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55. Limited cross-border infections in patients newly diagnosed with HIV in Europe

Author

Moutschen, M., Frentz, D., Wensing, A. M. J., Albert, Jan, Paraskevis, Dimitrios N., Abecasis, A. B., Hamouda, O., Jørgensen, L. B., Kücherer, C., Struck, D., Schmit, J. -C, Åsjö, Birgitta, Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Coughlan, S., De Wit, S., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A. -M, Boucher, C. A. B., Van de Vijver, D. A. M. C., Balluch, G., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Bruckova, M., Machala, L., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Salminen, M., Ristola, M., Suni, J., Sutinen, J., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Levi, I., Chemtob, D., Franzetti, M., Lai, A., Binda, F., Tramuto, F., Ciccozzi, M., Mussini, C., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Kessel, A., van Bentum, P. H. M., Brinkman, K., de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Jevtovic, D., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Garcia, F., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Säll, C., Mellgren, Å., Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Instituto de Higiene e Medicina Tropical (IHMT), Centro de Malária e outras Doenças Tropicais (CMDT), Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Frentz, D, Wensing, AMJ, Albert, J, Paraskevis, D, Abecasis, AB, Hamouda, O, Jørgensen, LB, Kücherer, C, Struck, D, Schmit, JC, Åsjö, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, De Wit, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, CAB, Van de Vijver, DAMC, Tramuto, F, Van Wijngaerden, Eric, Van Ranst, Marc, Van Laethem, Kristel, Derdelinckx, Inge, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Virology, and Graduate School

Subjects
Male, Epidemiology, Human immunodeficiency virus (HIV), Human immunodeficiency virus 1, HIV Infections, medicine.disease_cause, Virologie générale, phylogeny, Settore MED/42 - Igiene Generale E Applicata, Men who have sex with men, EMERGENCE, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Infection control, Cluster Analysis, 030212 general & internal medicine, Israel, Pathologie maladies infectieuses, travel, Phylogeny, 0303 health sciences, Molecular Epidemiology, Travel, Transmission (medicine), article, virus transmission, IMMUNODEFICIENCY-VIRUS TYPE-1, 3. Good health, Europe, female, Infectious Diseases, SUBTYPE B, DRUG-RESISTANT HIV-1, RNA, Viral, male homosexual, Adult, structural gene, Molecular Sequence Data, Newly diagnosed, Clusters, 03 medical and health sciences, male, SDG 3 - Good Health and Well-being, MOLECULAR EPIDEMIOLOGY, SWITZERLAND, Virology, geographic distribution, Humans, Transmission, In patient, human, 030304 developmental biology, nonhuman, Molecular epidemiology, business.industry, Research, high risk population, Virologie médicale, nucleotide sequence, Sequence Analysis, DNA, Human immunodeficiency virus 1 infection, major clinical study, unindexed sequence, 3121 General medicine, internal medicine and other clinical medicine, HIV-1, business, Europe, HIV-1, Transmission, Clusters, Demography, cluster analysis
Abstract

Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2013

56. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

Author

Moutschen, M., Theys, K., Deforche, K., Vercauteren, J., Libin, P., van de Vijver, D. A. M. C., Albert, Jan, Åsjö, Birgitta, Balotta, Claudia, Bruckova, M., Camacho, Ricardo J., Clotet, B., Coughlan, S., Grossman, Z., Hamouda, O., Horban, A., Korn, K., Kostrikis, Leontios G., Kücherer, C., Nielsen, C., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stockl, E., Riva, C., Ruiz, L., Liitsola, K., Schmit, J. -C, Schuurman, R., Sönnerborg, A., Stanekova, D., Stanojevic, M., Struck, D., Van Laethem, K., Wensing, A. M. J., Boucher, C. A. B., Vandamme, A. M., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Machala, L., Jrgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Ristola, M., Suni, J., Sutinen, J., K̈ucherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Issaris, C., Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Xilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., Hall, W., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., Levi, I., Chemtob, D., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Bentum, P. H. M., Brinkman, K., op de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paix̃ao, T., Duque, V., Araújo, F., Jevtovic, D. J., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Babic, Dunja Z., Tomazic, J., Vidmar, L., Karner, P., Gutíerrez, C., deMendoza, C., Erkicia, I., Domingo, P., Camino, X., Galindo, M. J., Blanco, J. L., Leal, M., Masabeu, A., Guelar, A., Llibre, J. M., Margall, N., Iribarren, J. A., Gutierrez, S., Baldov́i, J. F., Pedreira, J. D., Gatell, J. M., Moreno, S., de Mendoza, C., Soriano, V., Blaxhult, A., Heidarian, A., Karlsson, A., Aperia-Peipke, K., Bergbrant, I. -M, Gissĺen, M., Svennerholm, M., Björkman, Per, Bratt, G., Carlsson, M., Ekvall, H., Ericsson, M., Ḧofer, M., Johansson, B., Sonnerb̈org, A., Kuylenstierna, N., Ljungberg, B., Mäkitalo, S., Strand, A., Öberg, S., Virology, Erasmus MC other, Van Wijngaerden, Eric, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Centro de Malária e outras Doenças Tropicais (CMDT), Graduate School, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, UCL - (SLuc) Service de microbiologie, UCL - (SLuc) Service de médecine interne générale, Theys, K, Deforche, K, Vercauteren, J, Libin, P, van de Vijver, DA, Albert, J, Asjö, B, Balotta, C, Bruckova, M, Camacho, RJ, Clotet, B, Coughlan, S, Grossman, Z, Hamouda, O, Horban, A, Korn, K, Kostrikis, LG, Kücherer, C, Nielsen, C, Paraskevis, D, Poljak, M, Puchhammer Stockl, E, Riva, C, Ruiz, L, Liitsola, K, Schmit, JC, Schuurman, R, Sönnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Van Laethem, K, Wensing, AM, Boucher, CA, Vandamme, AM, Tramuto, F, and Vitale, F

