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1. Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infectionResearch in context

Author

Lihui Guo, Brent Appelman, Kirsten Mooij-Kalverda, Riekelt H. Houtkooper, Michel van Weeghel, Frédéric M. Vaz, Annemiek Dijkhuis, Tamara Dekker, Barbara S. Smids, Jan Willem Duitman, Marianna Bugiani, Paul Brinkman, Jonne J. Sikkens, H.A. Ayesha Lavell, Rob C.I. Wüst, Michèle van Vugt, René Lutter, M.A. van Agtmael, A.G. Algera, B. Appelman, F.E.H.P. van Baarle, M. Beudel, H.J. Bogaard, M. Bomers, P.I. Bonta, L.D.J. Bos, M. Botta, J. de Brabander, G.J. de Bree, S. de Bruin, M. Bugiani, E.B. Bulle, O. Chouchane, A.P.M. Cloherty, D. Buis, M.C.F.J. de Rotte, M. Dijkstra, D.A. Dongelmans, R.W.G. Dujardin, P.E. Elbers, L.M. Fleuren, S.E. Geerlings, T.B.H. Geijtenbeek, A.R.J. Girbes, A. Goorhuis, M.P. Grobusch, L.A. Hagens, J. Hamann, V.C. Harris, R. Hemke, S.M. Hermans, L.M.A. Heunks, M.W. Hollmann, J. Horn, J.W. Hovius, M.D. de Jong, R. Koing, E.H.T. Lim, N. van Mourik, J.F. Nellen, E.J. Nossent, F. Paulus, E. Peters, D. Piña-Fuentes, T. van der Poll, B. Preckel, J.M. Prins, S.J. Raasveld, T.D.Y. Reijnders, M. Schinkel, F.A.P. Schrauwen, M.J. Schultz, A.R. Schuurman, J. Schuurmans, K. Sigaloff, M.A. Slim, P. Smeele, M.R. Smit, C. Stijnis, W. Stilma, C.E. Teunissen, P. Thoral, A.M. Tsonas, P.R. Tuinman, M. van der Valk, D.P. Veelo, C. Volleman, H. de Vries, L.A. van Vught, M. van Vugt, D. Wouters, A.H. Zwinderman, M.C. Brouwer, W.J. Wiersinga, A.P.J. Vlaar, and D. van de Beek

Subjects
IDO2, PASC, Autophagy, Apoptosis, Kynurenine, Mitochondrial_activity, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology. Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC. We assessed tryptophan and its degradation products by UPLC-MS/MS. IDO2 activity, its potential consequences, and the involvement of the aryl hydrocarbon receptor (AHR) in IDO2 expression were determined in PBMC from another PASC cohort by immunohistochemistry (IHC) for IDO2, IDO1, AHR, kynurenine metabolites, autophagy, and apoptosis. These PBMC were also analyzed by metabolomics and for mitochondrial functioning by respirometry. IHC was also performed on autopsy brain material from two PASC patients. Findings: IDO2 is expressed and active in PBMC from PASC patients, as well as in brain tissue, long after SARS-CoV-2 infection. This is paralleled by autophagy, and in blood cells by reduced mitochondrial functioning, reduced intracellular levels of amino acids and Krebs cycle-related compounds. IDO2 expression and activity is triggered by SARS-CoV-2-infection, but the severity of SARS-CoV-2-induced pathology appears related to the generated specific kynurenine metabolites. Ex vivo, IDO2 expression and autophagy can be halted by an AHR antagonist. Interpretation: SARS-CoV-2 infection triggers long-lasting IDO2 expression, which can be halted by an AHR antagonist. The specific kynurenine catabolites may relate to SARS-CoV-2-induced symptoms and pathology. Funding: None.

Published
2023
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2. Improving indicator-condition guided testing for HIV in the hospital setting (PROTEST 2·0): A multicenter, interrupted time-series analysis

Author

Saskia J. Bogers, Maarten F. Schim van der Loeff, Anders Boyd, Udi Davidovich, Marc van der Valk, Kees Brinkman, Kim Sigaloff, Judith Branger, Nejma Bokhizzou, Godelieve J. de Bree, Peter Reiss, Jan E.A.M. van Bergen, Suzanne E. Geerlings, T. van Benthem, D. Bons, G.J. de Bree, P. Brokx, U. Davidovich, F. Deug, S.E. Geerlings, M. Heidenrijk, E. Hoornenborg, M. Prins, P. Reiss, A. van Sighem, M. van der Valk, J. de Wit, W. Zuilhof, N. Schat, D. Smith, M. van Agtmael, J. Ananworanich, D. Van de Beek, G.E.L. van den Berk, D. Bezemer, A. van Bijnen, J.P. Bil, W.L. Blok, S.J. Bogers, M. Bomers, A. Boyd, W. Brokking, D. Burger, K. Brinkman, N. Brinkman, M. de Bruin, S. Bruisten, L. Coyer, R. van Crevel, M. Dijkstra, Y.T. van Duijnhoven, A. van Eeden, L. Elsenburg, M.A.M. van den Elshout, E. Ersan, P.E.V. Felipa, T.B.H. Geijtenbeek, J. van Gool, A. Goorhuis, M. Groot, C.A. Hankins, A. Heijnen, M.M.J Hillebregt, M. Hommenga, J.W. Hovius, Y. Janssen, K. de Jong, V. Jongen, N.A. Kootstra, R.A. Koup, F.P. Kroon, T.J.W. van de Laar, F. Lauw, M.M. van Leeuwen, K. Lettinga, I. Linde, D.S.E. Loomans, I.M. van der Lubben, J.T. van der Meer, T. Mouhebati, B.J. Mulder, J. Mulder, F.J. Nellen, A. Nijsters, H. Nobel, E.L.M. Op de Coul, E. Peters, I.S. Peters, T. van der Poll, O. Ratmann, C. Rokx, M.F. Schim van der Loeff, W.E.M. Schouten, J. Schouten, J. Veenstra, A. Verbon, F. Verdult, J. de Vocht, H.J. de Vries, S. Vrouenraets, M. van Vugt, W.J. Wiersinga, F.W. Wit, L.R. Woittiez, S. Zaheri, P. Zantkuijl, A. Żakowicz, M.C. van Zelm, and H.M.L. Zimmermann

