Publications by authors named "Bruno Pozzetto"

155 Publications

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralization and commercial assays.

Clin Microbiol Infect 2021 Jan 13. Epub 2021 Jan 13.

Laboratoire de Virologie, Institut des Agents Infectieux, Laboratoire Associé Au Centre National de Référence des Virus des Infections Respiratoires, Hospices Civils de Lyon, Lyon, France; CIRI, Centre International de Recherche en Infectiologie, Team VirPath, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803622PMC
January 2021

A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity.

Cell Mol Immunol 2021 02 6;18(2):318-327. Epub 2021 Jan 6.

Department of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, Saint-Etienne, France.

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.
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http://dx.doi.org/10.1038/s41423-020-00588-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786875PMC
February 2021

Evaluation of high-throughput SARS-CoV-2 serological assays in a longitudinal cohort of patients with mild COVID-19: clinical sensitivity, specificity and association with virus neutralization test.

Clin Chem 2021 Jan 5. Epub 2021 Jan 5.

CIRI, Centre International de Recherche en Infectiologie, Team VirPath, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.

Background: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19.

Methods: 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of nine commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers.

Results: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3 (78.1-96.1) and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG and DiaSorin, respectively. None of commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC<0.76).

Conclusions: Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests including those targeting the RBD cannot substitute a VNT for the assessment of functional antibody response.
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http://dx.doi.org/10.1093/clinchem/hvaa336DOI Listing
January 2021

Bacterial and Viral Infection in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Implication for Antimicrobial Management and Clinical Outcome.

COPD 2021 Feb 23;18(1):53-61. Epub 2020 Dec 23.

Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, and GIMAP group (EA 3064), Faculty of Medicine de Saint-Etienne, University of Lyon, Lyon, France.

Patients with chronic obstructive pulmonary disease (COPD) exhibit frequent acute exacerbations (AE). The objectives of this study were first to evaluate the prevalence of pathogens associated to these episodes by combining conventional bacteriology and multiplex viral and bacterial PCR assays in sputum specimens, and second to determine whether C-reactive protein (CRP) value and clinical outcome could be influenced by the type of microbial agent(s) recovered from these samples. A cohort of 84 Tunisian patients hospitalized at the emergency room for AECOPD was investigated prospectively for the semi-quantitative detection of bacteria by conventional culture (the threshold of positivity was of 10 CFU/ml) and for the detection of viral genome and DNA of atypical bacteria by quantitative PCR using two commercial multiplex respiratory kits (Seegene and Fast-track). The two kits exhibited very similar performances although the Seegene assay was a bit more sensitive. A large number and variety of pathogens were recovered from the sputum samples of these 84 patients, including 15 conventional bacteria, one and 63 respiratory viruses, the most prevalent being rhinoviruses ( = 33) and influenza viruses ( = 13). From complete results available for 74 patients, the presence of bacteria was significantly associated with risk of recurrence at 6 and 12 months post-infection. The combination of these different markers appears useful for delineating correctly the antimicrobial treatment and for initiating a long-term surveillance in those patients with high risk of recurrent exacerbation episodes. A prospective study is required for confirming the benefits of this strategy aimed at improving the stewardship of antibiotics.
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http://dx.doi.org/10.1080/15412555.2020.1854210DOI Listing
February 2021

Longitudinal Study of Viral and Bacterial Contamination of Hospital Pediatricians' Mobile Phones.

Microorganisms 2020 Dec 16;8(12). Epub 2020 Dec 16.

GIMAP (Groupe Immunité des Muqueuses et Agents Pathogènes) EA-3064, Medicine Faculty of Saint-Etienne, Campus Santé-Innovations of Saint-Etienne, 42270 Saint-Priest-en-Jarez, France.

Mobile phones (MPs) of healthcare workers (HCWs) may represent an important source of transmission of infectious agents. This longitudinal study documents the contamination of these tools. Ten MPs handled by senior pediatricians were sampled once a week during 23 weeks in three pediatric wards of the University Hospital of Saint-Etienne, France. Cultures were performed for bacteria and multiplex PCR assays for a panel of respiratory and enteric viruses. A questionnaire on hygiene habits regarding phoning and care was filled-in by pediatricians before and after the study. From a total of 230 samples, 145 (63%) were contaminated by at least one pathogen. The MPs from emergency departments were the most impacted. Viruses were detected in 179 samples; bacteria were isolated in 59 samples. Contamination increased during the winter epidemic peak. A cross-contamination by between hands and MPs of different HCWs was demonstrated. The communication of the study results influenced the hygiene behaviors. This study highlights the contamination of MPs by pathogens that are resistant in the environment, and its sustainability along the winter season. The role of MPs as vectors of nosocomial infection needs to be better investigated.
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http://dx.doi.org/10.3390/microorganisms8122011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766489PMC
December 2020

Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial.