Subjects
Adult, Male, lcsh:Immunologic diseases. Allergy, Anti-HIV Agents, education, Virulence, HIV Infections, Drug resistance, Biology, Settore MED/42 - Igiene Generale E Applicata, Virus, polymorphism, 03 medical and health sciences, Viral Proteins, SDG 3 - Good Health and Well-being, Virology, Genotype, Drug Resistance, Viral, drug-naive, medicine, Humans, Prospective Studies, 030304 developmental biology, 0303 health sciences, Polymorphism, Genetic, 030306 microbiology, Research, protease, Viral Load, Reverse transcriptase, 3. Good health, CD4 Lymphocyte Count, Drug-naïve, Infectious Diseases, 3121 General medicine, internal medicine and other clinical medicine, Immunology, biology.protein, HIV-1, Female, Antibody, lcsh:RC581-607, Viral load, HIV-1 infected patient, medicine.drug, Peptide Hydrolases
Abstract

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 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. ispartof: Retrovirology vol:9 issue:1 ispartof: location:England status: published

Published
2012

57. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mc1, Mackie, N, Di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, Fm, Van Laethem, K, Bansi, L, van de Vijver DA, Geretti, Am, De Luca, A, Giacometti A, SEHERE c. o. n. s. o. r. t. i. u. m., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Carla Re, M, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, d'Arminio Monforte, A, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Bello, Fd, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Fadda, G, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, Pd, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E, Lengauer, T, Däumer, M, Hoffmann, D, Schülter, E, Müller, C, Oette, M, Reuter, S, Esser, S, Fätkenheuer, G, Rockstroh, J, Incardona, F, Rosen Zvi, M, Clotet, B, Thalme, A, Svedhem, V, Bratt, G, Gargiulo, F, Lapadula, G, Manca, N, Paraninfo, G, Quiros Roldan, E, Carosi, G, Castelnuovo, F, Vandamme, Am, Van Wijngaerden, E, Ainsworth, J, Anderson, J, Babiker, A, Dunn, D, Easterbrook, P, Fisher, M, Gazzard, B, Garrett, N, Gilson, R, Gompels, M, Hill, T, Johnson, M, Leen, C, Orkin, C, Phillips, A, Pillay, D, Porter, K, Post, F, Sabin, C, Sadiq, T, Schwenk, A, Walsh, J, Delpech, V, Palfreeman, A, Glabay, A, Lynch, J, Hand, J, de Souza, C, Perry, N, Tilbury, S, Churchill, D, Nelson, M, Waxman, M, Mandalia, S, Kall, M, Korat, H, Taylor, C, Ibrahim, F, Campbell, L, James, L, Brima, N, Williams, I, Youle, M, Lampe, F, Smith, C, Grabowska, H, Chaloner, C, Puradiredja, Di, Weber, J, Ramzan, F, Carder, M, Wilson, A, Dooley, D, Asboe, D, Pozniak, A, Cameron, S, Cane, P, Chadwick, D, Clark, D, Collins, S, Lazarus, L, Dolling, D, Fearnhill, E, Castro, H, Coughlin, K, Zuckerman, M, Booth, C, Goldberg, D, Hale, A, Kaye, S, Kellam, P, Leigh Brown, A, Smit, E, Templeton, K, Tilston, P, Tong, W, Zhang, H, Ushiro Lumb, I, Oliver, T, Bibby, D, Mitchell, S, Mbisa, T, Wildfire, A, Tandy, R, Shepherd, J, Maclean, A, Bennett, D, Hopkins, M, Garcia Diaz, A, Kirk, S, Sloot, P. M., Virology, Prosperi, M, Mackie, N, di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, F, van laethem, K, Bansi, L, van de Vijver, D, Geretti, A, de luca, A, and Mancuso, S

Subjects
Male, Drug Resistance, HIV Infections, Drug resistance, Cohort Studies, 0302 clinical medicine, Genotype, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Viral, 0303 health sciences, Proteolytic enzymes, Genotypic testing, HIV, Viral load, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Europe, Female, HIV-1, Humans, RNA, Viral, Viral Proteins, Drug Resistance, Viral, Mutation, Missense, Viral Load, Pharmacology, Infectious Diseases, 3. Good health, Cohort, Cohort study, Human, Microbiology (medical), Biology, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Viral Protein, 030306 microbiology, Anti-HIV Agent, Virology, Reverse transcriptase, Regimen, genotypic testing, viral load, Immunology, Mutation, RNA, Missense, Cohort Studie
Abstract

