Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01489008
https://hal-univ-perp.archives-ouvertes.fr/hal-01489008

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
BACKGROUND:Fever in infants younger than 3 months is generally a cause for concern because of the risk for a serious bacterial infection. The aim of this study was to describe clinical and biological features of Chikungunya infection in infants < 3 months of age hospitalized in Cayenne Hospital during the 2014-2015 outbreak.METHODS:We performed a preliminary retrospective study followed by a prospective study from March 2014 to February 2015. All infants younger than 3 months presenting with fever and hospitalized in Cayenne Hospital were included. The main diagnostic criteria were fever and positive Chikungunya PCR.RESULTS:One hundred and twenty infants were hospitalized with fever. The mean age was 46 days (SD± 22 days). The mean hospitalization duration was 7.4 days (SD± 6.1 days). Chikungunya infection was diagnosed in 26 children. The most important clinical findings were high (80.8% [77.5-84]) and prolonged fever (76.9%, [73.4-80.4]), irritability (96.2% [94.5-97.7]) and skin rash. (69.2%, [65.4-73]). Half of the infants presented edema of the extremities (hands and feet principally). However, in 15 %, Chikungunya infection was associated with a serious bacterial infection. Infants who presented with irritability, high fever and elevated PCT were at high risk for Chikungunya: OR 39, [9.2-243] (p < 0.001), with a specificity of 96.7 % and a negative predictive value of 89.4%. The area of the ROC curve was 0.96 CONCLUSIONS:: Our results confirm that Chikunguyna infection is a cause of high fever in infants younger than 3 months. Our data should be confirmed by larger studies.
ISSN: 0891-3668

inserm-01476019
http://www.hal.inserm.fr/inserm-01476019
http://www.hal.inserm.fr/inserm-01476019/document
http://www.hal.inserm.fr/inserm-01476019/file/2017%2C%20Elenga%20-%20Chikungunya%20Infection%20in%20hospitalized%20febrile%20infants.pdf
DOI : 10.1097/INF.0000000000001541

Éditeur(s) : Université de La Rochelle, Ecole doctorale Gay Lussac
Résumé : The thesis work is part of the very current issue on mass mortality outbreaks affecting Pacific oyster, C. gigas, spat and juveniles and questions about the involvement of pesticides in this phenomenon. The first part of this thesis was devoted to study the effects of pesticides on hemocyte parameters in the Pacific oyster (in vitro and in vivo). The immunomodulator effect of selected pesticides (alone or in mixture) has been explored principally through flow cytometry. The second part concerned the study of the effects of a pesticides mixture on OsHV-1 itself. No direct effects have been reported on the viral particles in presence of the pollutants. Moreover, pesticide effects on Pacific oysters were also explored through experimental pathology assays after treatment of animals with a polluant mixture. Results showed that pesticide treated oysters appeared more susceptible to the viral infection in experimental conditions. The third part concerned the study of autophagy in the Pacific oyster, C. gigas. The publication of the complete genome in 2012 has opened up new possibilities for the study of innate immunity in this species. The study of autophagy for the first time in oysters consisted in a first step in the in silico search for genes involved in this pathway and the corresponding proteins by Western blotting. Then, the role of this important process in innate immunity has been explored through reproduction infections tests with or without modulators of autophagy. Results showed that autophagy appeared as involved in defence mechanisms against viral and bacterial infection in Pacific oysters.
Le travail de thèse s’inscrit dans la problématique très actuelle des mortalités massives de naissain et de juvéniles d’huîtres creuses, C. gigas, et des questionnements autour de l’implication des pesticides dans ce phénomène. La première partie de la thèse a été consacrée à l’étude des effets de pesticides sur les capacités hémocytaires de l’huître creuse (in vitro et in vivo). L’effet immunomodulateur des xénobiotiques sélectionnés (seul ou en mélange) a été exploré principalement au travers de la cytométrie en flux. La deuxième partie de la thèse a concerné l’étude des effets d’un mélange de pesticides sélectionnés sur le virus OsHV-1 et l’infection qu’il induit chez l’huître creuse. Les effets des pesticides sur le virus lui-même ont été évalués. Les expériences réalisées non pas permis de mettre en évidence dans les conditions testées, de dégradation des particules virales en présence des polluants. D’autre part, leurs effets sur les huîtres elles-mêmes ont été explorés après traitement des animaux avec un mélange de pesticides lors d’essais de pathologie expérimentale. Il a ainsi pu être montré que des huîtres préalablement comtaminées par un mélange de pesticides à des concentrations retrouvées dans l’environnement semblaient être plus sensibles à l’infection virale. La troisième partie de la thèse a concerné l’étude de l’autophagie chez l’huître creuse, C. gigas. La publication du génome complet de cette espèce en 2012 a ouvert de nouvelles possibilités pour étudier l'immunité innée. L’étude de l’autophagie réalisée pour la première fois chez l’huître creuse a consisté lors d’une première étape en la recherche in silico de gènes impliqués dans cette voie et des protéines correspondantes par western blotting. Puis, le rôle de ce processus important dans l’immunité innée a été exploré au travers d’essais de reproduction d’infections en présence ou non de modulateurs de l’autophagie. Les résultats obtenus semblent montrer que l’autophagie soit un processus important pouvant être impliqué dans les capacités de défense de l’huître creuse vis-à-vis d’infections virales et bactériennes.