BMJ Open 2020 11 26;10(11):e042247. Epub 2020 Nov 26.

Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.

Introduction: New HIV prevention strategies are urgently required. The discovery of broadly neutralising antibodies (bNAbs) has provided the opportunity to evaluate passive immunisation as a potential prevention strategy and facilitate vaccine development. Since 2014, several bNAbs have been isolated from a clade C-infected South African donor, CAPRISA 256. One particular bNAb, CAP256-VRC26.25, was found to be extremely potent, with good coverage against clade C viruses, the dominant HIV clade in sub-Saharan Africa. Challenge studies in non-human primates demonstrated that this antibody was fully protective even at extremely low doses. This bNAb was subsequently structurally engineered and the clinical variant is now referred to as CAP256V2LS.

Methods And Analysis: CAPRISA 012B is the second of three trials in the CAPRISA 012 bNAb trial programme. It is a first-in-human, phase I study to assess the safety and pharmacokinetics of CAP256V2LS. The study is divided into four groups. Group 1 is a dose escalation of CAP256V2LS administered intravenously to HIV-negative and HIV-positive women. Group 2 is a dose escalation of CAP256V2LS administered subcutaneously (SC), with and without the dispersing agent recombinant human hyaluronidase (rHuPH20) as single or repeat doses in HIV-negative women. Groups 3 and 4 are randomised placebo controlled to assess two (CAP256V2LS+VRC07-523LS; CAP256V2LS+PGT121) and three (CAP256V2LS+VRC07-523LS+PGT121) bNAb combinations administered SC to HIV-negative women. Safety will be assessed by the frequency of reactogenicity and adverse events related to the study product. Pharmacokinetic disposition of CAP256V2LS alone and in combination with VRC07-523LS and PGT121 will be assessed via dose subgroups and route of administration.

Ethics And Dissemination: The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and the South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval (trial reference numbers: BREC00000857/2019 and SAHPRA 20200123). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.

Trial Registration Number: PACTR202003767867253; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-042247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692975PMC
November 2020

Performance of the COVID19SEROSpeed IgM/IgG Rapid Test, an Immunochromatographic Assay for the Diagnosis of SARS-CoV-2 Infection: a Multicenter European Study.

J Clin Microbiol 2021 01 21;59(2). Epub 2021 Jan 21.

Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.

This study assessed the diagnostic performance of the new COVID19SEROSpeed IgM/IgG rapid test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by quantitative reverse transcription-PCR (qRT-PCR) and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on prepandemic specimens was 98.1% (95% confidence interval [CI], 96.2% to 99.4%). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI, 0.83 to 0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen's kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement at ≥11 days post-symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated a higher positive percentage of agreement than all the enzyme-linked immunosorbent assay/chemiluminescence immunoassay (ELISA/CLIA) commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11 days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease.
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http://dx.doi.org/10.1128/JCM.02240-20DOI Listing
January 2021

Brief comparative evaluation of six open one-step RT-qPCR mastermixes for the detection of SARS-CoV-2 RNA using a Taqman probe.

J Clin Virol 2020 11 8;132:104636. Epub 2020 Sep 8.

Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, and GIMAP (Groupe Immunité des Muqueuses et Agents Pathogènes) EA-3064, Medicine Faculty of Saint-Etienne, Campus Santé-Innovations of Saint-Etienne, Member of University of Lyon, France. Electronic address:

Background: Facing the emergence of a new RNA virus, clinical laboratories are often helpless in the case of a shortage of reagents recommended by Reference Centres.

Objectives: To compare five open one step RT-qPCR reagents to the SuperScript™ III Platinum™ One-Step qRT-PCR kit (Invitrogen) considered as the reference one in France at the beginning of the pandemic for detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in respiratory specimens by using a laboratory-developed assay targeting the viral RNA dependant RNA polymerase (RdRp) gene.

Study Design: A total of 51 NUCLISENS easyMAG extracts from respiratory specimens was tested on ABI 7500 thermocycler with TaqMan Fast Virus 1-Step Master Mix (Applied Biosystems), Luna® Universal Probe One-Step RT-qPCR Kit (New England Biolabs), GoTaq® Probe 1- Step RT-qPCR System (Promega), LightCycler® Multiplex RNA Virus Master (Roche) and One-step PrimeScript RT-PCR kit (Takara). The CT values obtained using the 5 challenged reagents were compared to those obtained using the reference assay.

Results: The percentages of concordance were all above 95 %. When comparing the CT values of the 48 extracts exhibiting CT values < 35 obtained with the reference reagent, the results were similar between the reagents although the differences of CT values were quite dispersed.

Conclusions: All five reagents can be considered as alternative reagents to the reference for detecting SARS-CoV-2 RNA.
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http://dx.doi.org/10.1016/j.jcv.2020.104636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476897PMC
November 2020

Vaccination for Human Papillomavirus: an historic and bibliometric study.

