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1. Gender differences in the use of cardiovascular interventions in HIV‐positive persons; the D:A:D Study

Author

Hatleberg, Camilla I., Ryom, Lene, El?Sadr, Wafaa, Mocroft, Amanda, Reiss, Peter, De Wit, Stephane, Dabis, Francois, Pradier, Christian, Monforte, Antonella D'Arminio, Kovari, Helen, Law, Matthew, Lundgren, Jens D., Sabin, Caroline A., Calvo, G, Bonnet, F, Kirk, O, Morfeldt, L, Weber, R, Lind?Thomsen, A, Brandt, R Salbøl, Hillebreght, M, Zaheri, S, Wit, Fwnm, Scherrer, A, Schöni?Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Le Marec, F, Boerg, E, Thulin, E, Sundström, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Mateu, S, Torres, F, Petoumenos, K, Blance, A, Huang, R, Puhr, R, Laut, K, Kristensen, D, Phillips, An, Kamara, Da, Smith, Cj, Brandt, Rs, Raben, D, Matthews, C, Bojesen, A, Grevsen, Al, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Smit, C, Ross, M, Fux, Ca, Morlat, P, Friis?Møller, N, Kowalska, J, Bohlius, J, Bower, M, Fätkenheuer, G, Grulich, A, Sjøl, A, Meidahl, P, Iversen, Js, Hillebregt, M, Prins, Jm, Kuijpers, Tw, Scherpbier, Hj, Meer, Jtm, Godfried, Mh, Poll, T, Nellen, Fjb, Geerlings, Se, Vugt, M, Pajkrt, D, Bos, Jc, Wiersinga, Wj, Valk, M, Goorhuis, A, Hovius, Jw, Eden, J, Henderiks, A, Hes, Amh, Mutschelknauss, M, Nobel, He, Pijnappel, Fjj, Jurriaans, S, Back, Nkt, Zaaijer, Hl, Berkhout, B, Cornelissen, Mte, Schinkel, Cj, Thomas, Xv, Ziekenhuis, A De Ruyter, Berge, M, Stegeman, A, Baas, S, De Looff, L Hage, Ziekenhuis, C, Pronk, Mjh, Ammerlaan, Hsm, Munnik, E, Tjhie, J, Wegdam, Mca, Deiman, B, Scharnhorst, V, Weijsenfeld, Am, Ende, Me, Gorp, Ecm, Schurink, Cam, Nouwen, Jl, Verbon, A, Rijnders, Bja, Bax, Hi, Feltz, M, Bassant, N, Beek, Jea, Vriesde, M, Zonneveld, Lm, Oude?Lubbers, A, Berg?Cameron, Hj, Bruinsma?Broekman, Fb, Groot, J, Man, M Zeeuw?De, Boucher, Cab, Koopmans, Mpg, Kampen, Jja, Pas, Sd, Driessen, Gja, Rossum, Amc, Knaap, Lc, Flevoziekenhuis, E, Branger, J, Rijkeboer?Mes, A, Schippers, Ef, Ijperen, Jm, Geilings, J, Hut, G, Franck, Pfh, Eeden, A, Brokking, W, Groot, M, Elsenburg, Ljm, Damen, M, Isala, Is, Groeneveld, Php, Bouwhuis, Jw, Berg, Jf, Hulzen, Agw, Bliek, Gl, Bor, Pcj, Bloembergen, P, Wolfhagen, Mjhm, Ruijs, Gjhm, Kroon, Fp, Boer, Mgj, Bauer, Mp, Jolink, H, Vollaard, Am, Dorama, W, Holten, N, Claas, Ecj, Wessels, E, Den Hollander, Jg, Pogany, K, Roukens, A, Kastelijns, M, Smit, Jv, Smit, E, Struik?Kalkman, D, Tearno, C, Bezemer, M, Niekerk, T, Pontesilli, O, Lowe, Sh, Lashof, Aml Oude, Posthouwer, D, Ackens, Rp, Schippers, J, Vergoossen, R, Weijenberg?Maes, B, Loo, Ihm, Havenith, Tra, Leyten, Ems, Gelinck, Lbs, Hartingsveld, A, Meerkerk, C, Wildenbeest, Gs, Mutsaers, Jaem, Jansen, Cl, Mulder, Jw, Vrouenraets, Sme, Lauw, Fn, Broekhuizen, Mc, Paap, H, Vlasblom, Dj, Smits, Phm, Weijer, S, Moussaoui, R El, Bosma, As, Vonderen, Mga, Houte, Dpf, Kampschreur, Lm, Dijkstra, K, Faber, S, Weel, J, Kootstra, Gj, Delsing, Ce, De Plas, M Burg?Van, Heins, H, Lucas, E, Kortmann, W, Twillert¤, G, Stuart, Jwt Cohen, Diederen, Bmw, Pronk, D, Truijen?Oud, Fa, Reijden, Wa, Jansen, R, Brinkman¤, K, Berk, Gel, Blok, Wl, Frissen, Phj, Lettinga, Kd, Schouten, Wem, Veenstra, J, Brouwer, Cj, Geerders, Gf, Hoeksema, K, Kleene, Mj, Meché, Ib, Spelbrink, M, Sulman, H, Toonen, Ajm, Wijnands, S, Kwa, D, Witte, E, Koopmans, Pp, Keuter, M, Ven, Ajam, Hofstede, Hjm, Dofferhoff, Asm, Crevel, R, Albers, M, Bosch, Mew, Grintjes?Huisman, Kjt, Zomer, Bj, Stelma, Ff, Rahamat?Langendoen, J, Burger, D, Richter, C, Gisolf, Eh, Hassing, Rj, Beest, G, Van Bentum, Phm, Langebeek, N, Tiemessen, R, Swanink, Cma, Lelyveld, Sfl, Soetekouw, R, Hulshoff, N, Prijt, Lmm, Swaluw, J, Bermon, N, Herpers, Bl, Veenendaal, D, Verhagen, Dwm, Wijk, M, Brouwer, Ae, Kuipers, M, Santegoets, Rmwj, Ven, B, Marcelis, Jh, Buiting, Agm, Kabel, Pj, Bierman, Wfw, Scholvinck, H, Wilting, Kr, Stienstra, Y, Meulen, Pa, Weerd, Da, Ludwig?Roukema, J, Niesters, Hgm, Riezebos?Brilman, A, Leer?Buter, Cc, Knoester, M, Hoepelman, Aim, Mudrikova, T, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Barth, Re, Wassenberg, Mwm, Schadd, Em, Elst?Laurijssen, Dhm, Oers?Hazelzet, Eeb, Vervoort, S, Berkel, M, Schuurman, R, Verduyn?Lunel, F, Wensing, Amj, Peters, Ejg, Agtmael, Ma, Bomers, M, Vocht, J, Heitmuller, M, Laan, Lm, Pettersson, Am, Ang, Cw, Geelen, Spm, Wolfs, Tfw, Bont, Lj, Bezemer, Do, Sighem, Ai, Boender, Ts, Jong, A, Bergsma, D, Hoekstra, P, Lang, A, Grivell, S, Jansen, A, Rademaker, Mj, Raethke, M, Meijering, R, Schnörr, S, Groot, L, Akker, M, Bakker, Y, Claessen, E, Berkaoui, A El, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercié, P, Neau, D, Pellegrin, Jl, Tchamgoué, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, Mo, Gérard, Y, Blanco, P, Bouchet, S, Breilh, D, Fleury, H, Pellegrin, I, Chêne, G, Thiébaut, R, Wittkop, L, Lawson?Ayayi, S, Gimbert, A, Desjardin, S, Lacaze?Buzy, L, Petrov?Sanchez, V, André, K, Bernard, N, Caubet, O, Caunegre, L, Chossat, I, Courtault, C, Dauchy, Fa, Dondia, D, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Ferrand, H, Gerard, Y, Greib, C, Hessamfar, M, Imbert, Y, Lataste, P, Marie, J, Mechain, M, Monlun, E, Ochoa, A, Pistone, T, Raymond, I, Receveur, Mc, Rispal, P, Sorin, L, Valette, C, Vandenhende, Ma, Viallard, Jf, Wille, H, Wirth, G, Lafon, Me, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont?Salamé, G, Blaizeau, Mj, Decoin, M, Hannapier, C, Pougetoux, E Lenaud Et A., Delveaux, S, D' Ivernois, C, Diarra, F, Uwamaliya?Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Carr, A, Cooper, D, O'Sullivan, M, Nolan, D, Guelfi, G, Domingo, P, Sambeat, Ma, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, Clumeck, N, Gennotte, Af, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, Mc, Semaille, P, Laethem, Y, Neaton, J, Krum, E, Thompson, G, Luskin?Hawk, R, Telzak, E, Abrams, Di, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, Lr, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Losso, M, Pedersen, C, Ristola, M, Phillips, A, Rockstroh, J, Peters, L, Fischer, Ah, Laut, K Grønborg, Larsen, Jf, Podlekareva, D, Cozzi?Lepri, A, Shepherd, L, Schultze, A, Amele, S, Kundro, M, Schmied, B, Vassilenko, A, Mitsura, Vm, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Møller, Nf, Ostergaard, L, Wiese, L, Nielsen, Ln, Zilmer, K, Aho, I, Viard, J?P, Girard, P?M, Duvivier, C, Degen, O, Stellbrink, Hj, Stefan, C, Bogner, J, Chkhartishvili, N, Gargalianos, P, Szlávik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Elbirt, D, Sthoeger, Zm, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Staub, T, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak?Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer?Lisewska, I, Caldeira, L, Radoi, R, Panteleev, A, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Gatell, Jm, Miró, Jm, Moreno, S, Rodriguez, Jm, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, Jm, Falconer, K, Thalme, A, Sonnerborg, A, Blaxhult, A, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, Am, Simons, E, Johnson, Ma, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Thulin, G, Åkerlund, B, Koppel, K, Karlsson, A, Håkangård, C, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Marchetti, Gc, Perno, Cf, Schloesser, F, Viale, P, Ceccherini?Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, Mr, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Nozza, S, Roldan, E Quiros, Rossotti, R, Rusconi, S, Santoro, Mm, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, Pe, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, Mc, Piolini, R, Ridolfo, Al, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Di Martino, F, Gentile, I, Maddaloni, L, Cattelan, Am, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, Ma, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Sulekova, L Fontanelli, Iaiani, G, Latini, A, Mastrorosa, I, Plazzi, Mm, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Del Vecchio, R Fontana, Francisci, D, Di Giuli, C, Caramello, P, Orofino, Gc, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Dollet, K, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador?Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain?Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost?Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, Pm, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, Dl, Bucher, Hc, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Günthard, Hf, Haerry, D, Hasse, B, Hirsch, Hh, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, Rd, Ledergerber, B, Martinetti, G, De Tejada, B Martinez, Marzolini, C, Metzner, Kj, Müller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Scherrer, Au, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, and Yerly, S

Subjects
Medical care -- Utilization, Cardiovascular system -- Surgery, Sex factors in disease -- Analysis, HIV patients -- Statistics -- Care and treatment -- Demographic aspects, Health
Abstract

: Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV‐positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study. Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid‐lowering drugs (LLDs), angiotensin‐converting enzyme inhibitors (ACEIs), anti‐hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders. Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti‐hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow‐up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti‐hypertensives (1.17 [1.10, 1.25]). Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV‐positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions., Introduction HIV‐positive individuals are known to be at increased risk of cardiovascular disease (CVD) compared to the general population, partly due to an increased prevalence of some CVD risk factors, [...]

Published
2018
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3. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study