Droits : 2014 Université de La Rochelle
http://archimer.ifremer.fr/doc/00226/33740/32149.pdf
http://archimer.ifremer.fr/doc/00226/33740/

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Neonatal infection constitutes one of Senegal’s most important public health problems, with amortality rate of 41 deaths per 1,000 live births.Methods: Between January 2007 and March 2008, 242 neonates with suspected infection were recruited at threeneonatal intensive care units in three major tertiary care centers in Dakar, the capital of Senegal. Neonatal infections wereconfirmed by positive bacterial blood or cerebrospinal fluid culture. The microbiological pattern of neonatal infectionsand the antibiotic susceptibility of the isolates were characterized. In addition, the genetic basis for antibiotic resistanceand the genetic background of third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae were studied.Results: A bacteriological infection was confirmed in 36.4 % (88/242) of neonates: 22.7 % (30/132) during the early-onsetand 52.7 % (58/110) during the late-onset periods (p > 0.20). Group B streptococci accounted for 6.8 % of the 88 collectedbacterial isolates, while most of them were Enterobacteriaceae (n = 69, 78.4 %). Of these, 55/69 (79.7 %) were 3GC-R. TheblaCTX-M-15 allele, the blaSHV and the blaTEM were highly prevalent (63.5, 65.4 and 53.8 %, respectively), usually associatedwith qnr genes (65.4 %). Clonally related strains of 3GC-R Klebsiella pneumoniae and 3GC-R Enterobacter cloacae, the twomost commonly recovered 3GC-R Enterobacteriaceae (48/55), were detected at the three hospitals, underlining the roleof cross-transmission in their spread. The overall case fatality rate was 18.6 %.Conclusions:Measures should be taken to prevent nosocomial infections and the selection of resistant bacteria
ISSN: 1471-2334

Droits : http://creativecommons.org/licenses/by/
hal-01473613
https://hal.archives-ouvertes.fr/hal-01473613
https://hal.archives-ouvertes.fr/hal-01473613/document
https://hal.archives-ouvertes.fr/hal-01473613/file/High%20third-generation%20cephalosporin%20resistant%20Enterobacteriaceae%20prevalence%20rate%20among%20neonatal%20infections%20in%20Dakar%2C%20Senegal.pdf
DOI : 10.1186/s12879-016-1935-y

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways
ISSN: 1553-7366

Droits : http://creativecommons.org/licenses/by/
hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/file/journal.ppat.1005153.pdf
DOI : 10.1371/journal.ppat.1005153

