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M. Bovis and M UNIVERSIDAD COMPLUTENSE DE MADRID FACULTAD DE VETERINARIA Departamento de Sanidad Animal CENTRO DE VIGILANCIA SANITARIA VETERINARIA (VISAVET) Servicio de Micobacterias TESIS DOCTORAL EPIDEMIOLOGÍA MOLECULAR DE MYCOBACTERIUM BOVIS Y MYCOBACTERIUM CAPRAE EN ESPAÑA MEMORIA PARA OPTAR AL GRADO DE DOCTOR EUROPEO PRESENTADA POR Sabrina Rodríguez Campos Bajo la dirección de los doctores: Alicia Aranaz Martín Ana Mateos García Lucas Domínguez Rodríguez Madrid, 2012 ISBN: 978-84-616-1980-1 © Sabrina Rodríguez Campos Dña. Alicia Aranaz Martín, Profesora Contratada Doctor, Dña. Ana Mateos García, Profesora Titular, y D. Lucas Domínguez Rodríguez, Catedrático, del Departamento de Sanidad Animal de la Facultad de Veterinaria de la Universidad Complutense CERTIFICAN: Que la tesis doctoral que lleva por título “Epidemiología molecular de Mycobacterium bovis y Mycobacterium caprae en España” ha sido realizada por la licenciada en Veterinaria Dña. Sabrina Rodríguez Campos en el Departamento de Sanidad Animal de la Facultad de Veterinaria y en el Centro de Vigilancia Sanitaria Veterinaria de la Universidad Complutense bajo nuestra dirección, y estimamos que reúne los requisitos exigidos para optar al título de Doctor Europeo por la Universidad Complutense. Fdo. Alicia Aranaz Fdo. Ana Mateos Fdo. Lucas Domínguez En muchas ocasiones se ha hecho énfasis en la importancia de la colaboración entre científicos y políticos para el avance de los programas de erradicación (Task Force Bovine Tuberculosis Subgroup, 2006; Proceedings of the 4th International Conference on Mycobacterium bovis, 2006); la presente tesis doctoral es el resultado de la implicación y dedicación de muchas personas e instituciones, destacando el Ministerio de Medio Ambiente y Medio Rural y Marino y la Red Española de Vigilancia y Control de la Tuberculosis en Animales. La realización de esta tesis ha sido posible gracias a: Beca predoctoral de Formación de Profesorado Universitario. Ministerio de Educación. 2007-2011. Referencia AP2006-01630. Y ha sido consecuencia de la participación en los siguientes proyectos: Acción Coordinada de la Unión Europea: “Veterinary Network of Laboratories Researching into Improved Diagnosis and Epidemiology of Mycobacterial Diseases” (SSPE-CT-2004-501903) Proyecto Europeo: “Strategies for the eradication of bovine tuberculosis (TB-STEP)” (FP7-KBBE-2007-212414) Además, se ha realizado en el marco de los convenios de colaboración con las siguientes instituciones: Dirección General de Recursos Agrícolas y Ganaderos Ministerio de Medio Ambiente y Medio Rural y Marino Consejería de Economía e Innovación Tecnológica Comunidad de Madrid Consejería de Agricultura y Ganadería Junta de Castilla y León Red Española de Vigilancia y Control de la Tuberculosis en Animales: Laboratorio Central de Sanidad Animal de Santa Fe, Granada, MARM: F. Garrido Personal de los Laboratorios Regionales y de Investigación de las Comunidades Autónomas: C. Fornell, J.M. Gómez, A. Jiménez, I. Muñoz, J.A. Téllez, E.J. Villalba (Andalucía), N. Abacens, I. Belanche, J. Gracia, S. Izquierdo, J.M. Malo (Aragón), M.F. Copano, E. Fernández, I. Merediz, A. Balseiro (Asturias), P. Peláez, C. Pieltain, V. Vigo (Canarias), C. Fernández, F.M. Fernández, M.G. Gradillas, M. Gutiérrez, E. Sola (Cantabria), V. Alcaide, J. Alia, J. Alonso, M.R. Bermúdez, C. Fernández, P. García, E. Grande, F. Plaza, M.L. Rando, C. Rojas, A. Sánchez, J.A. Viñuelas (Castilla La Mancha), J.A. Anguiano, I. Burón, J. Cermeño, C. Domínguez, F. Fernández, A. Grau, S. Marques, O. Martín, C. Martínez, O. Mínguez, F. Moreno, F. Reviriego, I. Romero (Castilla y León), J. Gou (Cataluña), J.R. Puy (Euskadi), E. Dorado, C. Sanz (Extremadura), C. Calvo, D. Fernández, M. López, J.E. Mourelo, M. Muñoz (Galicia), C. Aguilo, M.J. Portau, C. Vidal (Islas Baleares), J.M. Cámara, J. Carpintero, C. Delso, R. Díaz, E. Fernández, C. Fernández-Zapata, M. García, E. Pages, J.J. Urquía (Madrid), J. Pastor, C. Rivas (Murcia), J, Eguiluz, F. Eslava, C. Fernández (Navarra), F.J. Puértolas, J.F. Soldevilla (La Rioja), C. Caballero y M. Lázaro (Valencia). Patrimonio Nacional: A. Jacoste y M. Moreno. Miembros de las Facultades de Veterinaria: S. Lavín, G. Mentaberre (Universidad Autónoma de Barcelona), I. García-Bocanegra, A. Perea (Universidad de Córdoba), A. García, J. Hermoso de Mendoza, A. Parra, (Universidad de Extremadura), E.F. Rodríguez- Ferri, O. González-Llamazares (Universidad de León), J. Blanco, M. Castaño, A.A. Díez- Guerrier, J.V. González, F. Mazzucchelli, C. Novoa, X. Pickering, M. Pizarro, G. Santurde, I. Simarro (Universidad Complutense de Madrid), A. Contreras, J.A. Navarro, J. Sánchez (Universidad de Murcia), A. Fernández, O. Quesada (Universidad de Las Palmas de Gran Canaria), y M.V. Latre (Universidad de Zaragoza). Compañeros de los Centros de Investigación en Sanidad Animal: M. Domingo, B. Pérez, S. López, D. Vidal (CRESA), J. Garrido, R. Juste (NEIKER), M. Galka, C. Sánchez, (P.N. Doñana), J. de la Fuente, C. Gortázar, J. Vicente (IREC-CSIC), A. Espí, y J.M. Prieto (SERIDA, Asturias). Unión de Criadores de Toros de Lidia: I. Carpio. Veterinarios oficiales: A.J. Domínguez, M. Fernández, J.M. Rubio (Ciudad Real), M. García, J. Guedeja, F. Osuna y J.L. del Pozo (Madrid). Veterinarios: P. Díez de Tejada, J.M. Fernández (A.D.S. Cabra del Guadarrama, Madrid), C. Gil, F. Moneo-López, I. Larrauri (Albacete), J. Cermeño, D. Martín (Badajoz), J.L. García (Burgos), A. Rodríguez, E. Sainz (Cáceres), P.J. Mora (Ciudad Real), J.M. Amigo, N. Castro, V. Collado, J.L. Cumbreño, J.M. Finat, M.P. Herranz, E. Legaz, L.M. Portas, J. Rodríguez, L. Sánchez, J.M. Sebastián, T. Yuste (Madrid), A. Santos (Toledo), J. Fonbellida (Zamora) y J. Rodríguez (Laboratorios Syva). Médicos: E. Gómez-Mampaso (H. Ramón y Cajal, Madrid), D. García de Viedma (Hospital Gregorio Marañón, Madrid) y R. Borrás (Facultad de Medicina, Valencia). Los directores y la doctoranda quieren hacer un agradecimiento especial a las siguientes instituciones y personas por su participación en la realización de esta tesis, sin cuya ayuda hubiese sido muy difícil completar: Subdirección General de Sanidad de la Producción Primaria Ministerio de Medio Ambiente y Medio Rural y Marino D. Lucio Carbajo Goñi Dña. Beatriz Muñoz Hurtado D. José Luis Sáez Llorente University College Dublin, Irlanda Dr. Stephen Gordon Animal Health and Veterinary Laboratories Agency Weybridge, Reino Unido Dr. Noel Smith Dr. Glyn Hewinson A mis padres A mis abuelos A Tony “Ves, Momo, las cosas son así: A veces tienes ante ti una calle larguísima. Te parece tan terriblemente larga, que nunca crees que podrás acabarla. Y entonces te empiezas a dar