Cerebrovascular complications in patients with community-acquired bacterial meningitis: occurrence and associated factors in the COMBAT multicenter prospective cohort.

BACKGROUND: Community-acquired bacterial meningitis is a rare but severe central nervous system infection that may be associated with cerebrovascular complications (CVC). Our objective is to assess the prevalence of CVC in patients with community-acquired bacterial meningitis and to determine the first-48 h factors associated with CVC. METHODS: We analyzed data from the prospective multicenter cohort study (COMBAT) including, between February 2013 and July 2015, adults with community-acquired bacterial meningitis. CVC were defined by the presence of clinical or radiological signs (on cerebral CT or MRI) of focal clinical symptom. Factors associated with CVC were identified by multivariate logistic regression. RESULTS: CVC occurred in 128 (25.3%) of the 506 patients in the COMBAT cohort (78 (29.4%) of the 265 pneumococcal meningitis, 17 (15.3%) of the 111 meningococcal meningitis, and 29 (24.8%) of the 117 meningitis caused by other bacteria). The proportion of patients receiving adjunctive dexamethasone was not statistically different between patients with and without CVC (p = 0.84). In the multivariate analysis, advanced age (OR = 1.01 [1.00-1.03], p = 0.03), altered mental status at admission (OR = 2.23 [1.21-4.10], p = 0.01) and seizure during the first 48 h from admission (OR = 1.90 [1.01-3.52], p = 0.04) were independently associated with CVC. CONCLUSIONS: CVC were frequent during community-acquired bacterial meningitis and associated with advanced age, altered mental status and seizures occurring within 48 h from admission but not with adjunctive corticosteroids.

Evaluation of the acceptability in France of the vaccine against papillomavirus (HPV) among middle and high school students and their parents.

BACKGROUND: The pathogenic and oncogenic roles of papillomavirus (HPV) infections have been documented and shown to occur in women as well as in men. While other countries have already extended their vaccination guidelines to include boys, in 2019 the French National Authority for Health validated implementation of HPV vaccination in the 2020 vaccination schedule. There is, however, a climate of distrust in regard to vaccination in France, and there have been few studies to date regarding the acceptability of HPV vaccination in boys in France. The aim of this study was, therefore, to evaluate the acceptability of extending the recommendations for HPV vaccination in men, among middle and high school students and their parents. METHODS: Our study (HPVac) was a prospective, multicenter, departmental, and descriptive survey applied to a sample of male middle and high school students attending schools in the Loire-Atlantique department and their parents. It took place from January 2017 to January 2018. RESULTS: We analyzed the information obtained from 127 parent questionnaires and 145 children questionnaires. In terms of acceptability, 36.6% (n = 53) of the children and 37.8% (n = 48) of the parents were in favour of being vaccinated or of having their children vaccinated against HPV (51.7% (n = 75) and 50.4% (n = 64), respectively, were undecided). The perception of a risk stemming from HPV infection was positively associated with acceptability of the HPV vaccine. Being against vaccines in general, being discouraged by their parents, parents thinking that their child is not at risk, and the belief that the vaccine is not mandatory were arguments cited and significantly associated with a willingness to be vaccinated. CONCLUSION: This study revealed a lack of information among boys and their parents about HPV and its vaccination. It also clearly showed that taking time to discuss the consequences of an infection and the merits of being vaccinated can help parents overcome their reluctance. The children then generally go along with their parent's choice.

Bilateral Pulmonary Embolism Following a Viper Envenomation in France: A Case Report and Review.

Complications following snake bites are not common in France. We report the case of a bilateral pulmonary embolism following a viper envenomation in France.A healthy 72-year-old female presented with a lower limb hematoma following a viper bite. She was admitted at the hospital 2 days later and received low-molecular-weight heparin because of bed rest. Seven days later, she complained of thoracic pain and respiratory failure, and a bilateral pulmonary was diagnosed, without biological sign of neither disseminated intravascular coagulation nor coagulation trouble. Repeated lower limbs Doppler ultrasound were normal.This case is particularly interesting because it is only the 7th reported case of pulmonary embolism following a snake envenomation; moreover, it happened in France where poisonous snakes are very rare.Several hypotheses have been made to explain this late localized coagulopathy: an increased level of unstable fibrin produced by thrombin-like glycoproteins from the venom is one of them.

Emergence of HCV resistance-associated variants in patients failing sofosbuvir-based regimens: an observational cohort.