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
In disease-endemic areas, histoplasmosis is the main differential diagnosis for tuberculosis among human immunodeficiency virus (HIV)-infected patients. However, no study has compared the two diseases. Thus, the objective of this study was to compare tuberculosis and histoplasmosis in HIV-infected patients. A population of 205 HIV-infected patients (99 with tuberculosis and 106 with histoplasmosis) hospitalized in Cayenne, French Guiana during January 1, 1997-December 31, 2008 were selected retrospectively from the French Hospital Database on HIV. Multivariate analysis showed that tuberculosis was associated with cough (adjusted odds ratio [AOR] = 0.20, 95% confidence interval [CI] = 0.05-0.73) and a C-reactive protein level > 70 mg/L (AOR = 0.98, 95% CI = 0.97-0.99). Variables associated with disseminated histoplasmosis were a γ-glutamyl transferase level > 72 IU/L (AOR = 4.99, 95% CI = 1.31-18.99), origin from French Guiana (AOR = 5.20, 95% CI = 1.30-20.73), disseminated localization (AOR = 6.40, 95% CI = 1.44-28.45), a concomitant opportunistic infection (AOR = 6.71, 95% CI = 1.50-29.96), a neutrophil count < 2,750 cells/mm(3) (AOR = 10.54, 95% CI = 2.83-39.24), a CD4 cell count < 60 cells/mm(3) (AOR = 11.62, 95% CI = 2.30-58.63), and a platelet count < 150,000/mm(3) (AOR = 19.20, 95% CI = 3.35-110.14). Tuberculosis and histoplasmosis have similarities, but some factors show a greater association with one of these diseases. Thus, adapted therapeutic choices can be made by using simple clinical and paraclinical criteria.
ISSN: 0002-9637

inserm-01065027
http://www.hal.inserm.fr/inserm-01065027
http://www.hal.inserm.fr/inserm-01065027/document
http://www.hal.inserm.fr/inserm-01065027/file/2014_Adenis_-_Tuberculosis_and_Histoplasmosis_among_HIV.pdf
DOI : 10.4269/ajtmh.13-0084

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure.
ISSN: 1553-7366

hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/file/Semen_CD4_T-accepted.pdf
PUBMED : 24348253

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Introduction. - Temocillin is an alternative to treat urinary tract infections with bacteria producing extended spectrum beta-lactamase (ESBL). The objective is to evaluate the use of temocillin in urinary tract infections. Materials and methods. - A systematic review of literature was carried out according to PRISMA criteria. All national and international recommendations have been reviewed regarding the indication of the use of temocillin in urology. Data collection on the use of temocillin in urinary tract infection has been performed from the Cochrane, LILACS and the Medline database. The following keywords were used: temocillin, extended spectrum. beta-lactamase, urinary tract infections, urine, prostate, epididymis, testis, diffusion, pharmacokinetics, pharmacodynamics. The selection was based on the methodology, language of publication (English/French), relevance to the topic and date of publication of the articles collected. The endpoint was to provide exhaustive scientific information allowing urologists to use this antibiotic in febrile urinary infections. Results. - Bacteria producing ESBL has a relatively high susceptible to temocillin, ranging from 61 % to 90 %. These rates would allow its use in probabilistic. The dosage recommended is currently, in the normo-renal patient, 4 g per day by intermittent infusion or continuously after a loading dose of 2g. Some studies argue, particularly in case of difficult clinical situations or obese patients, for administration of high doses (6 g/24 h) rather continuous infusion. There is no evident relationship between high doses and side effects. With an excellent urinary and prostatic diffusion, temocilllin might be recommend for the treatment of ESBL prostatitis. Conclusion. - Temocillin is known to have good urinary and prostatic diffusion. According to our results, this antibiotics is now a reliable alternative for the treatment of documented ESBL urinary tract infections. (C) 2017 Elsevier Masson SAS. All rights reserved.
ISSN: 1166-7087

hal-01659245
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659245
DOI : 10.1016/j.purol.2017.07.242
PUBMED : 28869169

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The genetic diversity of Plasmodium falciparum has been extensively studied in various parts of the world. However, limited data are available from Mauritania. The present study examined and compared the genetic diversity of P. falciparum isolates in Mauritania. METHODS: Plasmodium falciparum isolates blood samples were collected from 113 patients attending health facilities in Nouakchott and Hodh El Gharbi regions. K1, Mad20 and RO33 allelic family of msp-1 gene were determined by nested PCR amplification. RESULTS: K1 family was the predominant allelic type carried alone or in association with Ro33 and Mad20 types (90%; 102/113). Out of the 113 P. falciparum samples, 93(82.3%) harboured more than one parasite genotype. The overall multiplicity of infection was 3.2 genotypes per infection. There was no significant correlation between multiplicity of infection and age of patients. A significant increase of multiplicity of infection was correlated with parasite densities. CONCLUSIONS: The polymorphism of P. falciparum populations from Mauritania was high. Infection with multiple P. falciparum clones was observed, as well as a high multiplicity of infection reflecting both the high endemicity level and malaria transmission in Mauritania.
ISSN: 1475-2875

inserm-00936407
http://www.hal.inserm.fr/inserm-00936407
http://www.hal.inserm.fr/inserm-00936407/document
http://www.hal.inserm.fr/inserm-00936407/file/1475-2875-13-26.pdf
DOI : 10.1186/1475-2875-13-26

