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HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

10.1186/s40249-021-00894-5. 9. Brochado O, Martínez I (*), Berenguer J, Medrano L, González-García J, Jiménez-Sousa MA, Carrero A, Hontañón V, Navarro J, Guardiola JM, Pérez-Latorre L, Micán R, Fernández-Rodríguez A (‡), Resino S (* ‡). HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients. J Biomed Sci 2021; 28:23 (A; FI= 12.77; D1, Medicine, Research & Experimental; JCR 2021). PMID: 33785040. DOI: 10.1186/s12929-021-00718-6.

PUBMED

Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis.

12. García-Álvarez M, Pineda-Tenor D, Jiménez-Sousa Ma, Fernández-Rodríguez A, Guzmán-Fulgencio M; Resino S (*). Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis. Hepatology. 2014, 6(5):1541-1550. (A; FI= 11.05; D1, Gastroenterology & Hepatology; JCR 2014). PMID: 24975775. DOI: 10.1002/hep.27281.

PUBMED

FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.

13. Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, García-Álvarez M, Aldamiz-Echevarría T, Carrero A, Vázquez-Morón S, García-Broncano P, Diez C, Tejerina F, Guzmán-Fulgencio M, Resino S (*). FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients. BMC Med. 2014, 12:198. (A; FI= 7.34; D1, Medicine, General & Internal; JCR 2014). PMID: 25367448. DOI: 10.1186/s12916-014-0198-y.

PUBMED

HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy.

14. Guzmán-Fulgencio M, Berenguer J; Rallón N, Fernández-Rodríguez A, Miralles P, Soriano V, Jiménez-Sousa MA, Cosin J, Medrano J, García-Álvarez M, López JC, Benito JM, Resino S (*). HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy. AIDS 2013; 27(8):1231-1238. (A; FI= 6.55; D1, Infectious Diseases; JCR 2013). PMID: 23811951. DOI: 10.1097/QAD.0b013e32835f5b9c.

PUBMED

Eva Orviz, Anabel Negredo, Oskar Ayerdi, Ana Vázquez, Ana Muñoz-Gomez, Sara Monzón, Petunia Clavo, Angel Zaballos, Mar Vera, Patricia Sánchez, Noemi Cabello, Pilar Jiménez, Jorge A Pérez-García, Sarai Varona, Jorge Del Romero, Isabel Cuesta, Alberto Delgado-Iribarren, Montse Torres, Iñigo Sagastagoitia, Gustavo Palacios, Vicente Estrada, Maria Paz Sánchez-Seco, Grupo Viruela del Simio Madrid CNM/ISCIII/HCSC/Sandoval.

Eva Orviz, Anabel Negredo, Oskar Ayerdi, Ana Vázquez, Ana Muñoz-Gomez, Sara Monzón, Petunia Clavo, Angel Zaballos, Mar Vera, Patricia Sánchez, Noemi Cabello, Pilar Jiménez, Jorge A Pérez-García, Sarai Varona, Jorge Del Romero, Isabel Cuesta, Alberto Delgado-Iribarren, Montse Torres, Iñigo Sagastagoitia, Gustavo Palacios, Vicente Estrada, Maria Paz Sánchez-Seco, Grupo Viruela del Simio Madrid CNM/ISCIII/HCSC/Sandoval. Monkeypox outbreak in Madrid (Spain): Clinical and virological aspects. J Infect. 2022 Jul 10;S0163-4453(22)00415-7. doi: 10.1016/j.jinf.2022.07.005.

DOI

European mitochondrial haplogroups are associated with CD4+ T-cell recovery in HIV-infected patients on combination antiretroviral therapy.

15. ​Guzmán-Fulgencio M; Berenguer J, Micheloud D, Fernández-Rodríguez A; García–Álvarez M, Jiménez-Sousa MA, Bellón JM, Campos Y, Cosin J, Aldámiz-Echevarría T, Catalán P, López JC, Resino S (*). European mitochondrial haplogroups are associated with CD4+ T-cell recovery in HIV-infected patients on combination antiretroviral therapy. J Antimicrob Chemoth 2013; 68 (10): 2349–2357 (A; FI= 5.44; D1, Infectious Diseases; JCR 2013). PMID: 23749950. DOI: 10.1093/jac/dkt206.

PUBMED

María Paz Sánchez-Seco, María José Sierra, Agustín Estrada-Peña, Félix Valcárcel, Ricardo Molina, Eva Ramírez de Arellano, Angeles Sonia Olmeda, Lucía García San Miguel, Maribel Jiménez, Luis J Romero, Anabel Negredo; Group for CCHFv Research. Widespread Detection of Multiple Strains of Crimean-Congo Hemorrhagic Fever Virus in Ticks, Spain.