prisa, cada vez más prisa. Cada vez que levantas la vista, ves que la calle no se hace más corta. Y te esfuerzas más todavía, empiezas a tener miedo, al final estás sin aliento. Y la calle sigue estando por delante. Así no se debe hacer. Nunca se ha de pensar en toda la calle de una vez, ¿entiendes? Sólo hay que pensar en el paso siguiente, en la inspiración siguiente, en la siguiente barrida. Nunca nada más que en el siguiente. Entonces es divertido; eso es importante, porque entonces se hace bien la tarea. Y así ha de ser.” Beppo Barrendero De ‘Momo’ por Michael Ende Acknowledgements Agradecimientos Después de muchos años más de los que tenía previsto en un comienzo, he llegado a la conclusión de que cada uno de los días, algunos muy buenos y otros no tanto, ha merecido la pena. Quisiera expresar mi más sincero agradecimiento a todas las personas a cuyo lado no sólo he crecido como científica sino también como persona, y que han hecho posible la realización de este trabajo. A Alicia Aranaz, por permitirme continuar su trabajo sobre Mycobacterium bovis y su “hijo” Mycobacterium caprae. Gracias por tu apoyo científico y personal, por compartir tus sabidurías (“El realismo brilla por su ausencia”) y por aguantar con una sonrisa esta cabezota hispano-germana. He aprendido mucho de ti y te lo agradezco de corazón. A Ana Mateos y Lucas Domínguez por haber confiado en mí, acogiéndome en el Centro VISAVET sin conocerme apenas, habiéndome dado la oportunidad de formarme en mi primer puesto de trabajo, y por su disposición absoluta. Y más en especial a Lucas por haberme apoyado siempre con su interés y sus ideas, por preocuparse por mi futuro profesional y por sus valiosos consejos. Gracias por tu entusiasmo infatigable que, sobre todo en la última fase de la escritura, me ha dado mucho ánimo. A Lucía de Juan, por haberme llevado de la mano desde mi primer día en el Centro, siempre dispuesta a escucharme, a solucionar problemas, a dar ánimos y siempre pendiente de mí para que saliera esta tesis. Son innumerables las cosas que agradezco a mis compañeros micobacteriosos que han estado a mi lado durante esta etapa o durante parte de ella: Bea, Javi, Julio, Fran, Nuria, Elena, Nunu, Fernando, Taty, Alex, Elisa, Cris, Laura, Johanna, Carmen, Isabel y Esther - esta tesis es fruto del trabajo de un gran equipo y me siento afortunada de haber podido desarrollarla codo con codo con vosotros. ¡Sois geniales! Muchas gracias en especial a mis co-sufridores - Bea, Carmen, Javi y Julio - por su disposición absoluta a echar una mano y por sus ánimos, sobre todo en esa última etapa que parecía no terminar nunca. Bea, ha sido una suerte poder aprender de ti y contigo y te deseo lo mejor. Carmen, “pequeña”, te queda un poco de camino por delante, pero confío en que llegará la merecida recompensa por ser tan trabajadora. No quiero olvidarme de la gente de antaño: Ernesto Liébana, Anabel Vela, Natalia Montero y Cristina Lozano. Gracias por haber contribuido con vuestro esfuerzo y dedicación al desarrollo del grupo de micobacterias. A José Luis Sáez por su interés y la confianza en mi trabajo y por su apoyo constante. Mil gracias al Servicio de Informática y Comunicación - Sergio, Carlos, Edu y Rosae - por ese trabajo estupendo que hacéis día a día y que demasiadas veces pasa desapercibido.
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