http://hdl.handle.net/2268/104 Search this channel search http://orbi.ulg.ac.be/simple-search http://hdl.handle.net/2268/148093 Title: Leptospira spp. prevalence in small mammal populations in Cotonou, Benin <br/> <br/>Author, co-author: Houemenou, Gualbert; Ahmed, A.; Libois, Roland; Hartskeerl, R.A. <br/> <br/>Abstract: The aim of this study was to assess the Leptospira prevalence in small animals in Cotonou, the capital of Benin. Rodents and shrews were captured in urban and periurban settings and determined as species of the genera Rattus, Mastomys, and Crocidura. Kidney specimens of 90 animals were examined using a real-time PCR assay specific for leptospires that belong to pathogenic species. Leptospiral DNA was amplified from kidney tissues ranging from 13.3% (8/60) in Rattus rattus to 100.0% (1/1) in Crocidura spp. with an average of 18.9% (17/90) of the animals caught at 15 locations. Clade-specific Taqman PCR on 10 samples placed six of these within clade 1 comprising the species L. kirschneri, L. interrogans, L. meyeri, and L. noguchii and four within clade 2 consisting of species L. weilii, L. alexanderi, L. borgpetersenii, and L. santarosai. Phylogenetic analysis of partial sequences of the amplicons of seven samples of these 10 samples revealed that four of the clade 1 samples could equally be assigned to L. interrogans and L. kirschneri and three samples fromclade 2 belonged to L. borgpetersenii. Results presented in the paper indicate that small mammals present a major public health risk for acquiring leptospirosis in Cotonou, Benin and will contribute to a raised awareness amongst health care workers and decision makers and hence promote appropriate clinical management of cases. Wed, 08 May 2013 19:09:17 GMT http://hdl.handle.net/2268/147917 Title: NEONATAL INVASIVE GROUP B STREPTOCOCCAL (GBS) INFECTIONS IN EUROPE <br/> <br/>Author, co-author: MELIN, Pierrette; Berner, Reinhard; Afshar, Baharak; Baldassarri, Lucilla; Detcheva, Antoaneta; de la Rosa, Manuel; Kunze, Mirjam; Kriz, Paula; Efstratiou, Androulla; Hufnagel, Markus; Kilian, Mogens; SEIDEL, Laurence; Telford, John <br/> <br/>Abstract: Objectives: To describe clinical characteristics and capsular type of GBS isolates responsible of invasive infections in infants from Belgium, Bulgaria, Czech-Republic, Denmark, Germany, Italy, Spain and United Kingdom, representing one of the main objectives of the DEVANI (DEsign of a Vaccine Against Neonatal Infections) project. Methods: Surveillance of invasive GBS infections in infants was performed from mid-2008 through December 2010. For each case, a standardized case report form was filled. Samples from cases were processed using local procedures. GBS isolates were characterised in national central labs using standardised type-specific (Ia, Ib-IX) latex agglutination and molecular typing methods. Results: Data on 188 infants with invasive infection were analysed: 144 (60.6%) early onset diseases (EOD) and 74 (39.4%) late onset diseases (LOD). In EOD, mean/median ages at onset were 14/0 hours and the male:female ratio was 1.25. The predominant manifestation at onset was respiratory distress (42% cases); 83% cases were associated with sepsis/bacteremia, 15% with pneumonia and 6% with meningitis. Late-prenatal screening cultures were obtained from 51% of cases’ mothers and only half of these were positive for GBS. Non-elective C-section, intrapartum fever and rupture of membrane (>18h) were more frequent in EO-cases’ mothers versus healthy babies’ GBS-positive mothers. The major serotypes were III (43%), V (21%) and Ia (18%). In LOD, mean/median ages at onset were 42/34 days and the male:female ratio was 0.9. The predominant characteristic at onset was fever (62% cases); 70% cases were associated with sepsis and 30% with meningitis. Very rare manifestations were osteomyelitis and cellulitis. Serotype III was highly predominant (80.6%) followed mainly by Ia (12.5%). Death rates were 4.7/1.5% in EOD/LOD. Conclusions: Clinical presentations were associated with age at onset of infection. Serotype III predominated in neonatal infections. Prenatal screening was not universal neither sensitive. Study funded through the European Commission Seventh Framework. Mon, 06 May 2013 06:46:03 GMT http://hdl.handle.net/2268/147905 Title: Pili genes pattern in Group B streptococci from newborn infections and pregnant women in Europe (DEVANI Project) <br/> <br/>Author, co-author: Imperi, Monica; Rinaudo, Daniela; Creti, Roberta; Pataracchia, Marco; Rosini, Roberto; Nuccitelli, Annalisa; Kriz, Paula; Kilian, Mogens; Hufnagel, Markus; Efstratiou, Androulla; de la Rosa, Manuel; MELIN, Pierrette; Detcheva, Antoaneta; Baldassarri, Lucilla; Maione, Domenico <br/> <br/>Abstract: Objectives Evaluation of the presence and expression of genes coding for pili in a collection of group B streptococcci (GBS) isolated from newborn infection and pregnant women in the course of the DEVANI (Design of a Vaccine Against Neonatal Infection) project. Methods GBS isolates from pregnant women (PW) and cases of newborn infection (NI) were collected in 8 European countries (Belgium, Bulgaria, Czech Republic, Denmark, Germany, Italy, Spain, United Kingdom) during 2009/10 under the auspices of DEVANI. Total no. of strains examined was 1078 and 192 from PW and NI, respectively. Isolates were screened by multiplex PCR and FACS analysis to evaluate respectively gene presence and surface-exposure of pili. Results The most common gene patterns found were PI-2a alone, PI 1+2a and PI 1+2b, while the PI-2b gene alone was very rare. The most prominent result was that a majority of isolates from NI carried the PI-1+2b gene pattern, while the most common pattern among PW was PI-1+2a. Most of analyzed strains express at least one pilus on their surface. Conclusions All isolates contained at least one gene coding for pili. When present pili 2a and 2b were highly surface exposed. Sat, 04 May 2013 21:08:01 GMT http://hdl.handle.net/2268/147904 Title: Group B streptococci, a European perspective with results of the DEVANI project <br/> <br/>Author, co-author: MELIN, Pierrette <br/> <br/>Abstract: In 2011, neonatal group B streptococcal (GBS) diseases remain a global public health concern. Where consensus guidelines to detect and treat intrapartum women with GBS colonization have been widely adopted, incidence of neonatal early onset disease (EOD) has dramatically declined, however despite preventive strategies cases still occur. The strategy was not expected to prevent all cases and there are challenges and limitations to this preventive approach. The best strategy for European countries is still a matter of debate and intrapartum antimicrobial prophylaxis (IAP) is not widely recommended. To adopt the best preventive strategy, we first need better data assessing more accurately the true burden of GBS diseases in the different countries. Furthermore, as the current screening-based strategy for prevention is highly effective but imperfect, given the challenges, limitations and potential complications of maternal IAP, a new approach is still needed. Maternal immunization against GBS is an attractive alternative for the prevention of not only neonatal diseases but also stillbirths and maternal diseases. Vaccines against GBS may likely become the most effective and sustainable long-term preventive strategy. But the development of vaccines with global relevance has been hampered by changes in the distribution of GBS serotypes of strains causing diseases over time and in different parts of the world. A multivalent vaccine to cover against the more prevalent serotypes suitable for European populations might not be suitable for Asian or African populations. To overcome type-specificity, new developments target vaccines based on conserved surface antigenic proteins, such as Sip protein located at the cell surface of all GBS and on immunogenic proteins from GBS pili. A pilus-based GBS vaccine is appealing and could become a globally relevant reality. The DEVANI (DEsign of a Vaccine Against Neonatal Infections) programme funded through the European Commission Seventh Framework was launched on 1 January 2008 with the key objective being the assessment of European GBS epidemiology to facilitate the design of a new vaccine that will confer neonatal immunity through a durable maternal immune response. A major component was to undertake pan European surveillance of maternal colonisation, maternal GBS antibody responses and neonatal diseases in eight European countries. Through 2009 and 2010, all Belgian laboratories sending any neonatal GBS invasive isolate to the National Reference Centre for GBS were invited to bring their contribution to this project. Belgium, Bulgaria, Czech Republic, Denmark, Germany, Italy, Spain and the United Kingdom established specific GBS screening studies during 2008/10. Maternal vaginal/rectal swabs and sera were taken between 34-37 weeks gestation and processed using a standardised microbiological screening protocol. Samples from neonatal cases were processed using local procedures. For each pregnant woman and each case of GBS neonatal disease, standardized case report forms were filled. GBS isolates were characterised using standardised serological and molecular typing methods for detection of all ten GBS capsular polysaccharide types (Ia to IX). Furthermore all the collected isolates were screened by multiplex PCR and FACS analysis to evaluate respectively gene presence and surface-exposure of pili. And clonal analysis of these isolates was performed using multi-locus sequence typing (MLST). The main microbiological results of this pan European surveillance are following. Carriage rates