Incidence of hospital-acquired influenza in adults: A prospective surveillance study from 2004 to 2017 in a French tertiary care hospital.

BACKGROUND: Hospital-acquired influenza potentially leads to significant morbidity and mortality in already vulnerable patients, but its overall burden is not fully understood. We undertook this study to estimate the incidence and trends of hospital-acquired laboratory-confirmed influenza among adults, and to compare clinical characteristics between hospital-acquired and community-acquired influenza cases. METHODS: This was a prospective surveillance study over 11 years of adults with influenza-like-illness (ILI) hospitalized in surgery, medicine and geriatric wards in a tertiary acute-care hospital in Lyon, France. Nasal swabs were systematically collected from those with ILI and tested for influenza by reverse transcriptase-polymerase chain reaction at the national influenza reference laboratory (Lyon, France). RESULTS: Influenza was laboratory confirmed at a rate of 1 in 13 patients who developed ILI during their hospitalization. Having an underlying disease was an important characteristic of hospital-acquired ILI cases. Cardiovascular disease was the most frequent underlying condition in both influenza-positive and influenza-negative patients. Complications were more frequent for influenza-positive than influenza-negative patients. The influenza incidence rate was highest in the geriatric ward and increased over the study period. CONCLUSIONS: Hospital-acquired influenza poses a significant risk to already vulnerable patients. Longitudinal surveillance data are essential to support better recognition and monitoring of viral infections in hospitals.

Human herpesvirus 6 infection after autologous stem cell transplantation: A multicenter prospective study in adult patients.

OBJECTIVES: to prospectively evaluate the incidence and the clinical relevance on hematopoietic reconstitution of HHV-6 infection in autologous hematopoietic stem cell transplantation (ASCT) recipients. METHODS: HHV-6 DNA load was measured in whole blood specimens once during the 7 days before stem cell re-infusion and once a week after transplantation until hematopoietic recovery. Active HHV-6 infection was defined by 2 consecutive positive DNA loads. RESULTS: from July 2012 to February 2015, 196 adult patients undergoing ASCT were enrolled. Twenty-two (11.2%) patients developed active HHV-6 infection with a cumulative incidence of 19% at 40 days after transplantation. The onset of active HHV-6 infection occurred with a median of 13 days after stem cell re-infusion. HHV-6 infection was associated with an increased frequency of non-infectious complications (OR = 5.05; 95%CI 1.78-14.32; P < 0.001). Moreover, the severity of these non-infectious complications was higher in recipients exhibiting HHV-6 infection (OR = 4.62; 95%CI 1.32-16.2; p < 0.01). Delayed neutrophils 10 (IQR: 8-14) vs 8 (IQR: 6-11) days and platelets recoveries 15 (IQR: 11.8-18.5) vs 8 (IQR: 4-14) days were observed in patients with active HHV-6 infection compared to non-infected ones. CONCLUSIONS: in this study, 11.2% ASCT recipients presented active HHV-6 infection associated with significantly delayed hematologic reconstitution.

[Do liquid wastes from automated instruments in medical laboratories have their proper microbicide effect?] / Les rejets liquides des automates de biologie médicale ont-ils un effet microbicide propre qui permettrait de s'affranchir de leur traitement pour risque infectieux ?

Liquid wastes from clinical biology automated systems are currently evacuated in the urban network after chemical treatment to eliminate a possible risk of infection. Since these wastes are ecotoxic because of the presence of numerous chemical reagents, we studied their intrinsic microbicidal power towards a selection of infectious agents widely found in clinical specimens. The objective was to determine if an additional anti-infectious treatment before elimination is necessary. Thus, we evaluated the bactericidal effect of liquid wastes of several automated systems towards four bacterial species (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Enterococcus faecalis) and their virucidal activity against a non-enveloped virus, resistant in the environment (adenovirus). This effect was determined for different exposure times. Our results showed that the antibacterial activity was highly variable depending on the waste-bacteria pair considered (varying from no activity to complete sterilization of a strong bacterial inoculum). The liquid wastes were on the other hand globally inactive towards adenovirus.

Clinical management and viral genomic diversity analysis of a child's influenza A(H1N1)pdm09 infection in the context of a severe combined immunodeficiency.

INTRODUCTION: A child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013-2014 influenza season, despite cord blood transplantation and antiviral treatments. METHODS: Conventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens. RESULTS: The patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status. CONCLUSIONS: Conventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed.

HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns.

OBJECTIVES: Human herpes virus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may be associated with significant clinical manifestations. METHODS: Case control study of HHV-6 infections after allo-HSCT. Chromosomal integration (ciHHV-6) for viral loads ≥ 5.5-log10 copies/mL was investigated. Viral co-infections, T-cell recovery, risk factors and outcome were compared in HHV-6- and non-HHV-6-infected patients. Antiviral treatment strategies were reviewed. RESULTS: Among 366 adult allo-HSCT recipients, 75 HHV-6 infections occurred. Three (4%) recipients were ciHHV-6. HHV-6 infections were associated with CMV (p = 0.05; sdHR 1.73, CI 0.99-3.02) and/or BKV infections (p < 0.0001; sdHR 4.63, CI 2.04-10.53) but not EBV reactivation (p = 0.34). A slower CD8+ T-cells recovery was observed until 6 months after allo-HSCT in the HHV-6-infected group (p < 0.001), independently of acute and/or chronic graft-versus-host disease. The overall probability of survival after allo-HSCT was diminished for active HHV-6-infected patients (p = 0.0326). Cord blood unit recipients had a higher risk of developing HHV-6 infection compared to bone marrow recipients (p = 0.0007; sdHR 3.82, CI 1.76-8.27). Anti-HHV-6 treatment achieved complete response in only 2/3 of the cases. CONCLUSIONS: In this series of allo-HSCT recipients, 4% were ciHHV-6, active HHV-6 infection was likely associated with CMV and BKV co-reactivations, delayed CD8+ T-cell recovery and poorer outcome.

Synthesis of 5-haloethynyl- and 5-(1,2-dihalo)vinyluracil nucleosides: antiviral activity and cellular toxicity.

In this article, we report the synthesis of hitherto unknown 5-haloethynyl and 5-(1,2-dihalo)vinyluracil nucleosides in the 2'-deoxy, 3'-deoxy- and ribosyl series, and we discuss their in vitro anti-HIV and anti-HCV activities and cellular toxicitites. As a result, on the basis of their selectivity index (SI) obtained with the HCV replicon system, but also on their cytotoxicity on peripheral blood mononuclear, CEM and VERO cell lines, the best compounds were the 5-bromoethynyluridine (SI = 3.2) and the 5-(1-chloro-2-iodo)vinyluridine (SI > 2.8).