Subjects
HIV, HIV testing, Indicator condition, Tuberculosis, Cervical carcinoma, Cervical dysplasia, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Indicator-condition (IC) guided HIV testing is a feasible and cost-effective strategy to identify undiagnosed people living with HIV (PLHIV), but remains insufficiently implemented. We aimed to promote IC-guided HIV testing in seven ICs. Methods: Relevant departments in five hospitals of the Amsterdam region participated. HIV testing among adult patients without known HIV infection but with an IC was assessed using electronic health records during pre-intervention (January 2015–June 2020) and intervention (July 2020–June 2021) periods. The multifaceted intervention included audit and feedback. The primary endpoint was HIV testing ≤3 months before or after IC diagnosis and the effect of the intervention was evaluated using segmented Poisson regression. Findings: Data from 7986 patients were included, of whom 6730 (84·3%) were diagnosed with an IC in the pre-intervention period and 1256 (15·7%) in the intervention period. The proportion HIV tested ≤3 months before or after IC diagnosis increased from 36.8% to 47.0% (adjusted risk ratio [RR]= 1.16, 95% CI=1.03–1.30, p=0.02). For individual ICs, we observed significant increases in HIV testing among patients with cervical cancer or intraepithelial neoplasia grade 3 (adjusted RR=3.62, 95% CI=1.93–6.79) and peripheral neuropathy (adjusted RR=2.27 95% CI=1.48–3.49), but not the other ICs. Eighteen of 3068 tested patients were HIV positive (0.6%). Interpretation: Overall IC-guided testing improved after the intervention, but not for all ICs. Variations in effect by IC may have been due to variations in implemented developments, but the effect of separate elements could not be assessed. Funding: HIV Transmission Elimination Amsterdam (H-TEAM) initiative, Aidsfonds (grant number: P-42702).

Published
2022
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3. Lung Microbiota of Critically Ill Patients with COVID-19 Are Associated with Nonresolving Acute Respiratory Distress Syndrome

Author

Robert F. J. Kullberg, Justin de Brabander, Leonoor S. Boers, Jason J. Biemond, Esther J. Nossent, Leo M. A. Heunks, Alexander P. J. Vlaar, Peter I. Bonta, Tom van der Poll, JanWillem Duitman, Lieuwe D. J. Bos, W. Joost Wiersinga, Anno Saris, Heder De Vries, Lilian J. Meijboom, Siebe G. Blok, Alex R. Schuurman, Tom D.Y. Reijnders, Juan J. Garcia Vallejo, Hetty Bontkes, René Lutter, Harm Jan Bogaard, S. de Bruin, R. Koning, M.A. van Agtmael, A.G. Algera, F.E.H.P. van Baarle, D.J.C. Bax, M. Beudel, M. Bomers, M. Botta, G.J. de Bree, M. Bugiani, E.B. Bulle, O. Chouchane, A.P.M. Cloherty, P.E. Elbers, L.M. Fleuren, S.E. Geerlings, B.F. Geerts, T.B.H. Geijtenbeek, A.R.J. Girbes, A. Goorhuis, M.P. Grobusch, F.M.J. Hafkamp, L.A. Hagens, J. Hamann, V.C. Harris, R. Hemke, S.M. Hermans, M.W. Hollmann, J. Horn, J.W. Hovius, M.D. de Jong, N. van Mourik, J.F Nellen, F. Paulus, E. Peters, B. Preckel, S.J. Raasveld, M. Schinkel, M.J. Schultz, K. Sigaloff, M.R. Smit, C. Stijnis, W. Stilma, C.E. Teunissen, P. Thoral, A.M. Tsonas, M. van der Valk, D.P. Veelo, M. van Vugt, D. Wouters, A.H. Zwinderman, M.C. Brouwer, D. van de Beek, Internal medicine, Pulmonary medicine, CCA - Cancer Treatment and quality of life, VU University medical center, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, Center of Experimental and Molecular Medicine, Graduate School, Intensive Care Medicine, ACS - Microcirculation, AII - Inflammatory diseases, Pulmonology, Infectious diseases, and 01 Internal and external specialisms

Subjects
Pulmonary and Respiratory Medicine, Respiratory Distress Syndrome, Tumor Necrosis Factor-alpha, Critical Illness, Microbiota, host–microbial interactions, COVID-19, Critical Care and Intensive Care Medicine, Respiration, Artificial, RNA, Ribosomal, 16S, Humans, artificial respiration, lung microbiome, Lung
Abstract