Author

Steering, D, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Ryom, L, Hatleberg, Ci, Sabin, Ca, Kamara, D, Smith, C, Phillips, A, Mocroft, A, Bojesen, A, Grevsen, A, Matthews, C, Raben, D, Lundgren, Jd, Brandt, Rs, Rickenbach, M, Fanti, I, Hillebreght, M, Zaheri, S, Gras, L, Pernot, E, Mourabi, J, Sundström, A, Delforge, M, Fontas, E, Torres, F, Mcmanus, H, Wright, S, Kristensen, D, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kirk, O, Reiss, P, Smit, C, Ross, M, Fux, Ca, Morlat, P, Moranne, O, Kamara, Da, Weber, R, Pradier, C, Friis-Møller, N, Kowalska, J, Sabin, C, Law, M, d'Arminio Monforte, A, Dabis, F, Bruyand, M, Bonnet, F, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, Jm, Kuijpers, Tw, Scherpbier, Hj, van der Meer JT, Wit, Fw, Godfried, Mh, van der Poll, T, Nellen, Fj, Geerlings, Se, van Vugt, M, Pajkrt, D, Bos, Jc, Wiersinga, Wj, van der Valk, M, Goorhuis, A, Hovius, Jw, van Eden, J, Henderiks, A, van Hes AM, Mutschelknauss, M, Nobel, He, Pijnappel, Fj, Westerman, Am, Jurriaans, S, Back, Nk, Zaaijer, Hl, Berkhout, B, Cornelissen, Mt, Schinkel, Cj, Thomas, Xv, De Ruyter Ziekenhuis, A, van den Berge, M, Stegeman, A, Baas, S, de Looff, L, Versteeg, D, Pronk, Mj, Ammerlaan, Hs, Korsten-Vorstermans, Em, de Munnik ES, Jansz, Ar, Tjhie, J, Wegdam, Mc, Deiman, B, Scharnhorst, V, Kinderziekenhuis, E, van der Plas, A, Weijsenfeld, Am, van der Ende ME, de Vries-Sluijs TE, van Gorp EC, Schurink, Ca, Nouwen, Jl, Verbon, A, Rijnders, Bj, Bax, Hi, Hassing, Rj, van der Feltz, M, Bassant, N, van Beek JE, Vriesde, M, van Zonneveld LM, de Oude-Lubbers, A, van den Berg-Cameron HJ, Bruinsma-Broekman, Fb, de Groot, J, de Man de, Z, Broekhoven-Kruijne, Mj, Schutten, M, Osterhaus, Ad, Boucher, Ca, Driessen, Gj, van Rossum AM, van der Knaap LC, Visser, E, Branger, J, Duijf-van de Ven CJ, Haag, D, Schippers, Ef, van Nieuwkoop, C, Brimicombe, Rw, van IJperen, M, van der Hut, G, Franck, Pf, van Eeden, A, Brokking, W, Groot, M, Damen, M, Kwa, Is, Groeneveld, Ph, Bouwhuis, Jw, van den Berg JF, van Hulzen AG, van der Bliek GL, Bor, Pc, Bloembergen, P, Wolfhagen, Mj, Ruijs, Gj, Gasthuis, K, van Lelyveld SF, Soetekouw, R, Hulshoff, N, van der Prijt LM, Schoemaker, M, Bermon, N, van der Reijden WA, Jansen, R, Herpers, Bl, Veenendaal, D, Kroon, Fp, Arend, Sm, de Boer MG, Bauer, Mp, Jolink, H, Vollaard, Am, Dorama, W, Moons, C, Claas, Ec, Kroes, Ac, den Hollander JG, Pogany, K, Kastelijns, M, Smit, Jv, Smit, E, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, Sh, Oude Lashof, A, Posthouwer, D, Ackens, Rp, Schippers, J, Vergoossen, R, Weijenberg Maes, B, Savelkoul, Ph, Loo, Ih, Zuiderzee, Mc, Weijer, S, El Moussaoui, R, Heitmuller, M, Kortmann, W, van Twillert, G, Cohen Stuart JW, Diederen, Bm, Pronk, D, van Truijen-Oud FA, van der Reijden, W, Leyten, Em, Gelinck, Lb, van Hartingsveld, A, Meerkerk, C, Wildenbeest, Gs, Mutsaers, Ja, Jansen, Cl, van Vonderen MG, van Houte DP, Dijkstra, K, Faber, S, Weel, J, Kootstra, Gj, Delsing, Ce, van der Burgvan de Plas, M, Heins, H, Lucas, E, Brinkman, K, Frissen, Ph, Blok, Wl, Schouten, We, Bosma, As, Brouwer, Cj, Geerders, Gf, Hoeksema, K, Kleene, Mj, van der Meché IB, Toonen, Aj, Wijnands, S, van Ogtrop ML, Koopmans, Pp, Keuter, M, van der Ven AJ, ter Hofstede HJ, Dofferhoff, As, van Crevel, R, Albers, M, Bosch, Me, Grintjes-Huisman, Kj, Zomer, Bj, Stelma, Ff, Burger, D, Richter, C, van der Berg JP, Gisolf, Eh, Beest, G, van Bentum PH, Langebeek, N, Tiemessen, R, Swanink, Cm, Veenstra, J, Lettinga, Kd, Spelbrink, M, Sulman, H, Witte, E, Peerbooms, Pg, Mulder, Jw, Vrouenraets, Sm, Lauw, Fn, van Broekhuizen MC, Paap, H, Vlasblom, Dj, Oudmaijer Sanders, E, Smits, Ph, Rosingh, Aw, Verhagen, Dw, Geilings, J, van Kasteren ME, Brouwer, Ae, de Kruijf-van de Wiel BA, Kuipers, M, Santegoets, Rm, van der Ven, B, Marcelis, Jh, Buiting, Ag, Kabel, Pj, Bierman, Wf, Sprenger, Hg, Scholvinck, Eh, van Assen, S, Wilting, Kr, Stienstra, Y, de Groot-de Jonge, H, van der Meulen PA, de Weerd DA, Niesters, Hg, Riezebos-Brilman, A, van Leer-Buter CC, Hoepelman, Ai, Schneider, Mm, Mudrikova, T, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Barth, Re, Wassenberg, Mw, van Elst-Laurijssen DH, Laan, Lm, van Oers-Hazelzet EE, Patist, J, Vervoort, S, Nieuwenhuis, He, Frauenfelder, R, Schuurman, R, Verduyn-Lunel, F, Wensing, Am, Peters, Ej, van Agtmael MA, Perenboom, Rm, Bomers, M, de Vocht, J, Elsenburg, Lj, Pettersson, Am, Vandenbroucke-Grauls, Cm, Ang, Cw, Geelen, Sp, Wolfs, Tf, Bont, Lj, Nauta, N, Bezemer, Do, van Sighem AI, Hillebregt, M, Kimmel, V, Tong, Y, Lascaris, B, van den Boogaard, R, Hoekstra, P, de Lang, A, Berkhout, M, Grivell, S, Jansen, A, de Groot, L, van den Akker, M, Bergsma, D, Lodewijk, C, Meijering, R, Peeck, B, Raethke, M, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Tuijn, E, Veenenberg, L, Woudstra, T, Bakker, Y, de Jong, A, Broekhoven, M, Claessen, E, Rademaker, Mj, Munjishvili, L, Kruijne, E, Tuk, B, Bouchet, S, Breilh, D, Chêne, G, Dupon, M, Fleury, H, Gaborieau, V, Lacoste, D, Malvy, D, Mercié, P, Neau, D, Pellegrin, I, Pellegrin, Jl, Tchamgoué, S, Fagard, C, Lawson-Ayayi, S, Richert, L, Thiébaut, R, Wittkop, L, André, K, Bernard, N, Caunègre, L, Cazanave, C, Ceccaldi, J, Chossat, I, Courtault, C, Dauchy, Fa, De Witte, S, Dondia, D, Dupont, A, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Gerard, Y, Greib, C, Hessamfar-Joseph, M, Imbert, Y, Lataste, P, Lazaro, E, Marie, J, Mechain, M, Meraud, Jp, Monlun, E, Ochoa, A, Pillot-Debelleix, M, Pistone, T, Raymond, I, Receveur, Mc, Rispal, P, Sorin, L, Valette, C, Vandenhende, Ma, Vareil, Mo, Viallard, Jf, Wille, H, Wirth, G, Moreau, Jf, Lafon, Me, Reigadas, S, Trimoulet, P, Haramburu, F, Miremont-Salamé, G, Blaizeau, Mj, Crespel, I, Decoin, M, Delveaux, S, Diarra, F, D'Ivernois, C, Hanappier, C, Leleux, O, Le Marec, F, Lenaud, E, Mourali, J, Pougetoux, A, Uwamaliya-Nziyumvira, B, Tsaranazy, A, Valdes, A, Conte, V, Louis, I, Palmer, G, Sapparrart, V, Touchard, D, Petoumenos, K, Bendall, C, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Nicholson, J, Bloch, M, Franic, T, Baker, D, Vale, R, Carr, A, Cooper, D, Chuah, J, Ngieng, M, Nolan, D, Skett, J, Calvo, G, Mateu, S, Domingo, P, Sambeat, Ma, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, De Wit, S, Clumeck, N, Necsoi, C, Gennotte, Af, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, Mc, Semaille, P, Van, Y, Neaton, J, Bartsch, G, El-Sadr, Wm, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, Di, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, Lr, Sampson, J, Baxter, J, Losso, M, Kundro, M, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, Vm, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Hansen, Ab, Pedersen, C, Møller, Nf, Ostergaard, L, Dragsted, Ub, Nielsen, Ln, Zilmer, K, Smidt, J, Ristola, M, Aho, I, Katlama, C, Viard, Jp, Girard, Pm, Cotte, L, Duvivier, C, Rockstroh, J, Schmidt, R, van Lunzen, J, Degen, O, Stellbrink, Hj, Stefan, C, Bogner, J, Chkhartishvili, N, Kosmidis, J, Gargalianos, P, Xylomenos, G, Lourida, P, Sambatakou, H, Banhegyi, D, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Sthoeger, Zm, D'Arminio Monforte, A, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, D'Offizi, G, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Horban, A, Bakowska, E, Grzeszczuk, A, Flisiak, R, Parczewski, M, Pynka, M, Maciejewska, K, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Doroana, M, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Oprea, C, Rakhmanova, A, Trofimora, T, Khromova, I, Kuzovatova, E, Jevtovic, D, Shunnar, A, Staneková, D, Tomazic, J, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gatell, Jm, Miró, Jm, Gutierrez, M, Mateo, G, Laporte, Jm, Blaxhult, A, Flamholc, L, Falconer, K, Thalme, A, Sonnerborg, A, Ledergerber, B, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Elzi, L, Schmid, P, Kravchenko, E, Chentsova, N, Frolov, V, Kutsyna, G, Baskakov, I, Servitskiy, S, Kuznetsova, A, Kyselyova, G, Gazzard, B, Johnson, Am, Simons, E, Johnson, Ma, Orkin, C, Weber, J, Scullard, G, Fisher, M, Leen, C, Lundgren, J, Grarup, J, Cozzi-Lepri, A, Thiebaut, R, Peters, L, Fischer, Ah, Grønborg Laut, K, Larsen, Jf, Podlekareva, D, Grint, D, Shepherd, L, Schultze, A, Morfeldt, L, Thulin, G, Åkerlund, B, Koppel, K, Karlsson, A, Håkangård, C, Moroni, M, Angarano, G, Armignacco, O, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Perno, Cf, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bonfanti, P, Bonora, S, Borderi, M, Capobianchi, R, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Quiros Roldan, E, Rusconi, S, Cicconi, P, Formenti, T, Galli, L, Lorenzini, P, Giacometti, A, Costantini, A, Santoro, C, Suardi, C, Vanino, E, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, Pe, Piano, P, Vecchiet, J, Falasca, K, Sighinolfi, L, Segala, D, Cassola, G, Viscoli, G, Alessandrini, A, Piscopo, R, Mazzarello, G, Mastroianni, C, Belvisi, V, Castelli, A, Rizzardini, G, Ridolfo, Al, Piolini, R, Salpietro, S, Carenzi, L, Moioli, Mc, Puzzolante, C, Abrescia, N, Chirianni, A, Guida, Mg, Onofrio, M, Baldelli, F, Francisci, D, Parruti, G, Ursini, T, Magnani, G, Ursitti, Ma, D'Avino, A, Gallo, L, Nicastri, E, Capozzi, M, Libertone, R, Tebano, G, Cattelan, A, Mura, Ms, Caramello, P, Orofino, Gc, Sciandra, M, Pellizzer, G, Manfrin, V, Castelli, Ap, Dollet, K, Caissotti, C, Dellamonica, P, Bernard, E, Cua, E, De Salvador-Guillouet, F, Durant, J, Ferrando, S, Dunais, B, Mondain-Miton, V, Naqvi, A, Perbost, I, Prouvost-Keller, B, Pillet, S, Pugliese, P, Risso, K, Roger, Pm, Aubert, V, Bernasconi, E, Böni, J, Bucher, Hc, Burton-Jeangros, C, Dollenmaier, G, Egger, M, Fehr, J, Fellay, J, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, Hh, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Martinetti, G, Martinez de Tejada, B, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schüpbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Yerly, S., University College of London [London] (UCL), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Chemical Biology, Internal Medicine, Medical Microbiology & Infectious Diseases, Pediatrics, Virology, Mocroft, A:, Lundgren, Jd, Ross, M, Fux, Ca, Reiss, P, Moranne, O, Morlat., P, Monforte, Ad, Kirk, O, Ryom, L, for the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D), Study, Lazzarin, A, Castagna, A, Other departments, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Center of Experimental and Molecular Medicine, Graduate School, Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, APH - Health Behaviors & Chronic Diseases, Med Microbiol, Infect Dis & Infect Prev, MUMC+: DA MMI Staf (9), MUMC+: MA Alg Interne Geneeskunde (9), MUMC+: DA MMI Infectieserologie (9), MUMC+: DA MMI AIOS (9), RS: FHML non-thematic output, Mocroft, A, Lundgren, J, Fux, C, Morlat, P, Monforte, A, and Gori, A

Subjects
0301 basic medicine, Male, PROTEASE INHIBITOR, Epidemiology, Infectious Diseases, Immunology, Virology, Research Support, U.S. Gov't, P.H.S, HIV Infections, SDG 3 – Goede gezondheid en welzijn, Rate ratio, THERAPY, chemistry.chemical_compound, 0302 clinical medicine, HIV, antiretroviral, kidney disease, immune system diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, HIV Infection, 030212 general & internal medicine, Prospective Studies, Renal Insufficiency, Chronic, Prospective cohort study, Research Support, Non-U.S. Gov't, Antiretrovirals, virus diseases, Lopinavir, ASSOCIATION, Middle Aged, 3. Good health, Europe, Antiretrovirals, HIV, chronic kidney disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, NAIVE PATIENTS, CREATININE, Human, Cohort study, medicine.drug, Glomerular Filtration Rate, United State, Adult, medicine.medical_specialty, TENOFOVIR DISOPROXIL FUMARATE, RENAL-FUNCTION, Adolescent, Anti-HIV Agents, Atazanavir Sulfate, Renal function, Infectious Disease, Australia, Humans, Renal Insufficiency, Chronic, Tenofovir, United States, Young Adult, NO, 03 medical and health sciences, EFAVIRENZ, SDG 3 - Good Health and Well-being, Internal medicine, Journal Article, medicine, Creatinine, business.industry, Anti-HIV Agent, medicine.disease, 030112 virology, Atazanavir, INFECTED INDIVIDUALS, Prospective Studie, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, RISK-FACTORS, business, chronic kidney disease, Kidney disease
Abstract

BACKGROUND: Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR).METHODS: In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir.FINDINGS: Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], pINTERPRETATION: In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored.FUNDING: The Highly Active Antiretroviral Therapy Oversight Committee.

Published
2016

4. Seroprevalence of Hepatitis E Virus in Autoimmune Hepatitis Patients in the Netherlands

Author

van Gerven, NMF, Baltissen - van der Eijk, Annemiek, Pas, Suzan, Zaaijer, HL, de Boer, YS, Witte, BI, van Nieuwkerk, CMJ, Mulder, CJJ, de Man, Rob, Virology, and Gastroenterology & Hepatology

Subjects
SDG 3 - Good Health and Well-being, immune system diseases, viruses, virus diseases, digestive system diseases
Abstract

Background & Aims: In recent years chronic courses of hepatitis E virus (HEV) infection have been described in immunosuppressed individuals. This may implicate a potential role for HEV in the development of autoimmune diseases, including autoimmune hepatitis (AIH). Here we investigated the prevalence of HEV-antibodies in AIH patients in an endemic Central European country. Methods: HEV-specific immunoglobulin G (IgG) and HEV RNA were determined in 354 and 377 AIH patients, respectively. Clinical characteristics and disease outcome parameters were retrospectively collected. Results: No HEV viraemic patients were identified in this cohort. A total of 106 AIH patients (29.9%) tested positive for anti-HEV IgG, and this figure was slightly higher compared to the prevalence in a reference cohort including 5,329 healthy Dutch blood donors (26.7%; P>0.05). Conclusion: This is the largest study on the association between HEV infection and AIH. Apparently silent HEV infection is present in a significant proportion of AIH patients, yet appears not to have significant clinical repercussions in this immune compromised group of patients. Nevertheless, since acute hepatitis E may present with histological and biochemical features of AIH, the possibility of a (concomitant) HEV infection should be considered in this category of patients.

Published
2016

5. Variability and pathogenicity of hepatitis E virus genotype 3 variants

Author

Smith, DB, Ijaz, S, Tedder, RS, Hogema, B, Zaaijer, HL, Izopet, J, Bradley-Stewart, A, Gunson, R, Harvala, H, Kokki, I, and Simrrionds, P

Subjects
TRANSMISSION, viruses, Molecular Sequence Data, RECOMBINATION, CLASSIFICATION, FAMILY HEPEVIRIDAE, Virology, Germany, 07 Agricultural and Veterinary Sciences, INFECTION, Hepatitis E virus, Humans, PHYLOGENETIC ANALYSIS, Phylogeny, 11 Medical and Health Sciences, Netherlands, Science & Technology, Virulence, virus diseases, Genetic Variation, 06 Biological Sciences, Hepatitis E, Biotechnology & Applied Microbiology, Scotland, GENETIC-VARIABILITY, FULMINANT-HEPATITIS, DISEASE SEVERITY, France, Life Sciences & Biomedicine, GERMAN BLOOD-DONORS
Abstract

Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (P>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype.

