References of "Moutschen, Michel"
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See detailPneumococcal vaccination: what have we learnt so far and what can we expect in the future?
Torres, A.; Bonanni, P.; Hryniewicz, W. et al

in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (2014)

Individuals <2 years and >/=50 years of age, as well as those with other specific risk factors, are especially vulnerable to invasive pneumococcal disease (IPD). Conjugate vaccines have been developed ... [more ▼]

Individuals <2 years and >/=50 years of age, as well as those with other specific risk factors, are especially vulnerable to invasive pneumococcal disease (IPD). Conjugate vaccines have been developed against encapsulated bacteria such as Streptococcus pneumoniae to provide improved immune responses. The 7-valent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of vaccine-type pneumococcal diseases in children, including invasive disease and pneumonia and acute otitis media. There have also been significant declines in antimicrobial resistance in 7-valent vaccine serotypes and carriage of S. pneumoniae in the post-PCV7 era. Two to three years after the introduction of PCV13, there is emerging, global evidence of a reduced burden of pneumococcal diseases in children, including declines in IPD (UK and Germany) and nasopharyngeal carriage of PCV13 serotypes (Portugal and France). The functional immunogenicity of PCV13 in individuals >/=50 years of age has been demonstrated in clinical trials in comparison with the 23-valent pneumococcal polysaccharide vaccine and for children and adults 6 to 49 years of age. Between 2011 and 2013, PCV13 received market authorisation by the European Medicines Agency (EMA) for these additional age groups and is now available in Europe for the prevention of pneumococcal disease in all age groups. [less ▲]

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See detailObesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue
ESSER, Nathalie ULg; L'Homme, Laurent ULg; DE ROOVER, Arnaud ULg et al

in Diabetologia (2013), 56

Aims/hypothesis Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose ... [more ▼]

Aims/hypothesis Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose tissue is also heterogeneous in that its visceral component is more frequently associated with metabolic dysfunction than its subcutaneous component. The development of metabolic disorders is partly mediated by the NLR family pyrin domain containing-3 (NLRP3) inflammasome, which increases the secretion of inflammatory cytokines via activation of caspase-1. We compared the immunological profile and NLRP3 activity in adipose tissue between MUO and MHO individuals. Methods MHO and MUO phenotypes were defined, respectively, as the absence and the presence of the metabolic syndrome. Cellular composition and intrinsic inflammasome activity were investigated by flow cytometry, quantitative RTPCR and tissue culture studies in subcutaneous and visceral adipose tissue from 23 MUO, 21 MHO and nine lean individuals. Results We found significant differences between the three study groups, including an increased secretion of IL-1β, increased expression of IL1B and NLRP3, increased number of adipose tissue macrophages and decreased number of regulatory T cells in the visceral adipose tissue of MUO patients compared with MHO and lean participants. In macrophages derived from visceral adipose tissue, both caspase-1 activity and IL-1β levels were higher in MUO patients than in MHO patients. Furthermore, caspase-1 activity was higher in CD11c+CD206+ adipose tissue macrophages than in CD11c−CD206+ cells. Conclusions/interpretation The MUO phenotype seems to be associated with an increased activation of the NLPR3 inflammasome in macrophages infiltrating visceral adipose tissue, and a less favourable inflammatory profile compared with the MHO phenotype. [less ▲]

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See detailFirst report of Mortierella wolfii causing human disease
LAYIOS, Nathalie ULg; HAYETTE, Marie-Pierre ULg; HUWART, Aline ULg et al

Poster (2013, September)

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See detailFirst report of Mortierella wolfii causing human disease
LAYIOS, Nathalie ULg; HAYETTE, Marie-Pierre ULg; HUWART, Aline ULg et al

Conference (2013, September)

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See detailUse of Dried Blood Spot to Improve the Diagnosis and Management of HIV in Resource-Limited Settings
Adawaye, Chatté Idekhim ULg; Erick, Kamangou; Ali, Mahamat Moussa et al

in World Journal of AIDS (2013), 3

Over 75% of people infected with HIV live in countries where health resources are very limited for the diagnosis and biological monitoring of people infected by the virus. In resource-limited settings ... [more ▼]