Rationale: Bacterial lung microbiota are correlated with lung inflammation and acute respiratory distress syndrome (ARDS) and altered in severe coronavirus disease (COVID-19). However, the association between lung microbiota (including fungi) and resolution of ARDS in COVID-19 remains unclear. We hypothesized that increased lung bacterial and fungal burdens are related to nonresolving ARDS and mortality in COVID-19. Objectives: To determine the relation between lung microbiota and clinical outcomes of COVID-19-related ARDS. Methods: This observational cohort study enrolled mechanically ventilated patients with COVID-19. All patients had ARDS and underwent bronchoscopy with BAL. Lung microbiota were profiled using 16S rRNA gene sequencing and quantitative PCR targeting the 16S and 18S rRNA genes. Key features of lung microbiota (bacterial and fungal burden, α-diversity, and community composition) served as predictors. Our primary outcome was successful extubation adjudicated 60 days after intubation, analyzed using a competing risk regression model with mortality as competing risk. Measurements and Main Results: BAL samples of 114 unique patients with COVID-19 were analyzed. Patients with increased lung bacterial and fungal burden were less likely to be extubated (subdistribution hazard ratio, 0.64 [95% confidence interval, 0.42-0.97]; P = 0.034 and 0.59 [95% confidence interval, 0.42-0.83]; P = 0.0027 per log10 increase in bacterial and fungal burden, respectively) and had higher mortality (bacterial burden, P = 0.012; fungal burden, P = 0.0498). Lung microbiota composition was associated with successful extubation (P = 0.0045). Proinflammatory cytokines (e.g., tumor necrosis factor-α) were associated with the microbial burdens. Conclusions: Bacterial and fungal lung microbiota are related to nonresolving ARDS in COVID-19 and represent an important contributor to heterogeneity in COVID-19-related ARDS.

Published
2022
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4. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Author

