Laboratoire des Pathogenes Emergents

Sainte-Foy-lès-Lyon, France

Laboratoire des Pathogenes Emergents

Sainte-Foy-lès-Lyon, France
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Ferraris O.,Institute Of Recherche Biomedicale Des Armees | Moroso M.,Laboratoire des Pathogenes Emergents | Pernet O.,French Institute of Health and Medical Research | Pernet O.,University of California at Los Angeles | And 5 more authors.
Antiviral Research | Year: 2015

Abstract Crimean-Congo hemorrhagic virus (CCHFV) causes hemorrhagic fever with high case mortality rates and is endemic in south-eastern Europe, Africa, and Asia. The limited catalog of specific treatment, highlight the necessity to look for additional therapeutic solutions. Previous experiments suggested that CCHFV enters the cells via a clathrin dependent pathway. Therefore, we have evaluated the potential anti-CCHFV activity of several molecules targeting this entry possibility. We identified two molecules chloroquine and chlorpromazine. Neutralization and virus yield reduction assays were tested in Vero E6 and Huh7 cells on two different CCHFV strains. Several combinations, including ribavirin, were assayed to test a potential synergistic effect. The two molecules inhibited CCHFV, and depending on the virus and the cell lines, the 50% inhibitory concentration (IC50) values for chloroquine and chlorpromazine ranged from 28 to 43 and 10.8-15.7 μM, respectively. Time-of-addition studies demonstrated that these molecules had a direct effect on CCHFV infectivity and spread. The antiviral activity of the two molecules was still effective even when added up to 6 h post-infection and up to 24 h. The selectivity index ranging from 3 to 35 lead us to evaluate combinations with ribavirin. Combinations of ribavirin and chloroquine or chlorpromazine were synergistic against CCHFV. Though the low chlorpromazine selectivity index suggests the need for a chemical improvement, our present study highlights chloroquine as the main drug having the potential for drug repurposing. © 2015 Elsevier B.V. All rights reserved.


Bagnaud-Baule A.,bioMerieux | Bagnaud-Baule A.,Laboratoire des Pathogenes Emergents | Reynard O.,French Institute of Health and Medical Research | Perret M.,Laboratoire des Pathogenes Emergents | And 8 more authors.
PLoS ONE | Year: 2011

Each year, during winter months, human Metapneumovirus (hMPV) is associated with epidemics of bronchiolitis resulting in the hospitalization of many infants. Bronchiolitis is an acute illness of the lower respiratory tract with a consequent inflammation of the bronchioles. The rapid onset of inflammation suggests the innate immune response may have a role to play in the pathogenesis of this hMPV infection. Since, the matrix protein is one of the most abundant proteins in the Paramyxoviridae family virion, we hypothesized that the inflammatory modulation observed in hMPV infected patients may be partly associated with the matrix protein (M-hMPV) response. By western blot analysis, we detected a soluble form of M-hMPV released from hMPV infected cell as well as from M-hMPV transfected HEK 293T cells suggesting that M-hMPV may be directly in contact with antigen presenting cells (APCs) during the course of infection. Moreover, flow cytometry and confocal microscopy allowed determining that M-hMPV was taken up by dendritic cells (moDCs) and macrophages inducing their activation. Furthermore, these moDCs enter into a maturation process inducing the secretion of a broad range of inflammatory cytokines when exposed to M-hMPV. Additionally, M-hMPV activated DCs were shown to stimulate IL-2 and IFN-γ production by allogeneic T lymphocytes. This M-hMPV-mediated activation and antigen presentation of APCs may in part explain the marked inflammatory immune response observed in pathology induced by hMPV in patients. © 2011 Bagnaud-Baule et al.


PubMed | Laboratoire des Pathogenes Emergents, Institute Of Recherche Biomedicale Des Armees and French Institute of Health and Medical Research
Type: | Journal: Antiviral research | Year: 2015

Crimean-Congo hemorrhagic virus (CCHFV) causes hemorrhagic fever with high case mortality rates and is endemic in south-eastern Europe, Africa, and Asia. The limited catalog of specific treatment, highlight the necessity to look for additional therapeutic solutions. Previous experiments suggested that CCHFV enters the cells via a clathrin dependent pathway. Therefore, we have evaluated the potential anti-CCHFV activity of several molecules targeting this entry possibility. We identified two molecules chloroquine and chlorpromazine. Neutralization and virus yield reduction assays were tested in Vero E6 and Huh7 cells on two different CCHFV strains. Several combinations, including ribavirin, were assayed to test a potential synergistic effect. The two molecules inhibited CCHFV, and depending on the virus and the cell lines, the 50% inhibitory concentration (IC50) values for chloroquine and chlorpromazine ranged from 28 to 43 and 10.8-15.7 M, respectively. Time-of-addition studies demonstrated that these molecules had a direct effect on CCHFV infectivity and spread. The antiviral activity of the two molecules was still effective even when added up to 6h post-infection and up to 24h. The selectivity index ranging from 3 to 35 lead us to evaluate combinations with ribavirin. Combinations of ribavirin and chloroquine or chlorpromazine were synergistic against CCHFV. Though the low chlorpromazine selectivity index suggests the need for a chemical improvement, our present study highlights chloroquine as the main drug having the potential for drug repurposing.