Hum Vaccin Immunother 2020 Sep 21:1-9. Epub 2020 Sep 21.

Department of General Practice, Jacques Lisfranc Faculty of Medicine, Saint-Etienne-Lyon University , Saint-Etienne, France.

A systematic literature review was conducted to describe in a historical perspective the evolution of studies concerning HPV vaccination. The search identified 794 articles of which 568 were included. The first article was published in 2001, and the maximum annual number of publications was reached in 2014. The average number of authors per paper was 8.8. Papers originated from 49 different countries, with the USA accounted for the maximum number of publications (n = 217). Efficacy (46.5%) and safety (31.0%) were the most prevalent objectives. Clinical trials constituted the largest group of methods (37.9%). Chronological trends did not reveal any lasting curve-crossings, indicating that the priority topics have remained the same. The geographical origin of these studies raises questions about the transposability of the results to populations where HPV vaccination has been studied only a little. This study could help guide future research to less-studied research objectives, particularly for vaccines.
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http://dx.doi.org/10.1080/21645515.2020.1805991DOI Listing
September 2020

Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC).

Microorganisms 2020 Jul 20;8(7). Epub 2020 Jul 20.

GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France.

Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (T) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
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http://dx.doi.org/10.3390/microorganisms8071078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409252PMC
July 2020

Recurrence or Relapse of COVID-19 in Older Patients: A Description of Three Cases.

J Am Geriatr Soc 2020 10 13;68(10):2179-2183. Epub 2020 Aug 13.

Groupe Immunité des Muqueuses et Agents Pathogènes-EA3064, University Hospital of Saint-Etienne, Saint-Etienne, France.

Background: COVID-19 has infected millions of people worldwide, particularly in older adults. The first cases of possible reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported in April 2020 among older adults.

Design/setting: In this brief report, we present three geriatric cases with two episodes of SARS-CoV-2 infection separated by a symptom-free interval.

Participants: The participants of this brief report are three cases of hospitalized geriatric women.

Measurements/results: We note clinical and biological worsening during the second episode of COVID-19 for all three patients. Also, there is a radiological aggravation. The second episode of COVID-19 was fatal in all three cases.

Conclusion: This series of three geriatric cases with COVID-19 diagnosed two times apart for several weeks questions the possibility of reinfection with SARS-CoV-2. It raises questions in clinical practice about the value of testing for SARS-CoV-2 infection again in the event of symptomatic reoccurrence. J Am Geriatr Soc 68:2179-2183, 2020.
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http://dx.doi.org/10.1111/jgs.16728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361461PMC
October 2020

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

J Infect 2020 Nov 30;81(5):816-846. Epub 2020 Jun 30.

Infectious Diseases Department, University Hospital of Saint-Etienne, 42055 cedex 02 Saint-Etienne, GIMAP (EA 3064), France; University of Saint-Etienne, University of Lyon, Faculty of Medicine of Saint-Etienne, 42023 cedex 02 Saint-Etienne, France. Electronic address:

For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.
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http://dx.doi.org/10.1016/j.jinf.2020.06.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326402PMC
November 2020

Povidone Iodine: Properties, Mechanisms of Action, and Role in Infection Control and Decolonization.

Antimicrob Agents Chemother 2020 08 20;64(9). Epub 2020 Aug 20.

Pole de Microbiologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.

Nasal decolonization is an integral part of the strategies used to control and prevent the spread of methicillin-resistant (MRSA) infections. The two most commonly used agents for decolonization are intranasal mupirocin 2% ointment and chlorhexidine wash, but the increasing emergence of resistance and treatment failure has underscored the need for alternative therapies. This article discusses povidone iodine (PVP-I) as an alternative decolonization agent and is based on literature reviewed during an expert's workshop on resistance and MRSA decolonization. Compared to chlorhexidine and mupirocin, respectively, PVP-I 10 and 7.5% solutions demonstrated rapid and superior bactericidal activity against MRSA in and studies. Notably, PVP-I 10 and 5% solutions were also active against both chlorhexidine-resistant and mupirocin-resistant strains, respectively. Unlike chlorhexidine and mupirocin, available reports have not observed a link between PVP-I and the induction of bacterial resistance or cross-resistance to antiseptics and antibiotics. These preclinical findings also translate into clinical decolonization, where intranasal PVP-I significantly improved the efficacy of chlorhexidine wash and was as effective as mupirocin in reducing surgical site infection in orthopedic surgery. Overall, these qualities of PVP-I make it a useful alternative decolonizing agent for the prevention of infections, but additional experimental and clinical data are required to further evaluate the use of PVP-I in this setting.
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http://dx.doi.org/10.1128/AAC.00682-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449185PMC
August 2020

COVID-19 and Guillain-Barré syndrome: Response.