Bernard Surial, Adrià Ramírez Mena, Marie Roumet, Andreas Limacher, Colette Smit, Olivier Leleux, Amanda Mocroft, Marc van der Valk, Fabrice Bonnet, Lars Peters, Jürgen K. Rockstroh, Huldrych F. Günthard, Annalisa Berzigotti, Andri Rauch, Gilles Wandeler, I. Abela, K. Aebi-Popp, A. Anagnostopoulos, M. Battegay, E. Bernasconi, D.L. Braun, H.C. Bucher, A. Calmy, M. Cavassini, A. Ciuffi, G. Dollenmaier, M. Egger, L. Elzi, J. Fehr, J. Fellay, H. Furrer, C.A. Fux, H.F. Günthard, A. Hachfeld, D. Haerry, B. Hasse, H.H. Hirsch, M. Hoffmann, I. Hösli, M. Huber, D. Jackson-Perry, C.R. Kahlert, L. Kaiser, O. Keiser, T. Klimkait, R.D. Kouyos, H. Kovari, K. Kusejko, N. Labhardt, K. Leuzinger, Martinez de Tejada B, C. Marzolini, K.J. Metzner, N. Müller, J. Nemeth, D. Nicca, J. Notter, P. Paioni, G. Pantaleo, M. Perreau, A. Rauch, L. Salazar-Vizcaya, P. Schmid, R. Speck, M. Stöckle, P. Tarr, A. Trkola, G. Wandeler, M. Weisser, S. Yerly, M. van der Valk, S.E. Geerlings, A. Goorhuis, V.C. Harris, J.W. Hovius, B. Lempkes, F.J.B. Nellen, T. van der Poll, J.M. Prins, V. Spoorenberg, M. van Vugt, W.J. Wiersinga, F.W.M.N. Wit, C. Bruins, J. van Eden, I.J. Hylkema-van den Bout, A.M.H. van Hes, F.J.J. Pijnappel, S.Y. Smalhout, A.M. Weijsenfeld, N.K.T. Back, B. Berkhout, M.T.E. Cornelissen, R. van Houdt, M. Jonges, S. Jurriaans, C.J. Schinkel, K.C. Wolthers, H.L. Zaaijer, E.J.G. Peters, M.A. van Agtmael, R.S. Autar, M. Bomers, K.C.E. Sigaloff, M. Heitmuller, L.M. Laan, M. van den Berge, A. Stegeman, S. Baas, L. Hage de Looff, A. van Arkel, J. Stohr, B. Wintermans, M.J.H. Pronk, H.S.M. Ammerlaan, E.S. de Munnik, B. Deiman, A.R. Jansz, V. Scharnhorst, J. Tjhie, M.C.A. Wegdam, A. van Eeden, E. Hoornenborg, J. Nellen, W. Alers, L.J.M. Elsenburg, H. Nobel, M.E.E. van Kasteren, M.A.H. Berrevoets, A.E. Brouwer, B.A.F.M. de Kruijf-van de Wiel, A. Adams, M. Pawels-van Rijkevoorsel, A.G.M. Buiting, J.L. Murck, C. Rokx, A.A. Anas, H.I. Bax, E.C.M. van Gorp, M. de Mendonça Melo, E. van Nood, J.L. Nouwen, B.J.A. Rijnders, C.A.M. Schurink, L. Slobbe, T.E.M.S. de Vries-Sluijs, N. Bassant, J.E.A. van Beek, M. Vriesde, L.M. van Zonneveld, J. de Groot, J.J.A. van Kampen, M.P.G. Koopmans, J.C. Rahamat-Langendoen, J. Branger, R.A. Douma, A.S. Cents-Bosma, C.J.H.M. Duijf-van de Ven, E.F. Schippers, C. van Nieuwkoop, J. Geilings, S. van Winden, G. van der Hut, N.D. van Burgel, E.M.S. Leyten, L.B.S. Gelinck, F. Mollema, G.S. Wildenbeest, T. Nguyen, P.H.P. Groeneveld, J.W. Bouwhuis, A.J.J. Lammers, A.G.W. van Hulzen, S. Kraan, M.S.M. Kruiper, G.L. van der Bliek, P.C.J. Bor, S.B. Debast, G.H.J. Wagenvoort, A.H.E. Roukens, M.G.J. de Boer, H. Jolink, M.M.C. Lambregts, H. Scheper, W. Dorama, N. van Holten, E.C.J. Claas, E. Wessels, J.G. den Hollander, R. El Moussaoui, K. Pogany, C.J. Brouwer, D. Heida-Peters, E. Mulder, J.V. Smit, D. Struik-Kalkman, T. van Niekerk, O. Pontesilli, C. van Tienen, S.H. Lowe, A.M.L. Oude Lashof, D. Posthouwer, M.E. van Wolfswinkel, R.P. Ackens, K. Burgers, M. Elasri, J. Schippers, T.R.A. Havenith, M. van Loo, M.G.A. van Vonderen, L.M. Kampschreur, M.C. van Broekhuizen, null S, null Faber, A. Al Moujahid, G.J. Kootstra, C.E. Delsing, M. van der Burg-van de Plas, L. Scheiberlich, W. Kortmann, G. van Twillert, R. Renckens, J. Wagenaar, D. Ruiter-Pronk, F.A. van Truijen-Oud, J.W.T. Cohen Stuart, M. Hoogewerf, W. Rozemeijer, J.C. Sinnige, K. Brinkman, G.E.L. van den Berk, K.D. Lettinga, M. de Regt, W.E.M. Schouten, J.E. Stalenhoef, J. Veenstra, S.M.E. Vrouenraets, H. Blaauw, G.F. Geerders, M.J. Kleene, M. Knapen, M. Kok, I.B. van der Meché, A.J.M. Toonen, S. Wijnands, E. Wttewaal, D. Kwa, T.J.W. van de Laar, R. van Crevel, K. van Aerde, A.S.M. Dofferhoff, S.S.V. Henriet, H.J.M. ter Hofstede, J. Hoogerwerf, O. Richel, M. Albers, K.J.T. Grintjes-Huisman, M. de Haan, M. Marneef, M. McCall, D. Burger, E.H. Gisolf, M. Claassen, R.J. Hassing, G. ter Beest, P.H.M. van Bentum, M. Gelling, Y. Neijland, C.M.A. Swanink, M. Klein Velderman, S.F.L. van Lelyveld, R. Soetekouw, L.M.M. van der Prijt, J. van der Swaluw, J.S. Kalpoe, A. Wagemakers, A. Vahidnia, F.N. Lauw, D.W.M. Verhagen, M. van Wijk, W.F.W. Bierman, M. Bakker, R.A. van Bentum, M.A. van den Boomgaard, J. Kleinnijenhuis, E. Kloeze, A. Middel, D.F. Postma, H.M. Schenk, Y. Stienstra, M. Wouthuyzen-Bakker, A. Boonstra, H. de Jonge, M.M.M. Maerman, D.A. de Weerd, K.J. van Eije, M. Knoester, C.C. van Leer-Buter, H.G.M. Niesters, null T.Mudrikova, R.E. Barth, A.H.W. Bruns, P.M. Ellerbroek, M.P.M. Hensgens, J.J. Oosterheert, E.M. Schadd, A. Verbon, B.J. van Welzen, H. Berends, B.M.G. Griffioen-van Santen, I. de Kroon, F.M. Verduyn Lunel, A.M.J. Wensing, S. Zaheri, A.C. Boyd, D.O. Bezemer, A.I. van Sighem, C. Smit, M.M.J. Hillebregt, T.J. Woudstra, T. Rutkens, D. Bergsma, N.M. Brétin, K.J. Lelivelt, L. van de Sande, K.M. Visser.S.T. van der Vliet, F. Paling, L.G.M. de Groot-Berndsen, M. van den Akker, R. Alexander, Y. Bakker, A. El Berkaoui, M. Bezemer-Goedhart, E.A. Djoechro, M. Groters, L.E. Koster, C.R.E. Lodewijk, E.G.A. Lucas, L. Munjishvili, B.M. Peeck, C.M.J. Ree, R. Regtop, A.F. van Rijk, Y.M.C. Ruijs-Tiggelman, P.P. Schnörr, M.J.C. Schoorl, E.M. Tuijn, D.P. Veenenberg, E.C.M. Witte, I. Karpov, M. Losso, J. Lundgren, J. Rockstroh, I. Aho, L.D. Rasmussen, P. Novak, C. Pradier, N. Chkhartishvili, R. Matulionyte, C. Oprea, J.D. Kowalska, J. Begovac, J.M. Miró, G. Guaraldi, R. Paredes, L. Peters, J.F. Larsen, B. Neesgaard, N. Jaschinski, O. Fursa, D. Raben, D. Kristensen, A.H. Fischer, S.K. Jensen, T.W. Elsing, M. Gardizi, A. Mocroft, A. Phillips, J. Reekie, A. Cozzi-Lepri, A. Pelchen-Matthews, A. Roen, E.S. Tusch, W. Bannister, P. Bellecave, P. Blanco, F. Bonnet, S. Bouchet, D. Breilh, C. Cazanave, S. Desjardin, V. Gaborieau, A. Gimbert, M. Hessamfar, L. Lacaze-Buzy, D. Lacoste, M.E. Lafon, E. Lazaro, O. Leleux, F. Le Marec, G. Le Moal, D. Malvy, L. Marchand, P. Mercié, D. Neau, I. Pellegrin, A. Perrier, V. Petrov-Sanchez, M.O. Vareil, L. Wittkop, N. Bernard, D. Bronnimann H. Chaussade, D. Dondia, P. Duffau, I. Faure, P. Morlat, E. Mériglier, F. Paccalin, E. Riebero, C. Rivoisy, M.A. Vandenhende, L. Barthod, F.A. Dauchy, A. Desclaux, M. Ducours, H. Dutronc, A. Duvignaud, J. Leitao, M. Lescure, D. Nguyen, T. Pistone, M. Puges, G. Wirth, C. Courtault, F. Camou, C. Greib, J.L. Pellegrin, E. Rivière, J.F. Viallard, Y. Imbert, M. Thierry-Mieg, P. Rispal, O. Caubet, H. Ferrand, S. Tchamgoué, S. Farbos, H. Wille, K. Andre, L. Caunegre, Y. Gerard, F. Osorio-Perez, I. Chossat, G. Iles, M. Labasse-Depis, F. Lacassin, A. Barret, B. Castan, J. Koffi, N. Rouanes, A. Saunier, J.B. Zabbe, G. Dumondin, G. Beraud, M. Catroux, M. Garcia, V. Giraud, J.P. Martellosio, F. Roblot, T. Pasdeloup, A. Riché, M. Grosset, S. Males, C. Ngo Bell, C. Carpentier, Virology P. Bellecave, C. Tumiotto, G. Miremeont-Salamé, D. Arma, G. Arnou, M.J. Blaizeau, P. Camps, M. Decoin, S. Delveaux, F. Diarra, L. Gabrea, S. Lawson-Ayayi, E. Lenaud, D. Plainchamps, A. Pougetoux, B. Uwamaliya, K. Zara, V. Conte, M. Gapillout, Internal medicine, VU University medical center, Medical Microbiology and Infection Prevention, AII - Infectious diseases, CCA - Cancer biology and immunology, AII - Inflammatory diseases, AMS - Rehabilitation & Development, APH - Quality of Care, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Ethics, Law & Medical humanities, APH - Methodology, Midwifery Science, Amsterdam Reproduction & Development (AR&D), Infectious diseases, APH - Digital Health, APH - Personalized Medicine, APH - Aging & Later Life, APH - Global Health, Global Health, APH - Health Behaviors & Chronic Diseases, Center of Experimental and Molecular Medicine, General Internal Medicine, AII - Cancer immunology, Landsteiner Laboratory, Cardiology, ACS - Heart failure & arrhythmias, Obstetrics and Gynaecology, ARD - Amsterdam Reproduction and Development, Microbes in Health and Disease (MHD), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Global Health in the Global South (GHiGS), Institut de Recherche pour le Développement (IRD)- Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Hepatitis B virus, model validation, Hepatology, liver neoplasms, risk prediction models, liver cirrhosis, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], risk assessment, 610 Medicine & health, hepatocellular carcinoma, HIV infection, tenofovir, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 610 Medizin und Gesundheit
Abstract