Over 75% of people infected with HIV live in countries where health resources are very limited for the diagnosis and biological monitoring of people infected by the virus. In resource-limited settings, the use of DBS is a valuable alterna- tive. It has provided technical and economical alternative to the collection of blood in the tubes for testing HIV infec- tion. The DBS can be kept for over a year, it is economical in storage space and facilitates storage conditions because it can be stored at room temperature. It is more discreet and easier to carry over liquid samples that require tubes and other appropriate materials. The amount is sufficient for certain analyses of DNA generally, but may be insufficient for the analysis of viral RNA if the viral load is low. Its disadvantage is often associated with small amounts of blood col- lected available for testing, and the difficulties encountered in laboratories to extract the maximum possibilities without material contamination. DBS can be stored at room temperature (25°C - 35°C), at 4°C, −20°C or even −70°C. With PCR, the DBS is a suitable medium for the diagnosis of patients infected with HIV, virological monitoring by the VL and even analyzing viral genotype. It is a handy stand for the collection, transport and analyses of biological monitoring of HIV infection. It is indeed very suitable for environments with limited accessibility where it is difficult for specialized laboratories to monitor these patients. The DBS is suitable for resource-limited settings. [less ▲]

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See detailDual-specificity phosphatase 3 knockout female mice are resistant to LPS and to polymicrobial induced septic shock in TNF dependent manner.
Rahmouni, Souad ULg; Singh; Dejager, Lien et al

in Journal of Immunology (2013, May)

We report the generation of dual-specificity phosphatase 3 (DUSP3) deficient mice. These mice develop normally and do not exhibit any spontaneous phenotype. However, VHR-/- females, but not males, are ... [more ▼]

We report the generation of dual-specificity phosphatase 3 (DUSP3) deficient mice. These mice develop normally and do not exhibit any spontaneous phenotype. However, VHR-/- females, but not males, are resistant to LPS- and to polymicrobial infection-induced septic shock. After LPS injection, while VHR-/- males and VHR+/+ mice of both genders, displayed an increased serum levels of TNF-α and IFN, the levels of these cytokines remained significantly low in the VHR-/- females. In vitro experiments using peritoneal macrophages showed the same results suggesting that the systemic cytokines profiles observed are macrophages-dependent. Adoptive transfer of VHR-/- females bone marrow to irradiated VHR+/+ female mice, but not to VHR-/- or VHR+/+ males, protected them from death after administration of LPS. Interestingly, VHR-/- females were sensitive to TNF-α- induced lethality. We also report that the decrease of TNF-α production observed in VHR-/- female’s macrophages after LPS activation was associated with a decreased ERK1/2, but not MEK1/2, activation. Interestingly, pervanadate (PTP pan inhibitor) treatment prior to LPS activation restored ERK1/2 activation in the VHR-deficient macrophages, suggesting that VHR is targeting one of the ERK1/2 PTPs or DUSPs. These results, together with our observation that DUSP3 is the most highly expressed phosphatase in macrophages, suggest a key non-redundant role of VHR as positive regulator of TNF-α in innate immune response in females. [less ▲]

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See detailDifférences d’activité de l’inflammasome NLRP3 entre sujets obèses avec et sans anomalies métaboliques
Esser, Nathalie ULg; L'Homme, Laurent ULg; DE ROOVER, Arnaud ULg et al

in Diabètes & Métabolism (2013, March), 39(suppl 1), 102

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See detailseroprevalence of infectious markers among blood donors in Niamey (Niger)
MAYAKI, Z; Dardenne, Nadia ULg; KABB, R et al

in Revue d'Epidémiologie et de Santé Publique = Epidemiology and Public Health (2013), 61(3), 233-240

