Smolen K.K.,University of British Columbia |
Ruck C.E.,University of British Columbia |
Fortuno III E.S.,University of British Columbia |
Ho K.,University of British Columbia |
And 8 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014
Background Susceptibility to infection as well as response to vaccination varies among populations. To date, the underlying mechanisms responsible for these clinical observations have not been fully delineated. Because innate immunity instructs adaptive immunity, we hypothesized that differences between populations in innate immune responses may represent a mechanistic link to variation in susceptibility to infection or response to vaccination. Objective Determine whether differences in innate immune responses exist among infants from different continents of the world. Methods We determined the innate cytokine response following pattern recognition receptor (PRR) stimulation of whole blood from 2-year-old infants across 4 continents (Africa, North America, South America, and Europe). Results We found that despite the many possible genetic and environmental exposure differences in infants across 4 continents, innate cytokine responses were similar for infants from North America, South America, and Europe. However, cells from South African infants secreted significantly lower levels of cytokines than did cells from infants from the 3 other sites, and did so following stimulation of extracellular and endosomal but not cytosolic PRRs. Conclusions Substantial differences in innate cytokine responses to PRR stimulation exist among different populations of infants that could not have been predicted. Delineating the underlying mechanism(s) for these differences will not only aid in improving vaccine-mediated protection but possibly also provide clues for the susceptibility to infection in different regions of the world. © 2013 American Academy of Allergy, Asthma and Immunology.
Antela A.,Hospital Clinico Universitario |
Clumeck N.,Center Hospitalier University Saint Pierre |
Duiculescu D.,Dr Victor Babes Infectious And Tropical Diseases Hospital |
Eberhard A.,Medizinisches Versorgungszentrum Karlsplatz Research and Clinical Care Center |
And 9 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. METHODS: We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. RESULTS: A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P = 0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group. CONCLUSIONS: Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine. Copyright © 2013 Massachusetts Medical Society.
Verhofstede C.,Ghent University |
Brudney D.,University College London |
Reynaerts J.,Ghent University |
Vaira D.,University of Liège |
And 6 more authors.
HIV Medicine | Year: 2011
Objective: The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). Methods: GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut-off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. Results: In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances were observed at an FPR of 10%, and six RNA-R5/DNA-X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA-X4/DNA-R5 and seven RNA-R5/DNA-X4 discordances were seen at an FPR of 10%, and 10 RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs). Conclusions: GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia. © 2011 British HIV Association.
The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial
PubMed | Hasselt University, Ghent University, Center Hospitalier University Saint Pierre, AZ Delta Roeselare Menen and 3 more.
Type: | Journal: International journal of chronic obstructive pulmonary disease | Year: 2016
Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions.Patients with COPD, hospitalized for an AE, who have a smoking history of 10 pack-years and had 1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge.We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs.
Glupczynski Y.,Catholic University of Louvain |
Huang T.-D.,Catholic University of Louvain |
Bouchahrouf W.,Catholic University of Louvain |
Rezende De Castro R.,Catholic University of Louvain |
And 6 more authors.
International Journal of Antimicrobial Agents | Year: 2012
During a polymerase chain reaction (PCR)-based surveillance study of β-lactam resistance, 19 OXA-48-positive enterobacterial isolates were detected at nine Belgian hospitals from January 2010 to April 2011. Most cases were presumed to have been locally acquired and were detected in patients who had not travelled abroad. Clonally related outbreaks occurred in two different cities. The majority of isolates co-produced several β-lactamases as well as non-β-lactam resistance genes. This report highlights the rapid emergence and spread of OXA-48-producing Enterobacteriaceae in Belgium. © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Delince P.,Center Hospitalier University Saint Pierre |
Ghafil D.,Center Hospitalier University Saint Pierre
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2012
Purpose: Is it rational to recommend surgical reconstruction of the torn anterior cruciate ligament to every patient? Is conservative management still a valid option? Method: Through a literature review, we looked for the arguments from each side and checked their validity. Results: Unfortunately results of most studies cannot be compared because of the following reasons not exhaustively cited: studied populations differed with respect to age, sex, professional and sports activity level, lesions associated with ACL rupture, patient recruitment methods, time from injury to treatment and different therapeutic modalities. Furthermore, various methods were used to evaluate the clinical and radiological results and there was no consensus of their interpretation. Some authors assumed that the incidence of further meniscus lesions could probably be reduced if the torn ACL was surgically reconstructed. But, we have no evidence to believe that this would be due to the surgical repair rather than to a decrease of involvement in strenuous activities. At present it is not demonstrated that ACL-plasty can prevent osteoarthritis. Numerous factors could explain evolution to arthrosis whatever the treatment for the ACL-ruptured knee. Studies comparing surgical and conservative treatments confirm that ACL reconstruction is not the pre-requisite for returning to sporting activities. More recent and scientifically well-designed studies demonstrate that conservative treatment could give satisfactory results for many patients. They suggest some methods to help them choose the best treatment. Conclusion: At present there are no evidence-based arguments to recommend a systematic surgical reconstruction to any patient who tore his ACL. Knee stability can be improved not only by surgery but also by neuromuscular rehabilitation. Whatever the treatment, fully normal knee kinematics are not restored. While the patients wish to go back to their sport and want everything possible done to prolong their ability to perform these activities, they should be informed that the risk of further knee lesions and osteoarthritis remains high, whatever the treatment, surgical or conservative. Level of evidence: Systematic review of Level I, II, III and IV studies, Level IV. © 2011 Springer-Verlag.