among pregnant women in all countries ranged from 8% to 26%. The most common GBS capsular types were III (33%), Ia (25%) and V (8%). Among GBS from EOD, the major serotypes were III (43%), V (21%) and Ia (18%). In contrast among GBS isolated from neonatal late onset disease (LOD), serotype III was highly predominant (80.6%) followed mainly by Ia (12.5%). Analysis of the pattern of pili genes showed that all isolates contained at least one gene coding for pili. The most common gene patterns found were PI-2a alone, PI 1+2a and PI 1+2b, while the PI-2b gene alone was very rare. The most prominent result was that a majority of isolates from neonatal infections carried the PI-1+2b gene pattern, while the most common pattern among pregnant women was PI-1+2a. Most of analyzed strains express at least one pilus on their surface. The clonal analysis showed that 66 sequence types were found to belong to nine clonal complexes (CC). Among these nine CCs, five were prevailing and covered 92 % of GBS isolates tested. The GBS population in pregnant women was found to be more heterogeneous than the GBS isolated from neonatal infection cases. Among neonatal isolates, the most frequent CC was CC17 (43 %) known as a highly virulent clone. Among participating countries, there were no significant differences in the occurrence of clonal complexes. The analysis of the levels of specific antibodies as surrogate markers of protection is still ongoing. More detailed and additional results as the main conclusions will be presented. Sat, 04 May 2013 13:47:53 GMT http://hdl.handle.net/2268/147903 Title: GBS colonization and screening in pregnancy: how does it work in Europe? <br/> <br/>Author, co-author: MELIN, Pierrette <br/> <br/>Abstract: In Europe, as in North America, GBS infections among infants are associated to high morbidity and mortality even if some differences exist between different European countries. During the past two decades, major initiatives have been proposed to prevent early onset GBS disease (EOD) and they are still subject of controversy. Several European countries have issued guidelines for the prevention of neonatal GBS diseases, either universal screening-based or risk-based strategy, others have no official guidelines at all. In countries having guidelines, despite considerable efforts and economic resources spent on intrapartum antimicrobial prophylaxis for GBS EOD, cases continue to occur. Among these cases there are a lot of missed opportunities to administer IAP but there are also false negative screening. Therefore in the setting of a maternal GBS-screening program and successful implementation of the strategy, efforts to improve screening for GBS status remain important. The natural reservoir for GBS is the gastrointestinal tract and is likely the source for vaginal colonization. Among pregnant women, GBS carriage rate in the vaginal and rectal flora ranges from 10% up to 30%. Critical factors that influence the accuracy of detecting GBS maternal colonization are the choice of the body sites sampled, the timing of sampling and the use of selective culture media. The evolution of the different culture options to improve the GBS-screening strategy will be reviewed. If the optimal time for performing antenatal cultures is between 35 to 37 weeks’ gestation, as GBS carriage is highly variable, the predictive values of GBS antenatal cultures are not always as good predictors of the maternal GBS status at presentation for delivery as expected. Potential alternative to antenatal GBS-screening culture is the identification of GBS colonization at presentation for delivery. Use of a reliable, sensitive, easy to use rapid test should be cost effective leading to the prevention of more EOGBS cases while reducing the number of unnecessarily IAP. Advances of polymerase chain reaction (PCR) and fluorescence labeling technologies has provided new detection tools for bacterial identification. Therefore, commercialization of rapid detection of GBS through real-time PCR offers the potential for GBS detection among women without prenatal care or those in whom no antenatal culture was collected. However questions of costs and logistics remain unanswered. Could such rapid intrapartum test replace existing screening strategies or could it be used in conjunction with them? Colonizing rates and recommended screening procedures existing through Europe will be reviewed. Sat, 04 May 2013 13:35:11 GMT http://hdl.handle.net/2268/147897 Title: GBS AND THE NEONATE: PREVENTION STRATEGIES <br/> <br/>Author, co-author: MELIN, Pierrette <br/> <br/>Abstract: Streptococcus agalactiae, or group B streptococcus (GBS), remains the leading cause of neonatal sepsis and meningitis, early onset and late onset diseases (EOD, LOD). Where consensus guidelines to detect and treat intrapartum women with GBS colonization