163 results on '"Hovius JW"'
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2. Mapping the human genetic architecture of COVID-19
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Niemi, MEK, Karjalainen, J, Liao, RG, Neale, BM, Daly, M, Ganna, A, Pathak, GA, Andrews, SJ, Kanai, M, Veerapen, K, Fernandez-Cadenas, I, Schulte, EC, Striano, P, Marttila, M, Minica, C, Marouli, E, Karim, MA, Wendt, FR, Savage, J, Sloofman, L, Butler-Laporte, G, Kim, H-N, Kanoni, S, Okada, Y, Byun, J, Han, Y, Uddin, MJ, Smith, GD, Willer, CJ, Buxbaum, JD, Mehtonen, J, Finucane, H, Cordioli, M, Martin, AR, Zhou, W, Pasaniuc, B, Julienne, H, Aschard, H, Shi, H, Yengo, L, Polimanti, R, Ghoussaini, M, Schwartzentruber, J, Dunham, I, Chwialkowska, K, Francescatto, M, Trankiem, A, Balaconis, MK, Davis, L, Lee, S, Priest, J, Renieri, A, Sankaran, VG, van Heel, D, Deelen, P, Richards, JB, Nakanishi, T, Biesecker, L, Kerchberger, VE, Kenneth, J, Mari, F, Bernasconi, A, Ceri, S, Canakoglu, A, Wolford, B, Faucon, A, Dutta, AK, Schurmann, C, Harry, E, Birney, E, Nguyen, H, Nasir, J, Kaunisto, M, Solomonson, M, Dueker, N, Vadgama, N, Limou, S, Rahmouni, S, Mbarek, H, Darwish, D, Uddin, MM, Albertos, R, Perez-Tur, J, Li, R, Folkersen, L, Moltke, I, Koelling, N, Teumer, A, Kousathanas, A, Utrilla, A, Verdugo, RA, Zarate, R, Medina-Gomez, C, Gomez-Cabrero, D, Carnero-Montoro, E, Cadilla, CL, Moreno-Estrada, A, Garmendia, A, Moya, L, Sedaghati-Khayat, B, Boua, PR, Fave, M-J, Francioli, L, Lemacon, A, Migeotte, I, Patel, S, Varnai, R, Szentpeteri, JL, Sipeky, C, Colombo, F, von Hohenstaufen, K, Lio, P, Vallerga, C, Wang, Q, Tanigawa, Y, Im, H, Han, C, Song, H, Lim, J, Lee, Y, Kim, S, Im, S, Atanasovska, B, Ahmad, HF, Boer, C, Jansen, P, Franke, L, Kaja, E, Pasko, D, Kennis-Szilagyi, I, Kornilov, SA, Prijatelj, V, Prokic, I, Sivanadhan, I, Perumal, S, Esmaeeli, S, Pearson, NM, Auton, A, Shelton, JF, Shastri, AJ, Filshtein-Sonmez, T, Coker, D, Symons, A, Esparza-Gordillo, J, Aslibekyan, S, O'Connell, J, Ye, C, Weldon, CH, Perera, M, O'Leary, K, Tuck, M, O'Brien, T, Meltzer, D, O'Donnell, P, Nutescu, E, Yang, G, Alarcon, C, Herrmann, S, Mazurek, S, Banagan, J, Hamidi, Z, Barbour, A, Raffat, N, Moreno, D, Friedman, P, Ferwerda, B, van de Beek, D, Brouwer, MC, Vlaar, APJ, Wiersinga, WJ, Posthuma, D, Tissink, E, Zwinderman, AHK, Uffelmann, E, van Agtmael, M, Algera, AG, van Baarle, F, Bax, D, Beudel, M, Bogaard, HJ, Bomers, M, Bonta, PI, Bos, L, Botta, M, de Brabander, J, de Bree, G, de Bruin, S, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Dongelmans, D, Elbers, P, Fleuren, L, Geerlings, S, Geerts, B, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, MP, Hafkamp, F, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, SM, Heunks, L, Hollmann, M, Horn, J, Hovius, JW, de Jong, MD, Koning, R, van Mourik, N, Nellen, J, Nossent, EJ, Paulus, F, Peters, E, van der Poll, T, Preckel, B, Prins, JM, Raasveld, J, Reijnders, T, Schinkel, M, Schultz, MJ, Schuurman, A, Sigaloff, K, Smit, M, Stijnis, CS, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A, van der Valk, M, Veelo, D, de Vries, H, van Vugt, M, Wouters, D, Minnaar, RP, Kromhout, A, van Uffelen, KWJ, Wolterman, RA, Roberts, G, Park, D, Ball, CA, Coignet, M, McCurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Hong, EL, Rand, K, Girshick, A, Guturu, H, Baltzell, AH, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Bouysran, Y, Busson, A, Peyrassol, X, Wilkin, F, Pichon, B, Smits, G, Vandernoot, I, Goffard, J-C, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Jadot, L, Azarzar, S, Dellot, P, Gofflot, S, Claassen, S, Bertrand, A, Parzibut, G, Clarinval, M, Moermans, C, Malaise, O, El Kandoussi, K, Thonon, R, Huynen, P, Mesdagh, A, Melo, S, Jacques, N, Di Valentin, E, Giroule, F, Collignon, A, Radermecker, C, Lebrun, M, Peree, H, Latour, S, Barada, O, Sanchez, J, Josse, C, Boujemla, B, Meunier, M, Mariavelle, E, Anania, S, Gazon, H, Juszczak, D, Fadeur, M, Camby, S, Meuris, C, Thys, M, Jacques, J, Henket, M, Leonard, P, Frippiat, F, Giot, J-B, Sauvage, A-S, Von Frenckell, C, Mni, M, Wery, M, Staderoli, A, Belhaj, Y, Lambermont, B, Morrison, DR, Mooser, V, Forgetta, V, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Brassard, N, Durand, M, Schurr, E, Lepage, P, Ragoussis, J, Auld, D, Chasse, M, Kaufmann, DE, Lathrop, GM, Adra, D, Davis, LK, Cox, NJ, Below, JE, Sealock, JM, Faucon, AB, Shuey, MM, Polikowsky, HG, Petty, LE, Shaw, DM, Chen, H-H, Zhu, W, Ludwig, KU, Schroeder, J, Maj, C, Rolker, S, Noethen, MM, Fazaal, J, Keitel, V, Jensen, B-EO, Feldt, T, Kurth, I, Marx, N, Dreher, M, Pink, I, Cornberg, M, Illig, T, Lehmann, C, Schommers, P, Augustin, M, Rybniker, J, Knopp, L, Eggermann, T, Volland, S, Altmueller, J, Berger, MM, Brenner, T, Hinney, A, Witzke, O, Bals, R, Herr, C, Ludwig, N, Walter, J, Fuchsberger, C, Pattaro, C, De Grandi, A, Pramstaller, P, Emmert, D, Melotti, R, Foco, L, Mascalzoni, D, Gogele, M, Domingues, F, Hicks, A, Gignoux, CR, Wicks, SJ, Crooks, K, Barnes, KC, Daya, M, Shortt, J, Rafaels, N, Chavan, S, Goldstein, DB, Kiryluk, K, Sengupta, S, Chung, W, Reilly, MP, Khan, A, Wang, C, Povysil, G, Bhardwaj, N, Gharavi, AG, Ionita-Laza, I, Shang, N, O'Byrne, SM, Nandakumar, R, Menon, A, So, YS, Hod, E, Pendrick, D, Park, S-K, Kim, H-L, Kang, CK, Lee, H-J, Song, K-H, Yoon, KJ, Paik, N-J, Seok, W, Yoon, H, Joo, E-J, Chang, Y, Ryu, S, Park, WB, Park, JS, Park, KU, Ham, SY, Jung, J, Kim, ES, Kim, HB, Ellinghaus, D, Degenhardt, F, Caceres, M, Juzenas, S, Lenz, TL, Albillos, A, Julia, A, Heidecker, B, Garcia, F, Kurth, F, Tran, F, Hanses, F, Zoller, H, Holter, JC, Fernandez, J, Sander, LE, Rosenstiel, P, Koehler, P, de Cid, R, Asselta, R, Schreiber, S, Hehr, U, Prati, D, Baselli, G, Valenti, L, Bujanda, L, Banales, JM, Duga, S, D'Amato, M, Romero-Gomez, M, Buti, M, Invernizzi, P, Franke, A, Hov, JR, Karlsen, TH, Folseraas, T, Maya-Miles, D, Teles, A, Azuure, C, Wacker, EM, Uellendahl-Werth, F, Elabd, H, Arora, J, Lerga-Jaso, J, Wienbrandt, L, Ruehlemann, MC, Wendorff, M, Vadla, MS, Lenning, OB, Oezer, O, Myhre, R, Raychaudhuri, S, Tanck, A, Gassner, C, Hemmrich-Stanisak, G, Kaessens, J, Basso, MEF, Schulzky, M, Wittig, M, Braun, N, Wesse, T, Albrecht, W, Yi, X, Ortiz, AB, Garrido Chercoles, A, Ruiz, A, Mantovani, A, Holten, AR, Mayer, A, Cherubini, A, Protti, A, Aghemo, A, Gerussi, A, Ramirez, A, Braun, A, Barreira, A, Lleo, A, Kildal, AB, Glueck, A, Carreras Nolla, A, Latiano, A, Dyrhol-Riise, AM, Muscatello, A, Voza, A, Rando-Segura, A, Solier, A, Karina, B, Cortes, B, Mateos, B, Nafria-Jimenez, B, Schaefer, B, Bellinghausen, C, Ferrando, C, Quereda, C, Skurk, C, Thibeault, C, Spinner, CD, Lange, C, Hu, C, Cappadona, C, Bianco, C, Sancho, C, Hoff, DAL, Galimberti, D, Jimenez, D, Pestana, D, Toapanta, D, Azzolini, E, Scarpini, E, Helbig, ET, Urrechaga, E, Paraboschi, EM, Pontali, E, Reverter, E, Navas, E, Arana, E, Garcia Sanchez, F, Ceriotti, F, Malvestiti, F, Mesonero, F, Pezzoli, G, Lamorte, G, Neb, H, My, I, Hernandez, I, de Rojas, I, Galvan-Femenia, I, Heyckendorf, J, Badia, JR, Schneider, J, Goikoetxea, J, Kraft, J, Mueller, KE, Gaede, KI, Garcia-Etxebarria, K, Tonby, K, Heggelund, L, Izquierdo-Sanchez, L, Sumoy, L, Lippert, LJ, Terranova, L, Garbarino, L, Tellez, L, Roade, L, Ostadreza, M, Intxausti, M, Kogevinas, M, Gutierrez-Stampa, MA, Vehreschild, MJGT, Marquie, M, Castoldi, M, Cecconi, M, Boada, M, Seilmaier, MJ, Mazzocco, M, Rodriguez-Gandia, M, Imaz Ayo, N, Blay, N, Martinez, N, Cornely, OA, Palmieri, O, Tentorio, P, Rodrigues, PM, Espana, PP, Hoffmann, P, Bacher, P, Suwalski, P, de Pablo, R, Nieto, R, Badalamenti, S, Ciesek, S, Bombace, S, Wilfling, S, Brunak, S, Heilmann-Heimbach, S, Ripke, S, Bahmer, T, Landmesser, U, Protzer, U, Rimoldi, V, Skogen, V, Andrade, V, Moreno, V, Poller, W, Farre, X, Wang, X, Khodamoradi, Y, Karadeniz, Z, de Salazar, A, Palom, A, Garcia-Fernandez, A-E, Blanco-Grau, A, Zanella, A, Bandera, A, Nebel, A, Biondi, A, Caba Llero-Garralda, A, Gori, A, Lind, A, Fracanzani, AL, Peschuck, A, Pesenti, A, De la Horra, C, Milani, C, Paccapelo, C, Angelini, C, Cea, C, Muniz-Diaz, E, Sandoval, E, Calderon, EJ, Solligard, E, Aziz, F, Martinelli-Boneschi, F, Peyvandi, F, Blasi, F, Medrano, FJ, Rodriguez-Frias, F, Mueller, F, Grasselli, G, Costantino, G, Cardamone, G, Foti, G, Matullo, G, Kurihara, H, Afset, JE, Damas, JK, Ampuero, J, Martin, J, Erdmann, J, Bergan, J, Goerg, S, Ferrusquia-Acosta, J, Hernandez Quero, J, Delgado, J, Guerrero, JM, Risnes, K, Bettini, LR, Moreira, L, Gustad, LT, Santoro, L, Scudeller, L, Riveiro-Barciela, M, Schaefer, M, Carrabba, M, Valsecchi, MG, Hernandez-Tejero, M, Acosta-Herrera, M, D'Angio, M, Baldini, M, Cazzaniga, M, Ciccarelli, M, Bocciolone, M, Miozzo, M, Chueca, N, Montano, N, Faverio, P, Preatoni, P, Bonfanti, P, Omodei, P, Castro, P, Ferrer, R, Gualtierotti, R, Gallego-Duran, R, Morilla, R, Haider, S, Marsal, S, Aneli, S, Pelusi, S, Bosari, S, Aliberti, S, Dudman, S, Zheng, T, Pumarola, T, Gonzalez Cejudo, T, Monzani, V, Friaza, V, Peter, W, Dopazo, X, May, S, Grimsrud, MM, Gudbjartsson, DF, Stefansson, K, Sulem, P, Sveinbjornsson, G, Melsted, P, Norddahl, G, Moore, KHS, Thorsteinsdottir, U, Holm, H, Alarcon-Riquelme, ME, Bernardo, D, Martinez-Bueno, M, Rojo Rello, S, Magi, R, Milani, L, Metspalu, A, Laisk, T, Lall, K, Lepamets, M, Esko, T, Reimann, E, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Alavere, H, Metsalu, K, Puusepp, M, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Palotie, A, Rivolta, C, Bochud, P-Y, Bibert, S, Boillat, N, Nussle, SG, Albrich, W, Quinodoz, M, Kamdar, D, Suh, N, Neofytos, D, Erard, V, Voide, C, Bochud, PY, Friolet, R, Vollenweider, P, Pagani, JL, Oddo, M, zu Bentrup, FM, Conen, A, Clerc, O, Marchetti, O, Guillet, A, Guyat-Jacques, C, Foucras, S, Rime, M, Chassot, J, Jaquet, M, Viollet, RM, Lannepoudenx, Y, Portopena, L, Desgranges, F, Filippidis, P, Guery, B, Haefliger, D, Kampouri, EE, Manuel, O, Munting, A, Iou-Olivgeris, MP, Regina, J, Rochat-Stettler, L, Suttels, V, Tadini, E, Tschopp, J, Van Singer, M, Viala, B, Boillat-Blanco, N, Brahier, T, Hugli, O, Meuwly, JY, Pantet, O, Bochud, M, D'Acremont, V, Younes, SE, Albrich, WC, Cerny, A, O'Mahony, L, von Mering, C, Frischknecht, M, Kleger, G-R, Filipovic, M, Kahlert, CR, Wozniak, H, Negro, TR, Pugin, J, Bouras, K, Knapp, C, Egger, T, Perret, A, Montillier, P, di Bartolomeo, C, Barda, B, Carreras, A, Mercader, JM, Guindo-Martinez, M, Torrents, D, Garcia-Aymerich, J, Castano-Vinyals, G, Dobano, C, Gori, M, Mondelli, MU, Castelli, F, Vaghi, M, Rusconi, S, Montagnani, F, Bargagli, E, Franchi, F, Mazzei, MA, Cantarini, L, Tacconi, D, Feri, M, Scala, R, Spargi, G, Nencioni, C, Bandini, M, Caldarelli, GP, Spagnesi, M, Canaccini, A, Ognibene, A, Monforte, AD, Girardis, M, Antinori, A, Francisci, D, Schiaroli, E, Scotton, PG, Panese, S, Scaggiante, R, Della Monica, M, Capasso, M, Fiorentino, G, Castori, M, Aucella, F, Di Biagio, A, Masucci, L, Valente, S, Mandala, M, Zucchi, P, Giannattasio, F, Coviello, DA, Mussini, C, Bosio, G, Tavecchia, L, Crotti, L, Rizzi, M, La Rovere, MT, Sarzi-Braga, S, Bussotti, M, Ravaglia, S, Artuso, R, Perrella, A, Romani, D, Bergomi, P, Catena, E, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Di Pietro, M, Sabrina, R, Luchi, S, Barbieri, C, Acquilini, D, Andreucci, E, Paciosi, F, Segala, FV, Tiseo, G, Falcone, M, Lista, M, Poscente, M, De Vivo, O, Petrocelli, P, Guarnaccia, A, Baroni, S, Perticaroli, V, Furini, S, Dei, S, Benetti, E, Picchiotti, N, Sanarico, M, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Bergomi, M, Zguro, K, Capitani, K, Tanfoni, M, Fallerini, C, Daga, S, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, MA, Lo Rizzo, C, Pinto, AM, Beligni, G, Tommasi, A, Di Sarno, L, Palmieri, M, Carriero, ML, Alaverdian, D, Iuso, N, Inchingolo, G, Busani, S, Bruno, R, Vecchia, M, Belli, MA, Mantovani, S, Ludovisi, S, Quiros-Roldan, E, Antoni, MD, Zanella, I, Siano, M, Emiliozzi, A, Fabbiani, M, Rossetti, B, Zanelli, G, Bergantini, L, D'Alessandro, M, Cameli, P, Bennet, D, Anedda, F, Marcantonio, S, Scolletta, S, Guerrini, S, Conticini, E, Frediani, B, Spertilli, C, Donati, A, Guidelli, L, Corridi, M, Croci, L, Piacentini, P, Desanctis, E, Cappelli, S, Verzuri, A, Anemoli, V, Pancrazi, A, Lorubbio, M, Merlini, E, Miraglia, FG, Venturelli, S, Cossarizza, A, Vergori, A, Gabrieli, A, Riva, A, Andretta, F, Gatti, F, Parisi, SG, Baratti, S, Piscopo, C, Russo, R, Andolfo, I, Iolascon, A, Carella, M, Merla, G, Squeo, GM, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Sanguinetti, M, Giorli, A, Salerni, L, Parravicini, P, Menatti, E, Trotta, T, Coiro, G, Lena, F, Martinelli, E, Mancarella, S, Gabbi, C, Maggiolo, F, Ripamonti, D, Bachetti, T, Suardi, C, Parati, G, Botta, G, Di Domenico, P, Rancan, I, Bianchi, F, Colombo, R, van Heel, DA, Hunt, KA, Trembath, RC, Huang, QQ, Martin, HC, Mason, D, Trivedi, B, Wright, J, Finer, S, Griffiths, CJ, Akhtar, S, Anwar, M, Arciero, E, Ashraf, S, Breen, G, Chung, R, Curtis, CJ, Chowdhury, M, Colligan, G, Deloukas, P, Durham, C, Griffiths, C, Hurles, M, Hussain, S, Islam, K, Lavery, C, Lee, SH, Lerner, R, MacArthur, D, MacLaughlin, B, Martin, H, Miah, S, Newman, B, Safa, N, Tahmasebi, F, Smith, AV, Boughton, AP, Li, KW, LeFaive, J, Annis, A, Jannes, CE, Krieger, JE, Pereira, AC, Velho, M, Marques, E, Lima, IR, Tada, MT, Valino, K, McCarthy, M, Rosenberger, C, Lee, JE, Chang, D, Hammer, C, Hunkapiller, J, Mahajan, A, Pendergrass, S, Sucheston-Campbell, L, Yaspan, B, Lee, HS, Shin, E, Jang, HY, Kym, S, Kim, Y-S, Jeong, H, Kwon, KT, Kim, S-W, Kim, JY, Jang, YR, Kim, HA, Lee, JY, Choe, K-W, Kang, YM, Jee, SH, Jung, KJ, Parikh, V, Ashley, E, Wheeler, M, Rivas, M, Bustamante, C, Pinksy, B, Febbo, P, Farh, K, Schroth, GP, deSouza, F, Dalton, K, Christle, J, Deboever, C, Szalma, S, Rubinacci, S, Delaneau, O, Gorzynski, J, de Jong, H, Sutton, S, Youlton, N, Joshi, R, Jimenez-Morales, D, Hughes, C, Amar, D, Ioannidis, A, Hershman, S, Kirillova, A, Seo, K, Huang, Y, Shoura, M, Hammond, N, Watson, N, Raja, A, Huang, C, Sahoo, M, Wang, H, Zhen, J, Rakitko, A, Ilinsky, V, Yermakovich, D, Popov, I, Chernitsov, A, Kovalenko, E, Krasnenko, A, Plotnikov, N, Stetsenko, I, Kim, A, Cirulli, ET, Barrett, KMS, Bolze, A, White, S, Washington, NL, Lu, JT, Riffle, S, Tanudjaja, F, III, RJM, Leonetti, N, Neveux, I, Dabe, S, Grzymski, JJ, Minano, JIE, Aguirre, LA, Lopez-Collazo, E, Pazos, MDLM, Cerrato, L, Lozano-Rodriguez, R, Avendano-Ortiz, J, Terron Arcos, V, Marina Montalban-Hernandez, K, Valentin Quiroga, J, Pascual-Iglesias, A, Maroun-Eid, C, Martin-Quiros, A, Namkoong, H, Imoto, S, Katayama, K, Fukunaga, K, Kitagawa, Y, Sato, T, Hasegawa, N, Kumanogoh, A, Kimura, A, Ai, M, 