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load

Published
2011

58. Trends and Predictors of Transmitted Drug Resistance (TDR) and Clusters with TDR in a Local Belgian HIV-1 Epidemic

Author

Pineda-Pena, AC, Schrooten, Y, Vinken, L, Ferreira, F, Li, GD, Trovao, NS, Khouri, R, Derdelinckx, I, De Munter, P, Kucherer, C, Kostrikis, LG, Nielsen, C, Littsola, K, Wensing, A, Stanojevic, M, Paredes, R, Balotta, C, Albert, J (Jan), Boucher, Charles, Gomez-Lopez, A, van Wijngaerden, E, van Ranst, M, Vercauteren, J, Vandamme, AM, Van Laethem, K, Pineda-Pena, AC, Schrooten, Y, Vinken, L, Ferreira, F, Li, GD, Trovao, NS, Khouri, R, Derdelinckx, I, De Munter, P, Kucherer, C, Kostrikis, LG, Nielsen, C, Littsola, K, Wensing, A, Stanojevic, M, Paredes, R, Balotta, C, Albert, J (Jan), Boucher, Charles, Gomez-Lopez, A, van Wijngaerden, E, van Ranst, M, Vercauteren, J, Vandamme, AM, and Van Laethem, K

Abstract

We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (Cl): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures.

Published
2014

59. Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Author

Frentz, Dineke, van de Vijver, David, Abecasis, AB, Albert, J (Jan), Hamouda, O, Jorgensen, LB, Kucherer, C, Struck, D, Schmit, JC, Vercauteren, J, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, van Wijngaerden, E, Wensing, AMJ, Boucher, Charles, Frentz, Dineke, van de Vijver, David, Abecasis, AB, Albert, J (Jan), Hamouda, O, Jorgensen, LB, Kucherer, C, Struck, D, Schmit, JC, Vercauteren, J, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, van Wijngaerden, E, Wensing, AMJ, and Boucher, Charles

Abstract

Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (wTDRM) using data from the European Spread program. Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy. Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM. Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring.

Published
2014

62. HIV-1 fitness landscape models for indinavir treatment pressure using observed evolution in longitudinal sequence data are predictive for treatment failure

Author

Sangeda, RZ, Theys, K, Beheydt, G, Rhee, SY, Deforche, K, Vercauteren, J, Libin, P, Imbrechts, S, Grossman, Z, Camacho, RJ, Van Laethem, K, Pironti, A, Zazzi, M, Sonnerborg, A, Incardona, F, Luca, A, Torti, C, Ruiz, L, van de Vijver, David, Shafer, RW, Bruzzone, B, van Wijngaerden, E, Vandamme, AM, Sangeda, RZ, Theys, K, Beheydt, G, Rhee, SY, Deforche, K, Vercauteren, J, Libin, P, Imbrechts, S, Grossman, Z, Camacho, RJ, Van Laethem, K, Pironti, A, Zazzi, M, Sonnerborg, A, Incardona, F, Luca, A, Torti, C, Ruiz, L, van de Vijver, David, Shafer, RW, Bruzzone, B, van Wijngaerden, E, and Vandamme, AM

Abstract

We previously modeled the in vivo evolution of human immunodeficiency virus-1 (HIV-1) under drug selective pressure from cross-sectional viral sequences. These fitness landscapes (FLs) were made by using first a Bayesian network (BN) to map epistatic substitutions, followed by scaling the fitness landscape based on an HIV evolution simulator trying to evolve the sequences from treatment naive patients into sequences from patients failing treatment. In this study, we compared four FLs trained with different sequence populations. Epistatic interactions were learned from three different cross-sectional BNs, trained with sequence from patients experienced with indinavir (BNT), all protease inhibitors (PIs) (BNP) or all PI except indinavir (BND). Scaling the fitness landscape was done using cross-sectional data from drug naive and indinavir experienced patients (Fcross using BNT) and using longitudinal sequences from patients failing indinavir In pairwise FL comparisons we found significant correlation between fitness values for individual sequences, and this correlation improved after correcting for the subtype. Furthermore, FLs could predict the failing sequence under indinavir-containing combinations. At 12 and 48 weeks, all parameters from all FLs and indinavir GSS (both for Rega and HIVdb) were predictive of therapy outcome, except MR for FlongT and FlongP. The fitness landscapes have similar predictive power for treatment respon

Published
2013

63. Clinical evaluation of Rega 8: an updated genotypic interpretation system that significantly predicts HIV-therapy response

Author

Vercauteren, J, Beheydt, G, Prosperi, M, Libin, P, Imbrechts, S, Camacho, R, Clotet, B, De Luca, Andrea, Grossman, Z, Kaiser, R, Sönnerborg, A, Torti, C, Van Wijngaerden, E, Schmit, J, Zazzi, M, Geretti, A, Vandamme, A, Van Laethem, K., De Luca, Andrea (ORCID:0000-0002-8311-6935), Vercauteren, J, Beheydt, G, Prosperi, M, Libin, P, Imbrechts, S, Camacho, R, Clotet, B, De Luca, Andrea, Grossman, Z, Kaiser, R, Sönnerborg, A, Torti, C, Van Wijngaerden, E, Schmit, J, Zazzi, M, Geretti, A, Vandamme, A, Van Laethem, K., and De Luca, Andrea (ORCID:0000-0002-8311-6935)