Gauthier M.,Laboratoire des Pathogenes Emergents | Gauthier M.,Les Centres Du Groupe Haitien Detude Du Sarcome Of Kaposi Et Des Infections Opportunistes | Somoskivi A.,Foundation for Innovative New Diagnostics | Berland J-L.,Laboratoire des Pathogenes Emergents | And 7 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2014

SETTING: The uptake of tests endorsed by the World Health Organization to detect and appropriately confirm multidrug-resistant tuberculosis (MDR-TB) in lowincome countries remains insufficient. OBJECTIVE: To validate the implementation of lineprobe assays (LPA) and liquid culture to develop an algorithm to detect MDR-TB in the challenging setting of Haiti. METHODS: Through an EXPAND-TB (Expanding Access to New Diagnostics for TB) partnership, proficiency testing and validation of 221 acid-fast bacilli positive specimens were performed. Sensitivity, cost and processing time were analysed. RESULTS: Using liquid vs. solid culture shortened the turnaround time from 54 to 19 days, with a sensitivity of 100% vs. 98.6% and a total cost reduction of 13%. LPA detected all TB and MDR-TB cases at a lower cost than culture, in a mean time of 7.5 days. CONCLUSION: The combined use of molecular and liquid culture techniques accelerates the accurate diagnosis of TB and susceptibility testing against first-line drugs in a significantly shorter time, and is less expensive. The implementation of this new algorithm could significantly and accurately improve the screening and treatment follow-up of patients affected with TB and MDR-TB. © 2014 The Union.


De Pablos L.M.,University of Granada | Gonzalez G.,University of Granada | Rodrigues R.,Laboratoire des Pathogenes Emergents | Garcia Granados A.,University of Granada | And 2 more authors.
Journal of Natural Products | Year: 2010

The action of maslinic acid (2α,3β-dihydroxyolean-12-en-28-oic acid) (1), a pentacyclic derivative present in the pressed fruits of the olive (Olea europaea), has been studied against the tachyzoites of Toxoplasma gondii. The capability of tachyzoites to infect Vero cells treated with 1 was affected. The LD50 values were 58.2 μM for the isolated tachyzoites and 236 μM for the noninfected Vero cells. Zymograms of the T. gondii proteases incubated with 1 showed a dosage-dependent inhibition of some of the proteases. The parasites treated with 1 showed gliding motility and ultrastructural alterations. The present findings suggest that protease activity of the parasite required for cell invasion is the action target for maslinic acid (1). © 2010 The American Chemical Society and American Society of Pharmacognosy.


Thammavong C.,Institute Of La Francophonie Pour La Medecine Tropicale | Paboriboune P.,Center Christophe Merieux of Laos | Bouchard B.,Center Christophe Merieux of Laos | Harimanana A.,Institute Of La Francophonie Pour La Medecine Tropicale | And 4 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2011

BACKGROUND: Laos has a high prevalence of tuberculosis (TB) and a slowly increasing prevalence of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS). Sputum smear microscopy is the only method currently available for routine screening of pulmonary TB, although it only detects one in three cases among persons living with HIV (PLWH). Bleach treatment of sputum samples (bleach method) has been shown to significantly improve the sensitivity of the test; however, its effectiveness in PLWH remains to be determined in Laos. OBJECTIVES: To determine the performance of the bleach method as a diagnostic tool for pulmonary TB in PLWH and to assess its cost-effectiveness in Laos. RESULTS: Of 174 sputum samples collected from 92 patients, 29 were culture-positive for Mycobacterium tuberculosis in 17 patients. The sensitivity of the direct method and the bleach method was respectively 59% and 93%, and specificity was 100% for both methods. The incremental cost-effectiveness ratio for screening an additional case was US$17.40. CONCLUSION: The bleach method is simple, cheap, easy to perform and cost-effective in PLWH. Its implementation in laboratories involved in routine screening of pulmonary TB among PLWH would allow practitioners to start the treatment of this life-threatening co-infection earlier. © 2011 The Union.