have been widely adopted, incidence of neonatal EOD has dramatically declined. In response to both successful impacts on the incidence of GBS-EOD and analyses of missed opportunities, the first American guidelines for prevention issued in the 90s have since been adapted in several stages to improve their efficacy. In some countries in Europe, nationwide guidelines, whether screening-based or risk-based, for the prevention of neonatal GBS diseases have also been issued and adopted, with the expected impact on incidence of GBS-EOD. In spite of universal screening, in spite of the great progress that has been made, GBS-EOD continues to occur and the GBS burden remains a significant public health issue. Continuous efforts to improve screening for GBS status continue to be important and may be able to take advantage of new rapid diagnostic technologies. The current screening-based strategy for prevention is highly effective but imperfect. Given the challenges, limitations and potential complications of maternal intrapartum prophylaxis, a new approach is still needed. Maternal immunization against GBS is an attractive alternative for the prevention of not only neonatal diseases but also stillbirths and maternal diseases. Vaccines against GBS may likely become the most effective and sustainable long-term preventive strategy. Sat, 04 May 2013 11:18:38 GMT http://hdl.handle.net/2268/147651 Title: Human papillomavirus capsids trigger crosstalk between dendritic and NK cells <br/> <br/>Author, co-author: Langers, Inge; Renoux, Virginie; Pirotte, Zoé; Dortu, Estelle; BONIVER, Jacques; DELVENNE, Philippe; Jacobs, Nathalie <br/> <br/>Abstract: The immune system controls, at least partially, human papillomavirus (HPV) infection and subsequent tumour development as demonstrated by a higher tumour prevalence in immunodeficient patients. More than 90% of HPV-infected women will clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and although dendritic cells (DC) and NK cells play a key role in host resistance to virus and tumour, no study has been performed evaluating their crosstalk in this context. Virus-like particles (VLP) formed by the HPV major capsid protein L1 are licensed as vaccine against cervical cancer and we have recently shown that NK cells can directly interact with these HPV-VLP [1]. Here, we investigated the impact of this activation on NK-DC crosstalk. Interestingly, NK cells increase DC maturation induced by HPV-VLP as shown by an up-regulation of HLA-DR and CD86 on DC. Transwell experiments indicated that the expression of HLA-DR is cell-cell contact and soluble factor dependent, whereas only soluble factors seem to be required for CD86 expression. Moreover, in the presence of HPV-VLP and NK cells, DC produce higher amounts of IL12p70, while the production of the immunosuppressive cytokine IL10 remains unchanged. We also demonstrated that DC can up-regulate the expression of NK activation markers (CD69 and HLA-DR) in the presence of HPV-VLP. This up-regulation requires both cell-cell contact and soluble factors. Regarding HLA-DR marker, the increased expression on CD56bright cells is mediated by soluble factors, whereas cell-cell contacts are also important for HLA-DR expression on CD56dim cells. In the presence of DC activated by HPV-VLP, the function of NK cells is also modified since they become more cytotoxic against HPV+ cell line and secrete more IFN-γ. Our results suggest that NK-DC crosstalk could play a role in the immune response induced by HPV-VLP during vaccination protocols against cervical cancer. Mon, 29 Apr 2013 13:45:16 GMT http://hdl.handle.net/2268/147646 Title: A cross-sectional study to assess knowledge about HIV/AIDS transmission and prevention measures in company workers in Ecuador <br/> <br/>Author, co-author: Cabezas Guerra, Maria del Carmen; Fornasini, Marco; Dardenne, Nadia; Borja, Teresa; Albert, Adelin <br/> <br/>Abstract: Background: HIV/AIDS was first reported in Ecuador in 1984 and its prevalence has been increasing ever since. In 2009, the National AIDS Program reported 21,810 HIV/AIDS cases and confirmed that the worker population was amongst the most affected groups. The objective of this study was to assess knowledge about HIV transmission and prevention measures in company workers in Ecuador. Methods: A cross-sectional survey based on a random sample of 115 companies (1,732 workers), stratified by three large provinces and working sectors (commerce, manufacturing and real estate) was conducted. A validated instrument developed by Family Health International was used to evaluate HIV prevention knowledge and common local misconceptions about HIV transmission. Descriptive statistics, chi square test and logistic regression analysis were performed using SAS. Results: Incorrect knowledge about HIV/AIDS transmission were found in 49.1% (95% CI: 