Rev Neurol (Paris) 2020 09 15;176(7):636-637. Epub 2020 May 15.

University Hospital of Saint-Etienne, 42055 Saint-Etienne cedex 02, France.

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http://dx.doi.org/10.1016/j.neurol.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225720PMC
September 2020

Strategy using a new antigenic test for rapid diagnosis of Streptococcus pneumoniae infection in respiratory samples from children consulting at hospital.

BMC Microbiol 2020 04 7;20(1):79. Epub 2020 Apr 7.

GIMAP EA 3064 (Groupe Immunité des Muqueuses et Agents Pathogènes), University of Lyon, 42023, Saint-Etienne, France.

Background: Despite vaccination programs, Streptococcus pneumoniae remains among the main microorganisms involved in bacterial pneumonia, notably in terms of severity. The prognosis of pneumococcal infections is conditioned in part by the precocity of the diagnosis. The aim of this study was to evaluate the impact of a Rapid Diagnostic Test (RDT) targeting cell wall polysaccharide of Streptococcus pneumoniae and performed directly in respiratory samples, on the strategy of diagnosis of respiratory pneumococcal infections in children.

Results: Upper-respiratory tract samples from 196 children consulting at hospital for respiratory infection were tested for detecting S. pneumoniae using a newly-designed RDT (PneumoResp, Biospeedia), a semi-quantitative culture and two PCR assays. If positive on fluidized undiluted specimen, the RDT was repeated on 1:100-diluted sample. The RDT was found highly specific when tested on non-S. pneumoniae strains. By comparison to culture and PCR assays, the RDT on undiluted secretions exhibited a sensitivity (Se) and negative predictive value (NPV) of more than 98%. By comparison to criteria of S. pneumoniae pneumonia combining typical symptoms, X-ray image, and culture ≥10 CFU/ml, the Se and NPV of RDT on diluted specimens were 100% in both cases.

Conclusions: In case of negative result, the excellent NPV of RDT on undiluted secretions allows excluding S. pneumoniae pneumonia. In case of positive result, the excellent sensitivity of RDT on diluted secretions for the diagnosis of S. pneumoniae pneumonia allows proposing a suitable antimicrobial treatment at day 0.
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http://dx.doi.org/10.1186/s12866-020-01764-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137283PMC
April 2020

Validation of a New Rapid Detection Test for Detection of Neisseria meningitidis A/C/W/X/Y Antigens in Cerebrospinal Fluid.

J Clin Microbiol 2020 02 24;58(3). Epub 2020 Feb 24.

Institut Pasteur, Invasive Bacterial Infections Unit and National Reference Centre for Meningococci and Haemophilus influenzae, Paris, France.

Meningococcal meningitis remains a life-threatening disease worldwide, with high prevalence in the sub-Saharan meningitis belt. A rapid diagnosis is crucial for implementing adapted antimicrobial treatment. We describe the performances of a new immunochromatographic test (MeningoSpeed, BioSpeedia, France) for detecting and grouping Cerebrospinal fluids (CSFs) were collected from 5 African countries and France. For the rapid diagnostic test (RDT), the CSF sample was deposited on each of the 3 cassettes for a total volume of 90 μl. The results of the RDT were compared to those of a reference multiplex PCR assay detecting the major serogroups of on 560 CSF specimens. Five specimens were found uninterpretable by RDT (0.9%). The results of interpretable specimens were as follows: 305 positive and 212 negative samples by both techniques, 14 positive by PCR only, and 24 positive by RDT only (sensitivity, specificity, and positive and negative predictive values of 92.7%, 93.8%, 95.6%, and 89.8%, respectively, with an accuracy of 93.2% and a kappa test of 0.89; < 0.05). From 319 samples positive by PCR for serogroups A, C, W, X, or Y, the grouping results were concordant for 299 specimens (sensitivity of 93.0%, 74.4%, 98.1%, 100%, and 83.3% for serogroups A, C, W, X, and Y, respectively). The MeningoSpeed RDT exhibited excellent performances for the rapid detection of antigens. It can be stored at room temperature, requires a minimal amount of CSF, is performed in 15 minutes or less, and is easy to use at bedside.
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http://dx.doi.org/10.1128/JCM.01699-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041570PMC
February 2020

Tick-Borne Encephalitis in Auvergne-Rhône-Alpes Region, France, 2017-2018.

Emerg Infect Dis 2019 10;25(10):1944-1948

Three autochthonous cases of tick-borne encephalitis (TBE) acquired in rural areas of France where Lyme borreliosis, but not TBE, is endemic highlight the emergence of TBE in new areas. For patients with neurologic involvement who have been in regions where Ixodes ticks circulate, clinicians should test for TBE virus and other tickborne viruses.
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http://dx.doi.org/10.3201/eid2510.181923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759258PMC
October 2019

Case report: Recurrent peripheral facial paralysis following two influenza vaccinations in 2009 and 2016.