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection.Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves.Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of

Published
2023
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5. High incidence of HCV in HIV-negative men who have sex with men using pre-exposure prophylaxis

Author

Elske Hoornenborg, Liza Coyer, Anders Boyd, Roel Christiaan Alfons Achterbergh, Maarten Franciscus Schim van der Loeff, Sylvia Bruisten, Henry John Christiaan de Vries, Jelle Koopsen, Thijs J.W. van de Laar, Maria Prins, J.E.A.M. van Bergen, G.J. de Bree, P. Brokx, F. Deug, M. Heidenrijk, M. Prins, P. Reiss, M. van der Valk, U. Davidovich, S.E. Geerlings, E. Hoornenborg, A. Oomen, A. van Sighem, W. Zuilhof, M.L. Groot Bruinderink, R.C.A. Achterbergh, M. van Agtmael, J. Ananworanich, D. Van de Beek, G.E.L. van den Berk, D. Bezemer, A. van Bijnen, W.L. Blok, S. Bogers, M. Bomers, C.A.B. Boucher, W. Brokking, D. Burger, K. Brinkman, N. Brinkman, M. de Bruin, S. Bruisten, L. Coyer, R. van Crevel, C.G. Daans, L. Dellemann, M. Dijkstra, Y.T. van Duijnhoven, A. van Eeden, L. Elsenburg, M.A.M. van den Elshout, C. Ester, E. Ersan, P.E.V. Felipa, P.H.J. Frissen, T.B.H. Geijtenbeek, M.H. Godfried, J. van Gool, A. Goorhuis, M. Groot, C.A. Hankins, A. Heijnen, M.M.J. Hillebregt, A. Hogewoning, M. Hommenga, J.W. Hovius, Y. Janssen, K. de Jong, V. Jongen, N.A. Kootstra, R.A. Koup, F.P. Kroon, T.J.W. van de Laar, F. Lauw, M.M. van Leeuwen, K. Lettinga, I. Linde, D.S.E. Loomans, J.T. van der Meer, T. Mouhebati, B.J. Mulder, J. Mulder, F.J. Nellen, A. Nijsters, H. Nobel, P. Oostvogel, E.L.M. Op de Coul, E. Peters, I.S. Peters, T. van der Poll, O. Ratmann, C. Rokx, M.S. van Rooijen, M.F. Schim van der Loeff, W.E.M. Schoute, G.J. Sonder, J. Veenstra, A. Verbon, F. Verdult, J. de Vocht, H.J. de Vries, S. Vrouenraets, M. van Vugt, W.J. Wiersinga, F.W. Wit, L.R. Woittiez, S. Zaheri, P. Zantkuijl, M.C. van Zelm, A. Żakowicz, H.M.L. Zimmermann, Anatomy and neurosciences, Internal medicine, AII - Infectious diseases, ACS - Diabetes & metabolism, Medical psychology, Molecular cell biology and Immunology, Amsterdam Movement Sciences - Rehabilitation & Development, Amsterdam Movement Sciences, AMS - Rehabilitation & Development, APH - Quality of Care, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Global Health, Graduate School, Infectious diseases, Medical Microbiology and Infection Prevention, Dermatology, General practice, ACS - Heart failure & arrhythmias, APH - Personalized Medicine, APH - Aging & Later Life, Global Health, Neurology, Experimental Immunology, Center of Experimental and Molecular Medicine, APH - Digital Health, Internal Medicine, Medical Microbiology & Infectious Diseases, and Virology