46.6-51.6) of subjects. Incorrect knowledge was higher among males (OR=1.73 [1.39 –2.15]), older subjects (OR=1.35 [1.02 – 1.77]), subjects with lower education (OR=3.72 [2.44 – 5.65]), manual labor workers (OR=2.93 [1.82 – 4.73]) and subjects without previous exposure to HIV intervention programs (OR=2.26 [1.79 – 2.86]). Incorrect knowledge about preventive measures was found among 32.9% (95%CI: 30.6-35.2) of respondents. This proportion was higher among subjects with lower education (OR=2.28 [1.52 – 3.43]), married subjects (OR=1.34 [1.07 – 1.68]), manual labor workers (OR=1.80 [1.34 – 2.42]), and subjects not previously exposed to HIV intervention programs (OR=1.44 [1.14 – 1.83]). Conclusions: HIV intervention programs targeting company workers are urgently needed to improve knowledge and reduce HIV transmission in Ecuador. Mon, 29 Apr 2013 13:22:14 GMT http://hdl.handle.net/2268/147558 Title: La neuroinvasion dans les maladies à prions: étude de l'interface neuroimmune FDC - système nerveux sympathique <br/> <br/>Author, co-author: Demonceau, Caroline <br/> <br/>Abstract: Prion diseases are neurodegenerative diseases affecting the central nervous system (CNS) wherein the PrPd disease-associated prion infectious agent is an abnormal isoform of PrPc host-encoded cellular prion protein. The process through which the prion infectious agent is transferred to the CNS, the neuroinvasion, is still unknown, but secondary lymphoid organs seem to play an important role in prion amplification prior the invasion of the associated peripheral nervous system (PNS). In particular, modifications of follicular dendritic cells (FDC) and sympathetic nervous system (SNS) of lymphoid organs could influence the speed of neuroinvasion, and thus the length of the disease incubation period. It was shown that the lack of mature FDC prevents the replication of the infectious agent in secondary lymphoid organs. Likewise, sympathectomy delays the onset of the disease, and enhances sympathetic innervation reduces the incubation period. In mice, the relative positioning of FDC and sympathetic neural fibres plays a role in the incubation period following scrapie inoculation. This study thus focuses on the neuroimmune interface between FDC and sympathetic neural fibres. First, the number of close interactions between FDC and sympathetic neural fibres of five mouse strains with the same Prnpa genotype was estimated to check if it could explain the different incubation period observed after inoculation of primary bovine spongiform encephalopathy (BSE) infected-brain. Then we checked if scrapie infection, by oral or intraperitoneal route, could influence this neuroimmune interface between FDC and sympathetic neural fibres within Peyer’s patches (PP) and spleen of the C57BL/6 mouse strain. In the first part of this work, co-localizations between FDC and sympathetic neural fibres were observed in vivo within germinal centers (GC) of mouse spleen. Among the five mouse strains exhibiting the same Prnpa genotype, three strains (RIII-1, RIII-2 and 129/Ola) showed an incubation period about 100 days shorter than those of C57BL and C57BL/6 mouse strains when inoculated with primary BSE. Moreover, amplification by FDC seems an obligatory process before subsequent neuroinvasion as an intracerebral inoculation doesn’t reduce the incubation period observed with an intraperitoneal inoculation. A meticulous analysis revealed that the density of close interactions between FDC and sympathetic neural fibres is not higher for the three mouse strains with a shorter incubation period. However, these three mouse strains with a shorter incubation period after primary BSE inoculation have a higher proportion of FDC networks with close interactions than the mouse strains with a longer incubation period. These results suggest that it is not the quantity of sympathetic neural fibres close to FDC, but rather the percentage of FDC with close sympathetic neural endings that could influence the incubation period of prions diseases. In the second part of this work, it came out that prion infection did not result in neuronal loss within the PNS like observed in the CNS, and also did not modify the FDC-SNS neuroimmune interface of secondary lymphoid organs where PrPd deposits are observed within germinal centers. For a single mouse strain orally infected with scrapie, neither FDC networks hypertrophy nor sympathetic neural fibres closer than 10 μm from a FDC network were observed within GC of PP. Moreover, in our conditions, the prion strain did not seem to alter the neuroimmune interface between FDC and SNS in PP that could explain the different incubation periods observed with the 139A and ME7 scrapie strains. To check if prion infection does not modify the FDC-SNS neuroimmune interface, close interactions between FDC and sympathetic