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See detailRôle de la vitamine D dans l'infection par le VIH: revue des connaissances actuelles
Pirotte, Benoît ULg; Rassenfosse, Marie ULg; Collin, Romain ULg et al

in Revue Médicale de Liège (2013), 68(1), 25-31

La vitamine D possède des propriétés sur le métabolisme phosphocalcique mais aussi dans diverses pathologies telles que les maladies auto-immunes, les cancers, les maladies cardio-vasculaires, l’excès de ... [more ▼]

La vitamine D possède des propriétés sur le métabolisme phosphocalcique mais aussi dans diverses pathologies telles que les maladies auto-immunes, les cancers, les maladies cardio-vasculaires, l’excès de poids ou encore certaines infections. Nous nous intéressons ici aux relations frappantes qui existent entre la vitamine D et le VIH. Cette hormone joue assurément un rôle important dans l’infection par le VIH, tant au niveau squelettique qu’au niveau de l’évolution de la maladie elle-même. Nous remarquons en effet qu’un déficit en vitamine D est très souvent associé à l’infection par le VIH. De plus, un taux indétectable de cette hormone chez les patients séropositifs est associé à une infection cliniquement plus avancée et à une mortalité accrue. Ainsi, le déficit en vitamine D doit être considéré comme un cofacteur important de la progression de l’infection par le VIH. En effet, la vitamine D augmente l’activité des macrophages, entre autres via le processus d’autophagie, ce qui permet d’inhiber l’infection par le VIH-1. Nous parlerons ensuite de l’impact de certains traitements antirétroviraux sur l’altération du métabolisme de la vitamine D. Nous évaluerons enfin le bénéfice d’une supplémentation en vitamine D chez ces patients. [less ▲]

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See detailPerceptions de la pratique des essais cliniques sur le VIH/sida par les médecins prescripteurs des antirétroviraux agréés de Kinshasa (RD Congo)
Lubangi, MM; MOUTSCHEN, Michel ULg

in Bulletin de la Société de Pathologie Exotique (2012)

Le but de cette étude, réalisée entre novembre 2005 et janvier 2006 auprès des prescripteurs d’antirétroviraux (ARV), était de cerner leurs perceptions sur les enjeux contextuels liés à la pratique des ... [more ▼]

Le but de cette étude, réalisée entre novembre 2005 et janvier 2006 auprès des prescripteurs d’antirétroviraux (ARV), était de cerner leurs perceptions sur les enjeux contextuels liés à la pratique des essais sur le VIH/sida à Kinshasa. Pour effectuer le repérage de ces enjeux, un ques- tionnaire a été élaboré et finalisé à la suite de la phase explo- ratoire de notre enquête afin d’apprécier les points de vue des médecins agréés par le Programme national de lutte contre le sida du Congo (PNLS) et qui jouent le premier rôle dans le contexte de leur pratique professionnelle. Sur 50 médecins sollicités pour participer à notre enquête, 35 ont retourné le questionnaire, dix n’étaient pas disponibles au moment de l’enquête et cinq n’ont pas retourné le questionnaire à l’adresse et dans le délai que nous avions indiqués. Les résul- tats obtenus témoignent de la nécessité de renforcer les capa- cités des acteurs locaux. Un des objectifs visés par la conduite locale de ces essais étant le transfert des connais- sances, il est nécessaire, au vu des résultats, d’affirmer le rôle pédagogique du comité d’éthique local. Cela devra permettre de relever le défi de la contextualisation et de réduire les tensions susceptibles de compromettre le bon déroulement des essais cliniques. [less ▲]

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See detailHYGIENE ET PROBLEMES INFECTIEUX EN GERIATRIE
Moutschen, Michel ULg; FRIPPIAT, Frédéric ULg; CHRISTIAENS, Geneviève ULg et al

Conference (2012, June 14)

