Effectiveness of nirsevimab against RSV-bronchiolitis in paediatric ambulatory care: a test-negative case-control study.

Background: Respiratory syncytial virus (RSV) is the leading cause of lower-respiratory-tract infection in children. Nirsevimab, a monoclonal antibody against RSV, was implemented in a few countries in September 2023. However, its post-license effectiveness in ambulatory care settings is unknown. We aimed to assess the effectiveness of nirsevimab against RSV-bronchiolitis in outpatients aged <12 months. Methods: We conducted a test-negative case-control study based on a national ambulatory surveillance system. We included all infants aged <12 months who had bronchiolitis and results of an RSV rapid antigen test performed, visiting a network of 107 ambulatory paediatricians from September 15, 2023, to February 1, 2024. Case patients were infants with bronchiolitis and a rapid antigen test positive for RSV. Control patients were infants with bronchiolitis and a rapid antigen test negative for RSV. Effectiveness was assessed by a logistic regression model adjusted for potential confounders. A range of sensitivity analyses were conducted to assess the robustness of the findings. Findings: We included 883 outpatients who had bronchiolitis and results of an RSV rapid antigen test (453 were case patients, and 430 were control patients). Overall, 62/453 (13.7%) case patients and 177/430 (41.2%) control patients had been previously immunised for nirsevimab. The adjusted effectiveness of nirsevimab against RSV-bronchiolitis was 79.7% (95% CI 67.7-87.3). Sensitivity analyses gave similar results. Interpretation: This post-license study indicates that nirsevimab was effective in preventing RSV-bronchiolitis in ambulatory care settings. Funding: The study was supported by Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), French Pediatrician Ambulatory Association (AFPA) and unrestricted grants from GSK, MSD, Pfizer and Sanofi.

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.

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.

Whole Goat Milk-Based Formula versus Whey-Based Cow Milk Formula: What Formula Do Infants Enjoy More?-A Feasibility, Double-Blind, Randomized Controlled Trial.

(1) Background: While goat milk formula (GMF) is an alternative to cow milk formula (CMF), infants' preferences for one over the other have not been formally assessed. Specifically, our aim in this study was to determine whether infants experience fewer feeding behavior problems with whole milk-based GMF than with conventional whey-based CMF. (2) Methods: This was a multicenter, double-blind, randomized controlled trial with two-arm parallel assignment conducted in six pediatricians' offices in or near Paris, France, between June 2018 and 31 December 2021. Overall, 64 healthy infants (≤4 months old), predominantly formula-fed, were randomly assigned to either the whole milk-based GMF (n = 33) or whey-based CMF (n = 31) arm. Parents completed the Baby Eating Behavior Questionnaire (BEBQ) and the modified QUALIN questionnaire to evaluate infant feeding behavior and quality of life (psychomotor and socioemotional development), respectively, at inclusion (1 to 5 days before milk delivery) and the final visit (day 28 ± 3 after milk delivery). Informed consent was obtained for all recruited patients, and an ethical committee approved the study. (3) Results: Changes in BEBQ Enjoyment of Food and Slowness in Eating subscale scores from inclusion to final visit did not differ between arms. However, there were significant improvements in subscale scores for Food Responsiveness (GMF: 0.15 ± 1; CMF: -0.48 ± 0.81; p = 0.010) and General Appetite (GMF: 0.26 ± 1.2; CMF: -0.48 ± 0.88; p = 0.012), and modified QUALIN (GMF: 4.6 ± 9.4; CMF: -0.40 ± 7.6; p = 0.03) scores in favor of the GMF group. (4) Conclusions: In this double-blind, randomized controlled trial, GMF-fed infants exhibited a greater general appetite than CMF-fed infants, possibly due to differences in the composition of these formulas (i.e., protein and lipid profiles). In addition, GMF-fed infants enjoyed a better quality of life. There was no difference in food enjoyment between groups. These findings suggest that whole-milk-based GMF could be an attractive alternative to whey-based CMF. Clinical trial registration: NCT03488758 (clinicaltrials.gov).

