BACKGROUND:Group A Streptococcus (GAS) causes a wide range of infections, with substantial morbidity and mortality associated with invasive infections and suppurative complications. The diagnostic accuracy of rapid antigen detection tests (RADTs) is well established in children with pharyngitis, but not in extrapharyngeal infections. OBJECTIVES:To evaluate the diagnostic accuracy of RADTs for identifying GAS in children with extrapharyngeal infections. METHODS:Systematic review of diagnostic test accuracy. PROTOCOL:CRD420251108689 (PROSPERO). DATA SOURCES:PubMed and Web of Science (inception to November 2025). STUDY ELIGIBILITY CRITERIA:Studies evaluating RADTs in children with suspected extrapharyngeal infections caused by GAS. PARTICIPANTS:Children (0-18 years). TEST: RADTs for GAS. REFERENCE STANDARD:Bacterial culture and PCR. ASSESSMENT OF RISK OF BIAS:Quality Assessment of Diagnostic Accuracy Studies-2. METHODS OF DATA SYNTHESIS:Bivariate random-effects meta-analysis of sensitivity and specificity. Heterogeneity was evaluated through prespecified subgroup analyses and meta-regression. Robustness of the results was assessed through sensitivity analyses. RESULTS:We included 16 studies (23 RADT evaluations; 1737 unique patients; 2610 test results). Methodological quality varied across studies, with only four studies judged to have an overall low risk of bias. RADTs had a summary sensitivity of 92% (95% CI: 89-94) and a summary specificity of 99% (95% CI: 96-100). Sensitivity was similar across studies, whereas specificity varied according to infection type (p = 0.043), infection invasiveness (p <0.001), and the reference standard used (p <0.001). Sensitivity analyses restricted to various study subsets yielded consistent results. DISCUSSION:This systematic review found high sensitivity and very high, but variable, specificity of RADTs for identifying GAS in children with extrapharyngeal infections, particularly in those with pleural empyema. These findings suggest that RADTs may have a role in various clinical scenarios beyond pharyngitis, particularly when rapid results directly influence clinical management, but further high-quality studies are needed to define their precise role in diagnostic pathways for each infection type.

Abstract Background Pneumococcal nasopharyngeal colonization is the first step toward invasive pneumococcal disease (IPD). Respiratory syncytial virus (RSV) may trigger IPD, particularly for serotypes with low disease potential. We aimed to analyze the distribution of pneumococcal serotypes among pediatric IPD according to RSV circulation level. Methods We used data from 3 continuous French surveillance systems on IPD, pneumococcal carriage and RSV infections from 2008 to 2023. Based on the RSV epidemic threshold, we assessed the proportion of each serotype among IPD, depending on “RSV season” and “non-RSV season.” We assessed the correlation between the likelihood of serotype-specific involvement in IPD according to non-RSV season versus RSV season and the estimated disease potential of each serotype. Results Among 4574 IPD cases, the serotype distribution strongly varied during non-RSV season versus RSV season. The lower the disease potential of serotypes, the more RSV circulation enhanced their involvement in IPD (Rho=0.60, CI95% .28–.80, P = .0012). Conclusions The role of RSV in triggering IPD strongly varies across pneumococcal serotypes. The impact of RSV-targeted interventions should be evaluated in light of these data.

Objective: To investigate clinical and microbiological factors associated with persistent faecal carriage of extended spectrum beta-lactamase (ESBL) producing Escherichia coli in infants.Methods: Between 2010 and 2022, children aged 3 months to 2 years old were sampled in a community setting in France, at two visits, V1 and V2, 3 to 24 months apart, to screen for prolonged faecal carriage of ESBL-producing E. coli. Patient clinical information and whole genome sequence of each isolate were used for association studies.Results: A total of 4641 children were sampled. 375 (8%) carried an ESBL-producing Enterobacterales, among which 142 of ESBL-producing E. coli carriers were once again sampled at V2 and included in this study. 21.8% (n=31/142) and 18.4% (n=16/99) carried the same ESBL-producing E. coli clone for at least 3 and 6 months, respectively. B2 phylogroup, and among which ST131 clones were associated with an increased risk of persistent carriage. Multivariate analysis identified virulence associated genes involved in adhesion (papC/papGII allele and a tia-like gene) and encoding toxin (senB) as major risk factors for persistence. A genome wide association study highlighted the potential role of the frz metabolic operon, known to be involved in enterocytes adhesion/internalization.Conclusion: Main extraintestinal pathogenic E. coli genomic features (phylogenetic background, adhesion properties) are associated with ESBL-producing E. coli gut colonisation persistence in infants, which could potentially lead to an increased risk of febrile urinary tract infection in these patients.