Published
2015

6. Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy : not all AIDS-defining conditions are created equal

Author

Antiretroviral Therapy Cohort Collaboration Mocroft A, Sterne JA, Egger M, May M, Grabar S, Furrer H, Sabin C, Fatkenheuer G, Justice A, Reiss P, d'Arminio Monforte A, Gill J, Hogg R, Bonnet F, Kitahata M, Staszewski S, Casabona J, Harris R, Saag M, Chêne G, Costagliola D, Dabis F, D'Arminio Monforte A, de Wolf F, Ledergerber B, Mocroft A, Phillips A, Weller I, Sterne J, Abgrall S, Barin F, Bentata M, Billaud E, Boué F, Burty C, Cabié A, Cotte L, De Truchis P, Duval X, Duvivier C, Enel P, Fredouille Heripret L, Gasnault J, Gaud C, Gilquin J, Katlama C, Khuong MA, Lang JM, Lascaux AS, Launay O, Mahamat A, Mary Krause M, Matheron S, Meynard JL, Pavie J, Pialoux G, Pilorgé F, Poizot Martin I, Pradier C, Reynes J, Rouveix E, Simon A, Tattevin P, Tissot Dupont H, Viard JP, Viget N, Pariente Khayat A, Salomon V, Jacquemet N, Rivet A, Guiguet M, Kousignian I, Lanoy E, Lièvre L, Potard V, Selinger Leneman H, Bouvet E, Crickx B, Ecobichon JL, Leport C, Picard Dahan C, Yeni P, Tisne Dessus D, Weiss L, Salmon D, Sicard D, Auperin I, Roudière L, Fior R, Delfraissy JF, Goujard C, Jung C, Lesprit P, Desplanque N, Meyohas MC, Picard O, Cadranel J, Mayaud C, Bricaire F, Herson S, Clauvel JP, Decazes JM, Gerard L, Molina JM, Diemer M, Sellier P, Berthé H, Dupont C, Chandemerle C, Mortier E, Honoré P, Jeantils V, Tassi S, Mechali D, Taverne B, Gourdon F, Laurichesse H, Fresard A, Lucht F, Eglinger P, Faller JP, Bazin C, Verdon R, Boibieux A, Peyramond D, Livrozet JM, Touraine JL, Trepo C, Ravaux I, Delmont JP, Moreau J, Gastaut JA, Retornaz F, Soubeyrand J, Allegre T, Blanc PA, Galinier A, Ruiz JM, Lepeu G, Granet Brunello P, Esterni JP, Pelissier L, Cohen Valensi R, Nezri M, Chadapaud S, Laffeuillade A, May T, Rabaud C, Raffi F, Arvieux C, Michelet C, Borsa Lebas F, Caron F, Fraisse P, Rey D, Arlet Suau E, Cuzin L, Massip P, Thiercelin Legrand MF, Yasdanpanah Y, Pradinaud R, Sobesky M, Contant M, Montroni M, Scalise G, Braschi MC, Riva A, Tirelli U, Martellotta F, Pastore G, Ladisa N, Suter F, Arici C, Chiodo F, Colangeli V, Fiorini C, Carosi G, Cristini G, Torti C, Minardi C, Bertelli D, Quirino T, Manconi PE, Piano P, Cosco L, Scerbo A, Vecchiet J, D'Alessandro M, Santoro D, Pusterla L, Carnevale G, Lorenzotti S, Viganò P, Mena M, Ghinelli F, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Lo Caputo S, Grisorio B, Ferrara S, Grima P, Grima PF, Pagano G, Cassola G, Alessandrini A, Piscopo R, Toti M, Trezzi M, Soscia F, Tacconi L, Orani A, Perini P, Scasso A, Vincenti A, Chiodera F, Castelli P, Scalzini A, Palvarini L, Moroni M, Lazzarin A, Rizzardini G, Caggese L, Cicconi P, Galli A, Merli S, Pastecchia C, Moioli MC, Esposito R, Mussini C, Abrescia N, Chirianni A, Izzo CM, Piazza M, De Marco M, Viglietti R, Manzillo E, Colomba A, Abbadessa V, Prestileo T, Mancuso S, Ferrari C, Pizzaferri P, Filice G, Minoli L, Bruno R, Novati S, Baldelli F, Camanni G, Petrelli E, Cioppi A, Alberici F, Ruggieri A, Menichetti F, Martinelli C, De Stefano C, La Gala A, Ballardini G, Rizzo E, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Cauda R, Dianzani F, Ippolito G, Antinori A, Antonucci G, Ciardi M, Narciso P, Petrosillo N, Vullo V, De Luca A, Zaccarelli M, Acinapura R, De Longis P, Trotta MP, Noto P, Lichtner M, Capobianchi MR, Carletti F, Girardi E, Pezzotti P, Rezza G, Mura MS, Mannazzu M, Caramello P, Di Perri G, Orofino GC, Sciandra M, Grossi PA, Basilico C, Poggio A, Bottari G, Raise E, Ebo F, Pellizzer G, Buonfrate D, Resta F, Loso K, Cozzi Lepri A, Battegay M, Bernasconi E, Böni J, Bucher H, Bürgisser P, Cattacin S, Cavassini M, Dubs R, Elzi L, Erb P, Fischer M, Flepp M, Fontana A, Francioli P, Gorgievski M, Günthard H, Hirsch H, Hirschel B, Hösli I, Kahlert C, Kaiser L, Karrer U, Kind C, Klimkait T, Martinetti G, Martinez B, Müller N, Nadal D, Opravil M, Paccaud F, Pantaleo G, Rickenbach M, Rudin C, Schmid P, Schultze D, Schüpbach J, Speck R, Taffé P, Tarr P, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S, Gras LA, van Sighem AI, Smit 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B, Jou A, Conejero J, Tural C, Gatell JM, Miró JM, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Karlsson A, Persson PO, Flamholc L, Boffi E, Kravchenko E, Chentsova N, Barton S, Johnson AM, Mercey D, Johnson MA, Murphy M, Weber J, Scullard G, Fisher M, Brettle R, Gatell J, Gazzard B, Friis Møller N, Bannister W, Ellefson M, Borch A, Podlekareva D, Holkmann Olsen C, Kjaer J, Peters L, Reekie J, Raffanti S, Dieterch D, Becker S, Scarsella A, Fusco G, Most B, Balu R, Rana R, Beckerman R, Ising T, Fusco J, Irek R, Johnson B, Hirani A, DeJesus E, Pierone G, Lackey P, Irek C, Johnson A, Burdick J, Leon S, Arch J, Helm EB, Carlebach A, Müller A, Haberl A, Nisius G, Lennemann T, Stephan C, Bickel M, Mösch M, Gute P, Locher L, Lutz T, Klauke S, Knecht G, Khaykin P, Doerr HW, Stürmer M, Babacan E, von Hentig N, Beylot J, Dupon M, Longy Boursier M, Pellegrin JL, Ragnaud JM, Salamon R, Thiébaut R, Lewden C, Lawson Ayayi S, Mercié P, Moreau JF, Morlat P, Bernard N, Lacoste D, Malvy D, Neau D, 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D, Becker, S, Scarsella, A, Fusco, G, Most, B, Balu, R, Rana, R, Beckerman, R, Ising, T, Fusco, J, Irek, R, Johnson, B, Hirani, A, Dejesus, E, Pierone, G, Lackey, P, Irek, C, Johnson, A, Burdick, J, Leon, S, Arch, J, Helm, Eb, Carlebach, A, Müller, A, Haberl, A, Nisius, G, Lennemann, T, Stephan, C, Bickel, M, Mösch, M, Gute, P, Locher, L, Lutz, T, Klauke, S, Knecht, G, Khaykin, P, Doerr, Hw, Stürmer, M, Babacan, E, von Hentig, N, Beylot, J, Dupon, M, Longy Boursier, M, Pellegrin, Jl, Ragnaud, Jm, Salamon, R, Thiébaut, R, Lewden, C, Lawson Ayayi, S, Mercié, P, Moreau, Jf, Morlat, P, Bernard, N, Lacoste, D, Malvy, D, Neau, D, Blaizeau, Mj, Decoin, M, Delveaux, S, Hannapier, C, Labarrère, S, Lavignolle Aurillac, V, Uwamaliya Nziyumvira, B, Palmer, G, Touchard, D, Balestre, E, Alioum, A, Jacqmin Gadda, H, Bonarek, M, Coadou, B, Gellie, P, Nouts, C, Bocquentin, F, Dutronc, H, Lafarie, S, Aslan, A, Pistonne, T, Thibaut, P, Vatan, R, Chambon, D, De La Taille, C, Cazorla, C, Ocho, A, Viallard, Jf, Caubet, O, Cipriano, C, Lazaro, E, Couzigou, P, Castera, L, Fleury, H, Lafon, Me, Masquelier, B, Pellegrin, I, Breilh, D, Blanco, P, Loste, P, Caunègre, L, Bonnal, F, Farbos, S, Ferrand, M, Ceccaldi, J, Tchamgoué, S, De Witte, S, Buy, E, Alexander, C, Barrios, R, Braitstein, P, Brumme, Z, Chan, K, Cote, H, Gataric, N, Geller, J, Guillemi, S, Harrigan, Pr, Harris, M, Joy, R, Levy, A, Montaner, J, Montessori, V, Palepu, A, Phillips, E, Phillips, P, Press, N, Tyndall, M, Wood, E, Yip, B, Bhagani, S, Breen, R, Byrne, P, Carroll, A, Cuthbertson, Z, Dunleavy, A, Geretti, Am, Heelan, B, Johnson, M, Kinloch de Loes, S, Lipman, M, Madge, S, Marshall, N, Nair, D, Nebbia, G, Prinz, B, Shah, S, Swader, L, Tyrer, M, Youle, M, Chaloner, C, Grabowska, H, Holloway, J, Puradiredja, J, Ransom, D, Tsintas, R, Bansi, L, Fox, Z, Harris, E, Hill, T, Lampe, F, Lodwick, R, Smith, C, Amoah, E, Booth, C, Clewley, G, Garcia Diaz, A, Gregory, B, Janossy, G, Labbett, W, Thomas, M, Read, R, Krentz, H, Beckthold, B, Schmeisser, N, Alquézar, A, Esteve, A, Podzamczer, D, Murillas, J, Romero, A, Agustí, C, Agüero, F, Ferrer, E, Riera, M, Segura, F, Navarro, G, Force, L, Vilaró, J, Masabeu, A, García, I, Guadarrama, M, Montoliu, A, Ortega, N, Lazzari, E, Puchol, E, Sanchez, M, Blanco, Jl, Garcia Alcaide, F, Martinez, E, Mallolas, J, López Dieguez, M, García Goez, Jf, Sirera, G, Romeu, J, Negredo, E, Miranda, C, Capitan, Mc, Olmo, M, Barragan, P, Saumoy, M, Bolao, F, Cabellos, C, Peña, C, Sala, M, Cervantes, M, Jose Amengual, M, Navarro, M, Penelo, E, Barrufet, P, Raper, Jl, Mugavero, Mj, Willig, Jh, Schumacher, J, Chang, Pw, Westfall, Ao, Cloud, G, Lin, Hy, Acosta, Ep, Colette Kempf, M, Allison, Jj, Pisu, M., Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Infectious diseases, Other departments, General Internal Medicine, Graduate School, Global Health, Paediatric Infectious Diseases / Rheumatology / Immunology, and Medical Microbiology and Infection Prevention

Subjects
Male, Infectious diseases and international health [NCEBP 13], Lymphoma, 030312 virology, Esophageal candidiasis, Cohort Studies, 0302 clinical medicine, Interquartile range, 030212 general & internal medicine, AIDS-Related, Lymphoma, AIDS-Related, 0303 health sciences, Mortality rate, Progressive multifocal leukoencephalopathy, Hazard ratio, Prognosis, 3. Good health, Pathogenesis and modulation of inflammation [N4i 1], Infectious Diseases, Combination, Drug Therapy, Combination, Female, Infection and autoimmunity [NCMLS 1], Human, Microbiology (medical), Adult, medicine.medical_specialty, Prognosi, Anti-HIV Agents, antiretroviral therapy, Infectious Disease, Article, AIDS-Related Opportunistic Infection, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Drug Therapy, Internal medicine, medicine, Humans, AIDS-defining event, Proportional Hazards Models, AIDS-Related Opportunistic Infections/diagnosis/ mortality, Acquired Immunodeficiency Syndrome/complications/diagnosis/drug, therapy/ mortality, Anti-HIV Agents/ therapeutic use, AIDS-Related/diagnosis/mortality, Acquired Immunodeficiency Syndrome, AIDS-Related Opportunistic Infections, business.industry, Proportional hazards model, Poverty-related infectious diseases [N4i 3], Anti-HIV Agent, medicine.disease, mortality, Confidence interval, Immunology, Proportional Hazards Model, Cohort Studie, business
Abstract

Contains fulltext : 80963.pdf (Publisher’s version ) (Open Access) BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in

Published
2009

7. Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Author

Mocroft, A, Lundgren, JD, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, CA, Moranne, O, Morlat, P, Johnson, MA, Ryom, L, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, Tjhie, J, Mocroft, A, Lundgren, JD, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, CA, Moranne, O, Morlat, P, Johnson, MA, Ryom, L, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, and Tjhie, J

Abstract

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectiv

Published
2015

8. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D Study

Author

Mocroft, Amanda, Lundgren, Jens D, Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A, Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A, Ryom, Lene, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Kamara, DA, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, Tjhie, J, Rogers, Gary, Mocroft, Amanda, Lundgren, Jens D, Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A, Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A, Ryom, Lene, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Sabin, CA, Phillips, A, Weber, R, Pradier, C, d'Arminio Monforte, A, Dabis, F, El-Sadr, WM, De Wit, S, Kamara, D, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Salbøl Brandt, R, Rickenbach, M, Fanti, I, Krum, E, Hillebregt, M, Geffard, S, Sundström, A, Delforge, M, Fontas, E, Torres, F, McManus, H, Wright, S, Kjær, J, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kesselring, AM, Friis-Møller, N, Kowalska, J, Sabin, C, Bruyand, M, Kamara, DA, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, JM, Kuijpers, TW, Scherpbier, HJ, van der Meer, JTM, Wit, FWMN, Godfried, MH, van der Poll, T, Nellen, FJB, Geerlings, SE, van Vugt, M, Pajkrt, D, Bos, JC, Wiersinga, WJ, van der Valk, M, Goorhuis, A, Hovius, JW, van Eden, J, Henderiks, A, van Hes, AMH, Mutschelknauss, M, Nobel, HE, Pijnappel, FJJ, Westerman, AM, Jurriaans, S, Back, NKT, Zaaijer, HL, Berkhout, B, Cornelissen, MTE, Schinkel, CJ, Thomas, XV, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Versteeg, D, Pronk, MJH, Ammerlaan, HSM, Korsten-Vorstermans, EMHM, de Munnik, ES, Jansz, AR, Tjhie, J, and Rogers, Gary

Published
2015

9. Infecties van de Lever

Author

Zaaijer, HL, de Man, Rob, Hoepelman, AIM, Kroes, ACM, Sauerwein, RW, Verbrugh, HA, and Gastroenterology & Hepatology