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Hirofumi, Ikemura, Shinnosuke, Chubachi, Shotaro, Okamori, Satoshi, Terai, Hideki, Tanaka, Hiromu, Morita, Atsuho, Lee, Ho, Asakura, Takanori, Sasaki, Junichi, Morisaki, Hiroshi, Uwamino, Yoshifumi, Nanki, Kosaku, Mikami, Yohei, Tomono, Kazunori, Kato, Kazuto, Matsuda, Fumihiko, Takahashi, Meiko, Hizawa, Nobuyuki, Takeda, Yoshito, Hirata, Haruhiko, Shiroyama, Takayuki, Miyawaki, Satoru, Suzuki, Ken, Maeda, Yuichi, Nii, Takuro, Noda, Yoshimi, Niitsu, Takayuki, Adachi, Yuichi, Enomoto, Takatoshi, Amiya, Saori, Hara, Reina, Takahashi, Kunihiko, Anzai, Tatsuhiko, Hasegawa, Takanori, Ito, Satoshi, Koike, Ryuji, Endo, Akifumi, Uchimura, Yuji, Miyazaki, Yasunari, Honda, Takayuki, Tateishi, Tomoya, Tohda, Shuji, Ichimura, Naoya, Sonobe, Kazunari, Sassa, Chihiro, Nakajima, Jun, Nannya, Yasuhito, Omae, Yosuke, Takahashi, Kazuhisa, Harada, Norihiro, Hiki, Makoto, Takagi, Haruhi, Nakamura, Ai, Tagaya, Etsuko, Kawana, Masatoshi, Arimura, Ken, Ishiguro, Takashi, Takayanagi, Noboru, Isono, Taisuke, Takaku, Yotaro, Takano, Kenji, Anan, Ryusuke, Nakajima, Yukiko, Nakano, Yasushi, Nishio, Kazumi, Ueda, Soichiro, Hayashi, Reina, Tateno, Hiroki, Hase, Isano, Yoshida, Shuichi, Suzuki, Shoji, Mitamura, Keiko, Saito, Fumitake, Ueda, Tetsuya, Azuma, Masanori, Nagasaki, Tadao, Yasui, Yoshinori, Hasegawa, Yoshinori, Mutoh, Yoshikazu, Yoshiyama, Takashi, Shoko, Tomohisa, Kojima, Mitsuaki, Adachi, Tomohiro, Ishikawa, Motonao, Takahashi, Kenichiro, Watanabe, Kazuyoshi, Manabe, Tadashi, Ito, Fumimaro, Fukui, Takahiro, Funatsu, Yohei, Koh, Hidefumi, Hirai, Yoshihiro, Kawashima, Hidetoshi, Narita, Atsuya, Niwa, Kazuki, Sekikawa, Yoshiyuki, Saito, Fukuki, Yoshiya, Kazuhisa, Yoshihara, Tomoyuki, Suzuki, Yusuke, Nakayama, Sohei, Masuzawa, Keita, Nishi, Koichi, Nishitsuji, Masaru, Tani, Maiko, Inoue, Takashi, Hirano, Toshiyuki, Kobayashi, Keigo, Miyazawa, Naoki, Kimura, Yasuhiro, Sado, Reiko, Ogura, Takashi, Kitamura, Hideya, Murohashi, Kota, Nakachi, Ichiro, Baba, Rie, Arai, Daisuke, Fuke, Satoshi, Saito, Hiroshi, Kuwahara, Naota, Fujiwara, Akiko, Okada, Takenori, Baba, Tomoya, Noda, Junya, Mashimo, Shuko, Yagi, Kazuma, Shiomi, Tetsuya, Hashiguchi, Mizuha, Odani, Toshio, Mochimaru, Takao, Oyamada, Yoshitaka, Mori, Nobuaki, Izumi, Namiki, Nagata, Kaoru, Taki, Reiko, Murakami, Koji, Yamada, Mitsuhiro, Sugiura, Hisatoshi, Hayashi, Kentaro, Shimizu, Tetsuo, Gon, Yasuhiro, Fujitani, Shigeki, Tsuchida, Tomoya, Yoshida, Toru, Kagaya, Takashi, Kita, Toshiyuki, Sakagami, Satoru, Kimizuka, Yoshifumi, Kawana, Akihiko, Nakamura, Yoshihiko, Ishikura, Hiroyasu, Takata, Tohru, Kikuchi, Takahide, Taniyama, Daisuke, Nakamura, Morio, Kodama, Nobuhiro, Kaneyama, Yasunari, Maeda, Shunsuke, Nagasaki, Yoji, Okamoto, Masaki, Ishihara, Sayoko, Ito, Akihiro, Chihara, Yusuke, Takeuchi, Mayumi, Onoi, Keisuke, Hashimoto, Naozumi, Wakahara, Keiko, Ando, Akira, Masuda, Makoto, Wakabayashi, Aya, Watanabe, Hiroki, Sageshima, Hisako, Nakada, Taka-Aki, Abe, Ryuzo, Shimada, Tadanaga, Kawamura, Kodai, Ichikado, Kazuya, Nishiyama, Kenta, Yamasaki, Masaki, Hashimoto, Satoru, Kusaka, Yu, Ohba, Takehiko, Isogai, Susumu, Takada, Minoru, Kanda, Hidenori, Komase, Yuko, Sano, Fumiaki, Asano, Koichiro, Oguma, Tsuyoshi, Harada, Masahiro, Takahashi, Takeshi, Shibusawa, Takayuki, Abe, Shinji, Kono, Yuta, Togashi, Yuki, Izumo, Takehiro, Inomata, Minoru, Awano, Nobuyasu, Ogawa, Shinichi, Ogata, Tomouki, Ishihara, Shoichiro, Kanehiro, Arihiko, Ozaki, Shinji, Fuchimoto, Yasuko, Kitagawa, Yuichiro, Yoshida, Shozo, Ogura, Shinji, Nishiyama, Kei, Yoshida, Kousuke, Beppu, Satoru, Fukuyama, Satoru, Eriguchi, Yoshihiro, Yonekawa, Akiko, Inoue, Yoshiaki, Yamagata, Kunihiro, Chiba, Shigeru, Narumoto, Osamu, Nagai, Hideaki, Ooshima, Nobuharu, Motegi, Mitsuru, Sagara, Hironori, Tanaka, Akihiko, Ohta, Shin, Shibata, Yoko, Tanino, Yoshinori, Sato, Yuki, Yamada, Yuichiro, Hashino, Takuya, Shinoki, Masato, Iwagoe, Hajime, Imamura, Tomonori, Umeda, Akira, Shimada, Hisato, Endo, Mayu, Hayashi, Shinichi, Takahashi, Mai, Nakano, Shigefumi, Yatomi, Masakiyo, Maeno, Toshitaka, Ishii, Tomoo, Utsugi, Mitsuyoshi, Ono, Akihiro, Kanaoka, Kensuke, Ihara, Shoichi, Komuta, Kiyoshi, Boezen, Marike, Claringbould, Annique, Lopera, Esteban, Warmerdam, Robert, Vonk, Judith. M., van Blokland, Irene, Lanting, Pauline, Ori, Anil P. S., Obeidat, Ma’En, Hernández Cordero, Ana I., Sin, Don D., Bossé, Yohan, Joubert, Philippe, Hao, Ke, Nickle, David, Timens, Wim, van den Berge, Maarten, Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Perez, Emma F., Zöllner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Te, Sealfon, Stuart C., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Chaudhary, Kumardeep, Belbin, Gillian M., Preuss, Michael, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., Salib, Irene, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Zyndorf, Marissa, Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Abul-Husn, Noura S., Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Loos, Ruth J. F., Nadkarni, Girish N., Do, Ron, O’Reilly, Paul, Huckins, Laura M., Ferreira, Manuel A. R., Abecasis, Goncalo R., Leader, Joseph B., Cantor, Michael N., Justice, Anne E., Carey, Dave J., Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Horowitz, Julie E., Baras, Ari, Gass, Matthew C., Yadav, Ashish, Mirshahi, Tooraj, Jan Hottenga, Jouke, Bartels, Meike, de Geus, Eco J. C., Nivard, Michel G., Verma, Anurag, Ritchie, Marylyn D., Rader, Daniel, Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Zara, Federico, Salpietro, Vincenzo, Scala, Marcello, Iacomino, Michele, Scudieri, Paolo, Bocciardi, Renata, Minetti, Carlo, Riva, Antonella, Vari, Maria Stella, Rahier, Jean-Françoi, Giorgio, Elisa, Carli, Diana, Louis, Edouad, Bulik, Cynthia M., Landén, Mikael, Brusco, Alfredo, Ferrero, Giovanni Battista, Madia, Francesca, Fundín, Bengt, Ismail, Said I., Saad, Chadi, Al-Sarraj, Yaser, Badji, Radja Messai, Al-Muftah, Wadha, Al Thani, Asma, Afifi, Nahla, Klovins, Jani, Rovite, Vita, Rescenko, Raimond, Peculis, Raiti, Ustinova, Monta, Zeberg, Hugo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Johnson, Ruth, Geschwind, Daniel H., Freimer, Nelson, Butte, Manish J., Ding, Yi, Chiu, Alec, Chang, Timothy S., Boutros, Paul, Moutsianas, Louka, Caulfield, Mark J., Scott, Richard H., Walker, Susan, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Fowler, Tom, Rendon, Augusto, Chan, Georgia, Arumugam, Prabhu, Karczewski, Konrad J., Wilson, Daniel J., Spencer, Chris A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikola, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicola, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Soranzo, Nicole, Zhao, Jing Hua, Danesh, John, Di Angelantonio, Emanuele, Butterworth, Adam S., Sun, Yan V., Huffman, Jennifer E., Cho, Kelly, O’Donnell, Christopher J., Tsao, Phil, Gaziano, J. Michael, Peloso, Gina, Ho, Yuk-Lam, Mian, Michael, Scaggiante, Federica, Chang, Xiao, Glessner, Joseph R., Hakonarson, Hakon, Mcguigan, Peter J., Prockter Moore, Luke Stephen, Vizcaychipi, Marcela Paola, Hall, Kathryn, Campbell, Andy, Nichol, Ailstair, Ward, Geraldine, Page, Valerie Joan, Semple, Malcolm G., Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin L., Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nichola, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Chadwick, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chri, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, Drummond, Andrew, Durand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Christopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B., Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tama, Lillie, Patrick, Limb, Jame, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, Macmahon, Michael, Macnaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, Mccullough, Katherine, Mcewen, Ruth, Meda, Manjula, Mills, Gary H., Minton, Jane, Ward, Karl, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, Jame, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapa, Nelson, Mark, O’Shea, Matthew K., Otahal, Igor, Ostermann, Marlie, Pais, Mark, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Pooni, Jagtur Singh, Post, Frank, Price, David, Prout, Rachel, Rae, Nikola, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tama, Tatham, Kate, Thomas, Jo, Thompson, Chri, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Cole, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G., Workman, Andrew, Yates, Bryan, Young, Peter, Beale, Rupert, Bretherick, Andrew D., Clohisey, Sara, Fourman, Max Head, Furniss, Jame, Gountouna, Elvina, Grimes, Graeme, Haley, Chri, Harrison, David, Hayward, Caroline, Keating, Sean, Klaric, Lucija, Klenerman, Paul, Law, Andy, Meynert, Alison M., Millar, Jonathan, Pairo-Castineira, Erola, Parkinson, Nichola, Ponting, Chris P., Porteous, David J., Rawlik, Konrad, Richmond, Anne, Rowan, Kathy, Russell, Clark D., Shen, Xia, Shih, Barbara, Tenesa, Albert, Vitart, Veronique, Wang, Bo, Wilson, James F., Wu, Yang, Yang, Jian, Yang, Zhijian, Zechner, Marie, Zhai, Ranran, Zheng, Chenqing, Norman, Lisa, Pius, Riinu, Drake, Thomas M., Fairfield, Cameron J., Knight, Stephen R., Mclean, Kenneth A., Murphy, Derek, Shaw, Catherine A., Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Hendry, Ro, Scott-Brown, Jame, Begg, Colin, Hinds, Charle, Wai Ho, Antonia Ying, Horby, Peter W., Knight, Julian, Ling, Lowell, Maslove, David, Mcauley, Danny, Montgomery, Hugh, Nichol, Alistair, Openshaw, Peter J. M., Summers, Charlotte, Walsh, Timothy, Armstrong, Lisa, Bates, Hayley, Dooks, Emma, Farquhar, Fiona, Hairsine, Brigid, Mcparland, C., Packham, Sophie, Alldis, Zoe, Astin-Chamberlain, Raine, Bibi, Fatima, Biddle, Jack, Blow, Sarah, Bolton, Matthew, Borra, Catherine, Bowles, Ruth, Burton, Maudrian, Choudhury, Yasmin, Collier, David, Cox, Amber, Easthope, Amy, Ebano, Patrizia, Fotiadis, Stavro, Gurasashvili, Jana, Halls, Rosslyn, Hartridge, Pippa, Kallon, Delordson, Kassam, Jamila, Lancoma-Malcolm, Ivone, Matharu, Maninderpal, May, Peter, Mitchelmore, Oliver, Newman, Tabitha, Patel, Mital, Pheby, Jane, Pinzuti, Irene, Prime, Zoe, Prysyazhna, Oleksandra, Shiel, Julian, Taylor, Melanie, Tierney, Carey, Wood, Suzanne, Zak, Anne, Zongo, Olivier, Forsey, Miranda, Nicholson, Anne, Riches, Joanne, Vertue, Mark, Wasson, Christopher, Finn, Stephanie, Green, Jackie, Collins, Erin, King, Bernadette, Grauslyte, Lina, Hussain, Musarat, Pogreban, Tatiana, Rosaroso, Lace, Salciute, Erika, Franke, George, Wong, Joanna, George, Aparna, Akeroyd, Louise, Bano, Shereen, Bromley, Matt, Gurr, Lucy, Lawton, Tom, Morgan, Jame, Sellick, Kirsten, Warren, Deborah, Wilkinson, Brian, Mcgowan, Janet, Ledgard, Camilla, Stacey, Amelia, Pye, Kate, Bellwood, Ruth, Bentley, Michael, Loosley, Ronda, Mcguinness, Heather, Tench, Helen, Wolf-Roberts, Rebecca, Gibson, Sian, Lyle, Amanda, Mcneela, Fiona, Radhakrishnan, Jayachandran, Hughes, Alistair, Ali, Asifa, Brady, Megan, Dale, Sam, Dance, Annalisa, Gledhill, Lisa, Greig, Jill, Hanson, Kathryn, Holdroyd, Kelly, Home, Marie, Kelly, Diane, Kitson, Ro, Matapure, Lear, Melia, Deborah, Mellor, Samantha, Nortcliffe, Tonicha, Pinnell, Jez, Robinson, Matthew, Shaw, Lisa, Shaw, Ryan, Thomis, Lesley, Wilson, Alison, Wood, Tracy, Bayo, Lee-Ann, Merwaha, Ekta, Ishaq, Tahira, Hanley, Sarah, Antcliffe, David, Banach, Dorota, Brett, Stephen, Coghlan, Phoebe, Fernandez, Ziortza, Gordon, Anthony, Rojo, Roceld, Arias, Sonia Sousa, Templeton, Maie, Jha, Rajeev, Krishnamurthy, Vinodh, Lim, Lai, Bi, Rehana, Scholefield, Barney, Ashton, Lydia, Williams, Alison, Cheyne, Claire, Saunderson, Anne, Allan, Angela, Anderson, Felicity, Kaye, Callum, Liew, Jade, Medhora, Jasmine, Scott, Teresa, Trumper, Erin, Botello, Adriana, Polgarova, Petra, Stroud, Katerina, Meaney, Eoghan, Jones, Megan, Ng, Anthony, Agrawal, Shruti, Pathan, Nazima, White, Deborah, Daubney, Esther, Elston, Kay, Parker, Robert, Reddy, Amie, Turner-Bone, Ian, Wilding, Laura, Harding, Peter, Jacob, Reni, Jones, Cathy, Denmade, Craig, Croft, Maria, White, Ian, Lim, Li, Griffin, Denise, Muchenje, Nycola, Mupudzi, Mcdonald, Partridge, Richard, Conyngham, Jo-Anna, Thomas, Rachel, Wright, Mary, Corral, Maria Alvarez, Bastion, Victoria, Clarke, Daphene, David, Beena, Kent, Harriet, Lorusso, Rachel, Lubimbi, Gamu, Murdoch, Sophie, Penacerrada, Melchizedek, Thomas, Alastair, Valentine, Jennifer, Vochin, Ana, Wulandari, Retno, Djeugam, Brice, Dawson, Joy, Garrioch, Sweyn, Tolson, Melanie, Aldridge, Jonathan, de Almeida Martins, Laura Gome, Carungcong, Jaime, Beavis, Sarah, Dale, Katie, Gascoyne, Rachel, Hawes, Joanne, Pritchard, Kelly, Stevenson, Lesley, Whileman, Amanda, Cowley, Anne, Highgate, Judith, Crawley, Rikki, Crew, Abigail, Cunningham, Mishell, Daniels, Allison, Harrison, Laura, Hope, Susan, Inweregbu, Ken, Jones, Sian, Lancaster, Nicola, Matthews, Jamie, Nicholson, Alice, Wray, Gemma, Benham, Leonie, Bradshaw, Zena, Brown, Joanna, Caswell, Melanie, Melling, Sarah, Preston, Stephen, Slawson, Nicola, Stoddard, Emma, Warden, Scott, Combes, Edward, Joefield, Teishel, Monnery, Sonja, Beech, Valerie, Trotman, Sallyanne, Hopkins, Bridget, Scriven, Jame, Thrasyvoulou, Laura, Willis, Heather, Anderson, Susan, Birch, Janine, Collins, Emma, Hammerton, Kate, O’Leary, Ryan, Abernathy, Caroline, Foster, Louise, Gratrix, Andrew, Martinson, Vicky, Parkinson, Priyai, Stones, Elizabeth, Carbral-Ortega, Llucia, Kapoor, Ritoo, Loader, David, Castle, Karen, Brandwood, Craig, Smith, Lara, Clark, Richard, Birchall, Katie, Kolakaluri, Laurel, Baines, Deborah, Sukumaran, Anila, Mapfunde, Isheunesu, Meredith, Megan, Morris, Lucy, Ryan, Lucy, Clark, Amy, Sampson, Julia, Peters, Cecilia, Dent, Martin, Langley, Margaret, Ashraf, Saima, Wei, Shuying, Andrew, Angela, Chablani, Manish, Kirkby, Amy, Netherton, Kimberley, Bates, Michelle, Dasgin, Jo, Gill, Jaspret, Nilsson, Annette, Apetri, Elena, Basikolo, Cathrine, Blackledge, Bethan, Catlow, Laura, Charles, Bethan, Doonan, Reece, Harris, Jade, Harvey, Alice, Horner, Daniel, Knowles, Karen, Lee, Stephanie, Lomas, Diane, Lyons, Chloe, Marsden, Tracy, Mclaughlan, Danielle, Mcmorrow, Liam, Pendlebury, Jessica, Perez, Jane, Poulaka, Maria, Proudfoot, Nicola, Slaughter, Melanie, Slevin, Kathryn, Thomas, Vicky, Walker, Danielle, Michael, Angiy, Collis, Matthew, Clark, Martyn, Coulding, Martina, Jude, Edward, Mccormick, Jacqueline, Mercer, Oliver, Potla, Darsh, Rehman, Hafiz, Savill, Heather, Turner, Victoria, Davey, Miriam, Golden, David, Seaman, Rebecca, Hunt, Jodie, Dearden, Joy, Dobson, Emma, Mulcahy, Michelle, Munt, Sheila, O’Connor, Grainne, Philbin, Jennifer, Rishton, Chloe, Tully, Redmond, Winnard, Sarah, Cagova, Lenka, Fofano, Adama, Garner, Lucie, Holcombe, Helen, Mepham, Sue, Mitchell, Alice Michael, Mwaura, Lucy, Praman, K., Vuylsteke, Alain, Zamikula, Julie, Bercades, Georgia, Brealey, David, Hass, Ingrid, Maccallum, Niall, Martir, Glady, Raith, Eamon, Reyes, Anna, Smyth, Deborah, Taylor, Abigail, Hughes, Rachel Anne, Thomas, Helen, Rees, Alun, Duskova, Michaela, Phipps, Janet, Brooks, Suzanne, Edwards, Michelle, Alexander, Peter, Allen, Schvearn, Bradley-Potts, Joanne, Brantwood, Craig, Egan, Jasmine, Felton, Timothy, Padden, Grace, Ward, Luke, Moss, Stuart, Glasgow, Susannah, Beesley, Kate, Board, Sarah, Kubisz-Pudelko, Agnieszka, Lewis, Alison, Perry, Je, Pippard, Lucy, Wood, Di, Buckley, Clare, Brown, Alison, Gregory, Jane, O’Connell, Susan, Smith, Tim, Belagodu, Zakaula, Fuller, Bridget, Gherman, Anca, Olufuwa, Olumide, Paramsothy, Remi, Stuart, Carmel, Oakley, Naomi, Kamundi, Charlotte, Tyl, David, Collins, Katy, Silva, Pedro, Taylor, June, King, Laura, Coates, Charlotte, Crowley, Maria, Wakefield, Phillipa, Beadle, Jane, Johnson, Laura, Sargeant, Janet, Anderson, Madeleine, Jardine, Catherine, Williams, Dewi, Parris, Victoria, Quaid, Sheena, Watson, Ekaterina, Melville, Julie, Naisbitt, Jay, Joseph, Rosane, Lazo, Maria, Walton, Olivia, Neal, Alan, Hill, Michaela, Kannan, Thogulava, Wild, Laura, Allan, Elizabeth, Darlington, Kate, Davies, Ffyon, Easton, Jack, Kumar, Sumit, Lean, Richard, Menzies, Daniel, Pugh, Richard, Qiu, Xinyi, Davies, Llino, Williams, Hannah, Scanlon, Jeremy, Davies, Gwyneth, Mackay, Callum, Lewis, Joannne, Rees, Stephanie, Coetzee, Samantha, Gales, Alistair, Raj, Meena, Sell, Craig, Langton, Helen, Watters, Malcolm, Novis, Catherine, Arbane, Gill, Bociek, Aneta, Campos, Sara, Grau, Neu, Jones, Tim