Éditeur(s) : HAL CCSD
Résumé : National audience
Objective of the study An estimation of burden of serious fungal diseases in France is essential data to inform public health priorities on the importance of resources and research needed on these infections. In France, precise data are available for invasive fungal diseases but estimates for several other diseases such as chronic and immunoallergic diseases are by contrast less known. Materials and methods A systematic literature search was conducted using the Web of Science Platform. Published epidemiology papers reporting fungal infection rates from France were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. Results The model predicts high prevalences of severe asthma with fungal sensitization episodes (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides, estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively. Regarding invasive candidiasis, more than 10,000 cases per year are estimated, and a much higher number of recurrent vaginal candidiasis is probable but must be confirmed. Finally, this survey was an opportunity to report a first picture of the frequency of tinea capitis in France. Conclusion Using local and literature data of the incidence or prevalence of fungal infections, approximately 1,000,000 (1.47%) people in France are estimated to suffer from serious fungal infections each year. © 2016 Elsevier Masson SAS
Journal de Mycologie Medicale

hal-01467554
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467554
DOI : 10.1016/j.mycmed.2016.11.001
PUBMED : 27887809

Éditeur(s) : HAL CCSD
Résumé : Staphylococcus aureus is an opportunistic pathogen of humans and warm-blooded animals. It is foundin healthy carriage and can cause a wide range of infections in its hosts. The epithelial surface is theprincipal site of staphylococcal infection. The pathogens have evolved sophisticated mechanisms tohijack the main function of the host cells, thus promoting their invasion and colonization. Amongstthese effects are, alteration of host cell apoptosis, promotion of cell proliferation or conversely,inhibition of cell growth. Using human cervix cancer HeLa and mammary gland bovine MAC-Tepithelial cells, we studied the cytopathic effect of S. aureus and its ability to affect host cell cycle.Using microscopic examination, we found that S. aureus induced the cytopathic effect resulting in theenlargement of the host cells 72 hours post infection. Our experiments showed that the proliferationrate of the epithelial cells was slowed down in S. aureus-infected culture. Three different S. aureusstrains from human and animal origins were used and showed similar effect on both human and bovinecells. Microscopic analysis of DAPI-stained cells revealed huge decrease of mitotic indexes in infectedHeLa and Mac-T cells, synchronized by Double Thymidine Block. Using flow cytometry analysis, wefound that S. aureus induces G2/M phase delay in synchronous HeLa cells. By Western blot analysis,we showed that the G2/M phase delay was associated with accumulation of inactive phosphorylatedcyclin-dependent kinase Cdk1/cdc2, a key inducer of mitosis entry, and dephosphorylation of corehistone H3, an important component of the epigenetic landscape.These results suggest that the delay in G2/M phase transition of the infected epithelial cells may beone of the mechanisms employed by S. aureus to survive and to propagate inside the host. A fullcomprehension of the mechanisms associated to S. aureus-host cell interactions will undoubtedly helpto discover novel targets to treat staphylococcal infections.
EMBO
Villars sur Ollon, Switzerland