Vaccine 2019 08 13;37(35):4864-4866. Epub 2019 Jul 13.

Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, France.

A 57-year-old female experienced two successive peripheral facial paralysis (PFP) episodes following influenza immunization in 2009 and 2016 with two different vaccines. The similarity of chronology and semiology between the two events and the absence of alternative etiology plead for intrinsic accountability. Extrinsic accountability relies on previous case reports of PFP related to flu vaccination (26 cases in the French pharmacovigilance database and 4 cases in the medical literature).
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http://dx.doi.org/10.1016/j.vaccine.2019.07.025DOI Listing
August 2019

Interplay of nasal and rectal carriage of Staphylococcus aureus in intensive care unit patients.

Eur J Clin Microbiol Infect Dis 2019 Oct 4;38(10):1811-1819. Epub 2019 Jul 4.

GIMAP EA 3064 (Groupe Immunité des Muqueuses et Agents Pathogènes), Université Jean Monnet, Université de Lyon, St-Etienne, France.

The aim of this study was to investigate the relationship between nasal and rectal Staphylococcus aureus carriage in intensive care unit (ICU) patients and the occurrence of ICU-acquired infections related to S. aureus carriage. Three hundred and ninety-five patients admitted in ICU were screened for S. aureus nasal and rectal carriages and followed to record S. aureus infections during their stay. S. aureus strains were genotyped by arbitrarily primed PCR, spa-typing, microarray and whole genome sequencing. At ICU admission, 112 of 363 (30.9%) patients carried S. aureus including 61 (16.8%) exclusive nasal carriers, 40 (11.0%) combined nasal and rectal carriers and 11 (3.0%) exclusive rectal carriers. The 152 S. aureus isolates from nasal and rectal swabs belonged to 19 clonal complexes (CCs). Patients colonized in both nose and rectum harboured different strains in at least 40% of cases according to arbitrarily primed PCR data. Nasal carriers of CC5 S. aureus had an increased risk of rectal carriage (RR = 1.85, P < .05). S. aureus nasal and rectal carriage was a risk factor of S. aureus ICU-acquired infection (RR = 4.04; 95%CI [1.38-11.76]). Incidence rates of endogenous ICU-acquired infections in exclusive nasal carriers, exclusive rectal carriers and in both nasal and rectal carriers were 0.08 (5/61), 0.09 (1/11) and 0.03 (1/40), respectively (p = 0.47). Rectal swabbing increased the detection of S. aureus carriage and revealed an important diversity of S. aureus strains in ICU patients. Further studies are needed to understand how S. aureus rectal carriage increases the risk of endogenous ICU-acquired infections.
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http://dx.doi.org/10.1007/s10096-019-03613-zDOI Listing
October 2019

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

J Infect 2019 07 7;79(1):36-42. Epub 2019 May 7.

Hematology Department, Institut de Cancérologie Lucien Neuwirth, 108, bis avenue Albert Raymond, 42270 Saint-Priest-en-Jarez, France.

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.
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http://dx.doi.org/10.1016/j.jinf.2019.05.001DOI Listing
July 2019

Analytical performances of the BD Veritor™ System for the detection of respiratory syncytial virus and influenzaviruses A and B when used at bedside in the pediatric emergency department.

J Virol Methods 2019 08 29;270:66-69. Epub 2019 Apr 29.

Laboratory Group on Mucosal Immunity and Pathogens (GIMAP EA3064), Faculty of Medicine of Saint-Etienne, University of Lyon, France; Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, Saint-Etienne, France. Electronic address:

This study aims to evaluate the analytical performance of the BD Veritor™ rapid diagnostic assays (RDTs) for respiratory syncytial virus (RSV) and influenzaviruses when performed 24/7 at bedside by nurses in the pediatric emergency department (PED). The study was performed between 14/10/2015 and 19/03/2016 on nasopharyngeal aspirates (NPAs) collected from children consulting at the PED of the University Hospital of Saint-Etienne for bronchiolitis (RSV detection) or flu-like syndrome (influenzaviruses A/B detection). NPAs were tested 24/7 at the PED with the RDT and then sent to the Infectious Agents Department for routine analyses, first by immunofluorescence assay (IFA), then by nucleic acid amplification test (NAAT) considered as the gold standard in case of discrepancy between RDT and IFA results. For RSV detection, 205 NPAs was analyzed; the overall concordance between RDT and routine assays was of 97.6% (200/205). The sensitivity (Se), specificity (Sp), negative predictive value (NPV) and positive predictive value (PPV) were of 97.6% (160/164), 97.6% (40/41), 90.9% (40/44) and 99.4% (160/161), respectively. A total of 419 NPA was tested for influenzaviruses. For influenzavirus A, the overall concordance was of 98.8% (414/419); Se, Sp, NPV and PPV were of 100% (41/41), 98.7% (373/378), 100% (373/373) and 89.1% (41/46), respectively. For influenzavirus B, the overall concordance was of 97.9% (410/419); Se, Sp, NPV and PPV were of 96.6% (172/178), 98.8% (238/241), 97.5% (238/244) and 98.3% (172/175), respectively. Due to their excellent performances and their easy handle by non-laboratory personnel, these RDTs can be warmly recommended as point of care assays at the PED.
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http://dx.doi.org/10.1016/j.jviromet.2019.04.022DOI Listing
August 2019

Comparison of the Fully Automated FilmArray BCID Assay to a 4-Hour Culture Test Coupled to Mass Spectrometry for Day 0 Identification of Microorganisms in Positive Blood Cultures.