Subjects
Adult, Male, medicine.medical_specialty, Genotype, Hepatitis C virus, Sexual Behavior, Hepacivirus, medicine.disease_cause, Transgender Persons, Men who have sex with men, Pre-exposure prophylaxis, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Homosexuality, Male, Survival analysis, Phylogeny, Hepatology, AIDS-Related Opportunistic Infections, Unsafe Sex, business.industry, Transmission (medicine), Incidence (epidemiology), Incidence, Hazard ratio, virus diseases, HIV, Hepatitis C, Homosexuality, Middle Aged, medicine.disease, Risk factors, Reinfection, Molecular epidemiology, RNA, Viral, Female, business, Follow-Up Studies
Abstract

Background & Aims: HCV has emerged as a sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). We evaluated HCV incidence and its risk factors among HIV-negative MSM using HIV pre-exposure prophylaxis (PrEP). Methods: Participants of the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. Participants used daily or event-driven PrEP and could switch regimens during follow-up. We calculated incidence rates (IRs) for overall HCV infection and separately for primary and re-infection. A univariable Bayesian exponential survival model was used to identify risk factors associated with incident HCV infection. The HCV NS5B gene fragment (709 bp) was sequenced and compared to HCV isolates from HIV-positive MSM and other risk groups (n = 419) using phylogenetic analysis. Results: Among 350 participants contributing 653.6 person-years (PYs), we detected 15 HCV infections in 14 participants (IR = 2.30/100PY). There were 8 primary infections (IR = 1.27/100PY) and 7 re-infections (IR = 27.8/100PY). IR was 2.71/100PY in daily and 1.15/100PY in event-driven PrEP users. Factors associated with incident HCV infection were higher number of receptive condomless anal sex acts with casual partners (posterior hazard ratio [HR] 1.57 per ln increase; 95% credibility interval [CrI] 1.09–2.20), anal STI (posterior HR 2.93; 95% CrI 1.24–7.13), injecting drug use (posterior HR 4.69; 95% CrI 1.61–12.09) and sharing straws when snorting drugs (posterior HR 2.62; 95% CrI 1.09–6.02). We identified robust MSM-specific HCV clusters of subtypes 1a, 4d, 2b and 3a, which included MSM with and without HIV. Conclusions: HIV-negative MSM using PrEP are at risk of incident HCV infection, while identified risk factors are similar to those in HIV-positive MSM. Regular HCV testing is needed, especially for those with a previous HCV infection and those reporting risk factors. Lay summary: We report that hepatitis C virus infections are frequently acquired among HIV-negative men who have sex with men (MSM) using pre-exposure prophylaxis to prevent HIV infection. New infections occurred more frequently in those reporting receptive anal sex without using condoms, having an anal sexually transmitted infection, injecting drugs, and sharing straws when snorting drugs. The viruses found in HIV-negative men using pre-exposure prophylaxis are genetically similar to those in HIV-positive men, but not in other hepatitis C risk groups, suggesting that (sexual) transmission is occurring between HIV-positive MSM and HIV-negative MSM using pre-exposure prophylaxis. Clinical Trial number: Dutch trial registration number NTR5411.

Published
2020
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6. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals

Author

Colette Smit, Anders Boyd, Bart J A Rijnders, Thijs J W van de Laar, Eliane M Leyten, Wouter F Bierman, Kees Brinkman, Mark A A Claassen, Jan den Hollander, Anne Boerekamps, Astrid M Newsum, Janke Schinkel, Maria Prins, Joop E Arends, Eline L M Op de Coul, Marc van der Valk, Peter Reiss, M. van der Valk, S.E. Geerlings, A. Goorhuis, J.W. Hovius, B. Lempkes, F.J.B. Nellen, T. van der Poll, J.M. Prins, M. van Vugt, W.J. Wiersinga, F.W.M.N. Wit, M. van Duinen, J. van Eden, A. Hazenberg, A.M.H. van Hes, F.J.J. Pijnappel, S.Y. Smalhout, A.M. Weijsenfeld, S. Jurriaans, N.K.T. Back, H.L. Zaaijer, B. Berkhout, M.T.E. Cornelissen, C.J. Schinkel, K.C. Wolthers, E.J.G. Peters, M.A. van Agtmael, R.S. Autar, M. Bomers, K.C.E. Sigaloff, M. Heitmuller, L.M. Laan, C.W. Ang, R. van Houdt, M. Jonges, M. van den Berge, A. Stegeman, S. Baas, L. Hage de Looff, A. Buiting, A. Reuwer, J. Veenemans, B. Wintermans, M.J.H. Pronk, H.S.M. Ammerlaan, D.N.J. van den Bersselaar, E.S. de Munnik, B. Deiman, A.R. Jansz, V. Scharnhorst, J. Tjhie, M.C.A. Wegdam, A. van Eeden, J. Nellen, W. Brokking, L.J.M. Elsenburg, H. Nobel, M.E.E. van Kasteren, M.A.H. Berrevoets, A.E. Brouwer, A. Adams, R. van Erve, B.A.F.M. de Kruijf-van de Wiel, S. Keelan-Phaf, B. van de Ven, A.G.M. Buiting, J.L. Murck, T.E.M.S. de Vries-Sluijs, H.I. Bax, E.C.M. van Gorp, N.C. de Jong-Peltenburg, M. de Mendonça Melo, E. van Nood, J.L. Nouwen, B.J.A. Rijnders, C. Rokx, C.A.M. Schurink, L. Slobbe, A. Verbon, N. Bassant, J.E.A. van Beek, M. Vriesde, L.M. van Zonneveld, J. de Groot, C.A.B. Boucher, M.P.G. Koopmans, J.J.A. van Kampen, J. Branger, R.A. Douma, A.S. Cents-Bosma, C.J.H.M. Duijf-van de Ven, E.F. Schippers, C. van Nieuwkoop, J.M. van IJperen, J. Geilings, N.D. van Burgel, E.M.S. Leyten, G. van der Hut, L.B.S. Gelinck, F. Mollema, S. Davids-Veldhuis, C. Tearno, G.S. Wildenbeest, E. Heikens, P.H.P. Groeneveld, J.W. Bouwhuis, A.J.J. Lammers, S. Kraan, A.G.W. van Hulzen, M.S.M. Kruiper, G.L. van der Bliek, P.C.J. Bor, S.B. Debast, G.H.J. Wagenvoort, F.P. Kroon, M.G.J. de Boer, H. Jolink, M.M.C. Lambregts, A.H.E. Roukens, H. Scheper, W. Dorama, N. van Holten, E.C.J. Claas, E. Wessels, J.G. den Hollander, C.J. Brouwer, J.V. Smit, D. Struik-Kalkman, T. van Niekerk, R. El Moussaoui, K. Pogany, O. Pontesilli, S.H. Lowe, A.M.L. Oude Lashof, D. Posthouwer, M.E. van Wolfswinkel, R.P. Ackens, K. Burgers, J. Schippers, B. Weijenberg-Maes, I.H.M. van Loo, T.R.A. Havenith, M.G.A. van Vonderen, L.M. Kampschreur, S. Faber, R. Steeman-Bouma, A. Al Moujahid, G.J. Kootstra, C.E. Delsing, M. van der Burg-van de Plas, L. Scheiberlich, W. Kortmann, G. van Twillert, R. Renckens, D. Ruiter-Pronk, F.A. van Truijen-Oud, J.W.T. Cohen Stuart, E.R. Jansen, M. Hoogewerf, W. Rozemeijer, W.A. van der Reijden, J.C. Sinnige, K. Brinkman, G.E.L. van den Berk, W.L. Blok, K.D. Lettinga, M. de Regt, W.E.M. Schouten, J.E. Stalenhoef, J. Veenstra, S.M.E. Vrouenraets, H. Blaauw, G.F. Geerders, M.J. Kleene, M. Kok, M. Knapen, I.B. van der Meché, E. Mulder-Seeleman, A.J.M. Toonen, S. Wijnands, E. Wttewaal, D. Kwa, R. van Crevel, A.S.M. Dofferhoff, H.J.M. ter Hofstede, J. Hoogerwerf, M. Keuter, O. Richel, M. Albers, K.J.T. Grintjes-Huisman, M. de Haan, M. Marneef, R. Strik-Albers, J. Rahamat-Langendoen, F.F. Stelma, D. Burger, E.H. Gisolf, R.J. Hassing, M. Claassen, G. ter Beest, P.H.M. van Bentum, N. Langebeek, R. Tiemessen, C.M.A. Swanink, S.F.L. van Lelyveld, R. Soetekouw, L.M.M. van der Prijt, J. van der Swaluw, N. Bermon, R. Jansen, B.L. Herpers, D. Veenendaal, D.W.M. Verhagen, F.N. Lauw, M.C. van Broekhuizen, M. van Wijk, W.F.W. Bierman, M. Bakker, J. Kleinnijenhuis, E. Kloeze, A. Middel, D.F. Postma, Y. Stienstra, M. Wouthuyzen-Bakker, A. Boonstra, H. de Groot-de Jonge, P.A. van der Meulen, D.A. de Weerd, H.G.M. Niesters, C.C. van Leer-Buter, M. Knoester, A.I.M. Hoepelman, J.E. Arends, R.E. Barth, A.H.W. Bruns, P.M. Ellerbroek, T. Mudrikova, J.J. Oosterheert, E.M. Schadd, B.J. van Welzen, K. Aarsman, B.M.G. Griffioen-van Santen, I. de Kroon, M. van Berkel, C.S.A.M. van Rooijen, R. Schuurman, F. Verduyn-Lunel, A.M.J. Wensing, P. Reiss, S. Zaheri, A.C. Boyd, D.O. Bezemer, A.I. van Sighem, C. Smit, M. Hillebregt, A. de Jong, T. Woudstra, D. Bergsma, R. Meijering, L. van de Sande, T. Rutkens, S. van der Vliet, L. de Groot, M. van den Akker, Y. Bakker, A. El Berkaoui, M. Bezemer, N. Brétin, E. Djoechro, M. Groters, E. Kruijne, K.J. Lelivelt, C. Lodewijk, E. Lucas, L. Munjishvili, F. Paling, B. Peeck, C. Ree, R. Regtop, Y. Ruijs, M. Schoorl, P. Schnörr, A. Scheigrond, E. Tuijn, L. Veenenberg, K.M. Visser, E.C. Witte, Infectious diseases, Medical Microbiology and Infection Prevention, AII - Infectious diseases, APH - Global Health, Global Health, APH - Aging & Later Life, APH - Quality of Care, Center of Experimental and Molecular Medicine, Landsteiner Laboratory, AII - Inflammatory diseases, Obstetrics and Gynaecology, ARD - Amsterdam Reproduction and Development, Gastroenterology and Hepatology, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Digital Health, APH - Personalized Medicine, Internal medicine, ACS - Diabetes & metabolism, General practice, Internal Medicine, and Medical Microbiology & Infectious Diseases