BACKGROUND:Pneumococcal nasopharyngeal colonization is the first step toward invasive pneumococcal disease (IPD). Respiratory syncytial virus (RSV) may trigger IPD, particularly for serotypes with low disease potential.We aimed to analyse the distribution of pneumococcal serotypes among paediatric IPD according to RSV circulation level. METHODS:We used data from three continuous French surveillance systems on IPD, pneumococcal carriage and RSV infections from 2008 to 2023. Based on the RSV epidemics threshold, we assessed the proportion of each serotype among IPD, depending on "RSV season" and "non-RSV season". We assessed the correlation between the likelihood of serotype-specific involvement in IPD according to non-RSV season vs RSV season and the estimated disease potential of each serotype. RESULTS:Among 4,574 IPD cases, the serotype distribution strongly varied during non-RSV season vs RSV season. The lower the disease potential of serotypes, the more RSV circulation enhanced their involvement in IPD (Rho=0.60, CI95% 0.28 to 0.80, p-value = 0.0012). CONCLUSIONS:The role of RSV in triggering IPD strongly varies across pneumococcal serotypes. The impact of RSV-targeted interventions should be evaluated in light of these data.

BACKGROUND:Fusobacterium necrophorum is primarily involved in ear, nose and throat (ENT) infections, and exceptionally causes meningitis. We aimed at describing specific clinical features associated with cases of F. necrophorum meningitis. METHODS:Cases of F. necrophorum meningitis were prospectively collected by a network of 259 pediatric wards covering 60% of French pediatric wards between 2001 and 2024. Children were categorized in 2 groups: "isolated" meningitis and "complicated" meningitis, defined by ≥1 local or systemic complication (mastoiditis, subperiosteal or epidural abscess, Lemierre syndrome). RESULTS:A total of 27 cases of F. necrophorum meningitis were recorded. Median age was 4 years old (2-7 years) and only 2 were <1 year old. All children had a previous ENT infection, mainly acute otitis media (N = 21/27). Fusobacterium necrophorum was isolated in the cerebrospinal fluid (CSF) by culture (N = 16) or by polymerase chain reaction (PCR) (N = 3). One child had a positive 16S rRNA PCR in a cerebral abscess; other children had a CSF pleocytosis with a positive blood culture. Twenty children had a "complicated" meningitis, while 7 an "isolated" one. Median age was 4 years old in both groups. In the complicated group, 12 children underwent surgical drainage and 4 died. None of these children had a previous medical history. CONCLUSIONS:Our study highlights that, in addition to the well-known Lemierre syndrome, F. necrophorum should be considered in children ≥1 year old presenting with meningitis associated with acute otitis media, particularly when direct CSF examination or usual multiplex PCR fails to identify any bacteria. In such cases, 16S rRNA PCR and antibiotic treatment targeting anaerobic bacteria should be considered.

Background Acute otitis media (AOM) is the leading cause of antibiotic prescription in children. Respiratory syncytial virus (RSV) is suspected to play an important role in AOM. The aim of this study was to estimate the impact of RSV immunization on the rate of subsequent AOM in children, as this effect remains unknown. Methods We conducted an interrupted time-series analysis based on a French network involving 110 ambulatory pediatricians, trained in pediatric infectious diseases (PARI network). All ambulatory visits for AOM, from June 2017 to February 2025 were included. The main outcome was the monthly rate of pediatric ambulatory visits for AOM in infants aged < 12 months per 1000 pediatric ambulatory visits over time, assessed by a seasonally adjusted quasi-Poisson regression model. Bronchiolitis and urinary tract infections (UTI) were analyzed over the same period, as positive and negative controls, respectively. Results We included 70 452 cases of AOM, 13 284 bronchiolitis and 814 UTI. The rate of AOM per 1000 visits in infants aged < 12 months significantly decreased after RSV immunization implementation (-23.7%, 95% CI -37.6 to -9.7, P = .0014), whereas no significant change was observed in older age groups. We observed similar trends for bronchiolitis. The monthly rate of UTI did not significantly decrease. Conclusions RSV immunization led to a strong reduction of AOM rate in infants aged < 12 months. Beyond its efficacy in preventing RSV-related lower respiratory infections in infants aged < 12 months, RSV immunization may contribute to reduce the burden of AOM in children.