Biomed Res Int 2018 21;2018:7013470. Epub 2018 Nov 21.

GIMAP EA 3064 (Groupe Immunité des Muqueuses et Agents Pathogènes), University of Lyon, Faculty of Medicine of Saint-Etienne, Saint-Etienne, France.

Rapid bacterial identification of positive blood culture is important for adapting the antimicrobial therapy in patients with blood stream infection. The aim of this study was to evaluate the performance of the multiplex FilmArray Blood Culture Identification (BCID) assay by comparison to an in-house protocol based on MALDI-TOF MS identification of microcolonies after a 4-hour culture, for identifying on the same day the microorganisms present in positive blood culture bottles. One hundred and fifty-three positive bottles from 123 patients were tested prospectively by the 3 techniques of bacterial identification: 11 bottles yielding negative results by the 3 tests were considered false positive (7.2%). The reference MALDI-TOF MS technique identified 134 monomicrobial (87.6%) and 8 double infections (5.2%), which resulted in a total of 150 microorganisms. Globally, 137 (91.3%) of these 150 pathogens were correctly identified by the fully automated multiplex FilmArray BCID system at the species or genus level on day of growth detection, versus 117 (78.8%) by MALDI-TOF MS identification on nascent microcolonies after a 4-hour culture ( < 0.01). By combining the two approaches, 140 (93.5%) of the positive bottles were identified successfully at day 0. These results confirm the excellent sensitivity of the FilmArray BCID assay, notably in case of multimicrobial infection. Due to the limited number of targets included into the test, it must be coupled to another identification strategy, as that presented in this study relying on MALDI-TOF MS identification of microcolonies obtained after a very short culture period.
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http://dx.doi.org/10.1155/2018/7013470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280299PMC
April 2019

A serum protein factor mediates maturation and apoB-association of HCV particles in the extracellular milieu.

J Hepatol 2019 04 14;70(4):626-638. Epub 2018 Dec 14.

CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, F-69007 Lyon, France. Electronic address:

Background & Aims: In the sera of infected patients, hepatitis C virus (HCV) particles display heterogeneous forms with low-buoyant densities (<1.08), underscoring their lipidation via association with apoB-containing lipoproteins, which was proposed to occur during assembly or secretion from infected hepatocytes. However, the mechanisms inducing this association remain poorly-defined and most cell culture grown HCV (HCVcc) particles exhibit higher density (>1.08) and poor/no association with apoB. We aimed to elucidate the mechanisms of lipidation and to produce HCVcc particles resembling those in infected sera.

Methods: We produced HCVcc particles of Jc1 or H77 strains from Huh-7.5 hepatoma cells cultured in standard conditions (10%-fetal calf serum) vs. in serum-free or human serum conditions before comparing their density profiles to patient-derived virus. We also characterized wild-type and Jc1/H77 hypervariable region 1 (HVR1)-swapped mutant HCVcc particles produced in serum-free media and incubated with different serum types or with purified lipoproteins.

Results: Compared to serum-free or fetal calf serum conditions, production with human serum redistributed most HCVcc infectious particles to low density (<1.08) or very-low density (<1.04) ranges. In addition, short-time incubation with human serum was sufficient to shift HCVcc physical particles to low-density fractions, in time- and dose-dependent manners, which increased their specific infectivity, promoted apoB-association and induced neutralization-resistance. Moreover, compared to Jc1, we detected higher levels of H77 HCVcc infectious particles in very-low-density fractions, which could unambiguously be attributed to strain-specific features of the HVR1 sequence. Finally, all 3 lipoprotein classes, i.e., very-low-density, low-density and high-density lipoproteins, could synergistically induce low-density shift of HCV particles; yet, this required additional non-lipid serum factor(s) that include albumin.

Conclusions: The association of HCV particles with lipids may occur in the extracellular milieu. The lipidation level depends on serum composition as well as on HVR1-specific properties. These simple culture conditions allow production of infectious HCV particles resembling those of chronically-infected patients.