Published
2011

10. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

Author

Antiretroviral Therapy Cohort Collaboration, Mugavero, Mj, May, M, Harris, R, Saag, Ms, Costagliola, D, Egger, M, Phillips, A, Günthard, Hf, Dabis, F, Hogg, R, de Wolf, F, Fatkenheuer, G, Gill, Mj, Justice, A, D'Arminio Monforte, A, Lampe, F, Miró, Jm, Staszewski, S, Collaborators: Casabona J, Sterne J. A., Geneviè, C, del Amo, J, Fätkenheuer, G, Gill, J, Guest, J, Kitahata, M, Ledergerber, B, Mocroft, A, Reiss, P, Saag, M, Sterne, J, Sterne, Ja, Abgrall, S, Barin, F, Bentata, M, Billaud, E, Boué, F, Burty, C, Cabié, A, Cotte, L, De Truchis, P, Duval, X, Duvivier, C, Enel, P, Fredouille Heripret, L, Gasnault, J, Gaud, C, Gilquin, J, Grabar, S, Katlama, C, Khuong, Ma, Lang, Jm, Lascaux, As, Launay, O, Mahamat, A, Mary Krause, M, Matheron, S, Meynard, Jl, Pavie, J, Pialoux, G, Pilorgé, F, Poizot Martin, I, Pradier, C, Reynes, J, Rouveix, E, Simon, A, Tattevin, P, Tissot Dupon, H, Viard, Jp, Viget, N, Pariente Khayat, A, Salomon, V, Jacquemet, N, Rivet, A, Abgral, S, Guiguet, M, Kousignian, I, Lanoy, E, Lièvre, L, Potard, V, Selinger Leneman, H, Bouvet, E, Crickx, B, Ecobichon, Jl, Leport, C, Picard Dahan, C, Yeni, P, Tisne Dessus, D, Weiss, L, Salmon, D, Sicard, D, Auperin, I, Roudière, L, Fior, R, Delfraissy, Jf, Goujard, C, Jung, C, Lesprit, P, Desplanque, N, Meyohas, Mc, Picard, O, Cadranel, J, Mayaud, C, Bricaire, F, Herson, S, Clauvel, Jp, Decazes, Jm, Gerard, L, Molina, Jm, Diemer, M, Sellier, P, Berthé, H, Dupont, C, Chandemerle, C, Mortier, E, de Truchis, P, Honoré, P, Jeantils, V, Tassi, S, Mechali, D, Taverne, B, Gourdon, F, Laurichesse, H, Fresard, A, Lucht, F, Eglinger, P, Faller, Jp, Bazin, C, Verdon, R, Boibieux, A, Peyramond, D, Livroze, Jm, Touraine, Jl, Trepo, C, Ravaux, I, Tissot Dupont, H, Delmont, Jp, Moreau, J, Gastaut, Ja, Retornaz, F, Soubeyrand, J, Allegre, T, Blanc, Pa, Galinier, A, Ruiz, Jm, Lepeu, G, Granet Brunello, P, Esterni, Jp, Pelissier, L, Cohen Valensi, R, Nezri, M, Chadapaud, S, Laffeuillade, A, Laffeuillade, J, May, T, Rabaud, C, Raffi, F, Pugliese, P, Arvieux, C, Michelet, C, Borsa Lebas, F, Caron, F, Fraisse, P, Rey, D, Arlet Suau, E, Cuzin, L, Massip, P, Thiercelin Legrand MF, Yasdanpanah, Y, Pradinaud, R, Sobesky, M, Contant, M, Montroni, M, Scalise, G, Braschi, Mc, Riva, A, Tirelli, U, Cinelli, R, Pastore, G, Ladisa, N, Suter, F, Arici, C, Chiodo, F, Colangeli, V, Fiorini, C, Carosi, Giampiero, Cristini, G, Torti, Carlo, Minardi, C, Bertelli, D, Quirino, T, Manconi, Pe, Piano, P, Cosco, L, Scerbo, A, Vecchiet, J, D'Alessandro, M, Santoro, D, Pusterla, L, Carnevale, G, Zoncada, A, Viganò, P, Mena, M, Ghinelli, F, Sighinolfi, L, Leoncini, F, Mazzotta, F, Pozzi, M, Lo Caputo, S, Angarano, G, Grisorio, B, Saracino, A, Ferrara, S, Grima, P, Grima, F, Pagano, G, Cassola, G, Alessandrini, A, Piscopo, R, Toti, M, Trezzi, M, Soscia, F, Tacconi, L, Orani, A, Perini, P, Scasso, A, Vincenti, A, Chiodera, F, Castelli, P, Scalzini, A, Palvarini, L, Moroni, M, Lazzarin, A, Rizzardini, G, d'Arminio Monforte, A, Galli, A, Merli, S, Pastecchia, C, Moioli, Mc, Esposito, R, Mussini, C, Abresci, N, Chirianni, A, Izzo, Cm, Piazza, M, De Marco, M, Viglietti, R, Manzillo, E, Nappa, S, Colomba, A, Abbadessa, V, Prestileo, T, Mancuso, S, Ferrari, C, Pizzaferri, P, Filice, G, Minoli, L, Bruno, R, Novati, S, Baldelli, F, Tinca, M, Petrelli, E, Cioppi, A, Cioppi, F, Ruggieri, A, Menichetti, F, Martinelli, C, De Stefano, C, La Gala, A, Ballardini, G, Rizzo, E, Magnani, G, Ursitti, Ma, Arlotti, M, Ortolani, P, Cauda, R, Dianzani, F, Ippolito, G, Antinori, A, Antonucci, G, Ciardi, M, Narciso, P, Petrosillo, N, Vullo, V, De Luca, A, Zaccarelli, M, Acinapura, R, De Longis, P, Brandi, A, Trotta, Mp, Noto, P, Lichtne, M, Capobianch, Mr, Carletti, F, Girardi, E, Pezzotti, P, Rezza, G, Mura, Ms, Mannazzu, M, Caramello, P, Di Perri, G, Sciandra, M, Orofino, Gc, Grossi, Pa, Basilico, C, Poggio, A, Bottari, G, Raise, E, Ebo, F, Pellizzer, G, Buonfrate, D, Resta, F, Loso, K, Cozzi Lepri, A, Battegay, M, Bernasconi, E, Böni, J, Bucher, Hc, Bürgisser, P, Calmy, A, Cattacin, S, Cavassini, M, Dubs, R, Elzi, L, Fischer, M, Flepp, M, Fontana, A, Francioli, P, Furrer, H, Fux, C, Gorgievski, M, Günthard, H, Hirsch, H, Hirschel, B, Hösli, I, Kahlert, Ch, Kaiser, L, Karrer, U, Kind, C, Klimkait, T, Martinetti, G, Martinez, B, Martinez, N, Nadal, D, Opravil, M, Paccaud, F, Pantaleo, G, Rauch, A, Regenass, S, Rickenbach, M, Rudin, C, Schmid, P, Schultze, D, Schüpbach, J, Speck, R, Taffé, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Yerly, S, Gras, La, van Sighem AI, Smit, C, Prins, Jm, Branger, J, Eeftinck Schattenkerk JK, Gisolf, J, Godfried, Mh, Lange, Jm, Lettinga, Kd, van der Meer JT, Nellen, Fj, van der Poll, T, Ruys, Ta, Steingrover, R, Vermeulen, Jn, Vrouenraets, Sm, van Vugt, M, Wit, Fw, Kuijpers, Tw, Pajkrt, D, Scherpbier, Hj, van Eeden, A, Brinkman, K, van den Berk GE, Blok, Wl, Frissen, Ph, Roos, Jc, Schouten, We, Mulder, Jw, van Gorp EC, Wagenaar, J, Veenstra, J, Danner, Sa, Van Agtmael MA, Claessen, Fa, Perenboom, Rm, Rijkeboer, A, van Vonderen MG, Richter, C, van der Berg, J, Vriesendorp, R, Jeurissen, Fj, Kauffmann, Rh, Pogány, K, Bravenboer, B, Sprenger, Hg, van Assen, S, van Leeuwen JT, Doedens, R, Scholvinck, Eh, ten Kate RW, Soetekouw, R, van Houte, D, Polée, Mb, Kroon, Fp, van den Broek PJ, van Dissel JT, Schippers, Ef, Schreij, G, van der Geest, S, Lowe, S, Verbon, A, Koopmans, Pp, Van Crevel, R, de Groot, R, Keuter, M, Post, F, van der Ven AJ, Warris, A, van der Ende ME, Gyssens, Ic, van der Feltz, M, Nouwen, Jl, Rijnders, Bj, de Vries TE, Driessen, G, van der Flier, M, Hartwig, Ng, Juttman, Jr, van Kasteren ME, Van de Heul, C, Hoepelman, Im, Schneider, Mm, Bonten, Mj, Borleffs, Jc, Ellerbroek, Pm, Jaspers, Ca, Mudrikove, T, Schurink, Ca, Gisolf, Eh, Geelen, Sp, Wolfs, Tf, Faber, T, Tanis, Aa, Groeneveld, Ph, den Hollander JG, Duits, Aj, Winkel, K, Back, Nk, Bakker, Me, Berkhout, B, Jurriaans, S, Zaaijer, Hl, Cuijpers, T, Rietra, Pj, Roozendaal, Kj, Pauw, W, van Zanten AP, Smits, Ph, von Blomberg BM, Savelkoul, P, Pettersson, A, Swanink, Cm, Franck, Pf, Lampe, As, Jansen, Cl, Hendriks, R, Benne, Ca, Veenendaal, D, Storm, H, Weel, J, van Zeijl JH, Kroes, Ac, Claas, Hc, Bruggeman, Ca, Goossens, Vj, Galama, Jm, Melchers, Wj, Poort, Ya, Doornum, Gj, Niesters, Mg, Osterhaus, Ad, Schutten, M, Buiting, Ag, Swaans, Ca, Boucher, Ca, Schuurman, R, Boel, E, Jansz, Af, Veldkamp, A, Beijnen, Jh, Huitema, Ad, Burger, Dm, Hugen, Pw, van Kan HJ, Losso, M, Duran, A, Vetter, N, Karpov, I, Vassilenko, A, Clumeck, N, De Wit, S, Poll, B, Colebunders, R, Machala, L, Rozsypal, H, Sedlacek, D, Nielsen, J, Lundgren, J, Benfield, T, Kirk, O, Gerstoft, J, Katzenstein, T, Hansen, Ab, Skinhøj, P, Pedersen, C, Zilmer, K, Girard, Pm, Saint Marc, T, Vanhems, P, Dietrich, M, Manegold, C, van Lunzen, J, Stellbrink, Hj, Staszewsk, S, Bickel, M, Goebel, Fd, Rockstroh, J, Schmidt, R, Kosmidis, J, Gargalianos, P, Sambatakou, H, Perdios, J, Panos, G, Filandras, A, Karabatsaki, E, Banhegyi, D, Mulcahy, F, Yust, I, Turner, D, Burke, M, Pollack, S, Hassoun, G, Sthoeger, Z, Maayan, S, Chiesi, A, Borghi, R, Pristera, R, Mazzott, F, Gabbuti, A, Vullo, Lichtner, M, Montesarchio, E, Iacomi, F, Finazzi, R, Viksna, L, Chaplinskas, S, Hemmer, R, Staub, T, Bruun, J, Maeland, A, Ormaasen, V, Knysz, B, Gasiorowski, J, Horban, A, Prokopowicz, D, Wiercinska Drapalo, A, Boron Kaczmarska, A, Pynka, M, Beniowski, M, Mularska, E, Trocha, H, Antunes, F, Valadas, E, Mansinho, K, Matez, F, Duiculescu, D, Babes, V, Streinu Cercel, A, Vinogradova, E, Rakhmanova, A, Jevtovic, D, Mokrás, M, Staneková, D, González Lahoz, J, Sánchez Conde, M, García Benayas, T, Martin Carbonero, L, Soriano, V, Clotet, B, Jou, A, Conejero, J, Tural, C, Gatell, Jm, Blaxhult, A, Karlsson, A, Pehrson, P, Soravia Dunand, V, Kravchenko, E, Chentsova, N, Barton, S, Johnson, Am, Mercey, D, Johnson, Ma, Murphy, M, Weber, J, Scullard, G, Fisher, M, Brettle, R, Loveday, C, Gatell, J, Johnson, A, Vella, S, Gjørup, I, Friis Moeller, N, Bannister, W, Mollerup, D, Podlevkareva, D, Holkmann Olsen, C, Kjaer, J, Raffanti, S, Dieterch, D, Becker, S, Scarsella, A, Fusco, G, Most, B, Balu, R, Rana, R, Beckerman, R, Ising, T, Fusco, J, Irek, R, Johnson, B, Hirani, A, Dejesus, E, Pierone, G, Lackey, P, Irek, C, Burdick, J, Leon, S, Arch, J, Helm, Eb, Carlebach, A, Müller, A, Haberl, A, Nisius, G, Lennemann, T, Stephan, C, Mösch, M, Gute, P, Locher, L, Lutz, T, Klauke, S, Knecht, G, Khaykin, P, Doerr, Hw, Stürmer, M, Babacan, E, von Hentig, N, Beylot, J, Chêne, G, Dupon, M, Longy Boursier, M, Pellegrin, Jl, Ragnaud, Jm, Salamon, R, Thiébaut, R, Lewden, C, Lawson Ayayi, S, Mercié, P, Moreau, Jf, Morlat, P, Bernard, N, Lacoste, D, Malvy, D, Neau, D, Blaizeau, Mj, Decoin, M, Delveaux, S, Hannapier, C, Labarrère, S, Lavignolle Aurillac, V, Uwamaliya Nziyumvira, B, Palmer, G, Touchard, D, Balestre, E, Alioum, A, Jacqmin Gadda, H, Bonarek, M, Bonnet, F, Coadou, B, Gellie, P, Nouts, C, Bocquentin, F, Dutronc, H, Lafarie, S, Aslan, A, Pistonne, T, Thibaut, P, Vatan, R, Chambon, D, De La Taille, C, Cazorla, C, Ocho, A, Viallard, Jf, Caubet, O, Cipriano, C, Lazaro, E, Couzigou, P, Castera, L, Fleury, H, Lafon, Me, Masquelier, B, Pellegrin, I, Breilh, D, Blanco, P, Loste, P, Caunègre, L, Bonna, F, Farbos, S, Ferrand, M, Ceccaldi, J, Tchamgoué, S, De Witte, S, Buy, E, Akagi, L, Brandson, E, Druyts, E, Gataric, Kf, Harrigan, Pr, Harris, M, Hayden, A, Lima, V, Montaner, J, Moore, D, Wood, E, Yip, B, Zhang, W, Bhagani, S, Byrne, P, Carroll, A, Cuthbertson, Z, Dunleavy, A, Geretti, Am, Heelan, B, Johnson, M, Kinloch de Loes, S, Lipman, M, Madge, S, Marshall, N, Nair, D, Nebbia, G, Prinz, B, Swaden, L, Tyrer, M, Youle, M, Chaloner, C, Grabowska, H, Holloway, J, Puradiredja, J, Ransom, D, Tsintas, R, Bansi, L, Fox, Z, Harris, E, Hill, T, Lodwick, R, Reekie, J, Sabin, C, Smith, C, Amoah, E, Booth, C, Clewley, G, Garcia Diaz, A, Gregory, B, Labbett, W, Tahami, F, Thomas, M, Read, R, Krentz, H, Beckthold, B, Faetkenheuer, G, Casabona, J, Miró, Jl, Alquézar, A, Esteve, A, Podzamczer, D, Murillas, J, Romero, A, Agustí, C, Agüero, F, Ferrer, E, Riera, M, Segura, F, Segura, G, Force, L, Vilaró, J, Masabeu, A, García, I, Guadarrama, M, Montoliu, A, Ortega, N, Lazzari, E, Puchol, E, Sanchez, M, Blanco, Jl, Garcia Alcaide, F, Martinez, E, Mallolas, J, López Dieguez, M, García Goez JF, Sirera, G, Romeu, J, Negredo, E, Miranda, C, Capitan, Mc, Olmo, M, Barragan, P, Saumoy, M, Bolaof, F, Cabellos, C, Peña, C, Sala, M, Cervantes, M, Amengual, Mj, Navarro, M, Penelo, E, Barrufet, P, Willig, Jh, Raper, Jl, Allison, Jj, Kempf, Mc, Schumacher, Je, Wes, Ao, Lin, Hy, Pisu, M, Moneyham, L, Vance, D, Bachmann, L, Davies, Sl, Berner, E, Acosta, E, King, J, Savage, K, Nevin, C, Walton, Fb, Marler, Ml, Lawrence, S, Files Kennedy, B, Batey, Ds, Patil, Ma, Patil, U, Varshney, M, Gibson, E, Guzman, A, Rinehart, D, Justice, Ac, Fiellin, Da, Bryant, K, Rimland, D, Jones Taylor, C, Oursler, Ka, Titanji, R, Brown, S, Garrison, S, Rodriguez Barradas, M, Masozera, N, Goetz, M, Leaf, D, Simberkoff, M, Blumenthal, D, Leung, J, Butt, A, Hoffman, E, Gibert, C, Peck, R, Mattocks, K, Braithwaite, S, Brandt, C, Cook, R, Conigliaro, J, Crothers, K, Chang, J, Crystal, S, Day, N, Erdos, J, Freiberg, M, Kozal, M, Gaziano, M, Gerschenson, M, Good, B, Gordon, A, Goulet, J, Kraemer, K, Lim, J, Maisto, S, Miller, P, O'Connor, P, Papas, R, Rinaldo, C, Roberts, M, Samet, J, Cohen, D, Consorte, A, Gordon, K, Kidwai, F, Levin, F, Mcginnis, K, Rambo, M, Rogers, J, Skanderson, M, and Whitsett, F.