Les infections bactériennes néonatales précoces surviennent au cours des 7 premiers jours de vie. Elles sont devenues plus rares au fil du temps, même si leur incidence demeure plus élevée qu’à tout autre âge pédiatrique, en particulier chez le nouveau-né prématuré. Leur présentation clinique est souvent peu spécifique et peut rester discrète dans les premières heures d’évolution. Les infections bactériennes néonatales tardives surviennent, quant à elles, entre le 7e et le 90e jour de vie. Pendant des décennies, cette faible spécificité clinique a conduit à traiter un trop grand nombre de nouveau-nés par des antibiotiques à large spectre, souvent pour des durées prolongées. Aujourd’hui, l’enjeu est de mieux stratifier le risque infectieux afin de réserver l’antibiothérapie aux seuls nouveau-nés réellement à haut risque d’infection. Cette évolution est justifiée à la fois par les modifications de l’épidémiologie des infections néonatales précoces et par une meilleure connaissance des effets délétères d’une exposition antibiotique précoce, notamment la sélection de bactéries résistantes, l’altération de l’installation du microbiote et ses conséquences potentielles à long terme. Il est ainsi devenu essentiel de restreindre les indications des anti-infectieux, de privilégier les antibiotiques au spectre le plus étroit possible et de limiter les durées de traitement au strict nécessaire. Les hémocultures constituent l’examen biologique de référence pour confirmer le diagnostic. Au moins une hémoculture doit être réalisée avant toute antibiothérapie, dans des conditions rigoureuses d’asepsie, avec un volume de prélèvement suffisant (1 à 2mL) et à l’aide de flacons pédiatriques adaptés. Les bactéries responsables des infections bactériennes néonatales précoces ont peu évolué au cours des dernières années. Elles restent dominées par les streptocoques du groupe B et Escherichia coli, qui constituent les principales cibles du traitement probabiliste. Les infections à streptocoque du groupe B prédominent chez les nouveau-nés nés à terme, tandis que E. coli est plus fréquemment en cause chez les prématurés. Dans les infections bactériennes néonatales associées aux soins, les bactéries les plus souvent impliquées sont les staphylocoques à coagulase négative, suivis des entérobactéries. L’antibiothérapie probabiliste doit alors tenir compte du point d’appel infectieux, notamment cathéter veineux central, tube digestif ou poumon, de la gravité clinique et des résultats des prélèvements microbiologiques.

CONTEXT:Nirsevimab was implemented in Europe and the United States in September 2023. While its effectiveness in preventing respiratory syncytial virus (RSV)-bronchiolitis has been demonstrated by real-life studies, its impact on mid-term child health, quality of life, and parental absenteeism remains unstudied. METHODS:Infants under 1-year with a first bronchiolitis episode were recruited through the OURSYN study involving 37 primary care pediatricians in France between 2021 and 2025 (pre-nirsevimab period: 02/2021-03/2023 and nirsevimab period: 09/2023-03/2025). RSV status was determined by antigenic nasopharyngeal testing. At day 15, parents reported symptoms, quality of life (PedsQL Infant), and work absenteeism. Their associations with (i) RSV status, (ii) period of inclusion, and (iii) nirsevimab immunization status among RSV-positive cases were assessed using multivariable logistic regression adjusted for confounders. RESULTS:Among 1870 bronchiolitis cases included, 637 (34.0%) occurred during the nirsevimab period and 812 (43.4%) were RSV-related. Over the study period, at day 15, RSV-cases had more feeding difficulties (aOR = 1.41 [1.06-1.88]), longer daycare absence (4.7 vs. 3.2 days), and more parental absenteeism (aOR = 1.61 [0.99-2.62]) compared to RSV-negative. The proportion of RSV-cases decreased during the nirsevimab period compared with the pre-nirsevimab period (47.1% vs. 35.7% P < .001). Bronchiolitis cases recruited during this period had shorter daycare absences (3.2 vs. 4.3 days). Among RSV-cases, immunized infants had lower risk of persistent fever (aOR = 0.14 [0.01-0.79]). CONCLUSION:This large prospective study provides the first evidence that the mid-term burden of RSV-bronchiolitis in infants may be reduced following the implementation of nirsevimab, with potential benefits for infant health, quality of life and parental absenteeism.