Lay Summary: Hepatitis C virus (HCV) particles may associate with apoB and acquire neutral lipids after exiting cells, giving them low-buoyant density. The hypervariable region 1 (HVR1) is a majorviral determinant of E2 that controls this process. Besides lipoproteins, specific serum factors including albumin promote extracellular maturation of HCV virions. HCV particle production in vitro, with media of defined serum conditions, enables production of infectious particles resembling those of chronically infected patients.
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http://dx.doi.org/10.1016/j.jhep.2018.11.033DOI Listing
April 2019

Impact of HIV-1 primary drug resistance on the efficacy of a first-line antiretroviral regimen in the blood of newly diagnosed individuals in Bamako, Mali.

J Antimicrob Chemother 2019 01;74(1):165-171

Groupe Immunité des Muqueuses et Agents Pathogènes GIMAP EA3064, University of Saint-Etienne, University of Lyon, Saint-Etienne, France.

Background: To achieve the 90-90-90 targets assigned by UNAIDS, it is crucial to monitor ART in HIV-1-infected patients, especially in resource-limited countries.

Objectives: To evaluate the immunovirological response after 12 months of ART in newly HIV-1-diagnosed people in Bamako, Mali; to determine primary and acquired resistance rates to antiretroviral drugs; and to evaluate the impact of primary resistance on the efficacy of ART.

Patients And Methods: One hundred and nineteen HIV-1-infected people (88.2% women; median age 34 years) were enrolled between January and June 2014. HIV-1 RNA loads (Abbott RealTime HIV-1 assay) were tested in the blood before and at months 3, 6 and 12 after initiation of ART. Primary and acquired resistances to ART were evaluated by the Viroseq™ HIV-1 genotyping assay.

Results: During the study, 8.4% of people died and 37% were lost to follow-up. After 1 year of ART, an undetectable HIV-1 RNA viral load was found in 87.7% of cases. The overall rate of primary drug resistance mutations was 17.5% (3.2%, 15.9% and 0% for NRTIs, NNRTIs and PIs, respectively). These mutations were not associated with either higher mortality rates or larger numbers of virological failures. The acquired resistance rate was estimated at 3.1%.

Conclusions: Our study showed a high primary resistance level and a huge proportion of people non-adherent to the treatment programme. Reassuringly, almost 90% virological success and a low level of acquired mutations were observed in adherent people at month 12. Reinforced education, regular virological monitoring and early HIV-1 diagnosis may help to improve retention in the care system.
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http://dx.doi.org/10.1093/jac/dky382DOI Listing
January 2019

HaCaT epithelial cells as an innovative novel model of rhinovirus infection and impact of clarithromycin treatment on infection kinetics.

Virology 2018 10 1;523:27-34. Epub 2018 Aug 1.

Group for Mucosal Immunity and Pathogen Agents (GIMAP EA3064), Faculty of Medicine of Saint-Etienne, University of Lyon, France; Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, France.

The in vitro propagation of human rhinoviruses (RVs) is difficult because only few continuous human cell lines are permissive to these agents. We propose an innovative model of epithelial cell infection using a non-transformed continuous keratinocyte line from human origin (HaCaT cells). After infection with RV-A13, RV-A16 or RV-A19, HaCaT cells produced infectious particles without showing any observable cytopathic effect and overexpressed ICAM-1 (intercellular adhesion molecule 1), the major entry receptor of RVs. Furthermore, the treatment of HaCaT cells with 10 µM clarithromycin reduced the viral titer by 93% and 60% during the first and second days following viral infection, respectively, probably by down-regulating ICAM-1 expression. This original model of epithelial cell infection by RV could be useful to study chronic viral infection and bacterium-virus interactions at the cell level. These results also suggest that clarithromycin may be evaluated for treating in vivo infections associating RV to a susceptible bacterium.
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http://dx.doi.org/10.1016/j.virol.2018.07.025DOI Listing
October 2018

Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms.

Virulence 2018 ;9(1):1354-1363

a GIMAP EA 3064 (Groupe Immunité des Muqueuses et Agents Pathogènes) , University of Lyon , Saint-Etienne , France.

Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy.
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http://dx.doi.org/10.1080/21505594.2018.1504561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177244PMC
April 2019

Relationship between human immunodeficiency virus (HIV-1) infection and chronic periodontitis.

Expert Rev Clin Immunol 2018 04 12;14(4):315-327. Epub 2018 Apr 12.

g Department of Stomatology, Public Oral Health and Forensic Dentistry, School of Dentistry of Ribeirão Preto , University of São Paulo , Ribeirão Preto , Brazil.