Published
2008

11. Surveillance van pathogenen in Nederland - Detailkarakterisering van pathogenen die relevant zijn voor de openbare gezondheidszorg

Author

Avoort HGAM van der, Binnendijk RS van, Boer J den, Boxman ILA, Bruisten S, Duizer E, Duynhoven YTHP, Ende A van de, Erkens CGM, Giessen AW van de, Giessen J van der, Godeke GJ, Greeff SC de, Hahne S, Herremans MMPT, Heuvelink A, Hof S van, Kimman TG, Koopmans MPG, Kortbeek L, Kremer K, Kuijper EJ, Laar MJW van de, Loon AJM van, Luytjes W, Meijer A, Meijer CJLM, Mooi FR, Neeling H de, Notermans DW, Op de Coul ELM, Peeters MF, Pelt W van, Pinelli E, Plas SM van der, Reimerink J, Reubsaet F, Schouls LM, Schuurman R, Snijders PJF, Soolingen D van, Vennema H, Wannet WJB, Wielinga P, Wijngaard CC van den, Wilbrink B, Wolf F de, Zaaijer HL, Boot H, LTR, LIS, and VTV

Subjects
infectious deseases control, kiemsurveillance, prevention, preventie, pathogenen, detailkarakterisering, pathogen surveillance, charaterisation, bestrijding
Abstract

Increased surveillance of pathogens may for strengthen the prevention and control of infectious diseases. Infectious diseases cause a considerable burden of disease the Netherlands. Detailed characterization of pathogens will yield insight in changes of the pathogen itself, in changes in transmission patterns, and in changes in virulence and resistance. Therefore it is necessary to determine which pathogens should be studied, to what level of detail, and how they should be collected. In this report , the bacteria, viruses and parasites that give the the greatest burden of disease or present the greatest risk for the public health have been described in a standardized way. Several pathogens emerge from this study for which an increase in collection and characterization is desirable. Examples are: 1) Human papillomavirus, to improve assessment of the potential vaccine efficacy. 2) Influenza virus, to better characterize resistance to antiviral drugs. 3) Bordetella pertusis (whooping cough), to detect population changes that can influence vaccine efficacy. 4) Meticillin-resistance Staphylococcus aureus (MRSA), to reduce delays in contact-source tracing and containment. The pathogen surveillance in the Netherlands will be intensified on basis of this report. This enhanced surveillance will be executed in close co-operation with the peripheral microbiological laboratories.

Published
2007

12. Hepatitis B virus infected health care workers in the Netherlands, 2000-2008

Author

Daha, TJ, Bilkert-Mooiman, MAJ, Ballemans, C, Frijstein, G, Keeman, JN, de Man, Rob, van Steenbergen, JE, Weers-Pothoff, G, Zaaijer, HL, Daha, TJ, Bilkert-Mooiman, MAJ, Ballemans, C, Frijstein, G, Keeman, JN, de Man, Rob, van Steenbergen, JE, Weers-Pothoff, G, and Zaaijer, HL

Abstract

In response to the confirmed transmission of hepatitis B virus (HBV) from a surgeon to several patients in the Netherlands, a 'Committee for Prevention of Iatrogenic Hepatitis B' was established in 2000. During the years 2000-2008, the committee reviewed 99 cases of HBV-infected health care workers. Fifty of them were found to perform exposure prone procedures (EPPs). Because of high levels of HBV DNA (> 100,000 copies/ml), a ban on performing EPPs was applied in 11/50 cases; 25/50 low-viremic health care workers were allowed to continue EPPs while their HBV load was being monitored; and 14/50 cases had stopped working or changed profession. In five restricted workers who started oral antiviral treatment, HBV replication was persistently suppressed, enabling the ban on EPPs to be lifted. Throughout the European Union different levels of HBV viremia have been chosen, above which health care workers are not allowed to perform EPPs. It remains unknown how this affects the safety of patients. Application in the Netherlands of a European or a British guideline would have, respectively, doubled or tripled the number of restricted health care workers.

Published
2009

13. Surveillance van pathogenen in Nederland - Detailkarakterisering van pathogenen die relevant zijn voor de openbare gezondheidszorg

Author

Boot H, LTR, LIS, VTV, Avoort HGAM van der, Binnendijk RS van, Boer J den, Boxman ILA, Bruisten S, Duizer E, Duynhoven YTHP, Ende A van de, Erkens CGM, Giessen AW van de, Giessen J van der, Godeke GJ, Greeff SC de, Hahne S, Herremans MMPT, Heuvelink A, Hof S van, Kimman TG, Koopmans MPG, Kortbeek L, Kremer K, Kuijper EJ, Laar MJW van de, Loon AJM van, Luytjes W, Meijer A, Meijer CJLM, Mooi FR, Neeling H de, Notermans DW, Op de Coul ELM, Peeters MF, Pelt W van, Pinelli E, Plas SM van der, Reimerink J, Reubsaet F, Schouls LM, Schuurman R, Snijders PJF, Soolingen D van, Vennema H, Wannet WJB, Wielinga P, Wijngaard CC van den, Wilbrink B, Wolf F de, Zaaijer HL, Boot H, LTR, LIS, VTV, Avoort HGAM van der, Binnendijk RS van, Boer J den, Boxman ILA, Bruisten S, Duizer E, Duynhoven YTHP, Ende A van de, Erkens CGM, Giessen AW van de, Giessen J van der, Godeke GJ, Greeff SC de, Hahne S, Herremans MMPT, Heuvelink A, Hof S van, Kimman TG, Koopmans MPG, Kortbeek L, Kremer K, Kuijper EJ, Laar MJW van de, Loon AJM van, Luytjes W, Meijer A, Meijer CJLM, Mooi FR, Neeling H de, Notermans DW, Op de Coul ELM, Peeters MF, Pelt W van, Pinelli E, Plas SM van der, Reimerink J, Reubsaet F, Schouls LM, Schuurman R, Snijders PJF, Soolingen D van, Vennema H, Wannet WJB, Wielinga P, Wijngaard CC van den, Wilbrink B, Wolf F de, and Zaaijer HL

Abstract

RIVM rapport:Increased surveillance of pathogens may for strengthen the prevention and control of infectious diseases. Infectious diseases cause a considerable burden of disease the Netherlands. Detailed characterization of pathogens will yield insight in changes of the pathogen itself, in changes in transmission patterns, and in changes in virulence and resistance. Therefore it is necessary to determine which pathogens should be studied, to what level of detail, and how they should be collected. In this report , the bacteria, viruses and parasites that give the the greatest burden of disease or present the greatest risk for the public health have been described in a standardized way. Several pathogens emerge from this study for which an increase in collection and characterization is desirable. Examples are: 1) Human papillomavirus, to improve assessment of the potential vaccine efficacy. 2) Influenza virus, to better characterize resistance to antiviral drugs. 3) Bordetella pertusis (whooping cough), to detect population changes that can influence vaccine efficacy. 4) Meticillin-resistance Staphylococcus aureus (MRSA), to reduce delays in contact-source tracing and containment. The pathogen surveillance in the Netherlands will be intensified on basis of this report. This enhanced surveillance will be executed in close co-operation with the peripheral microbiological laboratories., Verdere intensivering van de analyse van pathogenen in Nederland is nodig om preventie en bestrijding van infectieziekten te verbeteren. Infectieziekten veroorzaken een aanzienlijke ziektelast in Nederland. Daarnaast gaat van infectieziekten ook een grote dreiging uit voor de openbare gezondheidszorg. Detailkarakterisering van pathogenen geeft inzicht in mogelijke veranderingen van de pathogeen zelf, zoals veranderde virulentie of resistentie. Daarnaast levert het ook inzicht in mogelijk veranderde transmissieroutes. Wel is het noodzakelijk om goed af te wegen welke pathogenen gekarakteriseerd moeten worden, tot welk detailniveau, en hoe groot de steekproef van een bepaalde pathogeen moet zijn om een representatief beeld te krijgen. In dit rapport zijn de bacterien, virussen en parasieten die de grootste ziektelast veroorzaken of de grootste bedreiging vormen voor de openbare gezondheidszorg op een gestandariseerde manier beschreven. In deze beschrijving is in het bijzonder aandacht besteed aan de relevantie van de pathogenen voor de openbare gezondheidszorg. Uit deze inventariserende studie komen een aantal pathogenen naar voren waarvan het wenselijk is om die intensiever te verzamelen en te karateriseren. Voorbeelden hiervan zijn: 1) Humaan papillomavirus, om de potentiele vaccineffectiviteit beter te kunnen inschatten. 2) Influenzavirus, om resistentie tegen antivirale middelen beter in kaart te brengen. 3) Bordetella pertusis (kinkhoest), om populatieveranderingen, die mogelijk de vaccineffectiviteit verlagen, beter te kunnen waarnemen. 4) Meticilline resistente Staphylococcus aureus (MRSA), om bron-en-contact opsporing en inperkingsmaatregelen te versnellen. Dit rapport zal als basis dienen voor de intensivering van de kiemsurveillance van pathogenen in Nederland, die in samenwerking met de perifere microbiologische laboratoria uitgevoerd zal gaan worden.

Published
2007

23. Blood safety markers in Dutch donors after relaxation of deferral for men who have sex with men: re-emergence of syphilis and HIV pre-exposure prophylaxis use.

Author

Quee FA, Slot E, van Leeuwen I, Brands R, Franssen EJF, Hogema BM, Zaaijer HL, and van de Laar TJW

Subjects
Humans, Male, Netherlands epidemiology, Adult, Middle Aged, Donor Selection, Female, Incidence, Young Adult, Syphilis epidemiology, Syphilis prevention & control, Blood Donors, Homosexuality, Male, HIV Infections prevention & control, HIV Infections epidemiology, Blood Safety, Pre-Exposure Prophylaxis
Abstract

Background: Less discriminatory donor selection policies for men who have sex with men (MSM) may impact transfusion safety in terms of higher residual risks for known transfusion-transmitted infections (TTIs), increased vulnerability toward new TTIs that are also transmitted via sex, and HIV infections masked by pre-exposure prophylaxis (PrEP)., Study Design and Methods: TTI trends in Dutch donors were studied over a 13-year period (2011-2023), characterized by successive relaxations of MSM deferral criteria. Structured posttest counseling was performed to determine risk factors in TTI-positive donors. PrEP drug levels were measured in 9977 donations from male donors living in urban areas and in 67 donors with active or resolved syphilis., Results: HIV incidence (from 5.8 to 1.5 per 1,000,000 donor years (DY)) and HBV incidence (from 12.4 to 4.5 per 1,000,000 DY) in Dutch donors decreased with less stringent MSM deferral criteria, while syphilis prevalence (from 26.4 to 44.1 per 100,000 new donors) and syphilis incidence (from 18.3 to 46.3 per 1,000,000 DY) increased over time. The proportion of MSM-related syphilis rose from 2% to 32% in new donors and from 12% to 27% in repeat donors. PrEP was detected in 2 of 9977 (0.02%) donations from male donors living in urban areas, and in 1 of 39 (2.6%) male donors with syphilis., Discussion: To date, phasing out donor deferral for MSM had no significant impact on transfusion safety in the Netherlands. However, rising syphilis rates and (recent) PrEP use in the blood donor population, albeit rare, suggest an influx of donors with higher sexual risk profiles and requires intensified TTI surveillance in donors., (© 2024 AABB.)

Published
2024
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24. The Elecsys® Anti-SARS-CoV-2 and Elecsys® Anti-SARS-CoV-2 S antibody assays: Differentiating between vaccination and infection, and assessing long-term performance.

Author

Quee FA, Hogema BM, Molier M, Slot E, van den Hurk K, and Zaaijer HL

Subjects
Humans, Longitudinal Studies, Female, Male, Middle Aged, COVID-19 Vaccines immunology, Adult, Enzyme-Linked Immunosorbent Assay, Netherlands epidemiology, COVID-19 Serological Testing methods, Blood Donors, Aged, Antibodies, Viral immunology, Antibodies, Viral blood, SARS-CoV-2 immunology, COVID-19 immunology, COVID-19 diagnosis, COVID-19 prevention & control, COVID-19 virology, Spike Glycoprotein, Coronavirus immunology, Vaccination
Abstract

Introduction: Serological surveillance is useful for assessing SARS-CoV-2 immunity in populations. To effectively study the presence and persistence of antibodies, it is necessary to distinguish between persons with past infection, and persons who only received vaccination. Knowledge of the duration of antibody persistence is essential for correct interpretation of surveillance results., Methods: Starting in April 2020, waning of SARS-CoV-2 antibodies was studied in a longitudinal cohort study of 495 SARS-CoV-2 antibody-positive Dutch blood donors, not pre-selected by PCR testing or disease severity. Additionally, in May 2021, a sample of donors representative for the Dutch population was tested for antibodies against the SARS-CoV-2 spike (S) protein, using the Wantai Ab ELISA and the Elecsys® Anti-SARS-CoV-2 S assay; and for antibodies against the nucleocapsid protein, which indicate past infection, using the Elecsys® Anti-SARS-CoV-2 assay., Results: The anti-S response in donors that were infected in April or May 2020 remained positive in 100% of donors in the Elecsys® Anti-SARS-CoV-2 S assay one year after infection, after which follow up of waning was no longer possible because of large scale vaccination. The anti-nucleocapsid response results were still positive in approximately 80% of donors two years after infection. In May 2021, 51% of the donors showed anti-S reactivity and 16.8% tested positive for anti-nucleocapsid antibodies., Conclusion: Infection with SARS-CoV-2 resulted in spike and nucleocapsid antibody levels still detectable in the majority of donors 1-2 years after infection. In May 2021, 51% of donors were vaccinated and 16.8% had had an infection. Thus, both Elecsys® SARS-CoV-2 antibody assays can be used to reliably assess the vaccination and infection status of individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Quee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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25. Changing epidemiology of parvovirus B19 in the Netherlands since 1990, including its re-emergence after the COVID-19 pandemic.