Iem V.,Village Capital | Somphavong S.,Village Capital | Somphavong S.,Institute Of La Francophonie Pour La Medecine Tropicale | Buisson Y.,Institute Of La Francophonie Pour La Medecine Tropicale | And 8 more authors.
BMC Infectious Diseases | Year: 2013

Background: It is estimated that Lao People's Democratic Republic (Lao PDR) ranks fifth among the seven countries most affected by TB in the WHO Western Pacific Region. However, because of late implementation of mycobacterial culture, no study on resistance to anti-TB drugs had been performed yet. The objective of this study was to document drug resistance rate among patients hospitalized for pulmonary TB in threeprovinces of Lao PDR.Methods: A cross-sectional study was conducted in three sites, one central and two regional hospitals, from April to November 2010. For each TB suspected patient sputum smear microscopy and culture on Lowenstein-Jensen media were performed. GenoType® MTBDRplus assay was used to test the susceptibility to isoniazid (INH) and rifampicin (RMP), GenoType® MTBDRsl for second-line drugs and GenoType® Mycobacterium CMAS for non-tuberculous mycobacteria (NTM).Results: Out of 104 positive culture on Lowenstein-Jensen, 87 (83.6%) were M. tuberculosis and 17 (16.4%) were NTM. Of 73 new TB cases, 5 isolates (6.8%) were resistant to INH. Of 14 previously treated cases, 2 isolates (14.3%) were resistant to INH and one isolate was XDR.Conclusion: Despite an overall rate of resistance still moderate, the frequency of mutations conferring INH monoresistance and identification of the first strain of XDR require strengthening surveillance of drug resistant tuberculosis in Lao PDR. © 2013 Iem et al.; licensee BioMed Central Ltd.


Fragnoud R.,bioMerieux | Fragnoud R.,Laboratoire des Pathogenes Emergents | Paranhos-Baccala G.,Laboratoire des Pathogenes Emergents | Bedin F.,bioMerieux
Virologie | Year: 2014

Dengue is an endemic viral disease present in inter-tropical countries. If dengue is usually benign, more severe forms (severe dengue [SD]) may lead to serious complications. The prognosis of SD is currently unreliable. To improve the prognosis, it could be necessary to know the key elements of the pathogenicity of the SD. Many hypotheses have been developed to explain a higher pathogenicity in SD patients. Numerous studies have highlighted the role of the host immune response and of the infecting virus strain. The development of these hypothesis allows to have a better understanding of the pathogenesis and consequently, to provide prognostic candidate-markers of SD, these markers being either associated with the host or with the virus. The present review proposes to paint a non-exhaustive picture of the most important hypothesis of dengue pathogenicity as well as potential prognostic markers of severe forms of dengue.


PubMed | Laboratoire des Pathoge`nes Emergents
Type: Journal Article | Journal: The European respiratory journal | Year: 2013

An unexplained increase in the incidence of parapneumonic empyema (PPE) in pneumonia cases has been reported in recent years. The present study investigated the genetic and biological specifications of new isolates of torque teno mini virus (TTMV) detected in pleural effusion samples from children hospitalised for severe pneumonia with PPE. A pathogen discovery protocol was applied in undiagnosed pleural effusion samples and led to the identification of three new isolates of TTMV (TTMV-LY). Isolated TTMV-LY genomes were transfected into A549 and human embryonic kidney 293T cells and viral replication was assessed by quantitative real-time PCR and full-length genome amplification. A549 cells were further infected with released TTMV-LY virions and the induced-innate immune response was measured by multiplex immunoassays. Genetic analyses of the three TTMV-LY genomes revealed a classic genomic organisation but a weak identity (<64%) with known sequences. We demonstrated the in vitro replication of TTMV-LY in alveolar epithelial cells and the effective release of infectious viral particles. We also showed a selective production of inflammatory mediators in response to TTMV infection. This study reports the description of replicative TTMV-LY isolated from parapneumonic effusions of children hospitalised with PPE, suggesting a potential role of the virus in the pathogenesis of pneumonia.


PubMed | Laboratoire des Pathogenes Emergents, Institute Pasteur Paris and University of Antananarivo
Type: | Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases | Year: 2016

The resurgence of invasive meningococcal disease caused by Neisseria meningitidis serogroup W with sequence type ST-11 (cc11) was observed in Madagascar in 2015-2016. Three cases were investigated in this study. Molecular characterization of the strains suggests the local transmission of a single genotype that may have been circulating for years.

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