Owen, Lim, Rosario, Marotti, Martina, Whitton, Christopher, Barron, Anthony, Collins, Ciara, Kaul, Sundeep, Passmore, Heather, Prendergast, Claire, Reed, Anna, Rogers, Paula, Shokkar, Rajvinder, Woodruff, Meriel, Middleton, Hayley, Polgar, Oliver, Nolan, Claire, Thwaites, Vicky, Mahay, Kanta, Sri-Chandana, Chunda, Scherewode, Joslan, Stephenson, Lorraine, Marsh, Sarah, Bancroft, Hollie, Bellamy, Mary, Carmody, Margaret, Daglish, Jacqueline, Moore, Faye, Rhodes, Joanne, Sangombe, Mirriam, Kadiri, Salma, Ayers, Amanda, Harrison, Wendy, North, Julie, Cavazza, Anna, Cockrell, Maeve, Corcoran, Eleanor, Depante, Maria, Finney, Clare, Jerome, Ellen, Mcphail, Mark, Nayak, Monalisa, Noble, Harriet, O’Reilly, Kevin, Pappa, Evita, Saha, Rohit, Saha, Sian, Smith, John, Knighton, Abigail, Gill, Mandy, Paul, Paul, Ratnam, Valli, Shelton, Sarah, Wynter, Inez, Baptista, David, Crowe, Rebecca, Fernandes, Rita, Herdman-Grant, Rosaleen, Joseph, Anna, Loveridge, Adam, Mckenley, India, Morino, Eriko, Naranjo, Andre, Simms, Richard, Sollesta, Kathryn, Swain, Andrew, Venkatesh, Harish, Khera, Jacyntha, Fox, Jonathan, Barber, Russell, Hewitt, Claire, Hilldrith, Annette, Jackson-Lawrence, Karen, Shepardson, Sarah, Wills, Maryanne, Butler, Susan, Tavares, Silvia, Cunningham, Amy, Hindale, Julia, Arif, Sarwat, George, Linsha, Twiss, Sophie, Wright, David, Holland, Maureen, Keenan, Natalie, Lyons, Marc, Wassall, Helen, Marsh, Chri, Mahenthran, Mervin, Carter, Emma, Kong, Thoma, Adanini, Oluronke, Bhatia, Nikhil, Msiska, Maine, Mew, Louise, Mwaura, Esther, Williams, Felicity, Wren, Lynn, Sutherland, Sara-Beth, Battle, Ceri, Brinkworth, Elaine, Harford, Rachel, Murphy, Carl, Newey, Luke, Rees, Tabitha, Williams, Marie, Arnold, Sophie, Hardy, John, Houlden, Henry, Moncur, Eleanor, Tariq, Ambreen, Tucci, Arianna, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Keshet-Price, Jocelyn, Randell, Georgina, Stammers, Katie, Abdelrazik, Marwa, Bakthavatsalam, Dhanalakshmi, Elhassan, Munzir, Ganesan, Arunkumar, Haldeos, Anne, Moreno-Cuesta, Jeronimo, Purohit, Dharam, Vincent, Rachel, Xavier, Kugan, Rohit, Kumar, Alasdair, Frater, Saleem, Malik, David, Carter, Jenkins, Samuel, Lamond, Zoe, Wall, Alanna, Reynolds, Jessica, Campbell, Helen, Thompsom, Maria, Dodds, Steve, Duffy, Stacey, Butcher, Deborah, O’Sullivan, Susie, Butterworth-Cowin, Nicola, Deacon, Bethan, Hibbert, Meg, Pothecary, Carla, Tetla, Dariusz, Woodford, Christopher, Durga, Latha, Kennard-Holden, Gareth, de Gordoa, Laura Ortiz-Ruiz, Peasgood, Emily, Phillips, Claire, Skinner, Denise, Gaylard, Jane, Mullan, Dee, Newman, Julie, Davies, Ellie, Roche, Lisa, Sathe, Sonia, Brimfield, Lutece, Daly, Zoe, Pogson, David, Rose, Steve, Collins, Amy, Khaliq, Waqa, Gude, Estefania Treu, Allen, Louise, Beranova, Eva, Crisp, Nikki, Deery, Joanne, Hazelton, Tracy, Knight, Alicia, Price, Carly, Tilbey, Sorrell, Turki, Salah, Turney, Sharon, Giles, Julian, Booth, Simon, Bell, Gillian, English, Katy, Katary, Amro, Wilcox, Louise, Campbell, Rachael, Clarke, Noreen, Whiteside, Jonathan, Mascarenhas, Mairi, Donaldson, Avril, Matheson, Joanna, Barrett, Fiona, O’Hara, Marianne, O’Keefe, Laura, Bradley, Clare, Collier, Dawn, Walker, Rachel, Maynard, Victoria, Patel, Tahera, Smith, Matthew, Kazi, Aayesha, Hartley, Janice, Dykes, Joseph, Hijazi, Muhammad, Keith, Sarah, Khan, Meherunnisa, Ryan-Smith, Janet, Springle, Philippa, Thomas, Jacqueline, Truman, Nick, Saad, Samuel, Coleman, Dabheoc, Fine, Christopher, Matt, Roseanna, Gay, Bethan, Dalziel, Jack, Ali, Syamlan, Goodchild, Drew, Harling, Rhiannan, Bhatterjee, Ravi, Goddard, Wendy, Davison, Chloe, Duberly, Stephen, Hargreaves, Jeanette, Bolton, Rachel, Verlander, Mark, Williams, Alexandra, Blackman, Helen, Creagh-Brown, Ben, Donlon, Sinead, Michalak-Glinska, Natalia, Mtuwa, Sheila, Pristopan, Veronika, Salberg, Armorel, Smith, Eleanor, Stone, Sarah, Piercy, Charle, Verula, Jerik, Burda, Dorota, Montaser, Rugia, Harden, Lesley, Mayangao, Irving, Marriott, Cheryl, Bradley, Paul, Harris, Celia, Cooper, Joshua, Finch, Cheryl, Liderth, Sarah, Quinn, Alison, Waddington, Natalia, Fidler, Katy, Tagliavini, Emma, Donnelly, Kevin, Abel, Lynn, Brett, Michael, Digby, Brian, Gemmell, Lisa, Hornsby, Jame, Macgoey, Patrick, O’Neil, Pauline, Price, Richard, Rodden, Natalie, Rooney, Kevin, Sundaram, Radha, Thomson, Nicola, Flanagan, Rebecca, Hughes, Gareth, Latham, Scott, Mckenna, Emma, Anderson, Jennifer, Hull, Robert, Rhead, Kat, Branney, Debbie, Frankham, Jordan, Pitts, Sally, White, Nigel, Cristiano, Daniele, Dormand, Natalie, Farzad, Zohreh, Gummadi, Mahitha, Liyanage, Kamal, Patel, Brijesh V., Salmi, Sara, Sloane, Geraldine, Varghese, Mathew, Zborowski, Anelise C., Bean, Sarah, Burt, Karen, Spivey, Michael, Eastgate-Jackson, Christine, Filipe, Helder, Martin, Daniel, Maharajh, Amitaa, Garcia, Sara Mingo, De Neef, Mark, Lynch, Ceri, Howe, Gwenllian Sera, Singh, Jayaprakash, Turner, Keri, Ellis, Hannah, Stroud, Natalie, Cherian, Shiney, Cutler, Sean, Heron, Anne Emma, Roynon-Reed, Anna, Williams, Gemma, Richards, Owen, Cheema, Yusuf, Ahmad, Norfaizan, Barker, Joann, Bauchmuller, Kri, Bird, Sarah, Cawthron, Kay, Harrington, Kate, Jackson, Yvonne, Kibutu, Faith, Lenagh, Becky, Masuko, Shamiso, Raithatha, Ajay, Wiles, Matthew, Willson, Jayne, Newell, Helen, Lye, Alison, Nwafor, Lorenza, Jarman, Claire, Rowland-Jones, Sarah, Foote, David, Cole, Joby, Thompson, Roger, Watson, Jame, Hesseldon, Lisa, Macharia, Irene, Chetam, Luke, Smith, Jacqui, Ford, Amber, Anderson, Samantha, Birchall, Kathryn, Housley, Kay, Walker, Sara, Milner, Leanne, Hanratty, Helena, Trower, Helen, Phillips, Patrick, Oxspring, Simon, Donne, Ben, Bevan, Emily, Martin, Jane, Trodd, Dawn, Watson, Geoff, Brown, Caroline Wrey, Bunni, Lara, Jennings, Claire, Latif, Monica, Marshall, Rebecca, Subramanian, Gayathri, Bandla, Nageswar, Gellamucho, Minnie, Davies, Michelle, Thompson, Christopher, Trim, Fiona, Eapen, Beena, Ahmed, Cecilia, Baines, Balvinder, Clamp, Sarah, Colley, Julie, Haq, Risna, Hayes, Anne, Hulme, Jonathan, Hussain, Samia, Joseph, Sibet, Kumar, Rita, Maqsood, Zahira, Purewal, Manjit, Chandler, Ben, Elliott, Kerry, Mallinson, Janine, Turnbull, Alison, Dent, Kathy, Horsley, Elizabeth, Akhtar, Muhmmad Nauman, Pearson, Sandra, Potoczna, Dorota, Spencer, Sue, Blakemore, Hayley, Borislavova, Borislava, Faulkner, Beverley, Gendall, Emma, Goff, Elizabeth, Hayes, Kati, Thomas, Matt, Worner, Ruth, Smith, Kerry, Stephens, Deanna, Delgado, Carlos Castro, Dawson, Deborah, Ding, Lijun, Durrant, Georgia, Ezeobu, Obiageri, Farnell-Ward, Sarah, Harrison, Abiola, Kanu, Rebecca, Leaver, Susannah, Maccacari, Elena, Manna, Soumendu, Saluzzio, Romina Peperman, Queiroz, Joana, Samakomva, Tinashe, Sicat, Christine, Texeira, Joana, Da Gloria, Edna Fernande, Lisboa, Ana, Rawlins, John, Mathew, Jisha, Kinch, Ashley, Hurt, William Jame, Shah, Nirav, Clark, Victoria, Thanasi, Maria, Yun, Nikki, Patel, Kamal, Crickmore, Vikki, Debreceni, Gabor, Wilkins, Joy, Nicol, Liz, Burn, Iona, Hambrook, Geraldine, Manso, Katarina, Penn, Ruth, Shanmugasundaram, Pradeep, Tebbutt, Julie, Thornton, Danielle, Rostron, Anthony, Roy, Alistair, Woods, Lindsey, Cornell, Sarah, Wakinshaw, Fiona, Rogerson, Kimberley, Jarmain, Jordan, Anderson, Peter, Archer, Katie, Austin, Karen, Davis, Caroline, Durie, Alison, Kelsall, Olivia, Thrush, Jessica, Vigurs, Charlie, Wood, Hannah-Louise, Tranter, Helen, Harrison, Alison, Cowley, Nichola, Mcalindon, Michael, Digby, Stephen, Low, Emma, Morgan, Aled, Cother, Naiara, Rankin, Tobia, Clayton, Sarah, Mccurdy, Alex, Allibone, Suzanne, Mary-Genetu, Roman, Patel, Amit, Mac, Ainhi, Murphy, Anthony, Mahjoob, Parisa, Nazari, Roonak, Worsley, Lucy, Fagan, Andrew, Mohamed Ali, Inthakab Ali, Beaumont, Karen, Blunt, Mark, Coton, Zoe, Curgenven, Hollie, Elsaadany, Mohamed, Fernandes, Kay, Ally, Sameena Mohamed, Rangarajan, Harini, Sarathy, Varun, Selvanayagam, Sivarupan, Vedage, Dave, White, Matthew, Fernandez-Roman, Jaime, Hamilton, David O., Johnson, Emily, Johnston, Brian, Martinez, Maria Lopez, Mulla, Suleman, Shaw, David, Waite, Alicia A. C., Waugh, Victoria, Welters, Ingeborg D., Williams, Karen, Bemand, Thoma, Black, Ethel, Rosa, Arnold Dela, Howle, Ryan, Jhanji, Shaman, Baikady, Ravishankar Rao, Tatham, Kate Colette, Thomas, Benjamin, Halkes, Matthew, Mercer, Pauline, Thornton, Lorraine, West, Joe, Baird, Tracy, Ruddy, Jim, Reece-Anthony, Rosie, Birt, Mark, Cowton, Amanda, Kay, Andrea, Kent, Melanie, Potts, Kathryn, Wilkinson, Ami, Naylor, Suzanne, Brown, Ellen, Clark, Michele, Purvis, Sarah, Cole, Jade, Davies, Rhy, Duffin, Donna, Hill, Helen, Player, Ben, Thomas, Emma, Williams, Angharad, Beith, Claire Marie, Black, Karen, Clements, Suzanne, Morrison, Alan, Strachan, Dominic, Taylor, Margaret, Clarkson, Michelle, D’Sylva, Stuart, Norman, Kathryn, Coventry, Tina, Fowler, Susan, Mcgregor, Amanda, Brady, Ailbhe, Chan, Rebekah, Mcivor, Shane, Prady, Helena, Whittle, Helen, Mathew, Bijoy, Clapham, Melanie, Harper, Rosemary, Poultney, Una, Rice, Polly, Mutch, Rachel, Baird, Yolanda, Butler, Aaron, Chadbourn, Indra, Folkes, Linda, Fox, Heather, Gardner, Amy, Gomez, Raquel, Hobden, Gillian, King, Kirsten, Margarson, Michael, Martindale, Tim, Meadows, Emma, Raynard, Dana, Thirlwall, Yvette, Helm, David, Margalef, Jordi, Greer, Sandra, Shuker, Karen, Smuts, Sara, Duffield, Joseph, Smith, Oliver, Mallon, Lewi, Claire, Watkin, Birkinshaw, Isobel, Carter, Joseph, Howard, Kate, Ingham, Joanne, Joy, Rosie, Pearson, Harriet, Roche, Samantha, Scott, Zoe, Knights, Ellen, Price, Alicia, Thomas, Alice, Thorpe, Chri, Abraheem, Azmerelda, Bamford, Peter, Cawley, Kathryn, Dunmore, Charlie, Faulkner, Maria, Girach, Rumanah, Jeffrey, Helen, Jones, Rhianna, London, Emily, Nagra, Imrun, Nasir, Farah, Sainsbury, Hannah, Smedley, Clare, Khade, Reena, Sundar, Ashok, Tsinaslanidis, George, Behan, Teresa, Burnett, Caroline, Hatton, Jonathan, Heeney, Elaine, Mitra, Atideb, Newton, Maria, Pollard, Rachel, Stead, Rachael, Birch, Jenny, Bough, Laura, Goodsell, Josie, Tutton, Rebecca, Williams, Patricia, Williams, Sarah, Winter-Goodwin, Barbara, Auld, Fiona, Donnachie, Joanne, Edmond, Ian, Prentice, Lynn, Runciman, Nikole, Salutous, Dario, Symon, Lesley, Todd, Anne, Turner, Patricia, Short, Abigail, Sweeney, Laura, Murdoch, Euan, Senaratne, Dhaneesha, Burns, Karen, Higham, Andrew, Anderson, Taya, Hawcutt, Dan, O’Malley, Laura, Rad, Laura, Rogers, Naomi, Saunderson, Paula, Allison, Kathryn Sian, Afolabi, Deborah, Whitbread, Jennifer, Jones, Dawn, Dore, Rachael, Lankester, Liana, Nikitas, Nikita, Wells, Colin, Stowe, Bethan, Spencer, Kayleigh, Cathcart, Susanne, Duffy, Katharine, Puxty, Alex, Puxty, Kathryn, Turner, Lynne, Ireland, Jane, Semple, Gary, Barry, Peter, Hilltout, Paula, Evitts, Jayne, Tyler, Amanda, Waldron, Joanne, Irvine, Val, Shelley, Benjamin, Akinkugbe, Olugbenga, Bamford, Alasdair, Beech, Emily, Belfield, Holly, Bell, Michael, Davies, Charlene, Jones, Gareth A. L., Mchugh, Tara, Meghari, Hamza, O’Neill, Lauran, Peters, Mark J., Ray, Samiran, Tomas, Ana Luisa, Gorman, Claire, Gupta, Abhinav, Timlick, Elizabeth, Brady, Rebecca, Bonner, Stephen, Hugill, Keith, Jones, Jessica, Liggett, Steven, Bashyal, Archana, Davidson, Neil, Hutton, Paula, Mckechnie, Stuart, Wilson, Jean, Flint, Neil, Rekha, Patel, Hales, Dawn, Cruz, Carina, Gopal, Shameer, Harris, Nichola, Lake, Victoria, Metherell, Stella, Radford, Elizabeth, Clement, Ian, Patel, Bijal, Gulati, A., Hays, Carole, Webster, K., Hudson, Anne, Webster, Andrea, Stephenson, Elaine, Mccormack, Louise, Slater, Victoria, Nixon, Rachel, Hanson, Helen, Fearby, Maggie, Kelly, Sinead, Bridgett, Victoria, Robinson, Philip, Almaden-Boyle, Christine, Austin, Pauline, Cabrelli, Louise, Cole, Stephen, Casey, Matt, Chapman, Susan, Whyte, Clare, Brayne, Adam, Fisher, Emma, Hunt, Jane, Jackson, Peter, Kaye, Duncan, Love, Nichola, Parkin, Juliet, Tuckey, Victoria, van Koutrik, Lynne, Carter, Sasha, Andrew, Benedict, Findlay, Louise, Adams, Katie, Bruce, Michelle, Connolly, Karen, Duncan, Tracy, T. -Michael, Helen, Lindergard, Gabriella, Hey, Samuel, Fox, Claire, Alfonso, Jordan, Durrans, Laura Jayne, Guerin, Jacinta, Hruska, Martin, Eltayeb, Ayaa, Lamb, Thoma, Hodgkiss, Tracey, Cooper, Lisa, Rothwell, Joanne, Dennis, Catherine, Mcgregor, Alastair, Srikaran, Sinduya, Sukha, Anisha, Davies, Kim, O’Brien, Linda, Omar, Zohra, Perkins, Emma, Lewis, Tracy, Sutherland, Isobel, Brooke, Hollie, Buckley, Sarah, Suarez, Jose Cebrian, Charlesworth, Ruth, Hansson, Karen, Norris, John, Poole, Alice, Rose, Alastair, Sandhu, Rajdeep, Sloan, Brendan, Smithson, Elizabeth, Thirumaran, Muthu, Wagstaff, Veronica, Metcalfe, Alexandra, Camsooksai, Julie, Humphrey, Charlotte, Jenkins, Sarah, Wadams, Beverley, Death, Yasmin, Adams, Colene, Agasou, Anita, Arden, Tracie, Bowes, Amy, Boyle, Pauline, Beekes, Mandy, Button, Heather, Capps, Nigel, Carnahan, Mandy, Carter, Anne, Childs, Danielle, Donaldson, Denise, Hard, Kelly, Hurford, Fran, Hussain, Yasmin, Javaid, Ayesha, Jones, Jame, Jose, Sanal, Leigh, Michael, Martin, Terry, Millward, Helen, Motherwell, Nichola, Rikunenko, Rachel, Stickley, Jo, Summers, Julie, Ting, Louise, Tivenan, Helen, Tonks, Louise, Wilcox, Rebecca, Bokhari, Maria, Lucas, Rachael, Mccormick, Wendy, Ritzema, Jenny, Sanderson, Amanda, Wild, Helen, Baxter, Nicola, Henderson, Steven, Kennedy-Hay, Sophie, Mcparland, Christopher, Rooney, Laura, Sim, Malcolm, Mccreath, Gordan, Brunton, Mark, Caterson, Je, Coles, Holly, Frise, Matthew, Rai, Sabi Gurung, Keating, Liza, Tilney, Emma, Bartley, Shauna, Bhuie, Parminder, Downes, Charlotte, Holding, Kathleen, Riches, Katie, Hilton, Mary, Hayman, Mel, Subramanian, Deepak, Daniel, Priya, Zitter, Letizia, Benyon, Sarah, Marriott, Suzie, Park, Linda, Keenan, Samantha, Gordon, Elizabeth, Quinn, Helen, Baines, Kizzy, Andrew, Gillian, Barclay, Lucy, Callaghan, Marie, Clark, Sarah, Hope, Dave, Marshall, Lucy, Mcculloch, Corrienne, Briton, Kate, Singleton, Jo, Birch, Sophie, Simpson, Kerry, Craig, Jayne, Demetriou, Carrie, Eckbad, Charlotte, Hierons, Sarah, Howie, Lucy, Mitchard, Sarah, Ramos, Lidia, Serrano-Ruiz, Alfredo, White, Katie, Kelly, Fiona, Amin, Vishal, Anastasescu, Elena, Anumakonda, Vikram, Karthik, Komala, Kausar, Rizwana, Reid, Karen, Smith, Jacqueline, Imeson-Wood, Janet, Bellini, Arianna, Bryant, Jade, Mayer, Anton, Pickard, Amy, Roe, Nichola, Sowter, Jason, Howlett, Alex, Criste, Kristine, Cusack, Rebecca, Golder, Kim, Golding, Hannah, Jones, Oliver, Leggett, Samantha, Male, Michelle, Marani, Martyna, Prager, Kirsty, Williams, Toran, Roberts, Belinda, Salmon, Karen, Gondo, Prisca, Hadebe, B., Kayani, Abdul, Masunda, Bridgett, Ahmed, Ashar, Morris, Anna, Jakkula, Sriniva, Long, Kate, Whiteley, Simon, Wilby, Elizabeth, Ogg, Bethan, Moultrie, Sam, Odam, M., Bewley, Jeremy, Garland, Zoe, Grimmer, Lisa, Gumbrill, Bethany, Johnson, Rebekah, Sweet, Katie, Webster, Denise, Efford, Georgia, Bennett, Sara, Goodwin, Emma, Jackson, Matthew, Kent, Alissa, Tibke, Clare, Woodyatt, Wiesia, Zaki, Ahmed, Daniel, Amelia, Finn, Joanne, Saha, Rajnish, Bremmer, Pamela, Allan, J., Geary, T., Houston, Gordon, Meikle, A., O’Brien, P., Bell, Dina, Boyle, Rosalind, Douglas, Katie, Glass, Lynn, Lee, Emma, Lennon, Liz, Rattray, Austin, Charnock, Rob, Mcfarland, Denise, Cosgrove, Denise, Attwood, Ben, Parsons, Penny, Carmody, Siobhain, Oblak, Metod, Popescu, Monica, Thankachen, Mini, Baruah, Rosie, Morris, Sheila, Ferguson, Susie, Shepherd, Amy, Altabaibeh, Abdelhakim, Alvaro, Ana, Gilbert, Kayleigh, Ma, Louise, Mostoles, Loreta, Parmar, Chetan, Simpson, Kathryn, Jetha, Champa, Booker, Lauren, Pratley, Anezka, Cosier, Tracey, Millen, Gemma, Schumacher, Natasha, Weston, Heather, Rand, Jame, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S., Bogaert, Debby, Chand, Meera, Cooke, Graham