Author

Russcher A, van Boven M, Benincà E, Verweij EJTJ, Molenaar-de Backer MWA, Zaaijer HL, Vossen ACTM, and Kroes ACM

Subjects
Humans, Netherlands epidemiology, Female, Pregnancy, Incidence, Parvoviridae Infections epidemiology, Pregnancy Complications, Infectious epidemiology, Pregnancy Complications, Infectious virology, SARS-CoV-2 isolation & purification, Pandemics, Erythema Infectiosum epidemiology, Blood Transfusion, Intrauterine, Adult, COVID-19 epidemiology, COVID-19 virology, Parvovirus B19, Human, Hydrops Fetalis epidemiology, Hydrops Fetalis virology
Abstract

Parvovirus B19V (B19V) infection during pregnancy can be complicated by potentially life-threatening fetal hydrops, which can be managed by intrauterine transfusion (IUT). This study investigates the long-term temporal patterns in the epidemiology of B19V and evaluates the impact on fetal hydrops, by combining data on B19V infections from the Dutch Sentinel Surveillance system in the period 1990 to 2023, Dutch blood banking data and hospital data on fetal hydrops. Using wavelet analysis, we identified annual epidemic cycles in the Netherlands in the period 1990-2019 and we identified superimposed multiannual cycles in the period 1990-2009. After 2009, no multiannual cycle could be identified, although the incidence fluctuated and correlates with number of IUT performed. As of 2020, weekly reports of B19V infection demonstrated a historically low incidence and B19V-DNA positive blood donors were nearly absent. From May 2020 to May 2023, no IUT for B19V-related hydrops was performed. In the spring of 2023, B19V infections re-emerged, reaching pre-pandemic epidemic levels. Due to the changes in B19V epidemiology over the last 30 years and the near-absence of B19V during the COVID-19 pandemic, the resulting low immunity levels may lead to rebound outbreaks. Alertness to severe complications such as fetal hydrops is warranted., (© 2024. The Author(s).)

Published
2024
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26. Teclistamab impairs humoral immunity in patients with heavily pretreated myeloma: importance of immunoglobulin supplementation.

Author

Frerichs KA, Verkleij CPM, Mateos MV, Martin TG, Rodriguez C, Nooka A, Banerjee A, Chastain K, Perales-Puchalt A, Stephenson T, Uhlar C, Kobos R, van der Holt B, Kruyswijk S, Kuipers MT, Groen K, Vishwamitra D, Skerget S, Cortes-Selva D, Doyle M, Zaaijer HL, Zweegman S, Verona RI, and van de Donk NWCJ

Subjects
Humans, Immunity, Humoral, Immunoglobulins, Intravenous therapeutic use, B-Cell Maturation Antigen therapeutic use, Dietary Supplements, Multiple Myeloma drug therapy, Antibodies, Bispecific therapeutic use, Antineoplastic Agents therapeutic use
Abstract

Abstract: Teclistamab and other B-cell maturation antigen (BCMA)-targeting bispecific antibodies (BsAbs) have substantial activity in patients with heavily pretreated multiple myeloma (MM) but are associated with a high rate of infections. BCMA is also expressed on normal plasma cells and mature B cells, which are essential for the generation of a humoral immune response. The aim of this study was to improve the understanding of the impact of BCMA-targeting BsAbs on humoral immunity. The impact of teclistamab on polyclonal immunoglobulins and B cell counts was evaluated in patients with MM who received once-weekly teclistamab 1.5 mg/kg subcutaneously. Vaccination responses were assessed in a subset of patients. Teclistamabinduced rapid depletion of peripheral blood B cells in patients with MM and eliminated normal plasma cells in ex vivo assays. In addition, teclistamab reduced the levels of polyclonal immunoglobulins (immunoglobulin G [IgG], IgA, IgE, and IgM), without recovery over time while receiving teclistamab therapy. Furthermore, response to vaccines against Streptococcus pneumoniae, Haemophilus influenzae type B, and severe acute respiratory syndrome coronavirus 2 was severely impaired in patients treated with teclistamab compared with vaccination responses observed in patients with newly diagnosed MM or relapsed/refractory MM. Intravenous immunoglobulin (IVIG) use was associated with a significantly lower risk of serious infections among patients treated with teclistamab (cumulative incidence of infections at 6 months: 5.3% with IVIG vs 54.8% with observation only [P < .001]). In conclusion, our data show severe defects in humoral immunity induced by teclistamab, the impact of which can be mitigated by the use of immunoglobulin supplementation. This trial was registered at www.ClinicalTrials.gov as #NCT04557098., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Published
2024
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27. Booster vaccinations and Omicron: the effects on SARS-CoV-2 antibodies in Dutch blood donors.

Author

Quee FA, Hogema BM, Slot E, Kruijer S, Molier M, van den Hurk K, and Zaaijer HL

Subjects
Humans, SARS-CoV-2, Antibodies, Viral, Vaccination, Blood Donors, COVID-19 epidemiology, COVID-19 prevention & control
Abstract

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster vaccination campaign and the emergence of SARS-CoV-2 Omicron variants impact the prevalence and levels of SARS-CoV-2 antibodies in the Netherlands. In this study we determined antibody levels across age groups, the impact of Omicron variant infections, and the effect of booster vaccinations on antibody levels., Methods: In September and December 2021 and in February 2022, over 2000 Dutch blood donors were tested for presence of SARS-CoV-2 antibodies. Donations were selected based on age, sex, and region of residence, to provide an optimal coverage and representation of the Dutch population., Results: Levels of vaccination-induced spike antibodies decreased over time in all age groups. Donors vaccinated with Janssen or AstraZeneca had significantly lower antibody levels than donors vaccinated with Pfizer or Moderna vaccine. Boostering with an mRNA vaccine elevated antibody levels in all age-groups irrespective of the initial vaccine. In donors aged < 56 years, the proportion of infected donors almost doubled between December 2021 and February 2022., Conclusion: The booster vaccination campaign increased antibody levels in all age-groups. After a booster vaccination, donors initially vaccinated with AstraZeneca or Janssen vaccine showed antibody levels similar to donors initially vaccinated with an mRNA vaccine. The emergence of the SARS-CoV-2 Omicron variant in the Netherlands caused a substantial increase in donors with infection-induced antibodies, especially among younger donors., (© 2023. The Author(s).)

Published
2023
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28. Assessing West Nile virus (WNV) and Usutu virus (USUV) exposure in bird ringers in the Netherlands: a high-risk group for WNV and USUV infection?

Author

de Bellegarde de Saint Lary C, Kasbergen LMR, Bruijning-Verhagen PCJL, van der Jeugd H, Chandler F, Hogema BM, Zaaijer HL, van der Klis FRM, Barzon L, de Bruin E, Ten Bosch Q, Koopmans MPG, Sikkema RS, and Visser LG

Abstract

Introduction: In 2020, the first Dutch West Nile virus (WNV) infected birds were detected through risk-targeted surveillance of songbirds. Retrospective testing of patients with unexplained neurological disease revealed human WNV infections in July and August 2020. Bird ringers are highly exposed to mosquito bites and possibly avian excrements during ringing activities. This study therefore investigates whether bird ringers are at higher risk of exposure to WNV and Usutu virus (USUV)., Methods: Dutch bird ringers were asked to provide a single serum sample (May - September 2021) and to fill out a survey. Sera were screened by protein microarray for presence of specific IgG against WNV and USUV non-structural protein 1 (NS1), followed by focus reduction virus neutralization tests (FRNT). Healthcare workers (2009-2010), the national immunity cohort (2016-2017) and blood donors (2021) were used as control groups without this occupational exposure., Results: The majority of the 157 participating bird ringers was male (132/157, 84%) and the median age was 62 years. Thirty-seven participants (37/157, 23.6%) showed WNV and USUV IgG microarray signals above background, compared to 6.4% (6/94) in the community cohort and 2.1% (2/96) in blood donors ( p  < 0.01). Two seroreactive bird ringers were confirmed WNV or USUV positive by FRNT. The majority of seroreactive bird ringers travelled to EU countries with reported WNV human cases (30/37, 81%) ( p  = 0.07). No difference was observed between bird ringers with and without previous yellow fever vaccination., Discussion: The higher frequency of WNV and/or USUV IgG reactive bird ringers indicates increased flavivirus exposure compared to the general population, suggesting that individuals with high-exposure professions may be considered to complement existing surveillance systems. However, the complexity of serological interpretation in relation to location-specific exposure (including travel), and antibody cross-reactivity, remain a challenge when performing surveillance of emerging flaviviruses in low-prevalence settings., Competing Interests: The authors declare that they have no financial and/or competing interests., (© 2023 The Authors.)

Published
2023
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29. Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Author

Biesbroek G, Kapitein B, Kuipers IM, Gruppen MP, van Stijn D, Peros TE, van Veenendaal M, Jansen MHA, van der Zee CW, van der Kuip M, von Asmuth EGJ, Mooij MG, den Boer MEJ, Landman GW, van Houten MA, Schonenberg-Meinema D, Tutu van Furth AM, Boele van Hensbroek M, Scherpbier H, van Meijgaarden KE, Ottenhoff THM, Joosten SA, Ketharanathan N, Blink M, Brackel CLH, Zaaijer HL, Hombrink P, van den Berg JM, Buddingh EP, and Kuijpers TW

Subjects
Child, Humans, Antibodies, Viral, Cytokines, Inflammation, Interleukin-6, SARS-CoV-2, Connective Tissue Diseases, COVID-19 complications, Mucocutaneous Lymph Node Syndrome complications
Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Biesbroek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2022
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31. Balancing non-discriminatory donor selection and blood safety in the Netherlands: Evaluation of an individual risk assessment of sexual behavior.

Author

Hahn B, Quee F, Prinsze FJ, Gregoire Y, O'Brien SF, Germain M, van de Laar T, Zaaijer HL, and van den Hurk K

Subjects
Blood Donors, Blood Safety, Donor Selection, Female, Homosexuality, Male, Humans, Male, Netherlands, Risk Assessment, Sexual Behavior, HIV Infections, Sexual and Gender Minorities
Abstract

Background: To better balance the safety of the blood supply and the inclusion of men who have sex with men (MSM), further improvements are needed to the risk management strategy employed in the Netherlands to reduce transfusion-transmissible infections (TTIs). A gender-neutral individual risk assessment could provide a solution by determining donor eligibility based on sexual behaviors known to increase the risk of TTIs. Our objective is to estimate the proportion of blood donors that would be deferred by such an assessment, as well as their discomfort answering such questions., Study Design and Methods: Two surveys were distributed in May 2020 to assess sexual behavior in blood donors in the last 4, 6, and 12 months, as well as their discomfort reporting such information. A combination of both surveys measured the extent to which discomfort was associated with reporting sexual behavior. A high-risk sexual behavior pattern was defined as having had multiple sexual partners and having engaged in anal sex, without consistent condom use., Results: Of all 2177 participating whole blood donors, 0.8% report engaging in high-risk sexual behaviors over the last 4 months and would therefore be ineligible to donate. When accounting for the additional proportion of donors that reported such questions would stop them from donating, 2.0% and 3.2% of female and male donors, respectively, would be lost., Discussion: Gender-neutral eligibility criteria based on high-risk sexual behaviors may reduce the overall number of eligible donors in the Netherlands, but could make blood donation more accessible to a broader group of donors., (© 2022 AABB.)

Published
2022
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32. A Prospective Five-Year Follow-up After peg-Interferon Plus Nucleotide Analogue Treatment or no Treatment in HBeAg Negative Chronic Hepatitis B Patients.

Author

Erken R, Loukachov VV, de Niet A, Jansen L, Stelma F, Helder JT, Peters MW, Zaaijer HL, Kootstra NA, Willemse SB, and Reesink HW

Abstract

Background: Currently available treatment options for chronic hepatitis B (CHB) are not recommended for HBeAg-negative patients with a low viral load. These patients may however benefit from treatment by achieving a functional cure, defined by HBsAg-loss and undetectable HBV DNA. This study evaluated the long-term effect of combination treatment with peg-interferon-alpha-2a (peg-IFN) and adefovir or tenofovir compared to no treatment in these patients., Methods: HBeAg-negative CHB patients with HBV-DNA levels < 20,000 IU/mL ( n  = 151) were previously randomised 1:1:1 for peg-IFN 180 μg/week plus either adefovir 10 mg/day or tenofovir 245 mg/day, or no treatment and treated for 48 weeks in an open-label study. In this prospective long-term follow-up study, patients were monitored yearly up to five years after end of treatment (week 308). The primary outcome was sustained HBsAg-loss and secondary outcome the dynamics of HBsAg and HBV-DNA levels over time., Results: Of the 131 followed patients, the HBsAg-status was known for 118 patients after five-year follow-up. HBsAg-loss occurred similarly ( P  = 0.703) in all arms: 8/43 (18.6%) peg-IFN + adefovir, 4/34 (11.7%) peg-IFN + tenofovir, and 6/41 (14.6%) among the untreated patients. The time to HBsAg-loss did not differ between groups ( P  = 0.641). Low baseline HBsAg levels and genotype A were independently associated with HBsAg-loss irrespective of allocation. HBsAg and HBV-DNA levels declined similarly during follow-up in all patient groups., Conclusions: This prospective randomised controlled study showed that HBsAg-loss overtime was not influenced by treatment with a combination of nucleotide analogue and Peg-IFN. Low baseline HBsAg levels can predict HBsAg-loss irrespective of treatment allocation., (© 2022 Indian National Association for Study of the Liver.)

Published
2022
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33. Ferritin-guided iron supplementation in whole blood donors: optimal dosage, donor response, return and efficacy (FORTE)-a randomised controlled trial protocol.

Author

Karregat J, Sweegers MG, Quee FA, Weekamp HH, Swinkels DW, Novotny VMJ, Zaaijer HL, and van den Hurk K

Subjects
Blood Donors, Dietary Supplements, Ferritins, Hemoglobins analysis, Humans, Iron, Iron, Dietary, Randomized Controlled Trials as Topic, Anemia, Iron-Deficiency drug therapy, Anemia, Iron-Deficiency prevention & control, Iron Deficiencies
Abstract

Background: Frequent whole blood donors have an increased risk of developing iron deficiency. Iron deficiency can have detrimental health effects when left untreated. Donation intervals are commonly too short to replenish iron stores and extending these reduces donor availability. Oral iron supplementation is known to shorten iron store recovery time but may also induce gastrointestinal complaints. We aim to optimise the effectiveness of iron supplements while minimising the risks of side effects. Therefore, we will evaluate the impact of different iron supplementation protocols in terms of dosage and frequency on ferritin and haemoglobin levels, gastrointestinal side effects, iron deficiency-related symptoms and donor return compared with placebo supplementation., Methods: Twelve hundred whole blood donors with ferritin levels ≤30 µg/L are included into a double-blind, randomised controlled trial. Participants are randomly allocated to one of six arms, administering capsules containing 0 mg, 30 mg or 60 mg of iron, either on alternate days or daily for 56 days. At baseline and 56, 122 and 182 days of follow-up, ferritin and haemoglobin levels are measured, and compliance, donor return, dietary iron intake, gastrointestinal, iron deficiency-related symptoms and general health are assessed by questionnaire., Ethics and Dissemination: This study will provide a comprehensive overview of the effects of different frequencies and dosages of administration of iron supplements on iron status and health effects, thereby considering individual differences in treatment adherence and lifestyle. The outcome will provide scientific evidence to guide the debate if and how oral iron supplements may support the recovery of whole blood donors with low ferritin levels., Trial Registration Number: NL8590; The Dutch trial registry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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34. Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study.