hal-01454214
https://hal.archives-ouvertes.fr/hal-01454214
PRODINRA : 171657

Éditeur(s) : Springer
Résumé : Batch culture experiments using viral enrichment were conducted to test the response of a coastal bacterial community to autochthonous (i.e., co-existing) or allochthonous riverine viruses. The effects of viral infections on bacterial dynamics and activity were assessed by epifluorescence microscopy and thymidine incorporation, respectively, whereas the effect of viral infection on bacterial community composition was examined by polymerase chain reaction-single strand conformation polymorphism 16S ribosomal RNA fingerprinting. The percentages of high nucleic acid-containing cells, evaluated by flow cytometry, were significantly correlated (r (2) = 0.91, n = 12, p < 0.0001) to bacterial production, making this value a good predictor of active cell dynamics along the study. While confinement and temperature were the two principal experimental factors affecting bacterial community composition and dynamics, respectively, additions of freshwater viruses had significant effects on coastal bacterial communities. Thus, foreign viruses significantly reduced net bacterial population increase as compared to the enrichment treated with inactivated virus. Moreover, freshwater viruses recurrently and specifically affected bacterial community composition, as compared to addition of autochthonous viruses. In most cases, the combined treatment viruses and freshwater dissolved organic matter helped to maintain or even enhance species richness in coastal bacterial communities in agreement to the 'killing the winner' hypothesis. Thus, riverine virus input could potentially influence bacterial community composition of the coastal bay albeit with modest modification of bulk bacterial growth.
Microbial Ecology (0095-3628) (Springer), 2009-02 , Vol. 57 , N. 2 , P. 295-306

Droits : 2009 Springer
http://archimer.ifremer.fr/doc/2009/publication-6636.pdf
DOI:10.1007/s00248-008-9428-1
http://archimer.ifremer.fr/doc/00000/6636/

Éditeur(s) : Université de Montpellier II
Résumé : Penaeid family shrimp constitute the first aquaculture product in the world in terms of commercial value. They are produced in third world countries of the sub-equatorial belt. Among the causes limiting their production, one is the presence of the WSSV (White Spot Syndrome Virus), a pathogenic agent that produces massive mortality. Our aim was to investigate the first stages of the viral infection, in order to be used as target of prophylactic actions. A fish cell line (SSN-1) was used as model to tentatively develop in vitro studies. Only defective particles were produced confirming the high specificity to crustacea of the infection with crustacean virus. Electron microscopy showed structural similarities between the WSSV and B, B2 and Baculo-B viruses of crabs. This suggests B2 may belong also to the family Nimaviridae, genus Whispovirus. This comparison with B2 virus gives the possibility to understand the role played by the tail-like extension of these viruses in the infectious process by attachment to the plasmic membrane at the beginning of the infection in its specific host.
Les crevettes de grande taille de la famille des Penaeidae constituent le premier produit aquacole en valeur commerciale à l'échelle planétaire. Elles sont produites à 99% dans les pays en voie de développement de la ceinture sub-équatoriale. Parmi les causes limitant leur production, le White Spot Syndrome Virus est l'agent pathogène ayant provoqué le plus des pertes dans le monde. Notre étude a été orientée vers la reconnaissance des premiers stades de l'infection, susceptibles d'être la cible d'une action prophylactique. Nous avons testé l'utilisation d'une lignée cellulaire de poisson SSN-1 afin d'étudier les possibilités d'un développement in vitro. Seules des particules défectives ont été produites confirmant la haute spécificité des infections à virus de crustacés. Les recherches en microscopie électronique ont montré une similarité structurale du WSSV avec les virus (B, B2 et Baculo-B) des crabes. Ceci suggère que ces agents (B2 et WSSV) seraient tout deux de la famille des Nimaviridae et du genre Whispovirus. La comparaison avec le virus B2 permet de comprendre le rôle clef joué par la partie caudale de ces virus dans l'infection par son attachement à la membrane plasmique lors de l'infection chez son hôte spécifique.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2008/these-6650.pdf
http://archimer.ifremer.fr/doc/00000/6650/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
IntroductionLeishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now.Methodology/Principles findingsWe subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%±23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates.Conclusions/SignificanceHere, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients.
ISSN: 1935-2727

pasteur-01583523
https://hal-riip.archives-ouvertes.fr/pasteur-01583523
DOI : 10.1371/journal.pntd.0005764
PUBMED : 28715422

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.
ISSN: 0934-9723

inserm-00872789
http://www.hal.inserm.fr/inserm-00872789
DOI : 10.1007/s10096-012-1730-7
PUBMED : 22930407