BACKGROUND: Real-life effectiveness data of new hepatitis C direct-acting antivirals are now required. The present study aims to assess the rate of sustained viral response (SVR) and virological failure (VF) in patients infected with chronic HCV treated with sofosbuvir (SOF)-based regimens in routine medical practice. METHODS: This observational study included a total of 106 patients infected with HCV genotypes (G)1-4, who initiated SOF-based regimens in 2014. Viral load was followed at baseline, week (W)2, W4, W12 (or W24) and W12 post-treatment. For all VFs, resistance-associated variants (RAVs) were determined at baseline and failure by sequencing of NS5A, NS5B and/or NS3 genes, using the Sanger method. RESULTS: SVR rate was 85% for the whole cohort, 91% for the patients who underwent the full treatment course. The distribution of HCV genotypes was as follows: G1 n=66 (1a=33, 1b=29; 62%), G2 n=8 (8%), G3a n=20 (19%) and G4 n=12 (11%). The main regimens used were SOF+daclatasvir (37%), SOF+ribavirin (33%), SOF+simeprevir (26%) and SOF+ledipasvir (3%). Twenty-five (23%) patients were HIV-coinfected and 1 was HBV-coinfected. Seventy (65%) patients had a prior treatment experience. All VF were relapses (n=9): 3 G1a, 1 G2, 4 G3a and 1 G4, and mutations conferring resistance to NS5A inhibitors were found but none for NS5B polymerase inhibitors. CONCLUSIONS: In a real-life context, the rate of SVR in DAA-treated HCV-infected patients is close to clinical Phase III trial results. RAVs emerged for all patients treated by the anti-NS5A daclatasvir, and persisted several weeks after the end of treatment.

Short communication: Paraoxonase 1 (PON1) in French HIV-infected patients under antiretroviral therapy: relationship with the metabolic syndrome and inflammation.

Our goal was to determine if paraoxonase 1 (PON1) activity relates to the presence of metabolic syndrome (MS) and inflammation in HIV patients treated with highly active antiretroviral therapy (HAART). This was a prospective, multicenter study including 269 patients receiving HAART for at least 1 year and a maximum of 4 years. PON1 and inflammatory markers [C reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA), and soluble tumor necrosis factor receptors 2 (sTNF-R2)] were compared between patients with or without MS and the association between inflammatory markers and PON1 was assessed by logistic regression analyses. MS was found in 18.2% of the patients. Inflammatory markers, with the exception of sTNF-R2, were significantly higher, while PON1 activity was significantly lower in the presence of metabolic syndrome. PON1 activity was significantly related to apolipoprotein C3, CD4 count, and sTNF-R2. It may be concluded that PON1 appears to be a marker for the metabolic syndrome in HIV-infected subjects. PON1 activity is related to dyslipidemia and the immunological status of the patients but is not fully determined by inflammation.

Metabolic syndrome in French HIV-infected patients: prevalence and predictive factors after 3 years of antiretroviral therapy.

Treatment of HIV infection with highly active antiretroviral therapy can induce metabolic complications and increase the risk of developing the metabolic syndrome (MS). The purpose of this study was to report the prevalence and the risk factors for MS in HIV-infected patients who started highly active antiretroviral therapy (HAART) after 2000. SYMET is a prospective, multicentric, cohort study evaluating the prevalence of MS in 269 patients who had received continuous HAART for 1 to 4 years up to September 2007. MS was defined according to the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) 2005 criteria. Cross-sectional assessment included clinical examination and fasting evaluation of metabolic, inflammatory, and oxidative parameters. Data were analyzed with Chi-square, Student, or Wilcoxon tests. Univariate and multivariate logistic regressions were performed to identify predictive factors for MS. The prevalence of MS was 18.2% after a median duration of HAART of 29.8 months. In multivariate analysis, predictive factors of MS were high non-HDL-cholesterol (OR=1.87; p<0.0001), high-sensitivity C-reactive protein levels (hsCRP) (OR=1.56; p=0.01), coinfection with hepatitis C virus (HCV) (OR=5.67; p=0.02), as well as age (OR=1.04; p=0.02) and duration of exposure to protease inhibitors (PI) (OR=1.03; p=0.02) or to abacavir (ABC) (OR=1.03; p=0.02). In this cohort of patients exposed to less than 4 years of HAART, MS prevalence was 18.2%. Older age, high hsCRP, HCV coinfection, and elevated non-HDL-cholesterol were risk factors for the MS. There was also a moderate significant association of increased risk of MS with cumulative PI and ABC exposure.

FcγRIIIa (CD16) induction on human T lymphocytes and CD16pos T-lymphocyte amplification.