Abstract

Clinically evaluating genotypic interpretation systems is essential to provide optimal guidance in designing potent individualized HIV-regimens. This study aimed at investigating the ability of the latest Rega algorithm to predict virological response on a short and longer period. MATERIALS METHODS: 9231 treatment changes episodes were extracted from an integrated patient database. The virological response after 8, 24 and 48 weeks was dichotomized to success and failure. Success was defined as a viral load below 50 copies/ml or alternatively, a 2 log decrease from the baseline viral load at 8 weeks. The predictive ability of Rega version 8 was analysed in comparison with that of previous evaluated version Rega 5 and two other algorithms (ANRS v2011.05 and Stanford HIVdb v6.0.11). A logistic model based on the genotypic susceptibility score was used to predict virological response, and additionally, confounding factors were added to the model. Performance of the models was compared using the area under the ROC curve (AUC) and a Wilcoxon signed-rank test.

Published
2013

67. Le traitement de la diarrhée aiguë évaluation critique par un groupe Interuniversitaire et recommandations partie III: Recommandations

Author

UCL - (SLuc) Service de gastro-entérologie, Urbain, D., Belaiche, J., De Vos, M., Fiasse, René, Hiele, M., Huijghebaert, S., Jacobs, F., Malonne, H., Speelman, P., Van Gompel, A., Van Gossum, A., Van Wijngaerden, E., UCL - (SLuc) Service de gastro-entérologie, Urbain, D., Belaiche, J., De Vos, M., Fiasse, René, Hiele, M., Huijghebaert, S., Jacobs, F., Malonne, H., Speelman, P., Van Gompel, A., Van Gossum, A., and Van Wijngaerden, E.

Abstract

Le traitement de la diarrhée aiguë évaluation critique par un groupe Interuniversitaire et recommandations partie III: Recommandations

Published
2002

69. INFECTIVE ENDOCARDITIS

Author

Herregods, M.C., primary, Hill, E., additional, Herijgers, P., additional, De Munter, P., additional, Vanderschueren, S., additional, Van Wijngaerden, E., additional, and Peetermans, W.E., additional

Published
2008
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82. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients.

Author

Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, Spriet I, Verbeken E, and Van Wijngaerden E

Abstract

RATIONALE: Invasive aspergillosis (IA) is an important cause of mortality in patients with hematologic malignancies. However, IA appears to be gaining a foothold in the intensive care unit (ICU) in patients without classical risk factors. A recent study described 89 cases of IA in patients in a medical ICU without leukemia or cancer. The diagnosis of IA remains difficult and is often established too late. Galactomannan (GM) is an exo-antigen released from Aspergillus hyphae while they invade host tissue. OBJECTIVES: This prospective single-center study was conducted to investigate the role of GM in bronchoalveolar lavage (BAL) fluid as a tool for early diagnosis of IA in the ICU. METHODS: All patients with risk factors identified in our earlier study were evaluated. BAL for culture and GM detection, serum GM levels, and computed tomography scan were obtained for all included patients with signs of pneumonia. Patients were classified as having proven, probable, or possible IA. MEASUREMENTS AND MAIN RESULTS: A total of 110 patients out of 1,109 admissions were eligible. There were 26 proven IA cases. Using a cutoff index of 0.5, the sensitivity and specificity of GM detection in BAL fluid was 88 and 87%, respectively. The sensitivity of serum GM was only 42%. In 11 of 26 proven cases, BAL culture and serum GM remained negative, whereas GM in BAL was positive. CONCLUSIONS: IA is common in immunocompromised, critically ill patients. GM detection in BAL fluid seems to be useful in establishing or excluding the diagnosis of IA in the ICU. [ABSTRACT FROM AUTHOR]

Published
2008
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83. Three cases of destructive native valve endocarditis caused byStaphylococcus lugdunensis.

Author

Van Hoovels, L., De Munter, P., Colaert, J., Surmont, I., Van Wijngaerden, E., Peetermans, W.E., and Verhaegen, J.

Subjects
ENDOCARDITIS, STAPHYLOCOCCUS, ANTIBIOTICS, COAGULASE, BODY fluids, MORTALITY
Abstract

Described here are three cases of acute native valve endocarditis due to the coagulase-negative pathogenStaphylococcus lugdunensiswith serious complications. Two of the three patients died despite optimal antibiotic therapy and cardiovascular surgery. These cases demonstrate the aggressive nature ofS. lugdunensisand emphasize the importance of identifying coagulase-negative staphylococci to the species level and not considering the isolation ofS. lugdunensisfrom normally sterile body fluids as contamination. On the contrary, when this organism is found in patients with endocarditis, early surgery should be considered. The possibility that this organism could be misidentified asS. aureusbecause of ‘autocoagulation’ and that commercial identification systems may misidentify it asS. haemolyticus,S. hominisorS. warnerishould also be remembered. [ABSTRACT FROM AUTHOR]

Published
2005
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84. Prevalence and correlates of nonadherence to antiretroviral therapy in a population of HIV patients using MEDICATION EVENT MONITORING SYSTEM.