Author

Haak BW, Brands X, Davids M, Peters-Sengers H, Kullberg RFJ, van Houdt R, Hugenholtz F, Faber DR, Zaaijer HL, Scicluna BP, van der Poll T, and Joost Wiersinga W

Subjects
Adult, Bacteria genetics, Case-Control Studies, Humans, Nasopharynx microbiology, Prospective Studies, Respiratory System microbiology, Community-Acquired Infections diagnosis, Microbiota genetics, Respiratory Tract Infections
Abstract

Background: Viruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults., Methods: We collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls., Results: We enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (P = .016, R2 = .01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC] .83), viruses (AUC .95) or mixed origin (AUC .81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC .93) separation between cases and controls., Conclusions: Relative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Published
2022
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35. Diagnostic performance of the ZEUS Borrelia VlsE1/pepC10 assay in European LB patients: a case-control study.

Author

Baarsma ME, Vrijlandt A, Ursinus J, Zaaijer HL, Jurriaans S, van Dam AP, and Hovius JW

Subjects
Antibodies, Bacterial, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Humans, Retrospective Studies, Sensitivity and Specificity, Serologic Tests, Borrelia, Borrelia burgdorferi, Lyme Disease diagnosis
Abstract

This retrospective case-control study assesses the sensitivity, specificity, and area under the curve of the ZEUS Borrelia VlsE1/pepC10 assay in comparison with the C6-ELISA in European patients with Lyme borreliosis, healthy blood donors, and potentially cross-reactive controls. We included a convenience series of 161 sera from patients with physician-confirmed early localized or disseminated Lyme borreliosis (n = 143), 400 sera from healthy blood donors and 44 sera with potentially cross-reactive antibodies, on which we performed the aforementioned serological assays and the recomLine immunoblot. Diagnostic parameters were compared in various single-tier and two-tier algorithms. The specificities of the C6-ELISA and the ZEUS Borrelia VlsE1/pepC10 were comparable in healthy blood donors (e.g., single-tier permissive: C6: 362/400, 90.5% [87.2-93.2]; VlsE1/pepC10: 361/400, 90.3% [86.9-93.0]). The C6-ELISA had an apparently higher sensitivity in EM sera (e.g., both time points combined: C6: 61/76, 80.3% [69.5-88.5]; VlsE1/pepC10: 54/76, 71.1% [59.5-80.9]), but these differences were all not-significant. Interestingly, the VlsE1/pepC10 assay had a significantly higher specificity in sera with potentially cross-reactive antibodies (e.g., single-tier permissive: C6: 34/44, 77.3% [62.2-88.5]; VlsE1/pepC10: 40/44, 90.9% [78.3-97.5]; p = 0.031). While the areas under the curve for both assays were excellent, that of the C6-ELISA exceeded that of the VlsE1/pepC10 (C6: AUC = 0.925; VlsE1/pepC10: AUC = 0.878; p = 0.003). The novel ZEUS Borrelia VlsE1/pepC10 assay has generally comparable diagnostic parameters to the C6-ELISA with potentially improved specificity in cross-reactive sera. Thus, it is a useful tool for the serodiagnosis of Lyme borreliosis in Europe., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2022
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36. Translating genomic exploration of the family Polyomaviridae into confident human polyomavirus detection.

Author

Kamminga S, Sidorov IA, Tadesse M, van der Meijden E, de Brouwer C, Zaaijer HL, Feltkamp MCW, and Gorbalenya AE

Abstract

The Polyomaviridae is a family of ubiquitous dsDNA viruses that establish persistent infection early in life. Screening for human polyomaviruses (HPyVs), which comprise 14 diverse species, relies upon species-specific qPCRs whose validity may be challenged by accelerating genomic exploration of the virosphere. Using this reasoning, we tested 64 published HPyV qPCR assays in silico against the 1781 PyV genome sequences that were divided in targets and nontargets, based on anticipated species specificity of each qPCR. We identified several cases of problematic qPCR performance that were confirmed in vitro and corrected through using degenerate oligos. Furthermore, our study ranked 8 out of 52 tested BKPyV qPCRs as remaining of consistently high quality in the wake of recent PyV discoveries and showed how sensitivity of most other qPCRs could be rescued by annealing temperature adjustment. This study establishes an efficient framework for ensuring confidence in available HPyV qPCRs in the genomic era., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Published
2021
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37. Hepatitis B core related antigen in relation to intrahepatic and circulating viral markers, before and after combination therapy.

Author

Erken R, Zaaijer HL, Willemse SB, Bakker E, Takkenberg BB, Reesink HW, and Kootstra NA

Subjects
Adult, Antiviral Agents therapeutic use, Biomarkers metabolism, Female, Follow-Up Studies, Hepatitis B virus genetics, Hepatitis B, Chronic immunology, Hepatitis B, Chronic virology, Humans, Liver immunology, Liver metabolism, Male, Prospective Studies, Viral Load, DNA, Viral genetics, Hepatitis B Core Antigens immunology, Hepatitis B virus isolation & purification, Hepatitis B, Chronic drug therapy, Liver pathology
Abstract

Introduction and Objectives: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment., Materials and Methods: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBV-pgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364)., Results: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (ρ 0.77, p < 0.001), intrahepatic HBV-DNA (ρ 0.73, p < 0.001) and plasma/serum HBV-DNA (ρ 0.80, p < 0.001), HBV-pgRNA (ρ 0.80, p < 0.001), and to lesser extend HBsAg (ρ 0.56, p < 0.001). Baseline HBcrAg-levels could not predict functional cure (FC) but HBcrAg-levels declined more strongly in patients who developed FC or HBeAg-loss. Furthermore, most correlations persisted at the end of treatment and follow-up., Conclusions: HBcrAg reflects cccDNA transcription activity more accurately than HBsAg and may replace HBV-DNA as a marker during future treatment regimens, especially when cccDNA transcription is targeted or nucleot(s)ide analogues are included in the treatment regime., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Published
2021
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38. Lower Incidence of Parvovirus-B19 Infections in Dutch Blood Donors during SARS-CoV-2 Pandemic.

Author

Molenaar-de Backer MW, Hogema BM, Koppelman MH, van de Laar TJ, Slot E, and Zaaijer HL

Subjects
Asymptomatic Infections epidemiology, Blood Transfusion, Carrier State virology, Humans, Netherlands epidemiology, Parvoviridae Infections transmission, SARS-CoV-2 isolation & purification, Blood Donors statistics & numerical data, COVID-19 epidemiology, Parvoviridae Infections epidemiology, Parvovirus B19, Human isolation & purification
Published
2021
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39. JC and Human polyomavirus 9 after kidney transplantation: An exploratory serological cohort study.

Author

Kamminga S, van Rijn AL, de Brouwer CS, Rotmans JI, Zaaijer HL, and Feltkamp MCW

Subjects
Blood Donors, Cohort Studies, Humans, Polyomaviridae, BK Virus, JC Virus, Kidney Transplantation adverse effects, Polyomavirus, Polyomavirus Infections, Tumor Virus Infections
Abstract

Introduction: Human polyomaviruses (HPyVs) cause disease in immunocompromised patients. BK polyomavirus (BKPyV) for instance persistently infects the kidneys. In kidney transplant recipients, (KTRs) BKPyV can cause allograft nephropathy. JCPyV, MCPyV, TSPyV and HPyV9 reside in the kidneys too, or have been detected in urine. In this study, we investigate exposure to JCPyV, MCPyV, TSPyV and HPyV9 after kidney transplantation by serological means., Materials and Methods: Serum samples from 310 KTR collected before and 6 months after transplantation (n = 620), from 279 corresponding kidney donors collected before transplantation, and from blood donor controls collected one year apart (n = 174) were assessed for HPyV species-specific IgG responses using a multiplex immunoassay. KTR HPyV IgG kinetics were compared to those of healthy blood donors by linear mixed modeling, and related to those of their donors by linear regression., Results: In the KTR, increased IgG levels during follow-up were observed for JCPyV (14.8%), MCPyV (7.1%), TSPyV (10.6%), and for HPyV9 (8.1%), while blood donor antibody levels remained stable. Seroconversion was observed for JCPyV (6.5%), MCPyV (2.3%), TSPyV (1.3%), and for HPyV9 (6.5%). The linear mixed model analysis showed that antibody increase was significant for JCPyV (p < 0.001) and HPyV9 (p < 0.001). Post-transplant JCPyV and HPyV9 antibody responses were associated with donor antibody levels against these HPyVs, respectively., Conclusions: KTR are exposed to JCPyV and HPyV9 after transplantation. Whether the allograft serves as the source, as indicated by the donor serostatus association, deserves further study., (Copyright © 2021. Published by Elsevier B.V.)

Published
2021
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40. Convalescent Plasma in a Patient with Protracted COVID-19 and Secondary Hypogammaglobulinemia Due to Chronic Lymphocytic Leukemia: Buying Time to Develop Immunity?

Author

Hanssen JLJ, Stienstra J, Boers SA, Pothast CR, Zaaijer HL, Tjon JM, Heemskerk MHM, Feltkamp MCW, and Arend SM

Abstract

It is not exactly clear yet which type of immune response prevails to accomplish viral clearance in coronavirus disease 2019 (COVID-19). Studying a patient with chronic lymphocytic leukemia and hypogammaglobulinemia who suffered from COVID-19 provided insight in the immunological responses after treatment with COVID-19 convalescent plasma (CCP). Treatment consisted of oxygen, repeated glucocorticosteroids and multiple dosages of CCP guided by antibody levels. Retrospectively performed humoral and cellular immunity analysis made clear that not every serological test for COVID-19 is appropriate for follow-up of sufficient neutralizing antibodies after CCP. In retrospect, we think that CCP merely bought time for this patient to develop an adequate cellular immune response which led to viral clearance and ultimately clinical recovery.

Published
2021
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41. Parvovirus B19 DNA detectable in hearts of patients with dilated cardiomyopathy, but absent or inactive in blood.

Author

Russcher A, Verdonschot J, Molenaar-de Backer MWA, Heymans SRB, Kroes ACM, and Zaaijer HL

Subjects
Adult, DNA, Viral, Heart, Humans, Cardiomyopathy, Dilated, Parvoviridae Infections diagnosis, Parvovirus B19, Human genetics
Abstract

Aims: Parvovirus B19 (B19V) is often assumed to be a cause of dilated cardiomyopathy (DCM), based on the quantification of B19V DNA in endomyocardial biopsies (EMB). Whether the presence of B19V DNA correlates with active infection is still debated. Application of the enzyme endonuclease to blood samples results in degradation of B19V DNA remnants but leaves viral particles intact, which enables differentiation between active and past infection. In this study, the susceptibility to degradation by endonuclease of B19V DNA in blood was compared between DCM patients and a control group of recent B19V infections., Methods and Results: Twenty blood samples from 20 adult patients with DCM, who previously tested positive for B19V DNA in EMB and/or blood, were tested with B19V PCR before and after application of endonuclease to the samples. Six blood samples tested positive for B19V DNA with a mean viral load of 2.3 × 10 4  IU/mL. In five samples, B19V DNA became undetectable after endonuclease (100% load reduction); in one sample DNA load showed a 23% log load reduction (viral load before endonuclease: 9.1 × 10 4  IU/mL; after: 6.5 × 10 3  IU/mL). Presence of cardiac inflammation did not differ between patients with B19V DNAemia (1/4) and patients without B19V DNAemia (6/14) (P value = 1.0). In all 18 control samples of proven recent B19V infections, DNA remained detectable after application of endonuclease, showing only a mean log load reduction of 2.3% (mean viral load before endonuclease: 8.1 × 10 11  IU/mL; after: 8.0 × 10 11  IU/mL). Load reduction differed significantly between the DCM group and the control group; indicating the presence of intact viral particles in the control group with proven active infection and the presence of DNA remnants in the DCM group (P value = 0.000)., Conclusion: During recent B19V infection, viral DNA levels in blood were unaffected by endonuclease. In contrast, B19V DNA in blood in patients with DCM became undetectable or strongly reduced after application of endonuclease. Circulating viral DNA in this subset of patients with presumed parvovirus-associated DCM does not consist of intact viral particles. Viral replicative activity cannot be assumed from demonstrating B19V DNA in cardiac tissue or in blood in DCM patients., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2021
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42. Blood donor screening in the Netherlands: Universal anti-HBc screening in combination with HBV nucleic acid amplification testing may allow discontinuation of hepatitis B virus antigen testing.

Author

van de Laar TJ, Hogema BM, Molenaar-de Backer MW, Marijt-van der Kreek T, and Zaaijer HL

Subjects
Adult, DNA, Viral blood, Hepatitis B blood, Hepatitis B diagnosis, Hepatitis B virus genetics, Hepatitis B virus immunology, Humans, Netherlands, Unnecessary Procedures, Viremia diagnosis, Viremia virology, Blood Donors, Blood Safety, Donor Selection, Hepatitis B prevention & control, Hepatitis B Antibodies blood, Hepatitis B Core Antigens immunology, Hepatitis B Surface Antigens blood, Hepatitis B virus isolation & purification, Nucleic Acid Amplification Techniques, Viremia blood
Abstract

Background: In the Netherlands, blood donor screening for hepatitis B virus (HBV) consists of HBsAg screening since the 1970s, HBV DNA minipool testing (MP-NAT) since 2008, and anti-HBc screening since 2011. Anti-HBc reactivity causes deferral only if anti-HBs titers are <200 IU/mL, or when anti-HBc was acquired during follow-up., Study Design and Methods: Over 5.5 million donations from 582,459 Dutch donors were screened for HBV DNA, HBsAg, anti-HBc, and, if anti-HBc positive, also for anti-HBs. The added value, expressed as the yield of (potentially) infectious and/or recent HBV infections versus unnecessary donor loss, was evaluated for each of the three HBV screening tests., Results: HBV donor screening identified 89 HBV-infected donors with at least two reactive HBV markers (MP-NAT, HBsAg and/or anti-HBc). Single HBV-marker yield was: 5 MP-NAT-only, 0 HBsAg-only, and 20 anti-HBc-only donors. In addition, anti-HBc screening yielded 1,067 potentially infectious donors at risk for occult HBV infection (OBI). In total, 4,126 (0.71%) donors were anti-HBc-reactive at first-time screening, and 1,098 (0.19%) seroconverted during follow-up. Anti-HBc-related donor loss was limited to 2,627 (0.45%) donors using anti-HBs titers and two-strike programs. Donor loss due to MP-NAT and HBsAg screening was extremely low: 0 and 128 donors, respectively., Conclusion: HBV donor screening could be limited to MP-NAT and anti-HBc screening. MP-NAT and anti-HBc improved blood safety by intercepting infectious donations from donors with recent infection or OBI, while HBsAg did not. Unnecessary donor loss related to anti-HBc screening is substantial but does not endanger the continuity of the blood supply., (© 2021 AABB.)