Introduction: Current studies show that, even in the era of antiretroviral therapies, HIV-1 infection is associated with more severe and frequent refractory chronic periodontitis. Areas covered: This review, based on a systematic analysis of the literature, intends to provide an update on factors that may be involved in the pathogenesis of periodontal disease in HIV-1-infected patients, including local immunosuppression, oral microbial factors, systemic inflammation, salivary markers, and the role of gingival tissue as a possible reservoir of HIV-1. Expert commentary: The therapeutic revolution of ART made HIV-1 infection a chronic controllable disease, reduced HIV-1 mortality rate, restored at least partially the immune response and dramatically increased life expectancy of HIV-1-infected patients. Despite all these positive aspects, chronic periodontitis assumes an important role in the HIV-1 infection status for activating systemic inflammation favoring viral replication and influencing HIV-1 status, and also acting as a possible reservoir of HIV-1. All these issues still need to be clarified and validated, but have important clinical implications that certainly will benefit the diagnosis and management of chronic periodontitis in HIV-1-infected patients, and also contributes to HIV-1 eradication.
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http://dx.doi.org/10.1080/1744666X.2018.1459571DOI Listing
April 2018

Platelet toll-like receptors are crucial sensors of infectious danger moieties.

Platelets 2018 Sep 13;29(6):533-540. Epub 2018 Mar 13.

a EA3064-GIMAP , University of Lyon-UJM , Saint-Etienne , France.

In addition to their haemostatic role and function in the repair of damaged vascular epithelium, platelets play a defensive role in innate immunity, having the capacity to produce and secrete various anti-infectious factors, as well as cytokines, chemokines and related products, to interact with other immune cells to modulate immune responses to pathogens. Thus, it is now widely acknowledged that platelets participate in inflammatory processes and infection resolution, most notably by expressing and using receptors to bind infectious pathogen moieties and contributing to pathogen clearance. The ability of platelets to sense external danger signals relates to the expression of certain innate immunity receptors, such as toll-like receptors (TLRs), and the activation of efficient cell signalling machinery. TLR engagement triggers platelet response, which results in adapted degranulation according to: the type of TLR engaged, the nature of the ligand and the milieu; together, the TLR-mediated event and other signalling events may be followed by aggregation. Platelets thus use complex tools to mediate a whole range of functions upon sensing danger. By linking the inflammatory and haemostatic platelet response to infection, TLRs play a central role. The extent of the inflammatory response to pathogen clearance is still a debatable issue and is discussed in this short review.
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http://dx.doi.org/10.1080/09537104.2018.1445842DOI Listing
September 2018

Cytomegalovirus and inflammatory bowel diseases, with a special focus on its role in ulcerative colitis.

Virologie (Montrouge) 2017 Dec;21(6):287-302

EA3064, Groupe immunité des muqueuses et agents pathogènes (Gimap), Campus Santé Innovations, Faculté de médecine, 10 rue de la Marandière, BP 80019, 42270 Saint-Priest-en-Jarez, Laboratoire des agents infectieux et hygiène, CHU de Saint-Étienne, France.

Cytomegalovirus (CMV) infects approximately 50 % of adults in France and persists lifelong as a latent agent in different organs, including the gut. A close relationship is observed between inflammation that favors viral expression, and viral replication that modulates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBD), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation in link with Th2 cytokines, together with immunomodulatory drugs used for controlling flares-up, favors viral reactivation within the gut, which increases mucosal inflammation ; it results in an important risk of impairing corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in case of CMV colitis), precipitating the need for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during IBD and underlines the interest of using ganciclovir for treating flares-up associated to CMV colitis in UC patients.
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http://dx.doi.org/10.1684/vir.2017.0713DOI Listing
December 2017

Epidemiology and clinical relevance of Staphylococcus aureus intestinal carriage: a systematic review and meta-analysis.

Expert Rev Anti Infect Ther 2017 08 27;15(8):767-785. Epub 2017 Jul 27.

a GIMAP EA 3064 (Groupe Immunité des Muqueuses et Agents Pathogènes) , University of Lyon , Saint-Etienne , France.

Introduction: Recent data highlight the importance of screening more than one site for improving the detection of S. aureus colonization. Intestinal carriage is frequently under-investigated and its clinical impact ought to be defined a better way. Areas covered: This review and meta-analysis provide an updated overview of prevalence, characteristics and clinical significance of S. aureus intestinal carriage in different populations, both for methicillin-susceptible and -resistant S. aureus strains. Expert commentary: Intestinal S. aureus carriage is documented with higher prevalence in children and in patients with S. aureus skin and soft tissue infections. This site of colonization was shown to be associated with a high risk of dissemination in the environment and with S. aureus infection. Intestinal carriage is frequently retrieved in nasal carriers, reflecting probably an association with a high bacterial load. Exclusive intestinal carriage present in one third of intestinal carriers can be associated with infection. Comparative genotyping analysis of different strains from nasal and extra-nasal sites of carriage, including the intestinal ones, in the same individuals, would allow a better comprehension of the pathophysiology of S. aureus endogenous infection. It could also permit to improve the prevention of these infections by decolonization of sites implicated in infection genesis.
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http://dx.doi.org/10.1080/14787210.2017.1358611DOI Listing
August 2017