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See detailAn improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rgammanull mice allows HIV replication and development of anti-HIV immune responses.
Singh, Maneesh; Singh, Pratibha; Gaudray, Gilles et al

in PLoS ONE (2012), 7(6), 38491

Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rgamma(null) (NSG) and NOD/SCID/IL2Rgamma(null) (NOG) mice need efficient human cell engraftment for long ... [more ▼]

Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rgamma(null) (NSG) and NOD/SCID/IL2Rgamma(null) (NOG) mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI) is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials. [less ▲]

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See detailTreatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients.
Theys, Kristof; Deforche, Koen; Vercauteren, Jurgen et al

in Retrovirology (2012), 9

BACKGROUND: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug ... [more ▼]

BACKGROUND: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. RESULTS: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. CONCLUSIONS: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level. [less ▲]

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See detailFidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials.
Crook, Derrick W.; Walker, A. Sarah; Kean, Yin et al

in Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America (2012), 55 Suppl 2

Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both ... [more ▼]

Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%-51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%-60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13-40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI. [less ▲]

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See detailDeleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity.
Lopez-Herrera, Gabriela; Tampella, Giacomo; Pan-Hammarstrom, Qiang et al

in American Journal of Human Genetics (2012), 90(6), 986-1001

Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive ... [more ▼]

Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral immune deficiency and features of autoimmunity shared genotype evidence for a linkage interval on chromosome 4q. Sequencing of positional candidate genes revealed that in each family, affected individuals had a distinct homozygous mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All LRBA mutations segregated with the disease because homozygous individuals showed hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were healthy. These mutations were absent in healthy controls. Individuals with homozygous LRBA mutations had no LRBA, had disturbed B cell development, defective in vitro B cell activation, plasmablast formation, and immunoglobulin secretion, and had low proliferative responses. We conclude that mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity. [less ▲]

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See detailA national cohort of HIV-infected patients in Belgium: design and main characteristics.
Van Beckhoven, D.; Buve, A.; Ruelle, J. et al

in Acta Clinica Belgica (2012), 67(5), 333-7

In Belgium, individual laboratory and treatment data of all HIV-infected patients seen in the 9 AIDS Reference Centres and 7 AIDS Reference Laboratories are collected prospectively since 2006. We present ... [more ▼]

In Belgium, individual laboratory and treatment data of all HIV-infected patients seen in the 9 AIDS Reference Centres and 7 AIDS Reference Laboratories are collected prospectively since 2006. We present here an analysis of patients recorded in the cohort database between 1st of January 2006 and 31st of December 2008. During that period, 11982 patients were under medical follow-up in Belgium. Sixty-one percent of the patients were male and the median age was 39.8 at the time of first recorded viral load. Among the patients whose nationality or probable mode of transmission was recorded, nearly half (48.0%) were Belgian and 38.3% originated from Sub-Saharan Africa; heterosexual contacts were reported in the majority of cases (56.0%) followed by homosexual contacts (35.3%). A total of 145 deaths were reported. Around three quarters of the patients were on ART. The median CD4 cell count rose from 470 cells/mm3 in 2006 to 501 cells/mm3 in 2008. This cohort enabled us to obtain comprehensive information on the numbers and characteristics of HIV-infected patients currently being followed up in Belgium, and on trends in antiretroviral therapy and biological results. This will serve for planning purposes, evaluation of access to care and as a source of information for further studies. [less ▲]

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See detailGentetics, environment and determinants of autoimmune diseases
MOUTSCHEN, Michel ULg

in Revue Médicale de Liège (2012), 67

We initiate this review article by a brief description of a few monogenic autoimmune diseases such as the APECED and the IPEX syndrome because they allow understand the fundamental mechanisms of self ... [more ▼]

We initiate this review article by a brief description of a few monogenic autoimmune diseases such as the APECED and the IPEX syndrome because they allow understand the fundamental mechanisms of self tolerance. Next we describe with more details the complex autoimmune diseases and discuss the recent data regarding the associated genetic and environmental factors and their modes of interaction. The conclusion of the article deals with the practical implications of this inherent complexity for the researcher and the clinician. [less ▲]

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