Published
2021
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43. Borrelia burgdorferi sensu lato seroconversion after intravenous immunoglobulin treatment: A cohort study.

Author

Lucke IM, Vrijlandt A, Lim J, van der Kooi AJ, van Schaik IN, Zaaijer HL, Hovius JW, and Eftimov F

Subjects
Antibodies, Bacterial, Cohort Studies, Humans, Immunoglobulin M, Immunoglobulins, Intravenous, Seroconversion, Seroepidemiologic Studies, Borrelia burgdorferi, Borrelia burgdorferi Group
Abstract

Objective: Intravenous immunoglobulin (IVIg) consists of pooled donor immunoglobulins (IgG), possibly including anti-Borrelia burgdorferi (Bbsl) antibodies. Apparent IVIg-related Bbsl seroconversion could lead to incorrect diagnosis of Lyme borreliosis. This cohort study was designed to determine how often IVIg treatment leads to apparent Bbsl seroconversion and whether antibodies disappear post-treatment., Methods: Sera from chronic inflammatory demyelinating polyneuropathy (CIDP) and myositis patients were analyzed, drawn pre-treatment and 6-12 weeks after the start of IVIg. In patients with apparent seroconversion, follow-up samples after treatment withdrawal were analyzed, if available. Patients treated with corticosteroids were included as controls. A two-tier protocol was used for serological testing consisting of the C6 Lyme ELISA (Oxford Immunotec) and confirmation by immunoglobulin M (IgM) and immunoglobulin G (IgG) immunoblot (Mikrogen ® )., Results: We included 61 patients: 51 patients were treated with IVIg and 10 with dexamethasone. Of the patients treated with IVIg, 42 had CIDP (82%) and were treated with Nanogam ® (Sanquin Plasma Products). Nine patients had myositis (18%) and were treated with Privigen ® (CSL Behring). Anti-Bbsl IgG seroprevalence pre-treatment was 3% (2/61). Apparent seroconversion during IVIg treatment occurred in 39% (20/51) of patients, all treated with Nanogam. Post-treatment seroreversion occurred in 92% (12/13) of patients with available follow-up samples; in 78% (7/9) seroreversion was observed within 3 months., Conclusions: Transient presence of anti-Bbsl IgG antibodies after IVIg is regularly observed. This effect appears to be dependent on the IVIg brand, probably reflecting variation in Bbsl exposure of plasma donors. Lyme borreliosis serological testing during, and weeks to months after, IVIg is therefore of limited utility., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Published
2021
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44. Comparison of Hepatitis E Virus Sequences from Humans and Swine, the Netherlands, 1998-2015.

Author

Hogema BM, Hakze-van der Honing RW, Molier M, Zaaijer HL, and van der Poel WHM

Subjects
Animals, Hepatitis E virology, Hepatitis E virus classification, Humans, Netherlands epidemiology, Phylogeny, RNA, Viral genetics, Sus scrofa virology, Swine Diseases virology, Viral Zoonoses transmission, Blood Donors, Genotype, Hepatitis E epidemiology, Hepatitis E virus genetics, Sequence Analysis, DNA, Swine virology
Abstract

Pigs are suspected to be a major source of zoonotic hepatitis E virus (HEV) infection in industrialized countries, but the transmission route(s) from pigs to humans are ill-defined. Sequence comparison of HEV isolates from pigs with those from blood donors and patients in 372 samples collected in the Netherlands in 1998 and 1999 and between 2008 and 2015 showed that all sequences were genotype 3 except for six patients (with travel history). Subgenotype 3c (gt3c) was the most common subtype. While the proportion of gt3c increased significantly between 1998 and 2008, it remained constant between 2008 and 2015. Among the few circulating HEV subtypes, there was no difference observed between the human and the pig isolates. Hepatitis E viruses in humans are very likely to originate from pigs, but it is unclear why HEV gt3c has become the predominant subtype in the Netherlands.

Published
2021
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45. Diagnostic Performance of the Novel BioPlex Lyme Serological Assays in European Patients with Lyme Disease.

Author

Baarsma ME, Ursinus J, Zaaijer HL, Kuiper H, and Hovius JW

Subjects
Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G, Immunoglobulin M, Netherlands, Polymers, Sensitivity and Specificity, Serologic Tests, Antibodies, Bacterial, Lyme Disease diagnosis
Abstract

Serodiagnosis of Lyme borreliosis (LB) comes with several drawbacks, among which is limited sensitivity in early disease. This study assesses the sensitivity and specificity of the novel BioPlex 2200 Lyme IgG and Lyme IgM assays. It also assesses potential improvements to the assays through receiver-operating characteristic (ROC) analysis. The BioPlex assays were performed on sera of 158 Dutch patients with physician-confirmed LB (both early localized and disseminated), 800 healthy blood donors from the Netherlands, and 90 cross-reactive controls. The BioPlex (Biopl) assays were compared with two commercial enzyme immunoassays (Euroimmun [Eur]/C6-ELISA) and one immunoblot (recomLine). The highest sensitivity in early LB was achieved with the BioPlex assays, which outperformed the Euroimmun and C6-ELISA (Biopl: 81/88, 92.1%; Eur: 64/88, 72.7%; C6: 72/88, 81.8%). Sensitivity of all assays was comparable in patients with disseminated LB. The BioPlex assays were outperformed in terms of specificity (all healthy blood donors, Biopl: 571/800, 71.4%; Eur: 711/800, 88.9%; C6: 727/800, 90.9%), but further analyses showed promising avenues following cutoff optimization. ROC analysis showed that 2/6 antigens of the combined BioPlex IgG and IgM assays had significantly higher areas under the curve (AUCs) than those of the other analyses. Potential modified versions of the assays based on these antigens largely outperformed the Euroimmun and C6-ELISA in EM patients (Biopl: 81/80, 92.1%) while maintaining a comparable or even higher specificity (Biopl: 714/800, 89.3%). The BioPlex 2200 Lyme IgG and Lyme IgM assays are promising tools for the serodiagnosis of early LB, with the potential to be used as a standalone test. Further research is necessary to validate the findings of this discovery cohort.

Published
2021
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46. Low awareness of past SARS-CoV-2 infection in healthy plasma donors.

Author

van den Hurk K, Merz EM, Prinsze FJ, Spekman MLC, Quee FA, Ramondt S, Slot E, Vrielink H, Huis In 't Veld EMJ, Zaaijer HL, and Hogema BM

Subjects
Adult, Antibodies, Viral blood, COVID-19 virology, Female, Health Status, Humans, Male, Middle Aged, Netherlands, SARS-CoV-2 isolation & purification, Severity of Illness Index, Surveys and Questionnaires, Blood Donors statistics & numerical data, COVID-19 pathology
Abstract

Awareness of infection with SARS-CoV-2 is crucial for the effectiveness of COVID-19 control measures. Here, we investigate awareness of infection and symptoms in relation to antibodies against SARS-CoV-2 in healthy plasma donors. We asked individuals donating plasma across the Netherlands between May 11 th and 18 th 2020 to report COVID-19-related symptoms, and we tested for antibodies indicative of a past infection with SARS-CoV-2. Among 3,676 with antibodies, and from questionnaire data, 239 (6.5%) are positive for SARS-CoV-2 antibodies. Of those, 48% suspect no COVID-19, despite the majority reporting symptoms; 11% of seropositive individuals report no symptoms and 27% very mild symptoms at any time during the first peak of the epidemic. Anosmia/ageusia and fever are most strongly associated with seropositivity. Almost half of seropositive individuals do not suspect SARS-CoV-2 infection. Improved recognition of COVID-19 symptoms, in particular, anosmia/ageusia and fever, is needed to reduce widespread SARS-CoV-2 transmission., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Published
2021
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47. Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity.

Author

Larsen MD, de Graaf EL, Sonneveld ME, Plomp HR, Nouta J, Hoepel W, Chen HJ, Linty F, Visser R, Brinkhaus M, Šuštić T, de Taeye SW, Bentlage AEH, Toivonen S, Koeleman CAM, Sainio S, Kootstra NA, Brouwer PJM, Geyer CE, Derksen NIL, Wolbink G, de Winther M, Sanders RW, van Gils MJ, de Bruin S, Vlaar APJ, Rispens T, den Dunnen J, Zaaijer HL, Wuhrer M, Ellen van der Schoot C, and Vidarsson G

Subjects
Adult, Aged, Antibodies, Viral blood, Antibodies, Viral chemistry, COVID-19 physiopathology, Cells, Cultured, Critical Illness, Cytomegalovirus immunology, Female, Fucose analysis, Glycosylation, HIV immunology, Hepatitis B Vaccines immunology, Humans, Immunoglobulin Fc Fragments chemistry, Immunoglobulin Fc Fragments immunology, Immunoglobulin G blood, Immunoglobulin G chemistry, Inflammation, Interleukin-6 biosynthesis, Interleukin-6 immunology, Macrophages immunology, Male, Middle Aged, Parvovirus B19, Human immunology, Severity of Illness Index, Spike Glycoprotein, Coronavirus immunology, Vaccines, Subunit immunology, Young Adult, Antibodies, Viral immunology, COVID-19 immunology, Immunoglobulin G immunology, SARS-CoV-2 immunology
Abstract

Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Published
2021
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48. Low SARS-CoV-2 seroprevalence in blood donors in the early COVID-19 epidemic in the Netherlands.

Author

Slot E, Hogema BM, Reusken CBEM, Reimerink JH, Molier M, Karregat JHM, IJlst J, Novotný VMJ, van Lier RAW, and Zaaijer HL

Subjects
Adolescent, Adult, Aged, Asymptomatic Diseases epidemiology, Betacoronavirus isolation & purification, COVID-19, Humans, Immunoglobulin G blood, Immunoglobulin M blood, Middle Aged, Netherlands, Pandemics, Prevalence, SARS-CoV-2, Seroepidemiologic Studies, Social Isolation, Young Adult, Antibodies, Viral blood, Blood Donors statistics & numerical data, Coronavirus Infections epidemiology, Pneumonia, Viral epidemiology
Abstract

The world is combating an ongoing COVID-19 pandemic with health-care systems, society and economies impacted in an unprecedented way. It is unclear how many people have contracted the causative coronavirus (SARS-CoV-2) unknowingly and are asymptomatic. Therefore, reported COVID-19 cases do not reflect the true scale of outbreak. Here we present the prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult population of the Netherlands, which is a highly affected country, using a high-performance immunoassay. Our results indicate that one month into the outbreak (i) the seroprevalence in the Netherlands was 2.7% with substantial regional variation, (ii) the hardest-hit areas showed a seroprevalence of up to 9.5%, (iii) the seroprevalence was sex-independent throughout age groups (18-72 years), and (iv) antibodies were significantly more often present in younger people (18-30 years). Our study provides vital information on the extent of exposure to SARS-CoV-2 in a country where social distancing is in place.

Published
2020
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49. Potential human transmission of amyloid β pathology: surveillance and risks.

Author

Lauwers E, Lalli G, Brandner S, Collinge J, Compernolle V, Duyckaerts C, Edgren G, Haïk S, Hardy J, Helmy A, Ivinson AJ, Jaunmuktane Z, Jucker M, Knight R, Lemmens R, Lin IC, Love S, Mead S, Perry VH, Pickett J, Poppy G, Radford SE, Rousseau F, Routledge C, Schiavo G, Schymkowitz J, Selkoe DJ, Smith C, Thal DR, Theys T, Tiberghien P, van den Burg P, Vandekerckhove P, Walton C, Zaaijer HL, Zetterberg H, and De Strooper B

Subjects
Alzheimer Disease etiology, Alzheimer Disease metabolism, Alzheimer Disease pathology, Amyloid beta-Peptides toxicity, Animals, Creutzfeldt-Jakob Syndrome metabolism, Creutzfeldt-Jakob Syndrome pathology, Creutzfeldt-Jakob Syndrome transmission, Humans, Neurodegenerative Diseases etiology, Neurodegenerative Diseases pathology, Parkinson Disease etiology, Parkinson Disease metabolism, Parkinson Disease pathology, Risk Factors, Amyloid beta-Peptides metabolism, Neurodegenerative Diseases metabolism, Population Surveillance
Abstract

Studies in experimental animals show transmissibility of amyloidogenic proteins associated with prion diseases, Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Although these data raise potential concerns for public health, convincing evidence for human iatrogenic transmission only exists for prions and amyloid β after systemic injections of contaminated growth hormone extracts or dura mater grafts derived from cadavers. Even though these procedures are now obsolete, some reports raise the possibility of iatrogenic transmission of amyloid β through putatively contaminated neurosurgical equipment. Iatrogenic transmission of amyloid β might lead to amyloid deposition in the brain parenchyma and blood vessel walls, potentially resulting in cerebral amyloid angiopathy after several decades. Cerebral amyloid angiopathy can cause life-threatening brain haemorrhages; yet, there is no proof that the transmission of amyloid β can also lead to Alzheimer's dementia. Large, long-term epidemiological studies and sensitive, cost-efficient tools to detect amyloid are needed to better understand any potential routes of amyloid β transmission and to clarify whether other similar proteopathic seeds, such as tau or α-synuclein, can also be transferred iatrogenically., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Published
2020
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50. When are infection risks of blood transfusion tolerable? Towards understanding the ethical views of stakeholders in the blood supply.

Author

Kramer K, Verweij MF, and Zaaijer HL

Subjects
Adult, Aged, Female, Humans, Male, Middle Aged, Transfusion Reaction epidemiology, Blood Donors ethics, Blood Safety ethics, Blood Transfusion ethics, Transfusion Reaction psychology
Abstract

Background and Objectives: The perception of transfusion-transmitted infections (TTIs) is sensitive to various concerns besides the probability and impact of infection, and some of these concerns may be ethically relevant. This paper aims to advance thinking about blood safety policies by exploring and explaining stakeholders' reasons to consider TTI risks tolerable or intolerable., Materials and Methods: Inspired by critical empirical ethics and phenomenological hermeneutics, we held interviews and focus group discussions to explore the moral experience of policymakers, hematologists, blood donors and recipients. Respondents were invited to discuss general concerns about the blood supply, to address the tolerability of TTI risks compared with other hazards and to comment on the costs of blood safety. Arguments for tolerance or intolerance towards TTI risks were analysed qualitatively., Results: Stakeholders' views could be clustered into seven categories: (1) clinical impact; (2) probability of infection; (3) avoidability of infection; (4) cost and health benefits; (5) other consequences of safety measures; (6) non-consequentialist ethical arguments; and (7) stakeholders' interests. Various arguments were offered that resonate with current ethical thinking about blood safety. Assuming that resources spent on inefficient blood safety measures could be applied more beneficially elsewhere, for example, responders typically expressed tolerance towards TTI risks. Some other arguments seem novel, for instance arguments for risk intolerance based on the low probability of infection and arguments for risk tolerance if patients have a poor prognosis., Conclusion: Understanding the moral experience of stakeholders enriches ethical debate about blood safety and prepares developing more widely acceptable policies., (© 2019 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Published
2019
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