S., Docherty, Annemarie B., Dunning, Jake, da Silva Filipe, Ana, Fletcher, Tom, Green, Christoper A., Harrison, Ewen M., Hiscox, Julian A., Ijaz, Samreen, Khoo, Saye, Lim, Wei Shen, Mentzer, Alexander J., Merson, Laura, Noursadeghi, Mahdad, Moore, Shona C., Palmarini, Massimo, Paxton, William A., Pollakis, Georgio, Price, Nichola, Rambaut, Andrew, Robertson, David L., Sancho-Shimizu, Vanessa, Scott, Janet T., de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Tedder, Richard S., Thomson, Emma C., Roger Thompson, A. A., Thwaites, Ryan S., Turtle, Lance C. W., Gupta, Rishi K., Palmieri, Carlo, Swann, Olivia V., Zambon, Maria, Dumas, Marc-Emmanuel, Griffin, Julian L., Takats, Zoltan, Chechi, Kanta, Andrikopoulos, Petro, Osagie, Anthonia, Olanipekun, Michael, Liggi, Sonia, Lewis, Matthew R., Correia, Gonçalo dos Santo, Sands, Caroline J., Takis, Panteleimon, Maslen, Lynn, Greenhalf, William, Shaw, Victoria, Mcdonald, Sarah E., Keating, Seán, Ahmed, Katie A., Armstrong, Jane A., Ashworth, Milton, Asiimwe, Innocent G., Bakshi, Siddharth, Barlow, Samantha L., Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin W. A., Clark, Jordan J., Clarke, Emily A., Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chri, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis W. S., Foster, Terry, Garcia-Dorival, Isabel, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L., Jones, Christopher B., Jones, Trevor R., Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A., Mancini, Maria, Mcdonald, Sarah, Mcevoy, Laurence, Mclauchlan, John, Metelmann, Soeren, Miah, Nahida S., Middleton, Joanna, Mitchell, Joyce, Murphy, Ellen G., Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E., Shears, Rebecca K., Small, Benjamin, Subramaniam, Krishanthi S., Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Carracedo, Alejandra Doce, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, Wrobel, Nicola, Mccafferty, Sarah, Morrice, Kirstie, Maclean, Alan, Armstrong, Ruth, Boz, Ceilia, Brown, Adam, Coutts, Audrey, Cullum, Louise, Day, Nicky, Donnelly, Lorna, Duncan, Esther, Fawkes, Angie, Finernan, Paul, Gilchrist, Tammy, Golightly, Ailsa, Hafezi, Katarzyna, Law, Dawn, Law, Rachel, Law, Sarah, Macgillivray, Louise, Mal, Hanning, Mcmaster, Ellie, Meikle, Jen, Oosthuyzen, Wilna, Paterson, Trevor, Stenhouse, Andrew, Swets, Maaike, Szoor-McElhinney, Helen, Taneski, Filip, Wackett, Tony, Ward, Mairi, Weaver, Jane, Coyle, Judy, Gallagher, Bernadette, Lidstone-Scott, Rebecca, Hamilton, Debbie, Schon, Katherine, Furlong, Anita, Biggs, Heather, Griffiths, Fiona, Andrews, Eleanor, Brickell, Kathy, Smyth, Michelle, Murphy, Lorna, Carson, Gail, Hardwick, Hayley, Donohue, Chloe, Pérez-Tur, Jordi [0000-0002-9111-1712], Martín, Javier [0000-0002-2202-0622], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts General Hospital [Boston], A list of authors and their affiliations appears in the Supplementary Information, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-21-COVR-0039,GenMIS-C,Recherche 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Bocciolone, M., Miozzo, M., Chueca, N., Montano, N., Faverio, P., Preatoni, P., Bonfanti, P., Omodei, P., Castro, P., Ferrer, R., Gualtierotti, R., Gallego-Durán, R., Morilla, R., Haider, S., Marsal, S., Aneli, S., Pelusi, S., Bosari, S., Aliberti, S., Dudman, S., Zheng, T., Pumarola, T., Cejudo, T.G., Monzani, V., Friaza, V., Peter, W., Dopazo, X., May, S., Grimsrud, M.M., Gudbjartsson, D.F., Stefansson, K., Sulem, P., Sveinbjornsson, G., Melsted, P., Norddahl, G., Swerford Moore, K.H., Thorsteinsdottir, U., Holm, H., Alarcón-Riquelme, M.E., Bernardo, D., Martínez-Bueno, M., Rello, S.R., Magi, R., Milani, L., Metspalu, A., Laisk, T., Läll, K., Lepamets, M., Esko, T., Reimann, E., Naaber, P., Laane, E., Pesukova, J., Peterson, P., Kisand, K., Tabri, J., Allos, R., Hensen, K., Starkopf, J., Ringmets, I., Tamm, A., Kallaste, A., Alavere, H., Metsalu, K., Puusepp, M., Kristiansson, K., Koskelainen, S., Perola, M., Donner, K., Kivinen, K., Palotie, A., Bochud, P.Y., Boillat, N., Nussle, S.G., Albrich, W., Pagani, J.L., Zu Bentrup, F.M., Viollet, R.M., Kampouri, E.E., Meuwly, J.Y., D'Acremont, V., Younes, S.E., Albrich, W.C., O'Mahony, L., Kleger, G.R., Kahlert, C.R., Negro, T.R., Carreras, A., Galván-Femenía, I., Farré, X., Cortés, B., Mercader, J.M., Guindo-Martinez, M., Torrents, D., Garcia-Aymerich, J., Castaño-Vinyals, G., Dobaño, C., Gori, M., Mondelli, M.U., Castelli, F., Vaghi, M., Rusconi, S., Montagnani, F., Bargagli, E., Franchi, F., Mazzei, M.A., Cantarini, L., Tacconi, D., Feri, M., Scala, R., Spargi, G., Nencioni, C., Bandini, M., Caldarelli, G.P., Spagnesi, M., Canaccini, A., Ognibene, A., D'Arminio Monforte, A., Girardis, M., Antinori, A., Francisci, D., Schiaroli, E., Scotton, P.G., Panese, S., Scaggiante, R., Monica, M.D., Capasso, M., Fiorentino, G., Castori, M., Aucella, F., Di Biagio, A., Masucci, L., Valente, S., Mandalà, M., Zucchi, P., Giannattasio, F., Coviello, D.A., Mussini, C., Bosio, G., Tavecchia, L., Crotti, L., Rizzi, M., La Rovere, 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Reid, K., Imeson-Wood, J., Bellini, A., Bryant, J., Pickard, A., Roe, N., Sowter, J., Howlett, A., Criste, K., Cusack, R., Golder, K., Golding, H., Jones, O., Leggett, S., Male, M., Marani, M., Prager, K., Williams, T., Roberts, B., Salmon, K., Gondo, P., Kayani, A., Masunda, B., Ahmed, A., Morris, A., Jakkula, S., Long, K., Whiteley, S., Wilby, E., Ogg, B., Moultrie, S., Bewley, J., Garland, Z., Grimmer, L., Gumbrill, B., Sweet, K., Webster, D., Efford, G., Bennett, S., Goodwin, E., Jackson, M., Kent, A., Tibke, C., Woodyatt, W., Zaki, A., Daniel, A., Finn, J., Bremmer, P., Houston, G., O'Brien, P., Bell, D., Boyle, R., Douglas, K., Glass, L., Lee, E., Lennon, L., Rattray, A., Charnock, R., McFarland, D., Cosgrove, D., Attwood, B., Parsons, P., Carmody, S., Oblak, M., Popescu, M., Thankachen, M., Baruah, R., Morris, S., Ferguson, S., Shepherd, A., Altabaibeh, A., Alvaro, A., Gilbert, K., Ma, L., Mostoles, L., Parmar, C., Jetha, C., Booker, L., Pratley, A., Cosier, T., Millen, G., Schumacher, N., Weston, H., Rand, J., Alex, B., Bach, B., Barclay, W.S., Bogaert, D., Chand, M., Cooke, G.S., Docherty, A.B., Dunning, J., da Silva Filipe, A., Fletcher, T., Green, C.A., Harrison, E.M., Hiscox, J.A., Ijaz, S., Khoo, S., Lim, W.S., Mentzer, A.J., Merson, L., Noursadeghi, M., Moore, S.C., Palmarini, M., Paxton, W.A., Pollakis, G., Price, N., Rambaut, A., Robertson, D.L., Sancho-Shimizu, V., Scott, J.T., de Silva, T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Tedder, R.S., Thomson, E.C., Roger Thompson, A.A., Thwaites, R.S., Turtle, LCW, Gupta, R.K., Palmieri, C., Swann, O.V., Zambon, M., Dumas, M.E., Griffin, J.L., Takats, Z., Chechi, K., Andrikopoulos, P., Osagie, A., Olanipekun, M., Liggi, S., Lewis, M.R., Correia, GDS, Sands, C.J., Takis, P., Maslen, L., Greenhalf, W., Shaw, V., McDonald, S.E., Ahmed, K.A., Armstrong, J.A., Ashworth, M., Asiimwe, I.G., Bakshi, S., Barlow, S.L., Booth, L., Brennan, B., Bullock, K., Catterall, BWA, Clark, J.J., Clarke, E.A., Cox, H., Dincarslan, O., Dunn, C., Dyer, P., Elliott, A., Evans, A., Finch, L., Fisher, LWS, Foster, T., Garcia-Dorival, I., Gunning, P., Hartley, C., Jensen, R.L., Jones, C.B., Jones, T.R., Khandaker, S., Kiy, R.T., Koukorava, C., Lake, A., Lant, S., Latawiec, D., Lavelle-Langham, L., Lefteri, D., Lett, L., Livoti, L.A., Mancini, M., McDonald, S., McEvoy, L., McLauchlan, J., Metelmann, S., Miah, N.S., Middleton, J., Mitchell, J., Murphy, E.G., Penrice-Randal, R., Pilgrim, J., Prince, T., Reynolds, W., Ridley, P.M., Sales, D., Shaw, V.E., Shears, R.K., Small, B., Subramaniam, K.S., Szemiel, A., Taggart, A., Tanianis-Hughes, J., Trochu, E., van Tonder, L., Wilcock, E., Zhang, J.E., Flaherty, L., Maziere, N., Cass, E., Carracedo, A.D., Carlucci, N., Holmes, A., Massey, H., Murphy, L., Wrobel, N., McCafferty, S., Morrice, K., MacLean, A., Armstrong, R., Boz, C., Coutts, A., Cullum, L., Day, N., Donnelly, L., Duncan, E., Fawkes, A., Finernan, P., Gilchrist, T., Golightly, A., Hafezi, K., Law, D., Law, R., Law, S., Macgillivray, L., Maclean, A., Mal, H., Mcmaster, E., Meikle, J., Oosthuyzen, W., Paterson, T., Stenhouse, A., Swets, M., Szoor-McElhinney, H., Taneski, F., Wackett, T., Ward, M., Weaver, J., Coyle, J., Gallagher, B., Lidstone-Scott, R., Hamilton, D., Schon, K., Furlong, A., Biggs, H., Griffiths, F., Andrews, E., Brickell, K., Smyth, M., Carson, G., Hardwick, H., Donohue, C., Neale, Benjamin M. [0000-0003-1513-6077], Apollo - University of Cambridge Repository, Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Niemi, M. E. K., Liao, R. G., Neale, B. M., Pathak, G. A., Andrews, S. J., Schulte, E. C., Karim, M. A., Wendt, F. R., Kim, H. -N., Uddin, M. J., Smith, G. D., Willer, C. J., Buxbaum, J. D., Martin, A. R., Balaconis, M. K., Sankaran, V. G., Brent Richards, J., Eric Kerchberger, V., Kenneth Baillie, J., Dutta, A. K., Uddin, M. M., Perez-Tur, J., Verdugo, R. A., Zarate, R., Medina-Gomez, C., Gomez-Cabrero, D., Cadilla, C. L., Boua, P. R., Fave, M. -J., Lemacon, A., Szentpeteri, J. L., Ahmad, H. F., Kornilov, S. A., Prokic, I., Pearson, N. M., Shelton, J. F., Shastri, A. J., Weldon, C. H., Brouwer, M. C., Vlaar, A. P. J., Joost Wiersinga, W., Algera, A. G., Bogaard, H. J., Bonta, P. I., Grobusch, M. P., Hermans, S. M., Hovius, J. W., de Jong, M. D., Nossent, E. J., Prins, J. M., Schultz, M. J., Stijnis, C. S., Minnaar, R. P., van Uffelen, K. W. J., Wolterman, R. A., Ball, C. A., Mccurdy, S., Hong, E. L., Baltzell, A. H., Goffard, J. -C., Peree, H., Leonard, P., Giot, J. -B., Sauvage, A. -S., Wery, M., Morrison, D. R., Chasse, M., Kaufmann, D. E., Mark Lathrop, G., Davis, L. K., Cox, N. J., Below, J. E., Sealock, J. M., Faucon, A. B., Shuey, M. M., Polikowsky, H. G., Petty, L. E., Shaw, D. M., Chen, H. -H., Ludwig, K. U., Schroder, J., Nothen, M. M., Jensen, B. -E. O., Altmuller, J., Berger, M. M., Gogele, M., Gignoux, C. R., Wicks, S. J., Barnes, K. C., Goldstein, D. B., Reilly, M. P., Gharavi, A. G., O'Byrne, S. M., So, Y. S., Park, S. -K., Kim, H. -L., Kang, C. K., Lee, H. -J., Song, K. -H., Yoon, K. J., Paik, N. -J., Joo, E. -J., Park, W. B., Park, J. S., Park, K. U., Ham, S. Y., Kim, E. S., Kim, H. B., Caceres, M., Lenz, T. L., Julia, A., Holter, J. C., Fernandez, J., Sander, L. E., Banales, J. M., Romero-Gomez, M., Hov, J. R., Karlsen, T. H., Wacker, E. M., Elabd, H., Ruhlemann, M. C., Vadla, M. S., Lenning, O. B., Ozer, O., Kassens, J., Figuera Basso, M. E., Ortiz, A. B., Chercoles, A. G., Holten, A. R., Kildal, A. B., Gluck, A., Nolla, A. C., Dyrhol-Riise, A. M., Spinner, C. D., Hoff, D. A. L., Jimenez, D., Pestana, D., Helbig, E. T., Paraboschi, E. M., Sanchez, F. G., Hernandez, I., Galvan-Femenia, I., Badia, J. R., Muller, K. E., Gaede, K. I., Lippert, L. J., Tellez, L., Gutierrez-Stampa, M. A., Vehreschild, M. J. G. T., Marquie, M., Seilmaier, M. J., Rodriguez-Gandia, M., Ayo, N. I., Martinez, N., Cornely, O. A., Rodrigues, P. M., Espana, P. P., Garcia-Fernandez, A. -E., Fracanzani, A. L., Muniz-Diaz, E., Calderon, E. J., Solligard, E., Medrano, F. J., Muller, F., Afset, J. E., Damas, J. K., Ferrusquia-Acosta, J., Quero, J. H., Guerrero, J. M., Bettini, L. R., Gustad, L. T., Valsecchi, M. G., D'Angio, M., Gallego-Duran, R., Cejudo, T. G., Grimsrud, M. M., Gudbjartsson, D. F., Moore, K. H. S., Alarcon-Riquelme, M. E., Martinez-Bueno, M., Rello, S. R., Lall, K., Bochud, P. -Y., Nussle, S. G., Meyer zu Bentrup, F., Merlet Viollet, R., Guery, B., Hugli, O., Gonseth Nussle, S., Estoppey Younes, S., Rochat Negro, T., Mercader, J. M., Castano-Vinyals, G., Dobano, C., Mondelli, M. U., Mazzei, M. A., Caldarelli, G. P., Monforte, A. D., Scotton, P. G., Monica, M. D., Mandala, M., Coviello, D. A., La Rovere, M. T., Segala, F. V., Mencarelli, M. A., Pinto, A. M., Carriero, M. L., Ann Belli, M., Antoni, M. D., Miraglia, F. G., Parisi, S. G., Squeo, G. M., Botta, G., Hunt, K. A., Trembath, R. C., Martin, H. C., Griffiths, C. J., Curtis, C. J., Huang, Q. Q., Lee, S. H., Macarthur, D., Maclaughlin, B., Smith, A. V., Boughton, A. P., Li, K. W., Lefaive, J., Jannes, C. E., Krieger, J. E., Pereira, A. C., Lima, I. R., Tada, M. T., Mccarthy, M., Lee, J. E., Lee, H. S., Jang, H. Y., Kim, Y. -S., Kwon, K. T., Kim, S. -W., Kim, J. Y., Jang, Y. R., Kim, H., Lee, J. Y., Choe, K. -W., Kang, Y. M., Jee, S. H., Jung, K. J., Schroth, G. P., Desouza, F., Cirulli, E. T., Schiabor Barrett, K. M., Washington, N. L., Lu, J. T., Ramirez, J. M., Grzymski, J. J., Minano, J. I. E., Aguirre, L. A., Lopez-Collazo, E., Lozano-Rodriguez, R., Avendano-Ortiz, J., Arcos, V. T., Montalban-Hernandez, K. M., Quiroga, J. V., Martin-Quiros, A., Nakada, T. -A., Vonk, J. M., Ori, A. P. S., Hernandez Cordero, A. I., Sin, D. D., Bosse, Y., Feng, Y. -C. A., Weiss, S. T., Karlson, E. W., Smoller, J. W., Murphy, S. N., Meigs, J. B., Woolley, A. E., Green, R. C., Perez, E. F., Zollner, S., Sloofman, L. G., Sebra, R. P., Collins, B. L., Sealfon, S. C., Jordan, D. M., Thompson, R. C., Belbin, G. M., Underwood, S. J., Hiester, L. L., Charney, A. W., Beckmann, N. D., Schadt, E. E., Abul-Husn, N. S., Cho, J. H., Kenny, E. E., Loos, R. J. F., Nadkarni, G. N., Huckins, L. M., Ferreira, M. A. R., Abecasis, G. R., Leader, J. B., Cantor, M. N., Justice, A. E., Carey, D. J., Josyula, N. S., Kosmicki, J. A., Horowitz, J. E., Gass, M. C., Hottenga, J. J., de Geus, E. J. C., Nivard, M. G., Ritchie, M. D., Verma, S. S., Vari, M. S., Rahier, J. -F., Bulik, C. M., Landen, M., Ferrero, G. B., Fundin, B., Ismail, S. I., Badji, R. M., Hultstrom, M., Geschwind, D. H., Butte, M. J., Chang, T. S., Caulfield, M. J., Scott, R. H., Odhams, C. A., Karczewski, K. J., Wilson, D. J., Spencer, C. A., Crook, D. W., Wyllie, D. H., O'Connell, A. M., Atkinson, E. G., Walters, R. K., Palmer, D. S., Goldstein, J. I., Kyle Satterstrom, F., Earle, S. G., Lin, S. -K., Rudkin, J. K., Zhao, J. H., Butterworth, A. S., Sun, Y. V., Huffman, J. E., O'Donnell, C. J., Michael Gaziano, J., Ho, Y. -L., Glessner, J. R., Mcguigan, P. J., Moore, L. S. P., Vizcaychipi, M. P., Page, V. J., Aldera, E. L., Cutino-Moguel, M. -T., Durand, I., Hawcutt, D. B., Macmahon, M., Macnaughton, E., Mccullough, K., Mcewen, R., O'Shea, M. K., Pooni, J. S., Wooton, D. G., Bretherick, A. D., Fourman, M. H., Meynert, A. M., Ponting, C. P., Porteous, D. J., Russell, C. D., Wilson, J. F., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Shaw, C. A., Ho, A. Y. W., Horby, P. W., Mcauley, D., Openshaw, P. J. M., Semple, M. G., Mcgowan, J., Mcguinness, H., Mcneela, F., Bayo, L. -A., Arias, S. S., Conyngham, J. -A., Corral, M. A., de Almeida Martins, L. G., Mclaughlan, D., Mcmorrow, L., Mccormick, J., Mitchell, A. M., Maccallum, N., Hughes, R. A., Jones, T. O., Mcphail, M., Mckenley, I., Sutherland, S. -B., de Gordoa, L. O. -R., Gude, E. T., Macgoey, P., Mckenna, E., Patel, B. V., Zborowski, A. C., Garcia, S. M., Howe, G. S., Heron, A. E., Mills, G. H., Brown, C. W., Akhtar, M. N., Delgado, C. C., Saluzzio, R. P., Da Gloria, E. F., Hurt, W. J., Wood, H. -L., Mcalindon, M., Mccurdy, A., Ali, I. A. M., Ally, S. M., Hamilton, D. O., Lopez Martinez, M., Waite, A. A. C., Welters, I. D., Rosa, A. D., Baikady, R. R., Tatham, K. C., Beith, C. M., Mcgregor, A., Mcivor, S., Allison, K. S., Jones, G. A. L., Mchugh, T., Peters, M. J., Tomas, A. L., Mckechnie, S., Mccormack, L., Michael, H. T., Durrans, L. J., Suarez, J. C., Death, Y., Mccormick, W., Mccreath, G., Rai, S. G., Mcculloch, C., Mcfarland, D., Barclay, W. S., Cooke, G. S., Docherty, A. B., Green, C. A., Harrison, E. M., Hiscox, J. A., Lim, W. S., Mentzer, A. J., Paxton, W. A., Robertson, D. L., Scott, J. T., Tedder, R. S., Thomson, E. C., Thwaites, R. S., Gupta, R. K., Swann, O. V., Dumas, M. -E., Griffin, J. L., Lewis, M. R., dos Santos Correia, G., Sands, C. J., Mcdonald, S. E., Ahmed, K. A., Armstrong, J. A., Asiimwe, I. G., Barlow, S. L., Catterall, B. W. A., Clark, J. J., Clarke, E. A., Fisher, L. W. S., Jensen, R. L., Jones, C. B., Jones, T. R., Kiy, R. T., Livoti, L. A., Mcdonald, S., Mcevoy, L., Mclauchlan, J., Miah, N. S., Moore, S. C., Murphy, E. G., Matthew Ridley, P., Shaw, V. E., Shears, R. K., Subramaniam, K. S., Eunice Zhang, J., Carracedo, A. D., Mccafferty, S., Turtle, L. C. W., Data Science Genetic Epidemiology Lab, Institute for Molecular Medicine Finland, HUS Helsinki and Uusimaa Hospital District, University of Helsinki, Research Programs Unit, Doctoral Programme in Population Health, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, and University of Zurich