Author

Deschamps AE, De Graeve V, Van Wijngaerden E, De Saar V, Vandamme A, Van Vaerenbergh K, Ceunen H, Bobbaers H, Peetermans WE, De Vleeschouwer PJ, and De Geest S

Abstract

Nonadherence to antiretroviral therapy (ART) jeopardizes good clinical outcome in people living with HIV. In a single-center prospective study, prevalence and correlates of nonadherence were investigated in 43 patients on ART. Nonadherence was assessed using Medication Event Monitoring System (MEMS), self-report and collateral report of treating physicians. Based on MEMS data, median taking adherence, dosing adherence, and timing adherence was 98% (interquartile range [IQR] = 5.3), 91.5% (IQR = 18), and 86% (IQR = 31.5), respectively. The median number of drug holidays per 100 days was 0.8 (IQR = 4.8). The prevalence of nonadherence measured by MEMS was 40%. Self-reported nonadherence and collateral report of nonadherence by physicians varied from 5% to 41% and 24% to 28%, respectively. Patients were categorized as adherent or nonadherent based on a clinically validated algorithm derived from MEMS parameters. Nonadherent patients used significantly more escaping coping strategies (p = 0.003) and planned problem solving strategies (p = 0.049), were prescribed significantly more antiretroviral medications (p = 0.02) and were significantly longer on ART (p = 0.04) than adherent patients. Identified correlates of nonadherence may help clinicians in detecting patients with HIV at risk for nonadherence and can support the development of adherence enhancing interventions. [ABSTRACT FROM AUTHOR]

Published
2004
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86. Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Author

Bailey, J., Ajana, F., Arribas, J.R., Brunetta, J., Halota, W., Raffi, F., Brinson, C., Eron, J., Post, F., Ward, D., Katlama, C., Pineda, J.A., Rauch, A., Vandercam, B., Molina, J.-M., Slim, J., Crofoot, G., Prelutsky, D., Shamblaw, D., Van Wijngaerden, E., Opsomer, M., Pulido, F., Brown, K., Henn, S., Santos Gil, I., Perez-Valero, I., Flamholc, L., Ruane, P., Ricart, C., De Wit, S., Rey, D., Post, F.A., Murphy, D., Negredo, E., Gatell, J.M., Gathe, J., DeJesus, E., Iribarren, J.A., Rashbaum, B., Fehr, J., Dretler, R., Brar, I., Hagins, D., Voskuhl, G., Jain, M., Henry, W.K., Gasiorowski, J., Mills, A., Rivero, A., Van Landuyt, E., Gutierrez, F., Petrovic, R., Gazzard, B.G., Piekarska, A., Walmsley, S., de Vente, J., Girardy, P.-M., Shafran, S., Rachlis, A., Bhatti, L., Knobel, H., Sogorb, J.P., Cunningham, D., Mounzer, K., Klein, M., Galindo, M.J., Clarke, A., Stoeckle, M., Fichtenbaum, C., Dietz, C., EMERALD study group, Olivet, H., Poizot-Martin, I., Nahass, R., Richmond, G., Eron, J.J., Wilkin, A., Benson, P., Morales-Ramirez, J., Lathouwers, E., Lucasti, C., Moutschen, M., Osiyemi, O., Casado, J., Gallant, J., Jezorwski, J., Teicher, E., Cotte, L., Vandekerckhove, L., Podzamczer, D., Gisslen, M., Gutierrez, M.D.M., Bredeek, U.F., Waters, L., Scribner, A., Orkin, C., Conway, B., Yazdanpanah, Y., Felizarta, F., Reynes, J., Johnson, M.A., Ustianowski, A., Thalme, A., Martorell, C., McDonald, C., Tashima, K., Berenguer, J., Florence, E., Huhn, G., Shalit, P., Ramgopal, M., Witor, A., Blaxhult, A., Scarsella, A., Horban, A., and Hufkens, V.

Subjects
3. Good health
Abstract

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.

87. Treatment of acute diarrhoea: update of guidelines based on a critical interuniversity assessment of medications and current practices

Author

Urbain D, Belaiche J, De Vos M, Fiasse R, Hiele M, Suzy Huijghebaert, Jacobs F, Malonne H, Speelman P, Van Gompel A, Van Gossum A, and Van Wijngaerden E

Subjects
Adult, Diarrhea, Adolescent, Child, Preschool, Acute Disease, Practice Guidelines as Topic, Infant, Newborn, Humans, Infant, Middle Aged, Child, Aged
Abstract

Further to a thorough analysis of the problem of acute diarrhoea and the therapeutic options, recommendations were defined following a multidisciplinary approach. These guidelines take into account the reality of frequent self-medication. They further differ as a function of age (children, primarily treated by ORS and for whom self-medication is not advised versus adults who can self-medicate), symptoms (uncomplicated diarrhoea versus dysentery) and location where the diarrhoea is contracted (at home or when travelling).