Éditeur(s) : HAL CCSD
Résumé : International audience
Background Mycobacterium ulcerans infection is the third most common mycobacterial disease in the world after tuberculosis and leprosy. To date, transmission pathways from its environmental reservoir to humans are still unknown. In South America, French Guiana has the highest reported number of M ulcerans infections across the continent. This empirical study aimed to characterise the epidemiology of M ulcerans infection in French Guiana between 1969 and 2013.MethodsData were collected prospectively mainly by two dermatologists at Cayenne Hospital’s dermatologydepartment between Jan 1, 1969, and Dec 31, 2013, for age, date of diagnosis, sex, residence, location of the lesion,type of lesion, associated symptoms, and diagnostic method (smear, culture, PCR, or histology) for all confirmed andsuspected cases of M ulcerans. We obtained population data from censuses. We calculated mean M ulcerans infectionincidences, presented as the number of cases per 100 000 person-years.Findings 245 patients with M ulcerans infections were reported at Cayenne Hospital’s dermatology department duringthe study period. M ulcerans infection incidence decreased over time, from 6·07 infections per 100 000 person-years(95% CI 4·46–7·67) in 1969–83 to 4·77 infections per 100 000 person-years (3·75–5·79) in 1984–98 and to3·49 infections per 100 000 person-years (2·83–4·16) in 1999–2013. The proportion of children with infections alsodeclined with time, from 42 (76%) of 55 patients in 1969–83 to 26 (31%) of 84 in 1984–98 and to 22 (21%) of 106 in1999–2013. Most cases occurred in coastal areas surrounded by marshy savannah (incidence of 21·08 per100 000 person-years in Sinnamary and 21·18 per 100 000 person-years in Mana). Lesions mainly affected limbs (lowerlimbs 161 [66%] patients; upper limbs 60 [24%] patients). We diagnosed no bone infections.Interpretation The decrease of M ulcerans infection incidence and the proportion of children with infections over a45 year period in this ultra-peripheral French territory might have been mostly driven by improving living conditions,prophylactic recommendations, and access to health care.
The Lancet Planetary Health

inserm-01545603
http://www.hal.inserm.fr/inserm-01545603
http://www.hal.inserm.fr/inserm-01545603/document
http://www.hal.inserm.fr/inserm-01545603/file/2017%2C%20Douine%20-%20Mycobacterium%20ulcerans%20infection%20%28Buruli%20ulcer%29.pdf
http://www.hal.inserm.fr/inserm-01545603/file/Comments.pdf

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated. OBJECTIVE: To assess whether human HSCs are susceptible to HCV infection. DESIGN: We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs. RESULTS: In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication. CONCLUSIONS: Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.
ISSN: 0017-5749

hal-01063909
https://hal.archives-ouvertes.fr/hal-01063909
DOI : 10.1136/gutjnl-2013-305634
PUBMED : 25063678

Éditeur(s) : HAL CCSD
Résumé : ABSTRACT Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. The exact reasons of the propensity of sickle cell patients to infection are not clear and are matter of debate. Besides, there is a striking variability of the clinical course of the disease between patients. This drew many scientists' attention. Genetic factors have been investigated as potential factor risks for infection in sickle cell patients, for example: HLA system; genes encoding Fc Human Immunoglobulin G receptor IIA, mannose-binding protein, and myeloperoxidase. Associations have been found, but all scientists agree that investigations have to be furthered. We investigated an association between HLA DRB1 and DQB1 polymorphism and infectious complications in sickle cell patients. Genotype frequencies were different between cases and controls for DRB1 locus. Indeed, HLA-DRB1*11 frequency was significantly higher in patients without infections than in patients with infections (χ² = 5.02; p = 0.025).
https://hal.archives-ouvertes.fr/hal-00387082

hal-00387082
https://hal.archives-ouvertes.fr/hal-00387082
https://hal.archives-ouvertes.fr/hal-00387082/document
https://hal.archives-ouvertes.fr/hal-00387082/file/MO_JOANNES_et_al_HLA_and_SCD.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. METHODOLOGY/PRINCIPAL FINDINGS: Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. CONCLUSIONS: Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.
ISSN: 1932-6203

hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945/document
https://hal.archives-ouvertes.fr/hal-00876945/file/Impactsur Short-Term-accepted.pdf
DOI : 10.1371/journal.pone.0037348

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33.
ISSN: 1932-6203

hal-00874120
https://hal.archives-ouvertes.fr/hal-00874120
https://hal.archives-ouvertes.fr/hal-00874120/document
https://hal.archives-ouvertes.fr/hal-00874120/file/Pathogenic_Mouse_Hepatitis-accepted.pdf
DOI : 10.1371/journal.pone.0074278