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Male ,45/43 ,Autoimmunity ,Autoimmunity/genetics ,Body Mass Index ,COVID-19/genetics ,COVID-19/virology ,Critical Illness ,Female ,Genetic Loci/genetics ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Geographic Mapping ,Hospitalization ,Host-Pathogen Interactions/genetics ,Humans ,Inflammation/complications ,Information Dissemination ,Multifactorial Inheritance ,Racial Groups/genetics ,SARS-CoV-2/pathogenicity ,Smoking ,environmental risk factors ,Q1 ,631/208 ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Genetics, Genome-wide association studies, SARS-CoV-2, Viral infection ,GWAS ,Aetiology ,Lung ,QC ,0303 health sciences ,HERITABILITY ,3. Good health ,covid-19 ,Science & Technology - Other Topics ,Identification (biology) ,Infection ,Human ,631/208/205/2138 ,Settore BIO/11 - Biologia Molecolare ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Clinical Research ,Biodefense ,Genetics ,GENOME-WIDE ASSOCIATION ,Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP] ,METAANALYSIS ,1000 Multidisciplinary ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Science & Technology ,Prevention ,Racial Groups ,Pneumonia ,genetic architecture ,Human genetics ,Genetic Loci ,genetic factors ,570 Life sciences ,biology ,030217 neurology & neurosurgery ,Medizin ,Infektionsmedicin ,Genome-wide association studies ,Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Pandemic ,2.1 Biological and endogenous factors ,pandemi ,Multidisciplinary ,article ,Public Health, Global Health, Social Medicine and Epidemiology ,Racial Group ,10124 Institute of Molecular Life Sciences ,Host-Pathogen Interaction ,Multidisciplinary Sciences ,Infectious Diseases ,Host-Pathogen Interactions ,Critical Illne ,COVID-19, GWAS, genetic factors, environmental risk factors, therapy ,Infectious Medicine ,Coronavirus disease 2019 (COVID-19) ,SUSCEPTIBILITY LOCI ,General Science & Technology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Computational biology ,Biology ,Vaccine Related ,692/699/255/2514 ,Environmental risk ,Mendelian randomization ,COVID-19 Host Genetics Initiative ,QH426 ,631/326/596/4130 ,030304 developmental biology ,Inflammation ,therapy ,SARS-CoV-2 ,Human Genome ,COVID-19 ,Genetic architecture ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,Emerging Infectious Diseases ,Good Health and Well Being ,Viral infection ,3111 Biomedicine - Abstract
Niemi, Mari E. K. et al. 39 páginas, figuras y tablas. Contiene material suplementario., The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
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- 2021
3. Gender differences in the use of cardiovascular interventions in HIV‐positive persons; the D:A:D Study
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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
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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, [...]
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- 2018
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4. Andere tekenbeetziekten
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Hoornstra, D., Sprong, H, Hovius, JW, and Hulscher, MEJL
- Published
- 2021
5. 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
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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
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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.
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- 2016
6. Cost-Effectiveness Of A Potential Combined Vaccine Against Lyme Borreliosis And Tick-Borne Encephalitis In Slovenia
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Mihajlović, J, primary, Hovius, JW, additional, Sprong, H, additional, Strle, F, additional, Bogovič, P, additional, and Postma, MJ, additional
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- 2017
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7. Development of a definition for rapid progression (RP) of renal function in HIV-positive persons:the D:A:D study
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Kamara, David A., Ryom, Lene, Ross, Michael, Kirk, Ole, Reiss, Peter, Morlat, Philippe, Moranne, Olivier, Fux, Christoph A., Mocroft, Amanda, Sabin, Caroline, Lundgren, Jens D., Smith, Colette J, D:A:D study, Group., Quiros, Roldan, Powderly B, M. E., Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Ryom, L, Sabin, Ca, Kamara, D, Smith, C, Phillips, A, Mocroft, A, Tverland, J, Mansfeld, M, Nielsen, J, Raben, D, Lundgren, Jd, 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, Iversen, J, Kirk, O, Reiss, P, Ross, M, Fux, Ca, Morlat, P, Moranne, O, Kesselring, Am, Kamara, Da, Weber, R, Pradier, C, Friis-Møller, N, Kowalska, J, Sabin, C, Law, M, d'Arminio Monforte, A, Dabis, F, Bruyand, M, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Zaheri, S, Gras, L, Prins, Jm, Kuijpers, Tw, Scherpbier, Hj, van der Meer JT, Wit, Fw, Godfried, Mh, van der Poll, D, Nellen, Fj, Lange, Jm, Geerlings, Se, van Vugt, M, Pajkrt, D, Bos, D, van der Valk, D, Grijsen, Ml, Wiersinga, Wj, Goorhuis, A, Hovius, Jw, Lowe, S, Lashof, A, Posthouwer, D, Ammerlaan, Hs, Pronk, Mj, van der Ende ME, de Vries-Sluijs TE, Schurink, Ca, Nouwen, Jl, Verbon, A, Rijnders, Bj, van Gorp EC, van der Feltz, M, Driessen, Gj, van Rossum AM, Branger, J, Schippers, F, van Nieuwkoop, C, van Elzakker EP, Groeneveld, Ph, Bouwhuis, Jw, Soetekouw, R, ten Kate RW, Kroon, Fp, van Dissel JT, Arend, Sm, de Boer MG, Jolink, H, ter Vollaard HJ, Bauer, Mp, den Hollander JG, Pogany, K, van Twillert, D, Kortmann, W, Stuart, Jw, Diederen, Bm, Leyten, Ms, Gelinck, Lb, Kootstra, Gj, Delsing, Ce, Brinkman, K, Blok, Wl, Frissen, Ph, Schouten, We, van den Berk GE, van Kasteren ME, Brouwer, Ae, Veenstra, J, Lettinga, Kd, Mulder, Jw, Vrouenraets, Sm, Lauw, Fn, van Eeden, A, Verhagen, Dw, Sprenger, Hg, Doedens, R, Scholvinck, Eh, van Assen, S, Bierman, Wf, Koopmans, Pp, Keuter, M, van der Ven AJ, ter Hofstede HJ, Dofferhoff, As, Warris, A, van Crevel, R, Hoepelman, Ai, Mudrikova, T, Schneider, Mm, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Wassenberg, Mw, Barth, Re, van Agtmael, M, Perenboom, Rm, Claessen, Fa, Bomers, M, Peters, Ej, 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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 Laethem, Y, Neaton, J, Bartsch, G, El-Sadr, Wm, 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, Lundgren, J, Cozzi-Lepri, A, Grint, D, Podlekareva, D, Peters, L, Reekie, J, Fischer, Ah, Losso, M, Elias, C, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, Vm, Suetnov, O, Colebunders, R, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Machala, L, Begovac, J, Jilich, D, Sedlacek, D, Kronborg, G, Gerstoft, J, Benfield, T, Larsen, M, Katzenstein, T, Hansen, Ab, Skinhøj, P, Pedersen, C, Ostergaard, L, Zilmer, K, Smidt, J, Ristola, M, Katlama, C, Viard, J, Girard, P, Livrozet, Jm, Vanhems, P, Rockstroh, J, Schmidt, R, van Lunzen, J, Degen, O, Stellbrink, Hj, Staszewski, S, Bickel, M, Kosmidis, J, Gargalianos, P, Xylomenos, G, Perdios, J, Panos, G, Filandras, A, Karabatsaki, E, Sambatakou, H, Banhegyi, D, Mulcahy, F, Yust, I, Turner, D, Burke, M, Pollack, S, Hassoun, G, Maayan, S, Vella, S, Esposito, R, Mazeu, I, Mussini, C, Arici, C, Pristera, R, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Chirianni, A, Montesarchio, E, Gargiulo, M, Antonucci, G, Testa, A, Narciso, P, Vlassi, C, Zaccarelli, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Zeltina, I, Chaplinskas, S, Hemmer, R, Staub, T, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Horban, A, Bakowska, E, Grzeszczuk, A, Flisiak, R, Boron-Kaczmarska, A, Pynka, M, Parczewski, M, Beniowski, M, Mularska, E, Trocha, H, Jablonowska, E, Malolepsza, E, Wojcik, K, Antunes, F, Doroana, M, Caldeira, L, Mansinho, K, Maltez, F, Duiculescu, D, Rakhmanova, A, Babes, V, Zakharova, N, Jevtovic, D, Mokráš, M, Staneková, D, Tomazic, J, González-Lahoz, J, Soriano, V, Labarga, P, Medrano, J, Moreno, S, Rodriguez, Jm, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gatell, Jm, Miró, Jm, Gutierrez, M, Karlsson, A, Mateo, G, Flamholc, L, Ledergerber, B, Francioli, P, Cavassini, M, Hirschel, B, Boffi, E, Kravchenko, E, Furrer, H, Battegay, M, Elzi, L, Chentsova, N, Frolov, V, Kutsyna, G, Servitskiy, S, Krasnov, M, Barton, S, Johnson, Am, Mercey, D, Johnson, Ma, Murphy, M, Weber, J, Scullard, G, Fisher, M, Leen, C, Morfeldt, L, Thulin, G, Åkerlund, B, Koppel, K, Håkangård, C, Moroni, M, Angarano, G, Antinori, A, 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, 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, Quiros, E, Rusconi, S, Cicconi, P, Formenti, T, Galli, L, Lorenzini, P, Giacometti, A, Costantini, A, Santoro, C, Suardi, C, Vanino, E, Verucchi, G, Quiros Roldan, E, 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, Caramma, I, Castelli, Ap, Rizzardini, G, Ridolfo, Al, Piolini, R, Salpietro, S, Carenzi, L, Moioli, Mc, Puzzolante, C, Onofrio, M, Abrescia, N, Guida, Mg, Baldelli, F, Francisci, D, Parruti, G, Ursini, T, Magnani, G, Ursitti, Ma, d' Avino, A, Gallo, L, Nicastri, E, Acinapura, R, Capozzi, M, Libertone, R, Tebano, G, Cattelan, A, Mura, Ms, Caramello, P, Orofino, Gc, Sciandra, M, Pellizzer, G, Manfrin, V, Caissotti, C, Dellamonica, P, Bernard, E, Cua, E, De Salvador- Guillouet, F, Durant, J, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Prouvost-Keller, B, Pillet, S, Pugliese, P, Rahelinirina, V, Roger, Pm, Dollet, K, Aubert, V, Barth, J, Bernasconi, E, Böni, J, Bucher, Hc, Burton- Jeangros, C, Calmy, A, Egger, M, Fehr, J, Fellay, J, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, Hh, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kovari, H, Martinetti, G, de Tejada BM, Metzner, K, Müller, N, Nadal, D, Pantaleo, G, Rauch, A, Regenass, A, Rudin, C, Schmid, P, Schultze, D, Schöni-Affolter, F, Schüpbach, J, Speck, R, Taffé, P, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Yerly, S., AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Dermatology, Medical Microbiology and Infection Prevention, Sea to Shore Alliance, University of Florida [Gainesville] (UF), Observatoire des Micro et Nano Technologies (OMNT - UMS 2920), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Département de santé publique, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital Larchet, Service de néphrologie, Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Department of primary care and population sciences, University College of London [London] (UCL), Research Department of Infection and Population Health [London], Economics, Umeå University, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Nanosciences et Cryogénie (INAC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
- Subjects
Adult ,Male ,CHRONIC KIDNEY-DISEASE ,Internationality ,FUNCTION DECLINE ,diagnosis ,nephrology ,Chronic kidney disease ,Estimated glomerular filtration rate ,HIV ,Kidney disease ,Rapid progression ,D:A:D study Group ,HIV Infections ,urologic and male genital diseases ,Sensitivity and Specificity ,Severity of Illness Index ,GLOMERULAR-FILTRATION-RATE ,renal insufficiency ,NO ,MORTALITY RISK ,ANTIRETROVIRAL THERAPY ,80 and over ,Humans ,chronic kidney disease ,estimated glomerular filtration rate ,hiv ,kidney disease ,rapid progression ,adult ,aged ,aged, 80 and over ,diagnosis, computer-assisted ,disease progression ,female ,glomerular filtration rate ,hiv infections ,humans ,internationality ,male ,middle aged ,renal insufficiency, chronic ,reproducibility of results ,sensitivity and specificity ,algorithms ,severity of illness index ,Diagnosis, Computer-Assisted ,Renal Insufficiency, Chronic ,ComputingMilieux_MISCELLANEOUS ,BODY-SURFACE AREA ,POPULATION ,Aged ,Aged, 80 and over ,INFECTED PATIENTS ,Reproducibility of Results ,1103 Clinical Sciences ,ASSOCIATION ,Urology & Nephrology ,Middle Aged ,chronic ,INDIVIDUALS ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,computer-assisted ,Disease Progression ,Female ,Algorithms ,Research Article ,Glomerular Filtration Rate - Abstract
BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. METHODS: Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR
- Published
- 2014
8. Mathematical Model to Synthesize Natural History of Tick Borne Encephalitis and Lyme Borreliosis for the Purpose of Cost-Effectiveness Analysis
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Mihajlovic, J, primary, Hovius, JW, additional, Sprong, H, additional, Strle, F, additional, Bogovic, P, additional, and Postma, MJ, additional
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- 2016
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9. Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study
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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
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- 2015
10. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D Study
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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
11. PIN64 - Cost-Effectiveness Of A Potential Combined Vaccine Against Lyme Borreliosis And Tick-Borne Encephalitis In Slovenia
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Mihajlović, J, Hovius, JW, Sprong, H, Strle, F, Bogovič, P, and Postma, MJ
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- 2017
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12. PRM118 - Mathematical Model to Synthesize Natural History of Tick Borne Encephalitis and Lyme Borreliosis for the Purpose of Cost-Effectiveness Analysis
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Mihajlovic, J, Hovius, JW, Sprong, H, Strle, F, Bogovic, P, and Postma, MJ
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- 2016
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13. Salivating for knowledge: potential pharmacological agents in tick saliva.