neural fibres already shown in the spleen were analyzed in the same mouse strain intraperitoneally infected with the 139A scrapie strain. In that case as well, no differences were observed in FDC network hypertrophy, in the in vivo density of sympathetic neural fibres closer than 10 μm from a FDC network, or in the proportion of well innervated FDC networks, compared to control mice. An in vitro model of coculture of splenic FDC from the same C57BL/6 mouse strain with nerve cells from dorsal root ganglia (DRG) also yielded similar results. FDC isolated from scrapie 139A infected mice exhibited the same neuritogenic or neurotrophic effects than FDC isolated from control mice. During these experiments, it was also noted that young-adult or middle-age mice showed both the same mean density of close interactions between FDC and SNS. However, with age, even if the splenic volume occupied by FDC networks halved, the proportion of FDC networks with close interactions almost doubled. It would be very interesting to check this last parameter in old mice that show some delay in neuroinvasion of prion disease but also to evaluate if this percentage of well innervated FDC network contributes to the prion pathogenesis within the spleen. In conclusion, scrapie 139A and ME7 strains don’t modify FDC-SNS neuroimmune interface of secondary lymphoid organs, not allowing explaining the different incubation period observed with equivalent infectious doses. Moreover, following an oral inoculation of prion, neuroinvasion within PP would not involve direct contact between FDC and sympathetic nerves, but rather another process still to be determined or implying other nerve fibres and/or mobile cells such as macrophages or dendritic cells. However, in the spleen, the percentage of FDC networks with close sympathetic neural fibres – rather than the number of sympathetic neural fibres close to the FDC network – observed for a given age, species and Prnp genotype at the time of inoculation could play a role in the different incubation periods observed for the same prion strain. The cellular compounds involved in the specific FDC microenvironment still have to be determined for each cell implied in the neuroinvasion process.; Les maladies à prions sont des maladies neurodégénératives du système nerveux central (SNC) où l’agent infectieux prion PrPd associé à la maladie est une isoforme anormale de la protéine prion cellulaire PrPc de l’hôte. Le processus par lequel l’agent infectieux prion est transféré au SNC, la neuroinvasion, est toujours inconnu à ce jour, mais les organes lymphoïdes secondaires semblent jouer un rôle important d’amplification du prion préalable à l’envahissement du système nerveux périphérique (SNP) associé. Plus particulièrement, des modifications au niveau des cellules folliculaires dendritiques (FDC) et du système nerveux sympathique (SNS) des organes lymphoïdes peuvent influencer la vitesse de neuroinvasion, et donc la durée des périodes d’incubation de la maladie. L’absence de FDC matures empêche la réplication de l’agent infectieux dans les organes lymphoïdes secondaires. De même, une sympathectomie retarde l’apparition de la maladie, et une hyper-innervation sympathique raccourcit la période d’incubation. Chez la souris, il a même été montré que la distance relative entre les FDC et les fibres nerveuses sympathiques jouait un rôle dans la période d’incubation suite à une inoculation par la tremblante. Dans ce travail, nous avons donc analysé principalement l’interface neuroimmune entre les FDC et les fibres nerveuses sympathiques. D’abord, nous avons voulu vérifier si le nombre d’interactions proches entre FDC et fibres nerveuses sympathiques chez cinq lignées de souris avec le même gène Prnpa pouvait être la cause des différentes périodes d’incubation observées lors d’une inoculation primaire à l’encéphalopathie spongiforme bovine (ESB). Ensuite, nous avons voulu savoir si l’infection par la tremblante, par voie orale ou intrapéritonéale, pouvait modifier cette interface neuroimmune entre les FDC et les fibres nerveuses sympathiques au niveau des plaques de Peyer et de la rate chez la lignée de souris C57BL/6. Lors de la première série d’expériences, des colocalisations entre les FDC et les fibres nerveuses sympathiques ont été mises en évidence in vivo dans les centres germinatifs (GC) de la rate de souris. Parmi cinq lignées de souris ayant un génotype Prnpa identique, trois lignées (RIII-1, RIII-2 et 129/Ola) ont montré une période d’incubation plus courte d’environ 100 jours que celle de deux autres (C57BL et C57BL/6) après une inoculation primaire de l’agent ESB. De plus, l’amplification par les FDC semble être obligatoire avant le processus de neuroinvasion ultérieure puisqu’une inoculation intracérébrale ne réduit pas la période d’incubation observée lors de l’inoculation