90. A public health value-based healthcare paradigm for HIV

Author

Paul De Munter, Jean-Christophe Goffard, Stefaan J. Vandecasteele, Eric Van Wijngaerden, Lucie Seyler, Françoise Uurlings, Peter Messiaen, Stéphane De Wit, Patrick Lacor, S. Callens, Eric Florence, Sophie Henrard, Rémy Demeester, Sebastian Vermeersch, Jean Cyr Yombi, Nathalie Ausselet, Lieven Annemans, Agnès Libois, Vermeersch, S., Demeester, RP, Ausselet, N, Callens, S, De Munter, P, Florence, E, Goffard, JC, Henrard, S, Lacor, P, MESSIAEN, Peter, Libois, A, Seyler, L, Uurlings, F, Vandecasteele, S.J., Van Wijngaerden, E, Yombi, JC, Annemans, L, De Wit, S, UZB Other, Clinical sciences, Microbiology and Infection Control, Internal Medicine, Public Health Sciences, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Pathologie infectieuse, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service de médecine interne générale

Subjects
medicine.medical_specialty, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, infectious diseases, 1ST, Value-based healthcare, Nursing, Patient-Centered Care, medicine, Internal Medicine, Humans, Indicators, Public health, Science & Technology, Frameworks, MEDICINE, Health Policy, Research, Public Health, Environmental and Occupational Health, HIV, PERFORMANCE, Health Care Sciences & Services, Value based healthcare, HIV Infections/epidemiology, Business, Health Facilities, Public aspects of medicine, RA1-1270, PAY, Life Sciences & Biomedicine, Delivery of Health Care
Abstract

Background HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. Methods A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. Results Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). Conclusions This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework’s implementation in practice.

Published
2022

92. RegaDB: community-driven data management and analysis for infectious diseases

Author

Dan Otelea, Eric Van Wijngaerden, Paul De Munter, Martine Peeters, Anne-Mieke Vandamme, Pieter Libin, Joke Snoeck, Stijn Imbrechts, Zehava Grossman, Stefan Wesner, Koen Deforche, Annelies De Bel, Luiz Carlos Junior Alcantara, Jean Ruelle, Ahidjo Ayouba, Simona Paraschiv, Matthias Assel, Kristof Theys, Fossie Ferreira, Gertjan Beheydt, Rolf Kaiser, Carlo Torti, Patrick Lacor, Ricardo Jorge Camacho, Maurizio Zazzi, Joana Cavaco-Silva, Kristel Van Laethem, Tulio de Oliveira, Charles A. Boucher, Giuseppe Lapadula, Peter M. A. Sloot, Ana Patricia Carvalho, Computational Science Lab (IVI, FNWI), Centro de Malária e outras Doenças Tropicais (CMDT), Libin, P, Beheydt, G, Deforche, K, Imbrechts, S, Ferreira, F, Van Laethem, K, Theys, K, Carvalho, A, Cavaco-Silva, J, Lapadula, G, Torti, C, Assel, M, Wesner, S, Snoeck, J, Ruelle, J, De Bel, A, Lacor, P, De Munter, P, Van Wijngaerden, E, Zazzi, M, Kaiser, R, Ayouba, A, Peeters, M, De Oliveira, T, Alcantara, L, Grossman, Z, Sloot, P, Otelea, D, Paraschiv, S, Boucher, C, Camacho, R, Vandamme, A, School of Computer Engineering, Cell biology, and Virology

Subjects
Statistics and Probability, Source code, Databases, Factual, Database Management Systems, Humans, Software, Virus Diseases, Computer science, Interface (Java), Data management, media_common.quotation_subject, Databases and Ontologies, Biochemistry, World Wide Web, Databases, 03 medical and health sciences, Documentation, SDG 3 - Good Health and Well-being, Database Management System, Molecular Biology, Factual, 030304 developmental biology, media_common, 0303 health sciences, 030306 microbiology, business.industry, Engineering::Computer science and engineering::Computer applications::Life and medical sciences [DRNTU], Applications Notes, Data science, 3. Good health, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, business, Human
Abstract

Summary: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyze patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface. Availability and implementation: Source code, binaries and documentation are available on http://regaweb.med.kuleuven.be/software/regadb/ RegaDB is written in the Java programming language, using a web-service oriented architecture. Contact: pieter.libin@rega.kuleuven.be Supplementary information: Supplementary material demonstrating the functionalities of the system is available at Bioinformatics online. Published version

Published
2013
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95. Evaluation and implementation of optimized antimicrobial dosing strategies in obese and underweight patients.

Author

Caubergs V, Van den Broucke E, Mertens B, Gijsen M, Peetermans WE, Van Wijngaerden E, Desmet S, Lagrou K, Declercq P, Quintens C, and Spriet I

Subjects
Humans, Male, Female, Middle Aged, Aged, Adult, Antimicrobial Stewardship, Anti-Infective Agents administration & dosage, Anti-Infective Agents therapeutic use, Inappropriate Prescribing statistics & numerical data, Inappropriate Prescribing prevention & control, Obesity complications, Obesity drug therapy, Thinness, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use
Abstract