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Hovius JW, Levi M, Fikrig E, Hovius, Joppe W R, Levi, Marcel, and Fikrig, Erol
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- 2008
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14. Tick-borne Diseases: Opening Pandora’s Box
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Jahfari, Setareh, Koopmans, Marion, Hovius, JW, Sprong, H, and Virology
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- 2017
15. Limited evidence of infection with other tick-borne pathogens in patients tested for Lyme neuroborreliosis in the Netherlands.
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Koetsveld J, Wagemakers A, Brouwer M, de Wever B, de Vries A, van Gucht S, Buskermolen A, van Beek D, Sprong H, and Hovius JW
- Abstract
Ixodes ricinus is the main vector of the causative agents of Lyme neuroborreliosis. This tick species can also transmit tick-borne encephalitis virus (TBEV), spotted fever group (SFG) Rickettsia and Borrelia miyamotoi to humans. These tick-borne pathogens are present in Dutch ticks and have also been associated with human neurological infections, but well characterized disease cases are seldom reported. We therefore assessed the evidence for TBEV, SFG Rickettsia or B. miyamotoi infection in clinically well-described patients suspected of Lyme neuroborreliosis. We retrospectively included patients with specific predefined clinical criteria from patients that were tested for Lyme neuroborreliosis between 2010 and 2014 at an academic Lyme borreliosis Center. Serology was performed on available serum samples, and cerebrospinal fluid (CSF) was tested by molecular methods. Out of 514 potentially eligible patients, 176 individual patients were included. None of CSF samples was positive for the tested tick-borne pathogens, except for one previously described patient with Borrelia miyamotoi disease (BMD). Serology revealed 27, 14 and three patients with antibodies against SFG Rickettsia, B. miyamotoi and TBEV, respectively. No distinctive clinical symptoms or signs could be associated with seropositivity against any of these tick-borne pathogens. Apart from the previously published BMD case, we were unable to find convincing evidence of new cases of tick-borne encephalitis, spotted fever rickettsiosis or BMD in a cohort of patients suspected of Lyme neuroborreliosis. While antibodies against these tick-borne pathogens were detected, we could not associate these findings to clinical symptoms or signs. Therefore, prospective studies on humans with tick exposure are necessary to describe the prevalence, etiology and clinical symptoms of these tick-borne diseases other than Lyme borreliosis and tick-borne encephalitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
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- 2024
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16. Exposure, infection and disease with the tick-borne pathogen Borrelia miyamotoi in the Netherlands and Sweden, 2007-2019.
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Hoornstra D, Stukolova OA, van Eck JA, Sokolova MI, Platonov AE, Hofhuis A, Vos ERA, Reimerink JH, van den Berg OE, van den Wijngaard CC, Lager M, Wilhelmsson P, Lindgren PE, Forsberg P, Henningsson AJ, and Hovius JW
- Abstract
The impact of the emerging tick-borne pathogen Borrelia miyamotoi is not fully understood. We utilised a protein array to investigate B. miyamotoi seroreactivity in various human populations in the Netherlands and Sweden. The IgM/IgG seroprevalence in Dutch healthy (2·5%, 95%CI 1·5-4·1) and population controls (2·0%, 95%CI 0·9-4·4) was lower (p = 0·01 and p = 0·01) compared to the tick-bite cohort (6·1%, 95%CI 3·9-9·5). In accordance, the Swedish healthy controls (1·0%, 95%CI 0·1-6·9) revealed a lower (p = 0·005 and p < 0·001) IgM/IgG seroprevalence compared to the tick-bite (8·9%, 95%CI 5·7-13·7) and fever after tick-bite cohort (16·5%, 95%CI 10·6-24·8). Altogether, 15 of 2175 individuals had serologic evidence of early B. miyamotoi infection. The risk of infection with B. miyamotoi was 0·7% (95%CI 0·3-1·4) in tick-bitten individuals, and of disease 7·3% (95%CI 2·6-12·8) in those with a febrile illness after tick-bite. Our findings provide insights into the risk of infection and disease with this pathogen in Europe., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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17. Bridging the gap: Insights in the immunopathology of Lyme borreliosis.
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Snik ME, Stouthamer NEIM, Hovius JW, and van Gool MMJ
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Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) genospecies transmitted by Ixodes spp. ticks, is a significant public health concern in the Northern Hemisphere. This review highlights the complex interplay between Bbsl infection and host-immune responses, impacting clinical manifestations and long-term immunity. Early localized disease is characterized by erythema migrans (EM), driven by T-helper 1 (Th1) responses and proinflammatory cytokines. Dissemination to the heart and CNS can lead to Lyme carditis and neuroborreliosis respectively, orchestrated by immune cell infiltration and chemokine dysregulation. More chronic manifestations, including acrodermatitis chronica atrophicans and Lyme arthritis, involve prolonged inflammation as well as the development of autoimmunity. In addition, dysregulated immune responses impair long-term immunity, with compromised B-cell memory and antibody responses. Experimental models and clinical studies underscore the role of Th1/Th2 balance, B-cell dysfunction, and autoimmunity in LB pathogenesis. Moreover, LB-associated autoimmunity parallels mechanisms observed in other infectious and autoimmune diseases. Understanding immune dysregulation in LB provides insights into disease heterogeneity and could provide new strategies for diagnosis and treatment., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
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- 2024
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18. Autochthonous Human Babesiosis Caused by Babesia venatorum, the Netherlands.
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Spoorenberg N, Köhler CF, Vermeulen E, Jurriaans S, Cornelissen M, Persson KEM, van Doorn I, Sprong H, Hovius JW, and Zonneveld R
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- Humans, Netherlands, Animals, Male, Splenectomy, Middle Aged, Ixodes parasitology, Babesiosis diagnosis, Babesiosis parasitology, Babesia genetics, Babesia isolation & purification, Babesia classification
- Abstract
Severe babesiosis with 9.8% parasitemia was diagnosed in a patient in the Netherlands who had previously undergone splenectomy. We confirmed Babesia venatorum using PCR and sequencing. B. venatorum was also the most prevalent species in Ixodes ricinus ticks collected around the patient's home. Our findings warrant awareness for severe babesiosis in similar patients.
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- 2024
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19. Persistent Symptoms After Lyme Disease: Clinical Characteristics, Predictors, and Classification.
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Baarsma ME and Hovius JW
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- Humans, Lyme Disease diagnosis, Post-Lyme Disease Syndrome
- Abstract
Persistent symptoms after an infection have been described for a number of infectious diseases, including Lyme disease. Studies have confirmed a moderate but consistent increase in the prevalence of such symptoms after Lyme disease, though the risk increase varies dependent on study design and the definition of persistent symptoms. Various possible predictors have been proposed, including a dysregulation of the immune system, metabolic changes, increased sensitization to pain signals, cognitive-behavioral factors, or-controversially-the persistence of the causative Borrelia bacteria or remnants thereof. Research on the precise roles of any of these factors is still ongoing. The lack of biological underpinning also makes it difficult to assess with certainty which patients' (generally nonspecific) persistent symptoms are etiologically related to the previous Lyme disease episode and which are not, particularly as these symptoms occur in the general population relatively frequently. The diagnostic criteria for posttreatment Lyme disease syndrome have shown their usefulness in both clinical and research settings but leave out a number of patients whose symptoms may fall just outside said criteria. Though the relationship between these symptoms and the previous Lyme disease episode may be very uncertain, we would argue that a uniform description and classification of these patients will aid in future research and patient management, regardless of the eventual underlying cause. Thus, we argue for an inclusive classification system for all persistent symptoms attributed to Lyme disease in order to promote validation of patient experiences and perspectives, while also maintaining scientific nuance regarding the very uncertain etiology of these patients' symptoms., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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20. Combining short- and long-read sequencing unveils geographically structured diversity in Borrelia miyamotoi .
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Hoornstra D, Kuleshov KV, Fingerle V, Hepner S, Wagemakers A, Strube C, Castillo-Ramírez S, Bockenstedt LK, Telford SR, Sprong H, Platonov AE, Margos G, and Hovius JW
- Abstract
Borrelia miyamotoi is an emerging Ixodes tick-borne human pathogen in the Northern hemisphere. The aim of the current study was to compare whole genome sequences of B. miyamotoi isolates from different continents. Using a combination of Illumina and PacBio platforms and a novel genome assembly and plasmid typing pipeline, we reveal that the 21 sequenced B. miyamotoi isolates and publically available B. miyamotoi genomes from North America, Asia, and Europe form genetically distinct populations and cluster according to their geographical origin, where distinct Ixodes species are endemic. We identified 20 linear and 17 circular plasmid types and the presence of specific plasmids for isolates originating from different continents. Linear plasmids lp12, lp23, lp41, and lp72 were core plasmids found in all isolates, with lp41 consistently containing the vmp expression site. Our data provide insights into the genetic basis of vector competence, virulence, and pathogenesis of B. miyamotoi ., Competing Interests: All authors declare no competing interests., (© 2024 The Authors.)
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- 2024
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21. Review of literature and clinical practice experience for the therapeutic management of Morgellons disease.
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Kemperman PMJH, Vulink NCC, Smit C, Hovius JW, and de Rie MA
- Abstract
Morgellons disease (MD) is a rare and contentious health condition characterized by dermatological symptoms including slow-healing skin lesions 'attributed' to fibres emerging from or under the skin. Patients also report sensations of crawling, biting and infestation with inanimate objects. This review examines the aetiology, patient characteristics, epidemiology, historical context, correlation with Lyme disease, role of internet, impact on quality of life and treatment approaches for MD. Despite ongoing debate, MD is not officially recognized in medical classifications, with differing views on its aetiology. Some link MD to Lyme disease, while others view it as a variant of delusional infestation. The literature suggests both psychiatric and environmental factors may contribute. The manuscript explores the association with substance abuse, psychiatric comorbidities, infectious agents and the role of internet communities in shaping perceptions. MD's impact on quality of life is significant, yet often overlooked. Treatment approaches are varied due to limited evidence, with low-dose antipsychotics being considered effective, but patient beliefs may influence adherence. A patient-centred, multidisciplinary approach is emphasized, considering both the physical and psychological dimensions of MD. Addressing the controversies surrounding MD while focusing on patient well-being remains a critical challenge for healthcare professionals., (© 2024 European Academy of Dermatology and Venereology.)
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- 2024
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22. A comprehensive genetic map of cytokine responses in Lyme borreliosis.
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Botey-Bataller J, Vrijmoeth HD, Ursinus J, Kullberg BJ, van den Wijngaard CC, Ter Hofstede H, Alaswad A, Gupta MK, Roesner LM, Huehn J, Werfel T, Schulz TF, Xu CJ, Netea MG, Hovius JW, Joosten LAB, and Li Y
- Subjects
- Humans, Male, Female, Interleukin-10 genetics, Adult, Genome-Wide Association Study, Middle Aged, Interleukin 1 Receptor Antagonist Protein genetics, Borrelia burgdorferi immunology, Borrelia burgdorferi genetics, Anti-Bacterial Agents, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Aged, Lyme Disease immunology, Lyme Disease genetics, Lyme Disease microbiology, Quantitative Trait Loci, Cytokines genetics, Cytokines metabolism
- Abstract
The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource., (© 2024. The Author(s).)
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- 2024
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23. Development of a sequence-based in silico OspA typing method for Borrelia burgdorferi sensu lato .
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Lee JT, Li Z, Nunez LD, Katzel D, Perrin BS Jr, Raghuraman V, Rajyaguru U, Llamera KE, Andrew L, Anderson AS, Hovius JW, Liberator PA, Simon R, and Hao L
- Subjects
- Bacterial Vaccines, Borrelia burgdorferi genetics, Borrelia burgdorferi classification, Borrelia burgdorferi Group genetics, Borrelia burgdorferi Group classification, Computer Simulation, Genome, Bacterial, High-Throughput Nucleotide Sequencing methods, Phylogeny, Serogroup, Antigens, Surface genetics, Bacterial Outer Membrane Proteins genetics, Lipoproteins genetics, Lyme Disease microbiology
- Abstract
Lyme disease (LD), caused by spirochete bacteria of the genus Borrelia burgdorferi sensu lato , remains the most common vector-borne disease in the northern hemisphere. Borrelia outer surface protein A (OspA) is an integral surface protein expressed during the tick cycle, and a validated vaccine target. There are at least 20 recognized Borrelia genospecies, that vary in OspA serotype. This study presents a new in silico sequence-based method for OspA typing using next-generation sequence data. Using a compiled database of over 400 Borrelia genomes encompassing the 4 most common disease-causing genospecies, we characterized OspA diversity in a manner that can accommodate existing and new OspA types and then defined boundaries for classification and assignment of OspA types based on the sequence similarity. To accommodate potential novel OspA types, we have developed a new nomenclature: OspA in silico type (IST). Beyond the ISTs that corresponded to existing OspA serotypes 1-8, we identified nine additional ISTs that cover new OspA variants in B. bavariensis (IST9-10), B. garinii (IST11-12), and other Borrelia genospecies (IST13-17). The IST typing scheme and associated OspA variants are available as part of the PubMLST Borrelia spp. database. Compared to traditional OspA serotyping methods, this new computational pipeline provides a more comprehensive and broadly applicable approach for characterization of OspA type and Borrelia genospecies to support vaccine development.
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- 2024
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24. Evaluation and 1-year follow-up of patients presenting at a Lyme borreliosis expertise centre: a prospective cohort study with validated questionnaires.
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van de Schoor FR, Baarsma ME, Gauw SA, Ursinus J, Vrijmoeth HD, Ter Hofstede HJM, Tulen AD, Harms MG, Wong A, van den Wijngaard CC, Joosten LAB, Hovius JW, and Kullberg BJ
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- Humans, Male, Prospective Studies, Female, Middle Aged, Follow-Up Studies, Adult, Surveys and Questionnaires, Aged, Prevalence, Cognitive Dysfunction epidemiology, Cognitive Dysfunction etiology, Pain etiology, Pain epidemiology, Arthralgia microbiology, Arthralgia epidemiology, Arthralgia etiology, Young Adult, Lyme Disease epidemiology, Lyme Disease diagnosis, Fatigue etiology, Fatigue epidemiology
- Abstract
Objectives: To describe the course of symptoms reported by patients with symptoms attributed to Lyme borreliosis (LB) without being subsequently diagnosed with LB., Methods: We performed a prospective cohort study with patients presenting at the outpatient clinic of two clinical LB centres. The primary outcome was the prevalence of persistent symptoms, which were defined as clinically relevant fatigue (CIS, subscale fatigue), pain (SF-36, subscale bodily pain), and cognitive impairment (CFQ) for ≥ 6 months and onset < 6 months over the first year of follow-up. Outcomes were compared with a longitudinal cohort of confirmed LB patients and a general population cohort. Prevalences were standardised to the distribution of pre-defined confounders in the confirmed LB cohort., Results: Participants (n = 123) reported mostly fatigue, arthralgia, myalgia, and paraesthesia as symptoms. The primary outcome could be determined for 74.8% (92/123) of participants. The standardised prevalence of persistent symptoms in our participants was 58.6%, which was higher than in patients with confirmed LB at baseline (27.2%, p < 0.0001) and the population cohort (21.2%, p < 0.0001). Participants reported overall improvement of fatigue (p < 0.0001) and pain (p < 0.0001) but not for cognitive impairment (p = 0.062) during the follow-up, though symptom severity at the end of follow-up remained greater compared to confirmed LB patients (various comparisons p < 0.05)., Conclusion: Patients with symptoms attributed to LB who present at clinical LB centres without physician-confirmed LB more often report persistent symptoms and report more severe symptoms compared to confirmed LB patients and a population cohort., (© 2024. The Author(s).)
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- 2024
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25. [Cutaneous Lyme disease: not always a rash with a central clearing].
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Hulshof MM, Starink MV, Lokin ASHJ, and Hovius JW
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- Humans, Acrodermatitis diagnosis, Acrodermatitis drug therapy, Acrodermatitis etiology, Lyme Disease complications, Lyme Disease diagnosis, Lyme Disease drug therapy, Skin Diseases, Erythema Chronicum Migrans diagnosis, Erythema Chronicum Migrans drug therapy, Erythema Chronicum Migrans etiology, Exanthema diagnosis, Exanthema etiology
- Abstract
During the past four decades the number of reported Lyme disease diagnoses in the Netherlands has increased to 27.000 a year, with a yearly incidence of Lyme disease between 111 (95% CI 106-115) to 131 (95% CI 126-136) per 100,000 person years. A large part of all Lyme disease diagnoses concern the skin; in the Netherlands, 77-89% erythema migrans, 2-3% borrelia lymfocytoom and 1-3% acrodermatitis chronica atrophicans. These skin manifestations have a variable clinical expression, reason why they can be difficult to diagnose. Early recognition and treatment is important to prevent the development of systemic manifestations.
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- 2024
26. Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications.
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Vrijmoeth HD, Ursinus J, Botey-Bataller J, Kuijpers Y, Chu X, van de Schoor FR, Scicluna BP, Xu CJ, Netea MG, Kullberg BJ, van den Wijngaard CC, Li Y, Hovius JW, and Joosten LAB
- Subjects
- Humans, Genome-Wide Association Study, Prospective Studies, Leukocytes, Mononuclear, Disease Susceptibility, Cytokines genetics, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases therapeutic use, Secretoglobins genetics, Lyme Disease genetics, Lyme Disease diagnosis, Borrelia burgdorferi genetics, Borrelia, Borrelia burgdorferi Group genetics
- Abstract
Background: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms., Methods: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients-divided into a discovery and validation cohort-were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments., Results: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses., Conclusions: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures., Trial Registration: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015-02-13)., (© 2024. The Author(s).)
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- 2024
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27. Tick-borne diseases in the North Sea region-A comprehensive overview and recommendations for diagnostics and treatment.
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Eikeland R, Henningsson AJ, Lebech AM, Kerlefsen Y, Mavin S, Vrijlandt A, Hovius JW, Lernout T, Lim C, Dobler G, Fingerle V, Gynthersen RM, Lindgren PE, and Reiso H
- Subjects
- Animals, Humans, North Sea, Tick-Borne Diseases diagnosis, Tick-Borne Diseases epidemiology, Tick-Borne Diseases therapy, Lyme Disease diagnosis, Lyme Disease epidemiology, Lyme Disease therapy, Babesiosis diagnosis, Babesiosis epidemiology, Babesiosis therapy, Encephalitis, Tick-Borne, Borrelia Infections
- Abstract
As part of the NorthTick project, co-funded by the European Union through the European Regional Development Fund and the North Sea Region Programme, specialists in the field of tick-borne diseases from seven North Sea countries co-operated with patient organisations and governmental health care institutions to provide this comprehensive overview of diagnostics and treatment recommendations in the region for Lyme borreliosis, Borrelia miyamotoi infection, tick-borne encephalitis, human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis and babesiosis. The main conclusion is that the recommendations in these northern countries are essentially the same, with very few differences. This overview presents the current diagnostics and provides useful clinical guidance., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
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- 2024
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28. Determinants of persistent symptoms after treatment for Lyme borreliosis: a prospective observational cohort study.