Background:Community-acquired bacterial infections (CABIs) remain a leading cause of pediatric morbidity and mortality. This study aimed to provide a contemporary description of pediatric CABIs requiring admission to pediatric intensive care units (PICUs) in France. Methods:The CAPRICE study is a prospective, multicenter cohort including all children with suspected CABIs who were admitted to 28 French PICUs from January to December 2024. Demographic, clinical, microbiologic, and outcome data were prospectively collected. The primary outcome was mortality at day 28 and secondary outcomes included sequelae at day 28, PICU length of stay, and total hospital stay. Independent predictors of mortality were identified by multivariable logistic regression. Results:Among 897 children, the median age was 1.9 years (IQR 0.2-8.8); 55% were male, and 30% had a chronic condition. The leading infections were lower respiratory tract infection (43%), meningitis (20%), and ear-nose-throat infections (13%). Septic shock occurred in 17% of cases. A pathogen was identified in 89% of cases: Bordetella pertussis (22%) and Mycoplasma pneumoniae (15%) were predominant, followed by Streptococcus pneumoniae (13%), and Staphylococcus aureus (11%). In all, 34% patients had viral co-infection and 70% required organ support. Overall mortality was 7%, increasing to 19% with septic shock. Independent predictors of death included multiple organ failure, meningitis, and B. pertussis infection. Sequelae occurred in 15% of survivors. Conclusions:Severe CABIs in French PICUs in 2024 were mainly caused by B. pertussis and M. pneumoniae, followed by S. pneumoniae and S. aureus. Mortality and morbidity of these infections remain substantial.

BACKGROUND:Cerebrospinal fluid (CSF) leakage is a recognized risk factor for bacterial meningitis. Few data are published concerning bacterial meningitis in children with CSF leakage, and the impact of 13 valent pneumococcal conjugate vaccination (PCV13) in this population is not well known. The aim of this study was to describe the epidemiology of bacterial meningitis in children with known CSF leakage. METHODS:Among all bacterial meningitis in children >3 months old, we analyzed those with known CSF leakage (meningeal breach and/or cochlear implant resulting in meningitis) in a nationwide prospective cohort between 2001 and 2024 in France, with 227 pediatric wards and 168 microbiology departments. RESULTS:Of 5879 cases of bacterial meningitis in children over 3 months old, 251 (4.3%) were associated with known CSF leakage. In this population, Streptococcus pneumoniae (78.9%) was the most frequent bacteria involved, followed by Haemophilus influenzae (10%), mainly non typeable strains. Two cases of Neisseria meningitidis were recorded and only in children with cochlear implant. For children with known CSF leakage, in late PCV13 period, PCV13, PCV15, PCV20, PCV21, and 23-valent polysaccharide vaccine serotypes accounted for 14%, 16.3%, 37.2%, 79.1%, and 27.9%, respectively. In this population, serotype 23B was the most frequent (18.6%), followed by 11A (9.3%), 15A (9.3%), 19F (7%), 3 (4.7%), and 19A (2.3%). CONCLUSION:Bacterial meningitis in children with known CSF leakage is largely due to pneumococci and now mainly due to serotypes not included in PCV13. Only two cases of meningococcal meningitis were found and only for children with cochlear implant.

