BACKGROUND:Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants. Nirsevimab, a long-acting monoclonal antibody targeting a conserved epitope on the prefusion F protein (site Φ), has shown high efficacy in clinical trials and early real-world studies. Although widespread resistance has not been reported, concerns remain about the emergence of escape variants, particularly among RSV-B viruses. During the 2024-25 RSV season in France, RSV-B predominated, providing a unique opportunity to examine breakthrough infections with RSV-B and resistance at a large scale. The study aimed to characterise RSV escape from nirsevimab using genotypic and phenotypic methods. METHODS:This POLYRES-2 project was a multicentre, national, observational study conducted in hospital settings (inpatients and outpatients) across France during the 2024-25 RSV season. We included infants aged 1 year or under with a RT-PCR-confirmed RSV infection in routine care, regardless of whether they had received nirsevimab. Infants were identified through hospital virology laboratory databases. Each participating centre was requested to include a balanced number of nirsevimab-exposed and non-exposed infected infants throughout the study period. Clinical data were retrieved from electronic medical records. We compared RSV susceptibility to nirsevimab in infants who received nirsevimab with that in nirsevimab-naive infants. Respiratory samples were sequenced for full-length RSV genomes. To ensure reliability, phylogenetic and mutational analyses were restricted to high-quality sequences with greater than or equal to 90% genome coverage and complete reads across the nirsevimab-binding site. Clinical RSV isolates were tested for neutralisation by nirsevimab. We analysed F candidate substitutions using a fusion inhibition assay. The primary outcomes were presence of resistance-associated substitutions (RASs) in the RSV F protein (site Φ) and phenotypic resistance to nirsevimab. FINDINGS:Among 1023 RSV-infected infants, 858 (83·9%) had full-length RSV genome sequences: 419 (48·8%) from nirsevimab-treated breakthrough infections (212 [50·6%] RSV-A, 207 [49·4%] RSV-B) and 439 (51·2%) from nirsevimab-naive infants (192 [43·7%] RSV-A, 247 [56·3%] RSV-B). RASs were identified in two of 195 RSV-A breakthrough infections (1·0%) and in 23 of 184 RSV-B breakthrough infections (12·5%). In RSV-A, the only RAS was F:K209E, conferring intermediate resistance. In RSV-B, resistance was more frequent and diverse than in RSV-A: 12 of 23 (52.2%) resistant viruses carried a substitution at residue 208 (F:N208D, F:N208I, F:N208K, F:N208S, or F:N208Y). Additional novel substitutions, including F:I64V/F:K65E, F:K68I, F:L204S, and F:P205S, also mediated resistance. Notably, a resistant RSV-B variant (F:N208S) was detected almost 1 year after prophylaxis. No resistant RSV was detected in nirsevimab-naive infants. INTERPRETATION:Resistance to nirsevimab in RSV-B can emerge in real-world settings, affecting around 12% of breakthrough infections and showing greater diversity than previously recognised, although the clinical impact remains constrained by available evidence. Detection of resistant variants long after prophylaxis highlights the need for extended genomic surveillance. Integration of clinical and virological data will be essential to sustain the long-term effectiveness of RSV monoclonal antibody programmes. FUNDING:This study was supported by a grant from the Agence Nationale de Recherche sur le Sida et les hépatites virales - Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention.

Respiratory syncytial virus (RSV) is a virus responsible for acute respiratory infections and is widely recognized as a major pathogen in the paediatric population. Thus, the burden of RSV in the adult population remains poorly understood, as epidemiological studies mainly rely on PMSI (Medicalization of Information Systems Program) data, which are coded for economic purposes, and because many adults RSV infections remain underdiagnosed. The aim of this study was to describe epidemiological and clinical characteristics of RSV infections in elderly population across four university hospitals in north-western France during the 2022–2023 epidemic season. This retrospective cohort included all patients aged 60 years and older who tested positive for RSV between September 1st, 2022, and January 31st, 2023, in four university hospitals. Viral detection was performed using molecular assays on respiratory samples. Clinical, demographic, biological, and coding data were collected from medical records and hospital information systems. Outcomes included need for oxygen therapy, intensive care admission, in-hospital mortality, length of stay, readmission within 90 days for a respiratory or cardiac reason, and changes in living arrangements. Statistical analyses used descriptive methods and standard tests for comparisons. A total of 647 patients were included. The mean age was 77.8 years, and most patients had at least one chronic medical condition, primarily respiratory or cardiac. 508 (78.5

Current French guidelines on the diagnosis of dengue infection recommend both nucleic acid testing and serology as tools for laboratory confirmation. This study aimed to evaluate the performance of the fully automated Virclia IgM assay for the diagnosis of dengue infection. Samples from patients with a suspicion of dengue were prospectively tested using the Virclia Dengue IgM assay (Vircell) and subsequently underwent additional investigations (dengue RT-PCR and conventional dengue IgM EIA) at the French Reference Center for Arboviruses. A total of 104 patients were included with a median age of 34.3 years old and a median time since symptom (TSS) of 6 days. Dengue RT-PCR was positive in 57 patients (54.8%). The agreement was excellent (90.5%; κ = 0.81) between RT-PCR and Virclia Dengue IgM assay on samples collected from Day 5 postsymptom onset. On these samples, the sensitivity and specificity of the Virclia IgM assay were 95.7% (95% CI: 84.7%-96.9%) and 96.4% (95% CI: 80.8%-100%), respectively. In addition, the agreement was also excellent between the Virclia Dengue IgM assay and the Euroimmun plate-based Dengue IgM ELISA (92.7%; κ = 0.85). In conclusion, the Virclia Dengue IgM assay showed a good performance in the diagnosis of dengue infection and can be recommended in addition to nucleic acid testing to broaden the diagnostic window. The automation coupled with the monotest format is well-adapted for nonendemic areas.