intrapéritonéale. Une analyse détaillée a révélé que la densité d’interactions proches entre FDC et fibres nerveuses sympathiques n’est pas plus élevée pour les trois lignées de souris avec une plus courte période d’incubation. Par contre, ces trois lignées de souris à courte période d’incubation pour l’ESB primaire ont une proportion de réseaux FDC avec des interactions proches plus élevée que les lignées de souris avec une plus longue période d’incubation. Ces résultats suggèrent donc que ce n’est pas la quantité de fibres nerveuses sympathiques proches des FDC, mais plutôt le pourcentage de FDC avec des terminaisons nerveuses sympathiques proches qui pourrait influencer la période d’incubation des maladies à prions. De la deuxième série d’expériences, il ressort que l’infection prion ne provoque pas, dans nos conditions expérimentales, une perte neuronale du SNP comme observé dans le SNC, et surtout ne modifie pas l’interface neuroimmune FDC-SNS des organes lymphoïdes secondaires où des dépôts PrPd sont bien observés au niveau des centres germinatifs. En effet, pour une même lignée de souris infectées par voie orale par la tremblante, ni une hypertrophie des réseaux FDC, ni des fibres nerveuses sympathiques éloignées de moins de 10 μm d’un réseau FDC n’ont été observées au niveau des centres germinatifs des plaques de Peyer (PP). De plus, la souche prion ne semble pas induire une interface neuroimmune différente entre FDC et SNS au niveau des PP pouvant expliquer les différentes périodes d’incubation observées pour les souches tremblantes 139A et ME7. Afin de vérifier que l’infection prion ne modifie pas l’interface neuroimmune FDC-SNS, les interactions proches entre FDC et fibres nerveuses sympathiques déjà observées au niveau de la rate ont été analysées pour la même lignée de souris infectées par voie intrapéritonéale uniquement par la tremblante 139A. Dans ce cas aussi, aucune différence par rapport aux souris contrôles n’a été observée pour l’hypertrophie des réseaux FDC, la densité de fibres nerveuses sympathiques éloignées de moins de 10 μm d’un réseau FDC in vivo, ou la proportion de réseaux FDC bien innervés. Un modèle in vitro de co-culture de FDC isolés de rate de la même lignée de souris C57BL/6 avec des cellules nerveuses issues de ganglions de la racine dorsale (DRG) a également donné des résultats dans ce sens. Les FDC provenant de souris infectées par la tremblante 139A ont des effets neuritogène ou neurotrophique identiques à ceux des FDC de souris contrôles. De ces deux séries d’expériences, il ressort aussi que des souris jeunes ou adultes présentent la même densité moyenne de fibres nerveuses sympathiques proches par volume de FDC. Cependant, avec l’âge, même si le volume de rate occupé par les réseaux FDC a diminué d’environ de moitié, la proportion de réseaux FDC avec des fibres nerveuses proches a presque doublé. Il serait donc intéressant de vérifier ce dernier paramètre chez des souris âgées ayant montré un retard dans la neuroinvasion des maladies à prions et ainsi voir si cette proportion de FDC bien innervés participe effectivement à la pathogenèse du prion au niveau de la rate. En conclusion, les souches tremblantes 139A et ME7 ne semblent pas modifier pas l’interface neuroimmune FDC et SNS des organes lymphoïdes secondaires, ce paramètre ne peut dès lors pas expliquer les périodes d’incubation différentes observées pour des doses infectieuses équivalentes. De plus, suite à une inoculation orale de l’agent infectieux prion, la neuroinvasion au niveau des PP n’impliquerait pas des contacts directs entre les FDC et les nerfs sympathiques, mais plutôt un autre processus encore à découvrir et faisant intervenir par exemple d’autres types de fibres nerveuses et/ou des cellules mobiles telles que les macrophages ou les cellules dendritiques. Par contre, au niveau de la rate, la proportion de FDC avec des fibres nerveuses sympathiques proches - plutôt que le nombre de fibres nerveuses sympathiques à proximité des FDC - établie pour un âge, une espèce et un génotype Prnp donnés au moment de l’infection, pourrait jouer un rôle dans les différentes périodes d’incubation observées pour une même souche prion. Les composants cellulaires impliqués dans le microenvironnement spécifique des FDC doivent encore être déterminés pour chaque type cellulaire impliqué dans le processus de neuroinvasion. Mon, 29 Apr 2013 09:10:04 GMT http://hdl.handle.net/2268/147512 Title: Pharma-clinics. Comment je traite ... Une infection par le VIH. II. Inhibiteurs nucléosidiques de la transcriptase reverse <br/> <br/>Author, co-author: Moutschen, Michel; Nkoghe, D.; Leonard, Philippe; Demonty, Jean Sun, 28 Apr 2013 19:59:52 GMT http://hdl.handle.net/2268/147511 Title: Pharma-clinics le médicament du mois. La nevirapine. Viramune <br/> <br/>Author, co-author: Nkoghe, D.; Leonard, Philippe; Moutschen, Michel; Demonty, Jean <br/> <br/>Abstract: Nevirapine is the first non nucleoside reverse transcriptase inhibitor registered in Belgium and indicated in the treatment of HIV-1 infection. In association with 2 nucleoside analogues, its efficiency is similar to a tritherapy with protease inhibitor, particularly in naive patients with low viral load. It has a good tolerance profile and is easy to take. Studies in progress should permit to widen its indications. Sun, 28 Apr 2013 19:58:44 GMT http://hdl.handle.net/2268/147510 Title: Pharma-clinics comment je traite ... une infection par le VIH. III. Les inhibiteurs non nucléosidiques de la transcriptase inverse <br/> <br/>Author, co-author: Nkoghe, D.; Moutschen, Michel; Leonard, Philippe; Demonty, Jean <br/> <br/>Abstract: Non nucleoside reverse transcriptase inhibitors (NNRTI) are a new arm in the treatment of the HIV infection. They inhibit the replication by direct non competitive binding to the enzyme, and do not require phosphorylation. The fast emergence of resistance in monotherapy obliges to use them in a triple association. The 103 mutation confers a cross-resistance. The most common adverse event is rash. Association with nucleoside analogues is additive or even synergistic. They are metabolized by the cytochrome P450. Within a combined therapy, their efficiency is comparable to protease inhibitors, notably in patients with low viral load. Sun, 28 Apr 2013 19:57:44 GMT http://hdl.handle.net/2268/147509 Title: Hydroxyuree et infection par le VIH <br/> <br/>Author, co-author: Nkoghe, D.; Kola, L.; Leonard, Philippe; Demonty, Jean; Moutschen, Michel <br/> <br/>Abstract: Hydroxyurea is an anticancerous product, used recently in the treatment of HIV-1 infection thanks to its inhibitory action in viral replication, potentialization of the nucleosides activity (particularly ddI or didanosine) and its cytostatic properties on CD4 and CD8 lymphocytes. Many studies showed its efficiency, as further drug, in initial regimen of a tritherapy (containing ddI) and salvage therapy. The dosage of 500 mg bid seems tolerated well by adults, and 20 mg/kg by children. Long-term tolerance remains unknown. With ddI, it could be proposed in developing countries. Sun, 28 Apr 2013 19:56:48 GMT http://hdl.handle.net/2268/147507 Title: Pharma-clinics comment je traite ... une infection par le VIH. IV. Les inhibiteurs de protease <br/> <br/>Author, co-author: Leonard, Philippe; Nkoghe, D.; Moutschen, Michel; Demonty, Jean <br/> <br/>Abstract: Protease inhibitors constitute the last class of antiretroviral drugs appeared on the market. They raised an enormous enthusiasm, reinforced by recent studies results. These molecules prevent the formation of infectious viral particles, while inhibiting a viral enzyme that plays a key role in the cycle of replication of the HIV. Their efficiency, especially in association, is recognized for all stages of the infection and the intervening of a resistance often requires many mutations. However, the unexpected adverse events such as lipodystrophy and some interactions can limit their utilization in first intention. Sun, 28 Apr 2013 19:54:10 GMT http://hdl.handle.net/2268/147506 Title: Comment je traite ... une infection par le VIH. I. Bases pathogéniques des choix thérapeutiques <br/> <br/>Author, co-author: Moutschen, Michel; Nkoghe, D.; Leonard, Philippe; Demonty, Jean Sun, 28 Apr 2013 19:45:18 GMT http://hdl.handle.net/2268/146370 Title: The human papillomavirus vaccine induces collaboration between dendritic cells and natural killer cells in vitro <br/> <br/>Author, co-author: Langers, Inge; Renoux, Virginie; Dortu, Estelle; Delvenne, Philippe; Jacobs, Nathalie Mon, 08 Apr 2013 09:31:23 GMT http://hdl.handle.net/2268/146368 Title: The human papillomavirus (HPV) vaccine induces collaboration between dendritic cells and natural killer cells in vitro <br/> <br/>Author, co-author: Langers, Inge; Renoux, Virginie; Dortu, Estelle; Delvenne, Philippe; Jacobs, Nathalie Mon, 08 Apr 2013 09:14:13 GMT http://hdl.handle.net/2268/146053 Title: Oncogenic human papillomavirus could directly interact with Natural Killer cells <br/> <br/>Author, co-author: Renoux, Virginie; Bastin, Renaud; Boniver, Jacques; Delvenne, Philippe; Jacobs, Nathalie Wed, 03 Apr 2013 09:28:43 GMT http://hdl.handle.net/2268/146051 Title: Oncogenic human papillomavirus could directly interact with Natural Killer cells <br/> <br/>Author, co-author: Renoux, Virginie; Bastin, Renaud; Boniver, Jacques; Delvenne, Philippe; Jacobs, Nathalie Wed, 03 Apr 2013 09:21:04 GMT http://hdl.handle.net/2268/146011 Title: Oncogenic human papillomavirus could directly interact with Natural Killer cells <br/> <br/>Author, co-author: Renoux, Virginie; Bastin, Renaud; Boniver, Jacques; Delvenne, Philippe; Jacobs, Nathalie Tue, 02 Apr 2013 13:14:42 GMT