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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.

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.

Verhofstede C.,Ghent University | Brudney D.,University College London | Reynaerts J.,Ghent University | Vaira D.,University of Liege | 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.

Walmsley S.L.,A+ Network | Antela A.,Hospital Clinico Universitario | Clumeck N.,Center Hospitalier University Saint Pierre | Duiculescu D.,Dr. Victor Babes Infectious and Tropical Diseases Hospital | And 10 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.

Smolen K.K.,University of British Columbia | Cai B.,University of British Columbia | Gelinas L.,University of British Columbia | Fortuno E.S.,University of British Columbia | And 9 more authors.
Journal of Immunology | Year: 2014

Innate immunity instructs adaptive immunity, and suppression of innate immunity is associated with an increased risk for infection. We showed previously that whole-blood cellular components from a cohort of South African children secreted significantly lower levels of most cytokines following stimulation of pattern recognition receptors compared with whole blood from cohorts of Ecuadorian, Belgian, or Canadian children. To begin dissecting the responsible molecular mechanisms, we set out to identify the relevant cellular source of these differences. Across the four cohorts represented in our study, we identified significant variation in the cellular composition of whole blood; however, a significant reduction in the intracellular cytokine production on the single-cell level was only detected in South African children's monocytes, conventional dendritic cells, and plasmacytoid dendritic cells. We also uncovered a marked reduction in polyfunctionality for each of these cellular compartments in South African children compared with children from the other continents. Together, our data identify differences in cell composition, as well as profoundly lower functional responses of innate cells, in our cohort of South African children. A possible link between altered innate immunity and increased risk for infection or lower response to vaccines in South African infants needs to be explored. © 2014 by The American Association of Immunologists, Inc.

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