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Vrijmoeth HD, Ursinus J, Harms MG, Tulen AD, Baarsma ME, van de Schoor FR, Gauw SA, Zomer TP, Vermeeren YM, Ferreira JA, Sprong H, Kremer K, Knoop H, Joosten LAB, Kullberg BJ, Hovius JW, and van den Wijngaard CC
- Subjects
- Humans, Prospective Studies, Anti-Bacterial Agents therapeutic use, Netherlands, Surveys and Questionnaires, Lyme Disease diagnosis, Lyme Disease drug therapy, Lyme Disease epidemiology
- Abstract
Background: Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology., Methods: In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n = 4000 and n = 2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice)., Findings: Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in ex vivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms., Interpretation: Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated., Funding: Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Ministry of Health, Welfare and Sport (VWS)., Competing Interests: Declaration of interests MEB, FRvdS and JWH report collaborations on LB diagnostics with Pfizer, Antigen Discovery Inc., Oxford Immunotec, AID/GenID, and InVitaLab; funding to institution and/or material supplied for research free of charge, no personal financial compensation. MEB reports support for travel expenses related to LB symposium at Massachusetts General Hospital. LABJ and BJK are co-inventor of Spirofind, an experimental in-house assay for Lyme borreliosis, which is owned by Radboudumc and will not be developed further as potential diagnostic test. CCvdW is a consortium partner and partner in sub-project in the NMCB consortium (The Dutch ME/CFS Cohort and Biobank Consortium) funded by Netherlands Organization for Health Research and Development (ZonMw, project numbers 10091012110027 and 10091012110018). The other authors report no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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29. Age-related changes in plasma biomarkers and their association with mortality in COVID-19.
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Michels EHA, Appelman B, de Brabander J, van Amstel RBE, Chouchane O, van Linge CCA, Schuurman AR, Reijnders TDY, Sulzer TAL, Klarenbeek AM, Douma RA, Bos LDJ, Wiersinga WJ, Peters-Sengers H, van der Poll T, van Agtmael M, Algera AG, Appelman B, van Baarle F, Beudel M, Bogaard HJ, Bomers M, Bonta P, Bos L, Botta M, de Brabander J, de Bree G, de Bruin S, Bugiani M, Bulle E, Buis DTP, Chouchane O, Cloherty A, Dijkstra M, Dongelmans DA, Dujardin RWG, Elbers P, Fleuren L, Geerlings S, Geijtenbeek T, Girbes A, Goorhuis B, Grobusch MP, Hagens L, Hamann J, Harris V, Hemke R, Hermans SM, Heunks L, Hollmann M, Horn J, Hovius JW, de Jong HK, de Jong MD, Koning R, Lemkes B, Lim EHT, van Mourik N, Nellen J, Nossent EJ, Olie S, Paulus F, Peters E, Pina-Fuentes DAI, van der Poll T, Preckel B, Prins JM, Raasveld J, Reijnders T, de Rotte MCFJ, Schinkel M, Schultz MJ, Schrauwen FAP, Schuurman A, Schuurmans J, Sigaloff K, Slim MA, Smeele P, Smit M, Stijnis CS, Stilma W, Teunissen C, Thoral P, Tsonas AM, Tuinman PR, van der Valk M, Veelo DP, Volleman C, de Vries H, Vught LA, van Vugt M, Wouters D, Zwinderman AHK, Brouwer MC, Wiersinga WJ, Vlaar APJ, and van de Beek D
- Subjects
- Humans, Aged, Biomarkers, Inflammation, Cytokines, Aging, COVID-19
- Abstract
Background: Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response and mortality in patients with COVID-19., Methods: We determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort., Results: 464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumour necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1 and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively)., Conclusions: Ageing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19., Competing Interests: Conflicts of interest: The authors declare no potential conflicts of interest., (Copyright ©The authors 2023.)
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- 2023
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30. [New infectious diseases in Europe; the effect of climate change, globalisation and human behaviour].
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Goorhuis AB, de Mast Q, Hovius JW, and van Nood E
- Subjects
- Humans, Climate Change, Europe epidemiology, Communicable Diseases epidemiology, Encephalitis, Tick-Borne epidemiology
- Abstract
Climate change directly and indirectly contributes to the emergence of vector and water borne infections. Other infectious diseases may be introduced to new geographical areas as a result of globalisation and changing human behaviour. Despite the still low absolute risk, the pathogenicity of some of these infections creates a significant challenge for clinicians. Awareness of changing disease epidemiology helps in timely recognition of such infections. Vaccination guidelines for emerging vaccine-preventable diseases, such as tick-borne encephalitis and leptospirosis, may need to be updated.
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- 2023
31. Clinical manifestations of Lyme neuroborreliosis in children: a review.
- Author
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Bruinsma RA, Zomer TP, Skogman BH, van Hensbroek MB, and Hovius JW
- Subjects
- Adult, Humans, Child, Child, Preschool, Anti-Bacterial Agents therapeutic use, Pain drug therapy, Lyme Neuroborreliosis complications, Lyme Neuroborreliosis diagnosis, Lyme Neuroborreliosis drug therapy, Facial Paralysis etiology
- Abstract
Lyme neuroborreliosis (LNB) is a manifestation of Lyme disease involving the central and peripheral nervous system. It is caused by the spirochete Borrelia burgdorferi, transmitted by tick bites to a human host. Clinical signs of LNB develop after the dissemination of the pathogen to the nervous system. The infection occurs in children and adults, but the clinical manifestations differ. In adults, painful meningoradicultis is the most common manifestation of LNB, while children often present with facial nerve palsy and/or subacute meningitis. Subacute headache can be the only manifestation of LNB in children, especially during the summer months in Lyme disease-endemic regions. Non-specific symptoms, such as loss of appetite, fatigue or mood changes, may also occur, especially in young children. A high level of suspicion and early recognition of the various clinical manifestations presented by children with LNB is essential to minimize delay in diagnosis and optimize management. This review provides an overview of the spectrum of clinical manifestations, and discusses diagnosis, antibiotic treatment, and clinical outcome of LNB in children., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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32. Detection of Borrelia burgdorferi sensu lato DNA in cerebrospinal fluid samples following pre-enrichment culture.
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Leth TA, Nymark A, Knudtzen FC, Larsen SL, Skov MN, Jensen TG, Bek-Thomsen M, Jensen HB, Hovius JW, Skarphédinsson S, Møller JK, and Andersen NS
- Subjects
- Adult, Humans, DNA, Real-Time Polymerase Chain Reaction, Cerebrospinal Fluid, Borrelia burgdorferi Group genetics, Lyme Neuroborreliosis diagnosis, Lyme Neuroborreliosis cerebrospinal fluid, Borrelia genetics
- Abstract
Molecular methods for diagnosing Lyme neuroborreliosis (LNB) have shown suboptimal diagnostic sensitivities. The objective of this study was to improve the clinical sensitivity of PCR detection of Borrelia burgdorferi sensu lato spirochetes by inoculating cerebrospinal fluid (CSF) from patients suspected of LNB directly into culture medium at the time of lumbar puncture, with this pursuing enrichment of Borrelia spirochetes before PCR analysis. Adult patients with symptoms suggestive of LNB were prospectively enrolled at two hospitals in the Region of Southern Denmark. The CSF-culture samples were incubated for at least eight weeks. During this period, culture sample aliquots were analysed for the presence of Borrelia DNA by separate PCR protocols in two independent clinical laboratories. The included patients were diagnosed with definite (n=12) or possible (n=2) LNB, and non-LNB (n=171) based on clinical and paraclinical findings. Patients in the LNB and the non-LNB group had a median duration from symptom onset to lumbar puncture of 40 days (IQR [23-90] days) and 120 days (IQR [32-365] days), respectively. Pre-enrichment growth of Borrelia spirochetes was accomplished from three patients (21 %) in the LNB group. The positive culture samples were confirmed by both the digital droplet PCR and the real-time PCR methods employed. All CSF samples were PCR negative in the non-LNB group. The results of this study do not support the use of Borrelia-specific PCR as a general routine diagnostic tool in adults. Still, they suggest it may prove of additional value in selected patients with a limited time from symptom onset to sample collection., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
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- 2023
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33. Corrections to "Prevalence of persistent symptoms after treatment for lyme borreliosis: a prospective observational cohort study" [The Lancet Regional Health - Europe 6 (2021) 100142].
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Ursinus J, Vrijmoeth HD, Harms MG, Tulen AD, Knoop H, Gauw SA, Zomer TP, Wong A, Friesema IHM, Vermeeren YM, Joosten LAB, Hovius JW, Kullberg BJ, and van den Wijngaard CC
- Abstract
[This corrects the article DOI: 10.1016/j.lanepe.2021.100142.]., (© 2023 The Author(s).)
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- 2023
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34. Persistent Borrelia burgdorferi Sensu Lato Infection after Antibiotic Treatment: Systematic Overview and Appraisal of the Current Evidence from Experimental Animal Models.
- Author
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Verschoor YL, Vrijlandt A, Spijker R, van Hest RM, Ter Hofstede H, van Kempen K, Henningsson AJ, and Hovius JW
- Subjects
- Animals, Humans, Anti-Bacterial Agents therapeutic use, Models, Animal, Lyme Disease diagnosis, Lyme Disease drug therapy, Borrelia burgdorferi Group, Ixodes
- Abstract
Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted by Ixodes tick species living in the temperate climate zones of the Northern Hemisphere. The clinical manifestations of Lyme borreliosis are diverse and treated with oral or intravenous antibiotics. In some patients, long-lasting and debilitating symptoms can persist after the recommended antibiotic treatment. The etiology of such persisting symptoms is under debate, and one hypothesis entails persistent infection by a subset of spirochetes after antibiotic therapy. Here, we review and appraise the experimental evidence from in vivo animal studies on the persistence of B. burgdorferi sensu lato infection after antibiotic treatment, focusing on the antimicrobial agents doxycycline and ceftriaxone. Our review indicates that some in vivo animal studies found sporadic positive cultures after antibiotic treatment. However, this culture positivity often seemed to be related to inadequate antibiotic treatment, and the few positive cultures in some studies could not be reproduced in other studies. Overall, current results from animal studies provide insufficient evidence for the persistence of viable and infectious spirochetes after adequate antibiotic treatment. Borrelial nucleic acids, on the contrary, were frequently detected in these animal studies and may thus persist after antibiotic treatment. We put forward that research into the pathogenesis of persisting complaints after antibiotic treatment for Lyme borreliosis in humans should be a top priority, but future studies should most definitely also focus on explanations other than persistent B. burgdorferi sensu lato infection after antibiotic treatment.
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- 2022
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35. Development and Validation of a Protein Array for Detection of Antibodies against the Tick-Borne Pathogen Borrelia miyamotoi.
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Hoornstra D, Stukolova OA, Karan LS, Sarksyan DS, Kolyasnikova NM, Markelov ML, Cherkashina AS, Dolgova AS, Sudina AE, Sokolova MI, Platonov AE, and Hovius JW
- Subjects
- Animals, Humans, Flagellin, Immunoglobulin G, Immunoglobulin M, Protein Array Analysis, Borrelia, Ixodes microbiology, Borrelia Infections immunology, Antibodies, Bacterial analysis
- Abstract
Current serological tests for the emerging tick-borne pathogen Borrelia miyamotoi lack diagnostic accuracy. To improve serodiagnosis, we investigated a protein array simultaneously screening for IgM and IgG reactivity against multiple recombinant B. miyamotoi antigens. The array included six B. miyamotoi antigens: glycerophosphodiester phosphodiesterase (GlpQ), multiple variable major proteins (Vmps), and flagellin. Sera included samples from cases of PCR-proven Borrelia miyamotoi disease (BMD), multiple potentially cross-reactive control groups (including patients with culture-proven Lyme borreliosis, confirmed Epstein-Barr virus, cytomegalovirus, or other spirochetal infections), and several healthy control groups from regions where Ixodes is endemic and regions where it is nonendemic. Based on receiver operating characteristic (ROC) analyses, the cutoff for reactivity per antigen was set at 5 μg/mL for IgM and IgG. The individual antigens demonstrated high sensitivity but relatively low specificity for both IgM and IgG. The best-performing single antigen (GlpQ) showed a sensitivity of 88.0% (95% confidence interval [CI], 78.9 to 93.5) and a specificity of 94.2% (95% CI, 92.7 to 95.6) for IgM/IgG. Applying the previous published diagnostic algorithm-defining seroreactivity as reactivity against GlpQ and any Vmp-revealed a significantly higher specificity of 98.5% (95% CI, 97.6 to 99.2) but a significantly lower sensitivity of 79.5% (95% CI, 69.3 to 87.0) for IgM/IgG compared to GlpQ alone. Therefore, we propose to define seroreactivity as reactivity against GlpQ and any Vmp or flagellin which resulted in a comparable sensitivity of 84.3% (95% CI, 74.7 to 90.8) and a significantly higher specificity of 97.9% (95% CI, 96.9 to 98.7) for IgM/IgG compared to GlpQ alone. In conclusion, we have developed and validated a novel serological tool to diagnose BMD that could be implemented in clinical practice and epidemiological studies. IMPORTANCE This paper describes the protein array as a novel serological test for the diagnosis of Borrelia miyamotoi disease (BMD), by reporting the methodology, the development of a diagnostic algorithm, and its extensive validation. With rising numbers of ticks and tick bites, tick-borne diseases, such as BMD, urgently deserve further societal and medical attention. B. miyamotoi is prevalent in Ixodes ticks across the northern hemisphere. Humans are exposed to, and infected by, B. miyamotoi and develop BMD in Asia, in North America, and to a lesser extent in Europe. However, the burden of infection and disease remains largely unknown, due to the noncharacteristic clinical presentation, together with the lack of awareness and availability of diagnostic tools. With this paper, we offer a novel diagnostic tool which will assist in assessing the burden of disease and could be implemented in clinical care.
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- 2022
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36. Digital disparities among healthcare workers in typing speed between generations, genders, and medical specialties: cross sectional study.
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Schuurman AR, Baarsma ME, Wiersinga WJ, and Hovius JW
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- Humans, Male, Female, Cross-Sectional Studies, Health Personnel, Physicians, Medicine, Education, Medical
- Abstract
Objective: To investigate the typing skills of healthcare professionals., Design: Cross sectional study., Setting: Two large tertiary medical centres in Amsterdam, the Netherlands., Participants: 2690 hospital employees working in patient care, research, or medical education., Main Outcome Measures: Participants completed a custom built, web based, Santa themed, typing test in 60 seconds and filled out an associated questionnaire. The primary outcome was corrected typing speed, defined as crude typing speed (words per minute) multiplied by accuracy (correct characters as a percentage of total characters in the final transcribed text). Feelings towards administrative tasks scored on the Visual Analogue Scale to Weigh Respondents' Internalised Typing Enjoyment (VAS-WRITE), in which 0 represents the most negative and 100 the most positive feelings towards administration, were also recorded., Results: Between 18 and 21 May 2021, a representative cohort of 2690 study participants was recruited (1942 (72.2%) were younger than 40 years; 2065 (76.8%) were women). Respondents' mean typing speed was 60.1 corrected words per minute (standard deviation 20.8; range 8.0-136.6) with substantial differences between professions and specialties, in which physicians in internal medicine were the fastest among the medical professionals. Typing speed decreased significantly with every age decade (rho -0.51, P<0.001), and people with a history of completing a typing course were more than 20% faster than those who had not (mean difference 12.1 words (standard error 0.8), (95% confidence interval 10.6 to 13.6), P<0.001). The corrected typing speed did not differ between genders (0.5 (0.9) words, (-1.4 to 2.4), P=0.61). Women were less negative towards administration than were men (mean difference VAS-WRITE score 7.68 (standard error 1.17), (95% confidence interval 5.33 to 10.03), P<0.001). Of all professional groups, medical staff reported the most negative feelings towards administration (mean VAS-WRITE score of 33.5 (standard deviation 22.9))., Conclusions: Important differences were reported in typing proficiency between age groups, professions, and medical specialties. Specific groups are at a disadvantage in an increasingly digitalised healthcare system, and these data could inform the implementation of training modules and alternative methods of data entry to level the playing field., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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37. Identification of novel conserved Ixodes vaccine candidates; a promising role for non-secreted salivary gland proteins.
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Trentelman JJA, de Vogel FA, Colstrup E, Sima R, Coumou J, Koetsveld J, Klouwens MJ, Nayak A, Ersoz J, Barriales D, Tomás-Cortázar J, Narasimhan S, Hajdusek O, Anguita J, and Hovius JW
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- Animals, Guinea Pigs, Humans, Rabbits, Salivary Glands, Salivary Proteins and Peptides genetics, Salivary Proteins and Peptides metabolism, Ixodes, Lyme Disease prevention & control, Vaccines
- Abstract
Ixodes ricinus and Ixodes scapularis are the main vectors for the causative agents of Lyme borreliosis and a wide range of other pathogens. Repeated tick-bites are known to lead to tick rejection; a phenomenon designated as tick immunity. Tick immunity is mainly directed against tick salivary gland proteins (TSGPs) and has been shown to partially protect against experimental Lyme borreliosis. TSGPs recognized by antibodies from tick immune animals could therefore be interesting candidates for an anti-tick vaccine, which might also block pathogen transmission. To identify conserved Ixodes TSGPs that could serve as a universal anti-tick vaccine in both Europe and the US, a Yeast Surface Display containing salivary gland genes of nymphal I. ricinus expressed at 24, 48 and 72 h into tick feeding was probed with either sera from rabbits repeatedly exposed for 24 h to I. ricinus nymphal ticks and/or sera from rabbits immune to I. scapularis. Thus, we identified thirteen TSGP vaccine candidates, of which ten were secreted. For vaccination studies in rabbits, we selected six secreted TSGPs, five full length and one conserved peptide. None of these proteins hampered tick feeding. In contrast, vaccination of guinea pigs with four non-secreted TSGPs - two from the current and two from a previous human immunoscreening - did significantly reduce tick attachment and feeding. Therefore, non-secreted TSGPs appear to be involved in the development of tick immunity and are interesting candidates for an anti-tick vaccine., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JT was employed by the Amsterdam UMC at time of the research, JT is currently employed at GSK., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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38. CD55 Facilitates Immune Evasion by Borrelia crocidurae, an Agent of Relapsing Fever.
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Arora G, Lynn GE, Tang X, Rosen CE, Hoornstra D, Sajid A, Hovius JW, Palm NW, Ring AM, and Fikrig E
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- Humans, Animals, Mice, Immune Evasion, Rodentia, Cytokines, Relapsing Fever epidemiology, Borrelia physiology, Blood Group Antigens
- Abstract
Relapsing fever, caused by diverse Borrelia spirochetes, is prevalent in many parts of the world and causes significant morbidity and mortality. To investigate the pathoetiology of relapsing fever, we performed a high-throughput screen of Borrelia-binding host factors using a library of human extracellular and secretory proteins and identified CD55 as a novel host binding partner of Borrelia crocidurae and Borrelia persica, two agents of relapsing fever in Africa and Eurasia. CD55 is present on the surface of erythrocytes, carries the Cromer blood group antigens, and protects cells from complement-mediated lysis. Using flow cytometry, we confirmed that both human and murine CD55 bound to B. crocidurae and B. persica. Given the expression of CD55 on erythrocytes, we investigated the role of CD55 in pathological B. crocidurae-induced erythrocyte aggregation (rosettes), which enables spirochete immune evasion. We showed that rosette formation was partially dependent on host cell CD55 expression. Pharmacologically, soluble recombinant CD55 inhibited erythrocyte rosette formation. Finally, CD55-deficient mice infected with B. crocidurae had a lower pathogen load and elevated proinflammatory cytokine and complement factor C5a levels. In summary, our results indicate that CD55 is a host factor that is manipulated by the causative agents of relapsing fever for immune evasion. IMPORTANCE Borrelia species are causative agents of Lyme disease and relapsing fever infections in humans. B. crocidurae causes one of the most prevalent relapsing fever infections in parts of West Africa. In the endemic regions, B. crocidurae is present in ~17% of the ticks and ~11% of the rodents that serve as reservoirs. In Senegal, ~7% of patients with acute febrile illness were found to be infected with B. crocidurae. There is little information on host-pathogen interactions and how B. crocidurae manipulates host immunity. In this study, we used a high-throughput screen to identify host proteins that interact with relapsing fever-causing Borrelia species. We identified CD55 as one of the host proteins that bind to B. crocidurae and B. persica, the two causes of relapsing fever in Africa and Eurasia. We show that the interaction of B. crocidurae with CD55, present on the surface of erythrocytes, is key to immune evasion and successful infection in vivo . Our study further shows the role of CD55 in complement regulation, regulation of inflammatory cytokine levels, and innate immunity during relapsing fever infection. Overall, this study sheds light on host-pathogen interactions during relapsing fever infection in vivo .
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- 2022
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39. Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production.
