Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study.

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.

Comparison of two automated commercial assays for routine detection of anti-hepatitis E Virus IgM antibodies in clinical samples.

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.

Secondary syphilis in a 14-month-old girl and child-to-mother transmission.

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.

Oropharyngeal samples versus lesion specimens at diagnosis in patients infected with monkeypox virus in Northern France.

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 Ct value = 29.5; interquartile range [IQR] = 24.7-34) was significantly lower than that in lesion samples (median Ct  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.

First case of fatal bacteremia due to Nocardia neocaledoniensis.

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.