Abstract The worldwide rise in the prevalence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli is a major public health concern. In Europe, ESBL carriage frequency increased then stabilized at about 6-8 %. Past antibiotic use and travel in countries with high ESBL frequency, notably South-East Asia, have repeatedly been identified as risk factors of ESBL carriage. Yet, the relative contributions of these mechanisms to the observed maintenance of a stable low frequency of ESBL in Europe remains unknown. Here, we used comprehensive data on the risk factors for carriage of ESBL-producing E. coli in the French community, alongside detailed microbiological characterization of both resistant and overall E. coli , to develop a biologically plausible mathematical model of ESBL resistance spread in France. The model also includes several mechanisms previously showed to favor coexistence such as population structure, variability in carriage duration and within-host dynamics. The level of resistance in the community implies resistant strains transmit 14% less than sensitive (95% credible interval 0.6-38%), and are cleared at a +23% larger rate (0.9-62%). ESBL resistance is predicted to be strongly associated with factors prolonging residence in the gut. Both the rate of antibiotic treatment and transmission strongly impact the frequency of ESBL in the community. In contrast, travel has little impact on ESBL frequency. Whether reducing treatment or transmission is best to reduce resistance depends on community-specific parameters. Our study opens perspectives for the quantitative study of resistance evolution and argues for future work to improve the characterization of the duration of carriage of commensal bacterial strains.

BACKGROUND:The bacterial determinants of Group A Streptococcus (GAS) associated with either invasive (IGASI) or non-invasive (NIGASI) infections remain controversial. METHODS:From 2014 to 2018, French children hospitalized for an IGASI were enrolled in a prospective multicenter study aimed at identifying bacterial virulence factors and predisposing immunologic and genetic factors. During the same period, age- and date-matched control children with NIGASI were enrolled. Whole genome sequencing was performed for all GAS isolates. The 27 specific single nucleotide polymorphisms characterizing the M1UK lineage were searched among the emm-1 isolates. RESULTS:A total of 192 GAS isolates were sequenced: 94 from the IGASI group and 98 from the NIGASI group. The emm-1 genotype predominated in the IGASI group (36% vs. 11% in NIGASI group, P < .05) and was followed by emm-4, emm-12, and emm-3 (12%, 11%, and 10% respectively). In the NIGASI group, emm-89 predominated (21% vs 7% in the IGASI group, P<.05). Among the 45 emm-1 isolates, 12 (27%) carried the mutations characterizing clone M1UK in both groups (7 in IGASI group and 5 in NIGASI group). The superantigenic toxins SpeA and SpeJ, SIC protein, and FCT type 1 pilus predominated in the IGASI group but were linked to emm-1 strains. Insertions/deletions in the covS regulator gene were observed in 5 invasive isolates versus 1 non-invasive isolate. CONCLUSIONS:Genotype emm-1 GAS strains remained the main cause of invasive infections in French children, associated to specific GAS virulence factors, and should be monitored together with the rapid spread of the M1UK lineage.

OBJECTIVE:To estimate the effectiveness of nirsevimab against respiratory syncytial virus (RSV)-associated acute otitis media (AOM) in ambulatory care. STUDY DESIGN:We conducted a test-negative design study, post hoc analysis using data from the prospective Oursyn study involving 37 primary care pediatricians across France from 2020 to 2025. Nasopharyngeal sampling for RSV was performed in infants younger than 1 year diagnosed with AOM during the first 2 RSV seasons with introduction of nirsevimab passive immunization (October 2023 to February 2024 and October 2024 to January 2025). The main outcome of the study was the detection of RSV status in infants with AOM. We performed a multivariable logistic regression with nirsevimab adjusted for age, sex, underlying chronic condition, prematurity, type of childcare, month, year, and geographic region of inclusion. Sensitivity analyses were performed as well. RESULTS:A total of 236 AOM events were included over the study period: 141 during the first season of nirsevimab implementation and 95 during the second season. Among infants with AOM, 41 (29.1%) and 15 (15.8%), respectively, tested positive for RSV. Nirsevimab-adjusted effectiveness was estimated to be 78.2% (95% CI 44.4-92.4) for the prevention of RSV-AOM in this sample. Sensitivity analyses found similar results. CONCLUSIONS:These findings highlight the broader protective effect of nirsevimab on complications of respiratory tract infections in infants. TRIAL REGISTRATION:NCT04743609.