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Kerstholt M, van de Schoor FR, Oosting M, Moorlag SJCFM, Li Y, Jaeger M, van der Heijden WA, Tunjungputri RN, Dos Santos JC, Kischkel B, Vrijmoeth HD, Baarsma ME, Kullberg BJ, Lupse M, Hovius JW, van den Wijngaard CC, Netea MG, de Mast Q, and Joosten LAB
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- Humans, Ligands, Toll-Like Receptor 4, Chemokines metabolism, Glucose, Lactates, Lipopolysaccharides, Lyme Disease
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Previous studies have shown that monocytes can be 'trained' or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.)
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- 2022
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40. Prevalence and clinical manifestation of Borrelia miyamotoi in Ixodes ticks and humans in the northern hemisphere: a systematic review and meta-analysis.
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Hoornstra D, Azagi T, van Eck JA, Wagemakers A, Koetsveld J, Spijker R, Platonov AE, Sprong H, and Hovius JW
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- Animals, Borrelia, Humans, Nymph, Prevalence, Prospective Studies, Seroepidemiologic Studies, Ixodes, Tick-Borne Diseases epidemiology
- Abstract
Background: Various studies have evaluated the infection of Ixodes ticks and humans with the relapsing fever spirochaete Borrelia miyamotoi. However, to our knowledge, the prevalence of infection and disease has not been assessed systematically. We aimed to examine the prevalence of B miyamotoi in Ixodes ticks and humans, and the disease it can cause, in the northern hemisphere., Methods: For this systematic review and meta-analysis, we searched PubMed and Web of Science up to March 1, 2021. Studies assessing Ixodes tick infection published since Jan 1, 2011 were eligible, whereas no time limitation was placed on reports of human infection and disease. We extracted B miyamotoi test positivity ratios and used a random-effects model to calculate estimated proportions of infected ticks, infected humans, and human disease with 95% CI. This study was registered with PROSPERO, CRD42021268996., Findings: We identified 730 studies through database searches and 316 additional studies that referenced two seminal articles on B miyamotoi. Of these 1046 studies, 157 were included in the review, reporting on 165 637 questing ticks, 45 608 unique individuals, and 504 well described cases of B miyamotoi disease in humans. In ticks, the highest prevalence of B miyamotoi was observed in Ixodes persulcatus (2·8%, 95% CI 2·4-3·1) and the lowest in Ixodes pacificus (0·7%, 0·6-0·8). The overall seroprevalence in humans was 4·4% (2·8-6·3), with significantly (p<0·0001) higher seroprevalences in the high-risk group (4·6%, 2·6-7·1), participants with confirmed or suspected Lyme borreliosis (4·8%, 1·8-8·8), and individuals suspected of having a different tick-borne disease (11·9%, 5·6-19·9) than in healthy controls (1·3%, 0·4-2·8). Participants suspected of having a different tick-borne disease tested positive for B miyamotoi by PCR significantly more often than did the high-risk group (p=0·025), with individuals in Asia more likely to test positive than those in the USA (odds ratio 14·63 [95% CI 2·80-76·41])., Interpretation: B miyamotoi disease should be considered an emerging infectious disease, especially in North America and Asia. Prospective studies and increased awareness are required to obtain further insights into the burden of disease., Funding: ZonMW and the European Regional Development Fund (Interreg)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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41. Diagnostic parameters of cellular tests for Lyme borreliosis in Europe (VICTORY study): a case-control study.
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Baarsma ME, van de Schoor FR, Gauw SA, Vrijmoeth HD, Ursinus J, Goudriaan N, Popa CD, Ter Hofstede HJ, Leeflang MM, Kremer K, van den Wijngaard CC, Kullberg BJ, Joosten LA, and Hovius JW
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- Antibodies, Bacterial, Case-Control Studies, Europe, Humans, Prospective Studies, Sensitivity and Specificity, Serologic Tests, Lyme Disease
- Abstract
Background: Cellular tests for Lyme borreliosis might be able to overcome major shortcomings of serological testing, such as its low sensitivity in early stages of infection. Therefore, we aimed to assess the sensitivity and specificity of three cellular tests., Methods: This was a nationwide, prospective, multiple-gate case-control study done in the Netherlands. Patients with physician-confirmed Lyme borreliosis, either early localised or disseminated, were consecutively included as cases at the start of antibiotic treatment. Controls were those without Lyme borreliosis from the general population (healthy controls) and those with potentially cross-reactive conditions (eg, autoimmune disease). We used three cellular tests for Lyme borreliosis (Spirofind Revised, iSpot Lyme, and LTT-MELISA) as index tests, and standard two-tier serological testing (STTT) as a comparator. Clinical data from Lyme borreliosis patients were collected at baseline and at 12 weeks after inclusion, and blood samples were obtained at baseline, 6 weeks, and 12 weeks. Control participants underwent clinical and laboratory assessments at baseline only., Findings: Cases comprised 271 patients with Lyme borreliosis (of whom 245 had early-localised Lyme borreliosis and 26 had disseminated disease) and controls comprised 228 participants without Lyme borreliosis from the general population and 41 participants with potentially cross-reactive conditions. Recruitment occurred between May 14, 2018, and March 16, 2020. The specificity of STTT in healthy controls (216 of 228 samples [94·7%, 95% CI 91·5-97·7]) was higher than that of the cellular tests: Spirofind (140 of 171 [81·9%, 76·1-87·2]), iSpot Lyme (32 of 103 [31·1%, 21·5-40·3]) and LTT-MELISA (100 of 190 [52·6%, 44·9-60·3]). Cellular tests had varying sensitivities: Spirofind (88 of 204 [43·1%, 36·4-50·4]), iSpot Lyme (51 of 94 [54·3%, 44·5-63·7]), and LTT-MELISA (66 of 218 [30·3%, 23·8-36·7]). The Spirofind and iSpot Lyme outperformed STTT for sensitivity, but were similar to the C6-ELISA (C6-ELISA: 135 of 270 [50·0%, 44·5-55·5]; STTT: 76 of 270 [28·1%, 23·0-33·6])., Interpretation: The cellular tests for Lyme borreliosis used in this study have a low specificity compared with serological tests, which leads to a high number of false-positive test results. We conclude that these cellular tests are unfit for clinical use at this stage., Funding: Netherlands Organization for Health Research and Development, AMC Foundation (Amsterdam UMC), and Ministry of Health of the Netherlands., Competing Interests: Declaration of interests The assays under study were supplied by AID/GenID (Strassberg, Germany), InVitaLab (Neuss, Germany), QIAGEN (Germantown, MD, USA), and Oxford Immunotec (Oxford, UK), either free of charge or at a reduced price; none of the authors have received any direct financial compensation from any of these companies for this project or any other project. MEB and JWH collaborate with Bio-Rad Laboratories, ZEUS Scientific, and Pfizer on unrelated projects on Lyme borreliosis. JWH collaborates with Antigen Discovery on unrelated projects on Lyme borreliosis; JWH has an application for a provisional patent related to Borrelia antigens pending. FRvdS and LABJ collaborate with Hycult Biotech on developing novel diagnostic tests for Lyme borreliosis. B-JK and LABJ are coinventors of the Spirofind, an experimental in-house assay for Lyme borreliosis, which is owned by Radboudumc and was licensed for development to Boulder Diagnostics (Boulder, Colorado, USA) and subsequently Oxford Immunotec (Oxford, UK) until 2018. The other authors report no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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42. Knowing the entire story - a focus group study on patient experiences with chronic Lyme-associated symptoms (chronic Lyme disease).
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Baarsma ME, Claassen SA, van der Horst HE, Hovius JW, and Sanders JM
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- Focus Groups, Humans, Patient Outcome Assessment, Post-Acute COVID-19 Syndrome, COVID-19 complications, Post-Lyme Disease Syndrome
- Abstract
Background: Healthcare providers frequently struggle to provide effective care to patients with chronic Lyme-associated symptoms (chronic Lyme disease, CLD), potentially causing these patients to feel misunderstood or neglected by the healthcare system. This study is the first to use a combined medical and communication science approach, and aims to assess patients' experiences with CLD & CLD-related care, identify themes and repertories in these patients' narrations, and provide potential ways to improve communication with them., Methods: Informed by the principles of 'clean language', we conducted focus groups with self-identified CLD patients (N = 15). We asked participants about their experiences with CLD and CLD-related healthcare. We performed thematic analyses using a bottom-up approach based in discourse analysis. We also sought to identify specific types of verbalizations (repertoires) across themes., Results: Participants thematised a heterogeneous set of CLD-associated symptoms, which they frequently labelled as 'invisible' to others. Their illness significantly affected their daily lives, impacting their work, social activities, relationships with loved ones, hobbies and other means of participating in society. Negative experiences with healthcare providers were near-universal, also in patients with short-lived CLD-associated symptoms. Verbalizations were notable for frequent use of communicative modes that implicitly create common ground between participants and that give a certain validity to personal experiences (impersonal 'you' and other forms of presupposition)., Conclusion: Central themes found in CLD patients' communication are 1. the experience of significant symptoms, 2. for which adequate relief is only rarely found from conventional medical practitioners, and 3. that are largely invisible to the outside world. Verbalizing these themes, patients use various repertoires for their shared experiences, such as a feeling of abandonment or not being heard by the medical system, feelings of loss with respect to their previous health, and the idea that they might have been better off had they been diagnosed sooner. Working with these repertoires will enable healthcare providers to establish a shared perspective with their CLD patients, thus engaging in more fruitful doctor-patient communication. We hypothesize that these findings are not unique to CLD, but may also be applicable to other conditions with an uncertain aetiology, such as Long COVID., (© 2022. The Author(s).)
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- 2022
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43. An intervention in general practice to improve the management of Lyme borreliosis in Denmark.
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Knudtzen FC, Jensen TG, Andersen NS, Johansen IS, Hovius JW, and Skarphédinsson S
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- Denmark epidemiology, Humans, Prospective Studies, Borrelia, General Practice, Lyme Disease diagnosis, Lyme Disease epidemiology, Lyme Disease therapy, Lyme Neuroborreliosis diagnosis, Lyme Neuroborreliosis epidemiology, Lyme Neuroborreliosis therapy
- Abstract
Background: Our objectives were to improve the following outcomes in patients with Lyme borreliosis (LB) through an educational intervention in general practice: (i) increase the number of hospital referrals on suspicion of LB, (ii) increase the number of cerebrospinal fluid (CSF) tests examined for Borrelia burgdorferi antibody index, (iii) decrease the number of serum-B. burgdorferi antibody tests ordered, (iv) shorten delay from symptom onset to hospital in Lyme neuroborreliosis (LNB) patients, (v) increase LB knowledge among general practitioners., Methods: A prospective non-blinded non-randomized intervention trial on the island of Funen, Denmark. The intervention included oral and written education about LB and was carried out in areas with an LNB incidence ≥4.7/100.000 between 22 January 2019 and 7 May 2019. Results were compared between the intervention group (49 general practices) and the remaining general practices in Funen (71 practices) 2 years before and after the intervention., Results: In the study period, 196 patients were referred on suspicion of LB, a 28.9% increase in the intervention group post-intervention, 59.5% increase in the control group (P = 0.47). The number of CSF-Borrelia-antibody index tests increased 20.8% in the intervention group, 18.0% in the control group (P = 0.68), while ordered serum-B. burgdorferi antibody tests declined 43.1% in the intervention group, 34.5% in the control group (P = 0.30). 25.1% had the presence of serum-B. burgdorferi antibodies. We found no difference in LNB pre-hospital delay before and after intervention or between groups (P = 0.21). The intervention group performed significantly better on a follow-up questionnaire (P = 0.02)., Conclusion: We found an overall improvement in LB awareness and referrals among general practitioners but could not show any effect of the intervention on clinical outcomes of LNB., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)
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- 2022
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44. Concerns about the external validity of the study 'prevalence of persistent symptoms after treatment for Lyme borreliosis: A prospective observational cohort study'-authors´ reply.
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van den Wijngaard CC, Ursinus J, Vrijmoeth HD, Knoop H, Wong A, Joosten LAB, Hovius JW, and Kullberg BJ
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Competing Interests: All authors have no conflicts of interests to disclose.
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45. Self-reported symptoms and health complaints associated with exposure to Ixodes ricinus-borne pathogens.
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Azagi T, Harms M, Swart A, Fonville M, Hoornstra D, Mughini-Gras L, Hovius JW, Sprong H, and van den Wijngaard C
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- Animals, Humans, Prospective Studies, Self Report, Encephalitis Viruses, Tick-Borne, Ixodes, Lyme Disease epidemiology
- Abstract
Background: The impact of infections with tick-borne pathogens (TBPs) other than Borrelia burgdorferi (s.l.) and tick-borne encephalitis virus (TBEV) on public health in Europe remains unclear. Our goal is to evaluate whether the presence of these TBPs in ticks can be associated with self-reported health complaints., Methods: We enrolled individuals who were bitten by I. ricinus between 2012 and 2015 and collected their relevant demographic and clinical information using a self-administered online questionnaire. A total of 4163 I. ricinus ticks sent by the participants were subject to molecular analyses for detection of specific TBPs. Associations between the presence of TBPs in ticks and self-reported complaints and symptoms were evaluated by means of a stepwise approach using a generalized linear model (GLM)., Results: Of 17 self-reported complaints and symptoms significant in the univariate analyses, 3 had a highly significant association (P < 0.01) with at least one TBP in the multivariate analysis. Self-reported Lyme borreliosis was significantly associated (P < 0.001) with B. burgdorferi (s.l.) infection. Facial paralysis was associated (P < 0.01) with infection with B. miyamotoi, N. mikurensis and R. helvetica. Finally, a significant association (P < 0.001) was found between nocturnal sweating and A. phagocytophilum., Conclusions: We found associations between the presence of TBPs in ticks feeding on humans and self-reported symptoms. Due to the subjective nature of such reports and the fact that infection was determined in the ticks and not in the patient samples, further prospective studies utilizing diagnostic modalities should be performed before any clinical outcome can be causally linked to infection with TBPs., (© 2022. The Author(s).)
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46. Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12.
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van de Schoor FR, Vrijmoeth HD, Brouwer MAE, Ter Hofstede HJM, Lemmers HLM, Dijkstra H, Boahen CK, Oosting M, Kullberg BJ, Hovius JW, van den Wijngaard CC, van de Veerdonk FL, Netea MG, and Joosten LAB
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- Humans, Interferon-gamma, Interleukin-12, Leukocytes, Mononuclear, RNA, Messenger, Borrelia burgdorferi, Lyme Disease
- Abstract
Laboratory diagnosis of Lyme borreliosis (LB) is mainly based on serology, which has limitations, particularly in the early stages of the disease. In recent years there have been conflicting reports concerning a new diagnostic tool using the cytokine interferon-gamma (IFN-γ). Previous studies have generally found low concentrations of IFN-γ in early LB infection. The goal of this study is to investigate IFN-γ regulation during early LB and provide insights into the host response to B. burgdorferi. We performed in vitro experiments with whole blood assays and peripheral blood mononuclear cells (PBMCs) of LB patients and healthy volunteers exposed to B. burgdorferi and evaluated the IFN-γ response using ELISA and related interindividual variation in IFN-γ production to the presence of single nucleotide polymorphisms. IFN-γ production of B. burgdorferi - exposed PBMCs and whole blood was amplified by the addition of interleukin-12 (IL-12) to the stimulation system. This effect was observed after 24 h of B. burgdorferi stimulation in both healthy individuals and LB patients. The effect was highly variable between individuals, but was significantly higher in LB patients 6 weeks since the start of antibiotic treatment compared to healthy individuals. IL-12 p40 and IL-18 mRNA were upregulated upon exposure to B. burgdorferi, whereas IL-12 p35 and IFN-γ mRNA expression remained relatively unchanged. SNP Rs280520 in the downstream IL-12 pathway, Tyrosine Kinase 2, was associated with increased IFN-γ production. This study shows that IL-12 evokes an IFN-γ response in B. burgdorferi exposed cells, and that LB patients and healthy controls respond differently to this stimulation.
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- 2022
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47. Diagnostic performance of the ZEUS Borrelia VlsE1/pepC10 assay in European LB patients: a case-control study.
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Baarsma ME, Vrijlandt A, Ursinus J, Zaaijer HL, Jurriaans S, van Dam AP, and Hovius JW
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- 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.)
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- 2022
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48. No molecular detection of tick-borne pathogens in the blood of patients with erythema migrans in Belgium.
- Author
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Geebelen L, Lernout T, Tersago K, Terryn S, Hovius JW, Docters van Leeuwen A, Van Gucht S, Speybroeck N, and Sprong H
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Babesia genetics, Babesia pathogenicity, Belgium epidemiology, Borrelia genetics, Borrelia pathogenicity, Erythema classification, Female, Fever diagnosis, Fever epidemiology, Fever etiology, Humans, Male, Middle Aged, Rickettsia genetics, Rickettsia pathogenicity, Tick Bites epidemiology, Ticks pathogenicity, Young Adult, Erythema epidemiology, Tick-Borne Diseases blood, Tick-Borne Diseases epidemiology, Ticks microbiology, Ticks parasitology
- Abstract
Background: A number of tick-borne pathogens circulate in the Belgian tick population in addition to the causative agent of Lyme borreliosis. However, so far, only a few patients with tick-borne diseases other than Lyme borreliosis have been reported in Belgium. The aim of this study was to investigate the occurrence of other human tick-borne infections in Belgium and their possible clinical manifestation., Methods: Patients with fever (> 37.5 °C) after a tick bite or those with erythema migrans (EM) were included in the study. EDTA-blood samples were screened for the presence of DNA from Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Anaplasma phagocytophilum, Neoehrlichia mikurensis, spotted fever group rickettsiae (genus Rickettsia), Babesia spp., Bartonella spp., Spiroplasma ixodetis and tick-borne encephalitis virus, using multiplex PCR methods. A questionnaire on, among others, demographics and clinical symptoms, was also filled in., Results: Over a period of 3 years, 119 patients with EM and 14 patients with fever after a recent tick bite were enrolled in the study. Three samples initially tested positive for N. mikurensis by quantitative PCR (qPCR), but the results could not be confirmed by other PCR methods, and repetition of the DNA extraction procedure and qPCR test was not successful. The qPCR test results for the other tick-borne pathogens were negative., Conclusions: In general, only a few patients with fever after a tick bite could be identified. Although no tick-borne pathogens were detected, their occurrence cannot be excluded based on the limited number of patients and the limitations inherent to current methodologies. This study underscores the possibility of false-positive PCR results and the necessity for the development of multiple independent tools for the sensitive and specific detection of emerging tick-borne pathogens., (© 2022. The Author(s).)
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- 2022
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49. Opinion: Methodological Shortcomings in the Study on a Prophage-based PCR Test for Lyme Borreliosis.
- Author
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van de Schoor FR, Baarsma ME, Leeflang MMG, Fingerle V, Margos G, Hovius JW, and van Dam AP
- Abstract
Competing Interests: MEB and JH: LB diagnostics in collaboration with various companies, although none of that work involved molecular detection of B. burgdorferi sensu lato. MEB and JH have not received any personal compensation from any of said companies, nor were any of said companies involved in any aspect of the current manuscript. VF: Research support: RKI/BMG, ESCMID, ECDC, StMGP/StMUG, INSTAND. Lecturing activities (honoraria, travel expenses): DIAMEDIS, Diasorin, Mikrogen, Seramun, Siemens, HLR. Consulting activities EQA schemes (no honoraria): QCMD, INSTAND, ECDC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2021
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50. Acute facial nerve palsy in children in a Lyme disease-endemic area in the Netherlands.
- Author
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Bruinsma RA, Smulders CA, Vermeeren YM, van Kooten B, Cats EA, van Hees B, van Hensbroek MB, Hovius JW, and Zomer TP
- Subjects
- Adolescent, Bell Palsy microbiology, Borrelia burgdorferi genetics, Borrelia burgdorferi physiology, Child, Child, Preschool, Facial Paralysis microbiology, Female, Humans, Lyme Neuroborreliosis microbiology, Male, Netherlands epidemiology, Bell Palsy epidemiology, Facial Paralysis epidemiology, Lyme Neuroborreliosis epidemiology
- Abstract
We assessed the prevalence of Lyme neuroborreliosis in children with acute facial nerve palsy in a Lyme-endemic region and patient characteristics associated with this. All children visiting one of three participating hospitals between January 2010 and December 2016 were included in the study. Of 104 children referred to the hospital with facial nerve palsy, 43% had Lyme neuroborreliosis and 57% idiopathic facial palsy. Characteristics significantly associated with Lyme neuroborreliosis were headache (55% versus 18%), meningeal irritation (21% versus 5%), presentation in summer months (69% versus 37%), and a previous tick bite (33% versus 7%)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
- Full Text
- View/download PDF
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