Purpose: We aimed to develop and implement dosing recommendations for antimicrobials in obese and underweight patients within an academic hospital, and assess their impact on antibiotic prescribing., Methods: A multi-step approach project was performed. First, obese and underweight patient prevalence and antimicrobial prescription frequency was determined in a point prevalence study. Second and third, a literature review and e-survey provided dosing evidence. Fourth, a consensus meeting was organized to formulate dosing recommendations. Fifth, these were implemented in our clinical validation service as six clinical rules continuously screening patients' records for potentially inappropriate prescriptions (PIPs). Uptake was evaluated by documenting the number of advices and acceptance rate. Last, an interrupted time series analysis (ITS) compared pre- and post-implementation periods to measure the impact of the intervention on residual PIPs/day. A residual PIP was defined as a PIP which persisted up to 48 h., Results: First, 41% of 15.896 hospitalized patients received antimicrobials over 20 days; of which 12% were obese and 9% underweight. Antibiotics were predominantly prescribed according to standard dosing regimens, adjusted to renal function. Next, six dosing recommendations, derived from literature, survey, and consensus, were implemented. In the fifth step, during an 18-week period, 219 advices were given, with 86% acceptance rate. Last, in the ITS analysis, at preintervention, a median of 75% residual PIPs/day existed, reduced to 0% postintervention. Use of clinical rules resulted in a significant immediate 84% relative reduction in residual PIPs (95% CI 0.55-0.94)., Conclusion: After conducting a literature review, e-survey, and seeking consensus from a panel of experts, dosing recommendations for antimicrobial treatment in both obese and underweight patients were developed. These recommendations have been successfully implemented into clinical practice, addressing the specific needs of these patient populations., Competing Interests: Declarations. Conflict of interest: I declare that the authors have no competing interests as defined by Springer, or other interests that might be perceived to influence the results and/or discussion reported in this paper. The authors have no relevant financial or non-financial interests to disclose. Ethical approval: This study involves human participants and was approved by the institutional and/or national research committee (Ethics Committee Research UZ Leuven, Belgium; S61615). Pharmacist recommendations were provided to the treating physician, who finally had to decide on treatment adaptation. Patients were therefore not obliged to provide informed consent., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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96. Attributable mortality of candidemia - Results from the ECMM Candida III multinational European Observational Cohort Study.

Author

Salmanton-García J, Cornely OA, Stemler J, Barać A, Steinmann J, Siváková A, Akalin EH, Arikan-Akdagli S, Loughlin L, Toscano C, Narayanan M, Rogers B, Willinger B, Akyol D, Roilides E, Lagrou K, Mikulska M, Denis B, Ponscarme D, Scharmann U, Azap A, Lockhart D, Bicanic T, Kron F, Erben N, Rautemaa-Richardson R, Goodman AL, Garcia-Vidal C, Lass-Flörl C, Gangneux JP, Taramasso L, Ruiz M, Schick Y, Van Wijngaerden E, Milacek C, Giacobbe DR, Logan C, Rooney E, Gori A, Akova M, Bassetti M, Hoenigl M, and Koehler P

Subjects
Humans, Male, Female, Middle Aged, Europe epidemiology, Aged, Risk Factors, Cohort Studies, Adult, Aged, 80 and over, Antifungal Agents therapeutic use, Case-Control Studies, Candidemia mortality, Candidemia microbiology, Candida isolation & purification, Candida classification
Abstract

Introduction: Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections., Methods: In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed., Results: One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004)., Conclusions: Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: The authors do not declare conflicts of interest related to the submitted manuscript. The funder of the study (Scynexis) had no role in study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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97. (1-3)-ß-D-glucan for the diagnosis of Nocardia infection in solid organ transplant recipients.

Author

Paumier M, Coussement J, Matignon M, Chauvet C, Bouvier N, Poncelet A, Dantal J, Scemla A, Ceunen H, Van Wijngaerden E, Kamar N, van der Beek MT, Wunderink HF, De Greef J, Candon S, Bougnoux ME, and Lebeaux D

Subjects
Humans, Glucans, Transplant Recipients, Nocardia Infections diagnosis, Nocardia Infections drug therapy, Nocardia, Organ Transplantation adverse effects
Abstract

Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.

Published
2024
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98. High Burden of COVID-19-Associated Pulmonary Aspergillosis in Severely Immunocompromised Patients Requiring Mechanical Ventilation.

Author

Feys S, Lagrou K, Lauwers HM, Haenen K, Jacobs C, Brusselmans M, Debaveye Y, Hermans G, Hoenigl M, Maertens J, Meersseman P, Peetermans M, Spriet I, Vandenbriele C, Vanderbeke L, Vos R, Van Wijngaerden E, Wilmer A, and Wauters J

Subjects
Adult, Animals, Humans, Critical Illness, Respiration, Artificial, Retrospective Studies, Immunocompromised Host, COVID-19 complications, COVID-19 epidemiology, Pulmonary Aspergillosis complications, Pulmonary Aspergillosis epidemiology, Invasive Pulmonary Aspergillosis
Abstract