Le programme de vaccination français contre les principales bactéries responsables des méningites communautaires est un des plus complet au monde : en effet, les vaccinations contre Haemophilus influenzae de sérotype b et les méningocoques des sérotypes B, ACYW sont obligatoires chez les nourrissons avec d’excellent taux de couvertures vaccinales diminuant de façon considérable l’incidence des méningites bactériennes. La vaccination pneumococcique conjuguée (7- puis 13 et 15 valences, l’extension au vaccin 20- valent étant en cours d’évaluation) est également obligatoire et a permis de diminuer l’incidence des méningites liées à ce germe mais surtout a considérablement modifié le profil des méningites à pneumocoque en faisant disparaître transitoirement les souches les plus résistantes aux bêta-lactamines en France. L’Observatoire national des méningites bactériennes de l’enfant du Groupe de pathologie infectieuse pédiatrique (GPIP) de la Société française de pédiatrie ainsi que le Centre national de référence des pneumocoques n’ont pas répertorié de cas de méningites dues à des pneumocoques résistants aux céphalosporines de troisième génération (C3G), même si des souches de profil moins favorable (sérotypes 11A, 15BC et A) ont émergé en 2021. Ces données récentes justifient globalement de reconduire les recommandations de 2016 et à limiter l’usage de la vancomycine à la phase secondaire de traitement des méningites à pneumocoque lorsque la CMI de la souche isolée vis-à-vis des injectables est >0,5 mg/L. Cette recommandation est susceptible d’évoluer si le pourcentage de souches résistantes devait ré-augmenter et une vigilance particulière est nécessaire sur ce point. Une alternative pourrait être, pour les souches de CMI>0,5 mg/L pour les C3G, d’utiliser la ceftaroline dont les CMI restent actuellement basses. Néanmoins, les données PK/PD pour cette molécule sont encore peu précises, notamment chez l’enfant et en présence d’une inflammation méningée. L’observatoire national des méningites de l’enfant est un outil précieux en raison de sa bonne exhaustivité et de sa pérennité depuis 20 ans. Le maintien de la surveillance épidémiologique permettra d’adapter si nécessaire, les nouveaux schémas thérapeutiques à l’évolution des profils de sensibilité des pneumocoques et aux changements sérotypiques éventuels à venir. Les abcès et empyèmes cérébraux communautaires sont des maladies rares, mais leur prise en charge nécessite une approche rigoureuse et spécifique, différente de celle des méningites. Une imagerie de qualité, un prélèvement bactériologique avant l’antibiothérapie dans la mesure du possible, et un traitement antibiotique incluant le métronidazole en plus du céfotaxime sont recommandés. Ces abcès cérébraux nécessitent toujours une collaboration multidisciplinaire, incluant les professionnels des maladies infectieuses et un avis neurochirurgical.