During serial assays designed to amplify natural killer (NK) cells in vitro, we observed that when peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus positive (HIV+) patients were stimulated for 2 weeks with an Epstein-Barr virus-infected B lymphoblastic cell line and interleukin-2, a well known procedure to amplify NK cells in vitro, 44.4 ± 18% CD3CD16 T lymphocytes were recovered together with NK cells, of which 78.2% expressed an αß T-cell receptor (TCR). To identify the T-cell compartment from which they originated (naive, antigen experienced, CD16, or CD16), we first compared the results obtained with HIV+ patients' PBMCs (where essentially all CD8 cells are antigen experienced) with those obtained from cord blood lymphocytes (essentially naive) and PBMC from healthy donors (with variable antigen experience). Two weeks after stimulation, αß TCR CD16 T lymphocytes increased from 0.3%, 2.2%, and 8.2% to 2.5%, 7.7%, and 36.3%, for cord blood, healthy donors, and HIV+ patients, respectively. Second, using cell-sorting experiments for CD16 cells and antibody-dependent cellular cytotoxicity assays, we demonstrated that a functional CD16 receptor could also be induced at the cell surface of αß TCR CD16 T lymphocytes. Together, these results demonstrate that under stimulation conditions known to induce NK cell proliferation, a subset of αß TCR CD16 T cells arises from antigen-experienced CD16 cells but also from antigen-experienced CD16 T lymphocytes, revealing the possibility to increase a patient's antibody-dependent cellular cytotoxicity potential through simple stimulation of this particular memory compartment.

Evaluation of the tuberculin skin test and the interferon-gamma release assay for TB screening in French healthcare workers.

INTRODUCTION: Using French cut-offs for the Tuberculin Skin Test (TST), results of the TST were compared with the results of an Interferon-gamma Release Assay (IGRA) in Healthcare Workers (HCW) after contact to AFB-positive TB patients. METHODS: Between May 2006 and May 2007, a total of 148 HCWs of the University Hospital in Nantes, France were tested simultaneously with IGRA und TST. A TST was considered to indicate recent latent TB infection (LTBI) if an increase of >10 mm or if TST >/= 15 mm for those with no previous TST result was observed. For those with a positive TST, chest X-ray was performed and preventive chemotherapy was offered. RESULTS: All HCWs were BCG-vaccinated. The IGRA was positive in 18.9% and TST >/= 10 mm was observed in 65.5%. A recent LTBI was believed to be highly probable in 30.4% following TST. Agreement between IGRA and TST was low (kappa 0.041). In 10 (16.7%) out of 60 HCWs who needed chest X-ray following TST the IGRA was positive. In 9 (20%) out of 45 HCWs to whom preventive chemotherapy was offered following TST the IGRA was positive. Of those considered TST-negative following the French guidelines, 20.5% were IGRA-positive. In a two-step strategy - positive TST verified by IGRA - 18 out of 28 (64.3%) IGRA-positive HCWs would not have been detected using French guidelines for TST interpretation. CONCLUSION: The introduction of IGRA in contact tracings of BCG-vaccinated HCWs reduces X-rays and preventive chemotherapies. Increasing the cut-off for a positive TST does not seem to be helpful to overcome the effect of BCG vaccination on TST.

European bat Lyssavirus transmission among cats, Europe.

We identified 2 cases of European bat lyssavirus subtype 1 transmission to domestic carnivores (cats) in France. Bat-to-cat transmission is suspected. Low amounts of virus antigen in cat brain made diagnosis difficult.

Impact of nevirapine or efavirenz co-administration on ritonavir-boosted amprenavir pharmacokinetics in HIV-infected patients.

The influence of nevirapine or efavirenz co-administration on ritonavir-boosted amprenavir pharmacokinetics was investigated in HIV-infected patients with a population pharmacokinetic approach. The analysis was performed with a population of 61 patients treated with fosamprenavir/ritonavir (700 mg/100 mg twice daily) combined with nucleoside/nucleotide reverse transcriptase inhibitors +/- enfuvirtide and no other antiretroviral drugs (group A, n = 46) or nevirapine (group B, n = 10) or efavirenz (group C, n = 5). No significant increase in amprenavir clearance [mean +/- standard deviation: 22.49 +/- 10.32 (group A) vs. 21.57 +/- 9.62 (group B) vs. 20.15 +/- 5.18 (group C) L/h] and no significant decrease in trough amprenavir plasma concentrations [1.75 +/- 0.95 (group A) vs. 1.82 +/- 0.72 (group B) vs. 1.55 +/- 0.66 (group C) mg/L] were found in groups B and C in comparison with group A, although nevirapine and efavirenz are inductors of protease inhibitors metabolism. These results suggest that fosamprenavir/ritonavir should be used at standard doses of 700 mg/100 mg twice daily when combined with efavirenz or nevirapine.

Acute respiratory failure revealing adult-onset Still's disease: diagnostic value of low glycosylated ferritin level.

The authors report three cases of adult-onset Still's disease with severe hypoxemic pulmonary involvement, mimicking severe pulmonary sepsis. Clinicians must be aware of this rare form of such disease. Low (<20%) glycosylated ferritin level in the presence of unexplained prolonged fever with leukocytosis can help in the diagnosis.