INTRODUCTION:Kidney transplant recipients are among the populations at risk for Hepatitis B Virus (HBV) reactivation, and close monitoring is needed for its early detection. METHODS:We describe a case of HBV reactivation in a patient who underwent kidney transplantation more than 30 years ago, with a known serological profile of past HBV infection. RESULTS:Reactivation occurred as a highly replicative infection that went undiagnosed for 7 years due to negative results for HB surface antigen (HBsAg) and high levels of anti-HBs antibodies. Viral genome sequencing showed a high number of mutations in the major hydrophilic region of HBsAg that could explain such a profile. DISCUSSION:This case highlights the usefulness of frequent and systematic HBV viral load testing in patients at risk of reactivation, with anti-hepatitis B core antibodies, regardless of HBsAg detection, aminotransferases, and anti-HBs antibody levels.

BACKGROUND:Nirsevimab, a long-acting monoclonal antibody, has been approved for the prevention of respiratory syncytial virus (RSV) infection in infants. In France, more than 210 000 single doses were administered in infants younger than 1 year during the 2023-24 season. In this context, the selection and spread of escape variants might be a concern. Here, we aimed to characterise RSV associated with breakthrough infection. METHODS:We did a multicentre, national, observational study in France during the 2023-24 RSV season in RSV-infected infants (aged <1 year) who either received or did not receive a dose of nirsevimab before their first RSV season. We excluded infants with insufficient information about nirsevimab treatment or without parental consent. We used respiratory samples collected in each laboratory for full-length RSV RNA sequencing to analyse changes in the nirsevimab binding site Ø. We tested clinical RSV isolates for neutralisation by nirsevimab. We analysed F candidate substitutions by fusion-inhibition assay. FINDINGS:Of the 695 RSV infected infants, we analysed 545 (78%) full-length RSV genome sequences: 260 (48%) from nirsevimab-treated breakthrough infections (236 [91%] RSV-A and 24 [9%] RSV-B) and 285 (52%) from untreated RSV-infected infants (236 [83%] RSV-A and 49 [17%] RSV-B). Analysis of RSV-A did not reveal any substitution in site Ø known to be associated with resistance to nirsevimab. Two (8%) of 24 RSV-B breakthrough infections had resistance-associated substitutions: F:N208D (dominant resistance-associated substitution) and a newly described F:I64M plus F:K65R combination (minority resistance-associated substitution), both of which induced high levels of resistance in the fusion-inhibition assay. INTERPRETATION:This study is, to the best of our knowledge, the largest genotypic and phenotypic surveillance study of nirsevimab breakthrough infections to date. Nirsevimab breakthrough variants remain very rare despite the drug's widespread use. The detection of resistance-associated substitutions in the RSV-B F protein highlights the importance of active molecular surveillance. FUNDING:ANRS Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention.

Diagnosis of hepatitis E virus (HEV) infection relies first on detection of IgM antibodies (Ab), sometimes completed with HEV RNA detection. This study aimed to compare the performance of two automated anti-HEV IgM Ab assays. Correlation between Virclia® (Vircell) and Liaison® (Diasorin) assays was carried out on 178 routine clinical samples. Both assays were run on 67 samples from HEV RT-PCR (Altona) screened patients, and 52 Wantai® EIA (Euroimmun) tested samples. An excellent correlation was observed between both assays with an overall agreement of 96.6% (172/178), and a kappa coefficient at 0.93. In HEV RNA positive group (n=43), IgM detection rate was 93.3% (14/15) in immunocompetent patients, with both assays. In immunocompromised patients, detection rate was 75% (21/28) and 71.4% (20/28) using Virclia® and Liaison XL® assays, respectively. Virclia® and Liaison® anti-HEV IgM assays have similar performance for the detection of anti-HEV IgM Ab.

The ongoing outbreak of monkeypox virus (MPXV) is the largest one in historically non-endemic countries. Early reports described atypical epidemiological and clinical presentations. We investigated MPXV DNA detection in oropharyngeal samples (OPS), and compared the viral load to that in lesion samples at diagnosis in patients infected with MPXV. We retrospectively included patients suspected to have monkeypox in Northern France, who underwent a MPXV PCR in the Virology Laboratory, University Hospital of Lille, from May 23 to August 18, 2022. Overall, a total of 228 patients (376 samples) were included. A positive result in at least one sample was found in 138 patients (60.5%). We compared PCR results between OPS and lesion samples (i.e., cutaneous or anal/rectal samples) in patients with both samples. A positive result in OPS was observed in 54 out of 60 patients (90%). The viral load in OPS (median C-t value = 29.5; interquartile range [IQR] = 24.7-34) was significantly lower than that in lesion samples (median C-t value = 17.8; IQR = 16.3 and 19.7) (p < 0.0001). This report shows that pharyngeal sampling does not bring additional information for the initial diagnosis in patients presenting with typical lesions.

Syphilis cases in childhood are usually associated with congenital transmission. Acquired transmission is uncommon, and primarily related to sexual abuse or close contact/nursing with infected family members. We here describe a case of syphilis in a 14-month-old girl resulting from intrafamilial infection, with a subsequent transmission to her mother.

Nocardia neocaledoniensis is an uncommon cause of human-infections. Few cases are reported in the literature. We describe the first case of bacteremia caused by N. neocaledoniensis. This article underlines the importance of mass spectrometry for easy and rapid identification of such bacterium.