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.

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.

Diagnostic Accuracy of SARS-CoV-2 Antigen Detection Test in Children: A Real-Life Study.

Naso-pharyngeal RT-PCR is the gold standard for the diagnosis of COVID-19, but there is a need for rapid and reliable tests. Some validation studies have used frozen aliquots mainly from adults. The aim of this real-life study was to test the performance of a SARS-CoV-2 rapid antigen test (SC2-RAT) in children. Symptomatic patients aged 0 to 17 years were recruited in the emergency department of the University Hospital of Creteil and in primary care pediatric practices from October 10, 2020 for 7 weeks. Each enrolled child had a SARS-CoV-2 RT-PCR test and a SC2-RAT from two distinct nasopharyngeal swabs. Among the 308 patients (mean [SD] age 4.9 [5.3] years), fever was the main symptom (73.4%), with no difference between COVID-19-negative and -positive groups. The prevalence of COVID-19 was 10.7% (95% CI 7.5-14.7). On the whole cohort, the sensitivity and specificity of the SC2-RAT compared to RT-PCR was 87.9% (95% CI 71.8-96.6) and 98.5% (95% CI 96.3-99.6). Considering samples with cycle threshold >25, the sensibility was lower: 63.6% (95% CI 30.8-89.1) and the specificity 99.6% (95% CI 98.0-100.0). The mean delay to obtain an SC2-RAT result was <15 min but was 3.2 h (SD 5.5) for an RT-PCR result. Contact with a COVID-19-positive person was more frequent for COVID-19-positive than -negative patients (n = 21, 61.6%, vs. n = 64, 24.6%; p < 0.01). In real life, SC2-RAT seems reliable for symptomatic children, allowing to detect contagious children.

Delayed Bronchiolitis Epidemic in French Primary Care Setting Driven by Respiratory Syncytial Virus: Preliminary Data from the Oursyn Study, March 2021.

We report early results from a prospective primary care bronchiolitis surveillance study in France in which a 10-week delayed epidemic was detected from February to March 2021. Among 225 children under 2 years with swab testing for a first bronchiolitis episode, 55% had a positive test for RSV, 0 for influenza, and 1 for severe acute respiratory syndrome coronavirus 2.

Assessment of SARS-CoV-2 infection by Reverse transcription-PCR and serology in the Paris area: a cross-sectional study.

BACKGROUND: Several studies indicated that children seem to be less frequently infected with SARS-CoV-2 and are potentially less contagious than adults. To examine the spread of SARS-CoV-2, we combined both Reverse transcription-PCR testing and serology in children in the most affected region in France, Paris, during the COVID-19 epidemic. METHODS: From 14 April 2020 to 12 May 2020, we conducted a cross-sectional, prospective, multicentre study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory paediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by Reverse transcription-PCR and a microsample of blood for micromethod serology. RESULTS: Among the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) were symptomatic. Reverse transcription-PCR and serology results were positive for 11 (1.8%) and 65 (10.7%) children, respectively, with no significant difference between asymptomatic and pauci-symptomatic children. Only three children were Reverse transcription-PCR-positive without any antibody response detected. The frequency of Reverse transcription-PCR SARS-CoV-2 positivity was significantly higher for children with positive than negative serology results (12.3% vs 0.6%, p<0.001). Contact with a person with confirmed COVID-19 increased the odds of Reverse transcription-PCR positivity (OR 7.8, 95% CI 1.5 to 40.7) and serology positivity (OR 15.1, 95% CI 6.6 to 34.6). CONCLUSION: In an area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with Reverse transcription-PCR SARS-CoV-2 positivity was very low (1.8%), but that of serology positivity was higher (10.7%). Most children with positive Reverse transcription-PCR results also had positive serology results. TRIAL REGISTRATION NUMBER: NCT04318431.