OBJECTIVES:Most of the clinical and economic burden of the respiratory syncytial virus (RSV) in pediatric populations is concentrated among infants aged <1 year. Since 2024, RSVpreF vaccine is available in France for the vaccination of pregnant women between 32 and 36 weeks of gestational age, from September to January. This study aimed to model the impact of alternative RSVpreF national vaccination strategies on RSV hospital burden. METHODS:A three-state Markov model - Susceptible to be infected, RSV-related hospitalization, and Death - was developed to assess the number of hospitalizations avoided by alternative vaccination strategies. The model population of 627,499 unique births in one year was split in two cohorts of infants born to vaccinated and unvaccinated women. Four strategies were modeled: no vaccination, vaccination between September and January (recommended), between May and January (extended), and year-round. Results were presented at a population level using a healthcare perspective, as cost per hospitalization avoided, and number needed to vaccinate (NNV). RESULTS:In the absence of vaccination, 38,625 RSV-related hospitalization among infants under 1 year of age were estimated annually, costing €120.0 million. Compared to no vaccination, the recommended strategy prevented 7,620 (-19.7%) RSV-related hospitalizations, 90.4% of them involved infants aged <3 months (99.5% aged <6 months). The related total cost was €126.4 million, corresponding to cost of €844 per hospitalization avoided, and an NNV of 21 vaccinations to avoid one hospitalization. Compared to the recommended strategy, the extended strategy avoided an additional 4,111 (-13.3%) hospitalizations, 42.0% of them involving infants aged <3 months (95.0% aged <6 months). The total cost of this strategy was €134.4 million (+6.3%), corresponding to a cost of €1,929 per additional hospitalization avoided. Total cost of the year-round strategy was €156.2 million, for 1,306 additional hospitalizations avoided. CONCLUSIONS:This is the first cost-effectiveness model to describe the public health impact of alternative vaccination strategies for RSV prevention in France. The number of hospitalizations avoided ranged from 7,600 stays in the recommended strategy, to more than 13,000 in the year-round strategy, corresponding to hospital savings between €24.7 million and €41.5 million. Alternative scenarios were shown to extend prevention to older age groups. Broader vaccination strategies, notably the extended strategy, had a positive impact on RSV hospital burden, with a limited impact on total costs.

BACKGROUND:Maternal respiratory syncytial virus (RSV) prefusion F (RSVpreF) vaccine and nirsevimab immunisation are two products recently implemented to reduce RSV-related lower respiratory tract infection (LRTI) in infants (nirsevimab since 2023 and RSVpreF since 2024). We aimed to assess the effectiveness of nirsevimab immunisation at birth versus RSVpreF maternal vaccination in preventing RSV-related LRTI hospitalisations in children before age 6 months. METHODS:This population-based retrospective cohort study used data from the French National Health Data System and included all children born across metropolitan France between Sept 1, 2024, and Feb 28, 2025, who either received nirsevimab at birth (nirsevimab group) or whose mothers received RSVpreF vaccine between 28 weeks and 36 weeks of gestation (RSVpreF group). Children who received neither immunisation, those born from mothers not aged 13-50 years, and those who could not be linked to their mother in the database were not included. Children were matched on birth date, region of birth, and sex. The primary outcome was RSV-related LRTI hospitalisation at age 6 months. Propensity score analysis adjusted for baseline characteristics. Secondary analyses were performed, notably assessing the influence of the timing of RSVpreF maternal vaccination during pregnancy on the main outcome. FINDINGS:During the study period, 164 140 children were included, of whom 83 978 (51·2%) were male and 80 162 (48·8%) female; mean gestation at birth was 39·4 weeks (SD 1·2), 103 062 (62·8%) received nirsevimab after birth, and 61 078 (37·2%) were born to mothers vaccinated with RSVpreF. 42 098 children from each group were matched. During the 6-month follow-up, 753 RSV-related LRTI hospitalisations occurred: 350 (0·83%) of 42 098 infants in the nirsevimab immunisation group and 403 (0·96%) of 42 098 infants in the RSVpreF vaccine group. After adjustment, nirsevimab was associated with a 22% reduction in the odds of RSV-related LRTI hospitalisation compared with RSVpreF vaccination (OR 0·78 [95% CI 0·70-0·86]). Although the odds of RSV-related LRTI hospitalisation were lower with nirsevimab than with RSVpreF vaccination when RSVpreF vaccination was given between 2 weeks and less than 4 weeks (0·45 [0·32-0·63]), between 4 weeks and less than 6 weeks (0·80 [0·68-0·95]), and between 6 weeks and less than 8 weeks before delivery (0·80 [0·60-0·99]), there was no difference between nirsevimab and RSVpreF given 8 weeks or more before delivery (1·01 [0·77-1·32]). INTERPRETATION:Compared with RSVpreF maternal vaccine, nirsevimab at birth was associated with a reduction in the odds of RSV-related LRTI hospitalisation at age 6 months in the 2024-25 RSV season. Exploratory secondary analyses suggest that an interval of at least 8 weeks between RSVpreF vaccination and delivery could provide protection not statistically different from nirsevimab at birth. These findings can guide future public health decisions. FUNDING:Assistance Publique-Hôpitaux de Paris Foundation.