Dauby N.,Free University of Colombia |
Goetghebuer T.,Center Hospitalier University Saint Pierre |
Kollmann T.R.,University of British Columbia |
Levy J.,Center Hospitalier University Saint Pierre |
Marchant A.,Free University of Colombia
The Lancet Infectious Diseases | Year: 2012
Chronic infections during pregnancy are highly prevalent in some parts of the world. Infections with helminths, Trypanosoma cruzi, Plasmodium spp, and HIV might affect the development of fetal immunity and susceptibility to postnatal infections independently of in-utero transmission of the pathogens. Fetal adaptive immune responses are common in neonates who have been exposed to maternal infection during pregnancy but not infected themselves. Such responses could affect the development of immunity to the homologous pathogens and their control during the first few years of life. Fetal innate and regulatory responses might also affect immunity to unrelated pathogens and responses to vaccines. Strategies to improve child health should integrate the possible clinical implications of in-utero exposure to chronic maternal infections. © 2012 Elsevier Ltd.
Prospective evaluation of Coris Influ-A&B Respi-Strip and of BinaxNOW Influenza A&B assay against viral culture and real-time PCR assay for detection of 2009 pandemic influenza A/H1N1v in Belgian patients.
Reynders M.,Center Hospitalier University Saint Pierre
Acta clinica Belgica | Year: 2012
Evaluation of the performance of two rapid (15') antigen detection tests (RAT), BinaxNOW Influenza A&B and Coris Influ-A&B Respi-Strip for the detection of A(H1N1)v2009. Between July 2009 and November 2009, 4105 respiratory specimens from patients with influenza-like illness attending seven public hospitals in Brussels were prospectively examined by two immunochromatographic RAT, followed by viral culture and/or specific real-time RT-PCR. Samples consisted predominantly of nasopharyngeal aspirates (NPA-41%), nasopharyngeal (NPS-37%) and throat swabs (TS-14%). The sensitivity and specificity of Coris RAT and BinaxNOW RAT were 36.6% and 99.7%, and 47% and 98.7% respectively compared to culture; and 33.7% and 99.6%; and 46.5% and 98.8% compared to RT-PCR. Significant differences in sensitivity could be observed when splitting up the samples by sample type and patient's age. NPA gave by far the highest sensitivities: 51.1- 62% for Coris compared to culture and 62.6-78.4% for BinaxNOW. Sensitivities in paediatric NPS varied less between different hospitals (34-41.9%) being still much higher than in adult NPS (11.4-20%). TS resulted in unsatisfactory results: 13% sensitivity in children and 10.5% in adults. Both RAT showed excellent specificities, but insufficient sensitivities. Consequently, negative results should be confirmed. NPA are clearly superior to NPS orTS, and they stay the sample of choice for viral diagnosis.
Payen M.C.,Center Hospitalier University Saint Pierre |
De Wit S.,Center Hospitalier University Saint Pierre |
Martin C.,Center Hospitalier University Saint Pierre |
Sergysels R.,Center Hospitalier University Saint Pierre |
And 3 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2012
Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed. © 2012 The Union.
PubMed | Center Hospitalier University Saint Pierre, Free University of Colombia and Vrije Universiteit Brussel
Type: Journal Article | Journal: Analytical and bioanalytical chemistry | Year: 2016
Therapeutic proteins are among the top selling drugs in the pharmaceutical industry. More than 60% of the approved therapeutic proteins are glycosylated. Nowadays, it is well accepted that changes in glycosylation may affect the safety and the efficacy of the therapeutic proteins. For this reason, it is important to characterize both the protein and the glycan structures. In this study, analytical and data processing methods were developed ensuring an easier characterization of glycoprofiles. N-glycans were (i) enzymatically released using peptide-N-glycosidase F (PNGase F), (ii) reduced, and (iii) analyzed by hydrophilic interaction liquid chromatography coupled to a high-resolution mass spectrometer (HILIC-HRMS). Glycosylation changes were analyzed in human plasma immunoglobulin G samples which had previously been artificially modified by adding other glycoproteins (such as ribonuclease B and fetuin) or by digesting with enzyme (neuraminidase). Principal component analysis (PCA) and classification through soft independent modelling by class analogy (SIMCA) were used to detect minor glycosylation changes. Using HILIC-MS-PCA/SIMCA approach, it was possible to detect small changes in N-glycosylation, which had not been detected directly from the extracted-ion chromatograms, which is current technique to detect N-glycosylation changes in batch-to-batch analysis. The HILIC-MS-PCA/SIMCA approach is highly sensitive approach due to the sensitivity of MS and appropriate data processing approaches. It could help in assessing the changes in glycosylation, controlling batch-to-batch consistency, and establishing acceptance limits according to the glycosylation changes, ensuring safety and efficacy. Graphical abstract N-glycosylation characterization using LC-MS-PCA approach.