Subjects
0301 basic medicine, Adult, Male, Epidemiology, Immunology, HIV Infections, Hepacivirus, Antiviral Agents, Men who have sex with men, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Virology, Medicine, Humans, 030212 general & internal medicine, Homosexuality, Male, Substance Abuse, Intravenous, Netherlands, Retrospective Studies, Proportional hazards model, business.industry, Coinfection, Incidence (epidemiology), Incidence, Retrospective cohort study, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 030112 virology, Chronic infection, Infectious Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Cohort, HIV-1, Female, business, Demography
Abstract

Contains fulltext : 232443.pdf (Publisher’s version ) (Closed access) BACKGROUND: In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015. METHODS: In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years. FINDINGS: Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5·2 per 1000 person-years [95% CI 5·0-5·5]). The highest incidence was observed in men who have sex with men (MSM; 7·7 per 1000 person-years [7·3-8·2]) and was lower in people who inject drugs (PWID; 1·7 per 1000 person-years [0·7-4·1]) and other key populations (1·0 per 1000 person-years [0·8-1·2]). In MSM, incidence increased in 2007 to 14·3 per 1000 person-years and fluctuated between 8·7 and 13·0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6·1 cases per 1000 person-years and remained steady between 4·1 and 4·9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26·9 per 1000 person-years [95% CI 23·9-30·3]). The highest incidence rate was observed in MSM (38·5 per 1000 person-years [33·9-43·7]) and was lower in PWID (10·9 per 1000 person-years [3·5-33·8]) and other key populations (8·9 per 1000 person-years [6·3-12·5]). In MSM, reinfection incidence fluctuated between 38·0 and 88·9 per 1000 person-years from 2006 to 2015, reaching 55·6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41·4 per 1000 person-years, followed by further decreases to 24·4 per 1000 person-years in 2017 and 11·4 per 1000 person-years in 2019. INTERPRETATION: The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures. FUNDING: Dutch Ministry of Health, Welfare, and Sport.

Published
2021
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7. Prevalence of Coxiella Burnetii in Ticks After a Large Outbreak of Q Fever

Author

Ellen Tijsse-Klasen, K. Emil Hovius, M. Langelaar, C.B.M. Maassen, J.W. Hovius, A. de Bruin, Y. T. H. P. Van Duynhoven, Eva Špitalská, Manoj Fonville, Hein Sprong, F. Gassner, S.E. van Wieren, E.J. Scholte, Ard M. Nijhof, Frans Jongejan, and Willem Takken

Subjects
Veterinary medicine, Ixodes ricinus, General Veterinary, General Immunology and Microbiology, biology, Epidemiology, Transmission (medicine), Public Health, Environmental and Occupational Health, Outbreak, Q fever, bacterial infections and mycoses, biology.organism_classification, medicine.disease, Coxiella burnetii, Infectious Diseases, Borrelia, parasitic diseases, medicine, bacteria, Veterinary public health, Anaplasma
Abstract

Q fever has emerged as an important human and veterinary public health problem in the Netherlands with major outbreaks in three consecutive years. Goat farms are probably the prime source from which Coxiella burnetii have spread throughout the environment, infecting people living in the vicinity. Coxiella burnetii infection not only spilled over from animal husbandry to humans but could also have spread to neighbouring wildlife and pets forming novel reservoirs and consequently posing another and lingering threat to humans, companion animals and livestock. In these cases, transmission routes other than airborne spread of contaminated aerosols may become significant. Therefore, the role of ticks in the transmission of Coxiella burnetii in the current situation was investigated. A total of 1891 questing Ixodes ricinus ticks and 1086 ticks feeding on pets, wildlife and livestock were tested by a recently developed multiplex Q-PCR. All ticks were negative, except for a few ticks feeding on a herd of recently vaccinated sheep. Coxiella-positive ticks were not detected after resampling this particular herd three months later. Based on these data we conclude that the current risk of acquiring Q fever from questing ticks in the Netherlands is negligible. However, for future risk assessments, it might be relevant to sample more ticks in the vicinity of previously C. burnetii infected goat farms and to assess whether C. burnetii can be transmitted transovarially and transstadially in I. ricinus ticks.

Published
2011
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