by debriefing and feedback, whereas the control group received the standard teaching program. The main objective of this formative OSCE program was to develop skills in taking a structured medical history and communication. All participants took a final summative OSCE. The primary endpoint was the summative OSCE mark in each group. A questionnaire was also administered to the intervention-group students to collect their feedback. A qualitative analysis, using a convenience sample, was conducted by gathering data pertaining to the process through on-site participative observation of the formative OSCE program. RESULTS: Twenty students were included in the intervention group; 776 in the control group. We observed a significant improvement with each successive formative OSCE session in communication skills and in taking a structured medical history (p<0.0001 for both skills). Students from the intervention group performed better in a summative OSCE that assessed the structuring of a medical history (median mark 16/20, IQR [15; 17] versus 14/20, [13; 16], respectively, p = 0.012). Adjusted analyses gave similar results. The students from the intervention group reported a feeling of improved competence and a reduced level of stress at the time of the evaluation, supported by the qualitative data showing the benefits of the formative sessions. CONCLUSION: Our findings suggest that an early formative OSCE program is suitable for the pre-clinical years of medical education and is associated with improved student performance in domains targeted by the program.

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.

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.

The principles of curative antibiotic treatments.

Knowledge of infectious diseases and their treatments is constantly evolving. New infectious agents are regularly discovered, due mainly to improvement of identification techniques, especially the development of molecular biology and mass spectrometry. While changes in the epidemiology of infectious diseases are not always predictable or readily understood, several factors regularly enter into consideration, such as not only the natural history of diseases and the impact of vaccinations, but also the excessive and irrational use of antibiotics. Antibiotic resistance is now recognized as one of the major challenges for humanity, especially since few new molecules have been put on the market in recent years. These molecules are reserved for serious infections caused by bacteria resistant to other antibiotics and should be prescribed only by infectious disease specialists trained in their use. Rationalization of antibiotic therapy is therefore one of the keys to reducing antibiotic resistance and the spread of resistant bacteria. In this guide, with regard to each clinical situation, the bacterial target(s) of antibiotic treatment, the preferred antibiotic choice, and the therapeutic alternatives will be specified. Comments on diagnosis and treatment of the infection will be added if necessary.

Antimicrobial treatment of urinary tract infections in children.

Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations published by the Groupe de Pathologie Infectieuse de Pédiatrique (GPIP-SFP). Except in rare situations (newborns, neutropenia, sepsis), a positive urine dipstick for leukocytes and/or nitrites should precede a urine culture examination and any antibiotic therapy. After rising steadily between 2000 and 2012, the proportion of Escherichia coli strains resistant to extended-spectrum ß-lactamases (E-ESBL) has remained stable over the last ten years (between 7% and 10% in pediatrics). However, in many cases no oral antibiotic is active on E-ESBL leading either to prolonged parenteral treatment, or to use of a non-orthodox combination such as cefixime + clavulanate. With the aim of avoiding penem antibiotics and encouraging outpatient management, this guide favors initial treatment of febrile urinary tract infections (suspected or actual E-ESBL infection), with amikacin. Amikacin remains active against the majority of E-ESBL strains. It could be prescribed as monotherapy for patients in pediatric emergency departments or otherwise hospitalized patients.

Definitions and implications of the pharmacokinetic-pharmacodynamic parameters of antibiotics in pediatric clinical practice.

Knowledge of infectious diseases and their treatments is constantly evolving. New infectious agents are regularly discovered, mainly due to improvement of identification techniques, especially the development of molecular biology and mass spectrometry. While changes in the epidemiology of infectious diseases are not always predictable or readily understood, several factors regularly enter into consideration, such as not only the natural history of diseases, the impact of vaccinations, but also the excessive and irrational use of antibiotics. Antibiotic resistance is now recognized as one of the major challenges for humanity, especially since few new molecules have been put on the market in recent years. These molecules are reserved for serious infections caused by bacteria resistant to other antibiotics and should only be prescribed by infectious diseases specialists trained in their use. Rationalization of antibiotic therapy is therefore one of the keys to reducing antibiotic resistance and the spread of resistant bacteria. In this guide, for each clinical situation, the bacterial target(s) of antibiotic treatment, the preferred antibiotic choice, and the therapeutic alternatives will be specified. Comments on the diagnosis and treatment of the infection will be added if necessary.

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.

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.

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.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

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.

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study.

BACKGROUND: During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. METHODS AND FINDINGS: Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. CONCLUSIONS: Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. TRIAL REGISTRATION: ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258.

Investigation of Concurrent Pneumococcal Meningitis in Two Children Attending the Same Day-Care Center.

Only a few clusters of invasive pneumococcal disease have been described globally in children, and most of these cases occurred before pneumococcal vaccination implementation. Two unusual cases of pneumococcal meningitis, occurring in the same daycare center over a 3-day period, were reported. Both cerebrospinal fluid (CSF) were sent to the National reference center for pneumococci. In addition, we decided to perform a pneumococcal carriage study on all children and staff of the daycare center to analyze the pneumococcal serotypes circulating in this DCC and to discuss an antibiotic chemoprophylaxis. CSF culture was positive for pneumococcus, and serotype 25A was identified by latex agglutination. The second case had negative CSF culture, but CSF antigen test and gene amplification results were positive for Streptococcus pneumoniae. Serotype 12F was identified by using molecular biology. The absence of correlation between these strains was confirmed by multi-locus sequence typing. In the carriage study, we included 29 children (median age 1.9 years, interquartile range 1.4-2.5) and 10 adults. Among the children, 24 carried Streptococcus pneumoniae (83%). The main serotypes isolated were 23A for 6 children and 25A for 5 children; serotypes were non-typeable for 3 children. Only 1 of 10 adults tested carried Streptococcus pneumoniae (serotype 12F). Despite this temporo-spatial pattern, the cases were unrelated and not due to carriage of a particular serotype. No specific action has been taken for the other children attending this DCC, and no other case of bacterial meningitis occurred.

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.

Reassessing the Performance of the "Step-By-Step" Approach to Febrile Infants 90 Days of Age and Younger in the Context of the COVID-19 Pandemic: A Multicentric Retrospective Study.

BACKGROUND: Infants with COVID-19 can often present with fever without source, which is a challenging situation in infants <90 days old. The "step-by-step" algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm. METHODS: We performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the "step-by-step" algorithm to 4 clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk (ill-appearing, ≤21 days old, with leukocyturia or procalcitonin level ≥0.5 ng/mL). RESULTS: Among the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but 1 infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill-appearance (72%), an age ≤21 days (27%), or leukocyturia (19%). All these infants had procalcitonin values <0.5 ng/mL and only 1 had C-reactive protein level >20 mg/L. CONCLUSIONS: The "step-by-step" algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants <90 days old.

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.