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated with increased mortality rates. The increasing proportion of severely immunocompromised patients with COVID-19 who require mechanical ventilation warrants research into the incidence and impact of CAPA during the vaccination era., Methods: We performed a retrospective, monocentric, observational study. We collected data from adult patients with severe COVID-19 requiring mechanical ventilation who were admitted to the intensive care unit (ICU) of University Hospitals Leuven, a tertiary referral center, between 1 March 2020 and 14 November 2022. Probable or proven CAPA was diagnosed according to the 2020 European Confederation for Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) criteria., Results: We included 335 patients. Bronchoalveolar lavage sampling was performed in 300 (90%), and CAPA was diagnosed in 112 (33%). The incidence of CAPA was 62% (50 of 81 patients) in European Organisation for Research and Treatment of Cancer (EORTC)/Mycosis Study Group Education and Research Consortium (MSGERC) host factor-positive patients, compared with 24% (62 of 254) in host factor-negative patients. The incidence of CAPA was significantly higher in the vaccination era, increasing from 24% (57 of 241) in patients admitted to the ICU before October 2021 to 59% (55 of 94) in those admitted since then. Both EORTC/MSGERC host factors and ICU admission in the vaccination era were independently associated with CAPA development. CAPA remained an independent risk factor associated with mortality risk during the vaccination era., Conclusions: The presence of EORTC/MSGERC host factors for invasive mold disease is associated with increased CAPA incidence and worse outcome parameters, and it is the main driver for the significantly higher incidence of CAPA in the vaccination era. Our findings warrant investigation of antifungal prophylaxis in critically ill patients with COVID-19., Competing Interests: Potential conflicts of interest. S. F. and L. V. report PhD funding from the Research Foundation–Flanders (FWO; grants 11M6922N and 11E9819N). S. F. reports receipt of travel grants from Pfizer and Gilead and speaker fees from Healthbook. K. L. received consultancy fees from MRM Health, Merck Sharp and Dohme (MSD), and Mundipharma, speaker fees and travel support from Pfizer and Gilead, and a service fee from Thermo Fisher Scientific and TECOmedical and participated on an advisory board for MSD. Y. D. received travel grants from Pfizer (travel/congress attendance support) and declares participation on advisory boards for Pfizer and MSD. G. H. and R. V. are senior clinical research fellows of FWO. G. H. received travel fees from Eurosets for the 2023 Extracorporeal Life Support Organization meeting. M. H. received grants from Astellas, Gilead, MSD, Pfizer, Euroimmun, IMMY, Mundipharma, F2G, Pulmocide, and Scynexis and research funding from Gilead Sciences, Astellas, Mundipharma, Euroimmun, MSD, Pulmocide, IMMY, Scynexis, F2G, and Pfizer. J. M. received grants from Bio-Rad, Gilead Sciences, MSD, F2G, Mundipharma, and Pfizer; personal fees and nonfinancial support from Astellas, Basilea, Gilead Sciences, MSD, F2G, Mundipharma, and Pfizer; and personal fees from Bio-Rad. M. P. received travel fees from Pfizer (March 2023; registration for the 2023 International Symposium on Intensive Care & Emergency Medicine (ISICEM) in Brussels, Belgium). I. S. received funding from the Clinical Research Fund, University Hospitals Leuven, investigator-initiated grants from Pfizer, and speaker and travel fees from Pfizer, Gilead, and MSD, and reports participation on an advisory board for Pfizer and Gilead, and receipt of study drugs from MSD. L. V. received support for public doctoral defense from Pfizer and travel fees for conference attendance from Gilead Sciences and Pfizer and reports a PhD fellowship (grant 11E9819N) from FWO. R. V. reports an FWO fellowship and grant (grant G060322N). E. V. W. received travel fees from Gilead (for travel, hotel, and registration). J. W. received investigator-initiated grants from Pfizer, Gilead, and MSD and speaker and travel fees from Pfizer, Gilead, and MSD, and declares participation on advisory boards of Pfizer and Gilead and receipt of study drugs from MSD. J. W. also reports funding from the European Union's Horizon 2020 research and innovation program (grant 847507 HDM-FUN) and FWO project funding (grant G053121N). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2024
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99. Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes.

Author

Christensen KT, Pierard F, Bonsall D, Bowden R, Barnes E, Florence E, Ansari MA, Nguyen D, de Cesare M, Nevens F, Robaeys G, Schrooten Y, Busschots D, Simmonds P, Vandamme AM, Van Wijngaerden E, Dierckx T, Cuypers L, and Van Laethem K

Subjects
Male, Humans, Hepacivirus genetics, Phylogeny, Homosexuality, Male, Belgium epidemiology, High-Throughput Nucleotide Sequencing, Substance Abuse, Intravenous complications, HIV Infections, Sexual and Gender Minorities, Hepatitis C, HIV Seropositivity
Abstract

The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium.

Published
2023
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100. A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Author

Vanderbeke L, Jacobs C, Feys S, Reséndiz-Sharpe A, Debaveye Y, Hermans G, Humblet-Baron S, Lagrou K, Meersseman P, Peetermans M, Seldeslachts L, Vanstapel A, Vande Velde G, Van Wijngaerden E, Wilmer A, Verbeken E, De Hertogh G, and Wauters J

Subjects
Adult, Aged, Female, Humans, Male, Middle Aged, Autopsy, Intensive Care Units, Retrospective Studies, Hospital Mortality, COVID-19 mortality, COVID-19 pathology, Influenza, Human mortality, Influenza, Human pathology, Invasive Pulmonary Aspergillosis diagnosis, Invasive Pulmonary Aspergillosis mortality, Invasive Pulmonary Aspergillosis pathology, Invasive Pulmonary Aspergillosis virology
Abstract

Rationale: Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated. Objectives: We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 ICU fatalities in a tertiary care center. Methods: In this monocentric, descriptive, retrospective case series, we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure who underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the Intensive Care Medicine influenza-associated pulmonary aspergillosis and the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) COVID-19-associated pulmonary aspergillosis consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. Measurements and Main Results: In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as a missed diagnosis upon autopsy in 8% of proven cases ( n  = 1/12), yet it was most frequently found as confirmation of a probable antemortem diagnosis ( n  = 11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed the highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza ( n  = 3) and COVID-19 ( n  = 3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Conclusions: A proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case fatalities. Our findings highlight an important need for VAPA awareness, with an emphasis on mycological bronchoscopic work-up.

Published
2023
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