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Despite the particular focus given to influenza since the 2009 influenza A(H1N1) pandemic, true burden of influenza-associated critical illness remains poorly known. The aim of this study was to identify factors influencing influenza burden imposed on intensive care units (ICUs) in a catchment population during recent influenza seasons. From 2008 to 2013, all adult patients admitted with a laboratory-confirmed influenza infection to one of the ICUs in the catchment area were prospectively included. A total of 201 patients (mean age: 63 ± 16, sex-ratio: 1.1) were included. The influenza-related ICU-bed occupancy rate averaged 4.3% over the five influenza seasons, with the highest mean occupancy rate (16.9%) observed during the 2012 winter. In-hospital mortality for the whole cohort was 26%. Influenza A(H1N1)pdm infections (pdm in the mentioned nomenclature refers to Pandemic Disease Mexico 2009), encountered in 51% of cases, were significantly associated with neither longer length of stay nor higher mortality (ICU and hospital) when compared to infections with other virus subtypes. SOFA score (OR, 1.12; 95% CI, 1.04–1.29) was the only independent factor significantly associated with a prolonged hospitalization. These results highlight both the frequency and the severity of influenza-associated critical illness, leading to a sustained activity in ICUs. Severity of the disease, but not A(H1N1)pdm virus, appears to be a major determinant of ICU burden related to influenza. [ABSTRACT FROM AUTHOR]

BACKGROUND p16INK4a Is overexpressed in almost all precancerous and carcinomatous lesions of the uterine cervix, secondary to interference between high-risk human papillomaviruses (hr-HPVs) and the retinoblastoma gene product. Overexpression of p16INK4a has also been identified in patients with high-grade urothelial lesions, both cytologically and histologically. However, the etiological role of HPV has not been documented except in inverted papillomas, low-grade bladder tumors, and younger patients. We therefore attempted to verify if HPV DNA was detectable in p16INK4a-positive urothelial tumors. METHODS A total of 90 urinary cytology samples (33 negative/low-grade cases and 57 high-grade proliferations) were analyzed for p16INK4a and HPV DNA. HPV genotyping was performed by polymerase chain reaction using a low-density DNA microarray enabling the detection of 35 HPVs. A reasoned approach combining tissue genotyping and in situ hybridization (ISH) for hr-HPVs was used in patients with urinary HPV. RESULTS Low-risk HPV (HPV-84) and hr-HPVs (HPV-16, -31, and -70) were detected. The prevalence of hr-HPVs in the urine was low: 5 of 82 patients (6.1%) and only 4 of 50 patients (8.0%) with high-grade urothelial malignancy. p16INK4a overexpression was noted in 49 high-grade samples (85.9%). In patients with p16INK4a-positive tumor cells and hr-HPV in the urine, HPV genotyping and ISH for hr-HPVs were negative in matched tissue sections. CONCLUSIONS Our study shows a low prevalence of hr-HPVs in the urine of patients with high-grade urothelial malignancy. In those, p16INK4a overexpression occurs in the absence of demonstrable HPV DNA in the tissue sections, contrary to what is noted in gynecopathology. Cancer (Cancer Cytopathol) 2014;122:760-769. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of interests SF has served as a speaker for GlaxoSmithKline, AstraZeneca, MSD, Pfizer, Cepheid, and Moderna. IE received support by R-Biopharm for attending meetings. CR has served as a speaker for Pfizer and received support by Tecan for attending meetings. J-MP has served as an advisor or speaker for Abbott, Abbvie, Gilead, and GlaxoSmithKline. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Similarly to many respiratory viruses, respiratory syncytial virus (RSV) is surprising in its ability to reinfect children and adults who have already been immunized. It is not so much in the evolution of its genome that we must look for the cause, but more probably in the structure/function of its viral proteins, which are capable of interfering with the immune response and memory. After an incubation of three to eight days, RSV infection most often results in nasopharyngitis with little or no fever. RSV infection of the respiratory epithelium is characterized by marked mucus production, desquamation of infected respiratory cells and persistent impairment of mucociliary transport. The extension of the infection to the lower respiratory tract therefore contributes to the formation of mucous plugs obstructing the lumen of the bronchioles. This is the cause of the clinical most commonly associated with RSV infection: bronchiolitis in newborns and infants which is a frequent reason for hospitalization due to secondary respiratory and digestive complications. The recent data from the literature, however, indicate that by far the most frequent complication is a community infection: acute otitis media. RSV infections are therefore a very common reason for the prescription of antibiotics., Competing Interests: J.-S. Casalegno déclare faire partie du comité scientifique d’une étude non rémunérée menée par Pfizer sur le VRS.

Hemagglutinin (HA) and neuraminidase (NA) are major glycoproteins expressed on the surface of influenza virus. They have complementary and antagonistic functions that facilitate in the life cycle of the virus. The functional equilibrium generated between HA and NA can impact the evolution and adaptation of influenza virus strains within the human reservoir. This functional equilibrium is referred to as the "HA-NA balance". An imbalanced HA-NA can restrict the multiplication and transmission capacity of influenza viruses. Moreover, this equilibrium is likely a limiting factor against species crossover for the virus. In light of such considerations, the HA-NA balance should be precisely studied to gain a better understanding of the emergence of pandemic and seasonal influenza virus strains. This review describes the concept of the HA-NA balance, the methods used to study it, plus a discussion of the HA-NA balance in the evolution of the pandemic influenza A H1N1 strains that plagued the world in 1918 and 2009.

Avian Influenza viruses emergences are more frequent than pandemic events. Since 1976 several cases of human infections with avian or swine Influenza, such as H1, H3, H5, H6, H7, H9, and H10, have been reported. However only H1N1pdm09 caused a pandemic. The enhance surveillance at international level provides a rapid detection of these zoonotic infections. For each iterative emergence, one should ask if it is necessary to produce a new vaccine. The identification of a vaccine candidate and the production of the corresponding vaccine seed is a careful approach in order to get ready to produce the vaccine in the context of a pandemic. Indeed, identification of a vaccine candidate and the production of the corresponding vaccine seed have already been done for several emergent viruses. However, stockpiling and use of vaccine was only done for H5N1. The H5N1 and H1N1pdm09 experiences highlighted that vaccine production must undergo several necessary steps before use. Vaccine composition and immunization schedules are dependent of virus history and pre-existing immunity of the exposed population. Indeed immunization schedules appear to differ according to the viruses. The evaluation of post-vaccine humoral immunization response suggest that immunization against Influenza sub-types that previously circulated in human population may only require one injection whereas a new sub-type may need two injections with an adjuvant. Actually, new dosage formulation based on live attenuated vaccines, virosomes, or pseudo-particles are up-coming and may provide alternative to a conventional arsenal. Vaccine production is the major part of the public health answers to Influenza emergence. Vaccine use, during national vaccination campaign, requires a good compliance from both healthworker and population. Success or failure depends on the population perceived risk and its compliance to the selected vaccine strategy.