María Paz Sánchez-Seco, María José Sierra, Agustín Estrada-Peña, Félix Valcárcel, Ricardo Molina, Eva Ramírez de Arellano, Angeles Sonia Olmeda, Lucía García San Miguel, Maribel Jiménez, Luis J Romero, Anabel Negredo; Group for CCHFv Research. Widespread Detection of Multiple Strains of Crimean-Congo Hemorrhagic Fever Virus in Ticks, Spain. Emerg Infect Dis. 2022 Feb;28(2):394-402. doi: 10.3201/eid2802.211308.

DOI

Negredo A, Sánchez-Ledesma M, Llorente F, Pérez-Olmeda M, Belhassen-García M, González-Calle D, Sánchez-Seco MP, Jiménez-Clavero MÁ. Retrospective Identification of Early Autochthonous Case of Crimean-Congo Hemorrhagic Fever, Spain, 2013

Negredo A, Sánchez-Ledesma M, Llorente F, Pérez-Olmeda M, Belhassen-García M, González-Calle D, Sánchez-Seco MP, Jiménez-Clavero MÁ. Retrospective Identification of Early Autochthonous Case of Crimean-Congo Hemorrhagic Fever, Spain, 2013. Emerg Infect Dis. 2021 Jun;27(6):1754-1756. doi: 10.3201/eid2706.204643.

DOI

Negredo A, Sánchez-Arroyo R, Díez-Fuertes F, de Ory F, Budiño MA, Vázquez A, Garcinuño Á, Hernández L, la Hoz González C, Gutiérrez-Arroyo A, Grande C, Sánchez-Seco P. Fatal Case of Crimean-Congo Hemorrhagic Fever Caused by Reassortant Virus, Spain, 2018.

Negredo A, Sánchez-Arroyo R, Díez-Fuertes F, de Ory F, Budiño MA, Vázquez A, Garcinuño Á, Hernández L, la Hoz González C, Gutiérrez-Arroyo A, Grande C, Sánchez-Seco P. Fatal Case of Crimean-Congo Hemorrhagic Fever Caused by Reassortant Virus, Spain, 2018. Emerg Infect Dis. 2021 Apr;27(4):1211-1215. doi: 10.3201/eid2704.203462.

DOI

Laura Davó, Laura Herrero, Maria Paz Sánchez-Seco, Nuria Labiod, David Roiz, Elena Gómez-Díaz, Lourdes Hernandez, Jordi Figuerola and Ana Vázquez. Real-time PCR assay to detect Granada virus and the related Massilia and Arrabida phleboviruses

Laura Davó, Laura Herrero, Maria Paz Sánchez-Seco, Nuria Labiod, David Roiz, Elena Gómez-Díaz, Lourdes Hernandez, Jordi Figuerola and Ana Vázquez. Real-time PCR assay to detect Granada virus and the related Massilia and Arrabida phleboviruses. Davó et al. Parasit Vectors. 2020 May 29;13(1):270. doi: 10.1186/s13071-020-04110-5.

DOI

María Velasco, María Paz Sánchez-Seco, Carolina Campelo, Fernando de Ory, Oriol Martin, Laura Herrero, Octavio J. Salmerón Béliz, Teodora Minguito, Mª Carmen Campos, Francisca Molero, Alejandro Algora and Ana Vázquez. Imported Human West Nile Virus Lineage 2 Infection in Spain

María Velasco, María Paz Sánchez-Seco, Carolina Campelo, Fernando de Ory, Oriol Martin, Laura Herrero, Octavio J. Salmerón Béliz, Teodora Minguito, Mª Carmen Campos, Francisca Molero, Alejandro Algora and Ana Vázquez. Imported Human West Nile Virus Lineage 2 Infection in Spain: Neurological and Gastrointestinal Complications. Viruses 2020 Jan 29;12(2):156. doi: 10.3390/v12020156.

DOI

Negredo A, Habela MÁ, Ramírez de Arellano E, Diez F, Lasala F, López P, Sarriá A, Labiod N, Calero-Bernal R, Arenas M, Tenorio A, Estrada-Peña A, Sánchez-Seco MP. Survey of Crimean-Congo Hemorrhagic Fever Enzootic Focus, Spain, 2011-2015

Negredo A, Habela MÁ, Ramírez de Arellano E, Diez F, Lasala F, López P, Sarriá A, Labiod N, Calero-Bernal R, Arenas M, Tenorio A, Estrada-Peña A, Sánchez-Seco MP. Survey of Crimean-Congo Hemorrhagic Fever Enzootic Focus, Spain, 2011-2015. Emerg Infect Dis. 2019 Jun;25(6):1177-1184. doi: 10.3201/eid2506.180877.

DOI

Ramírez de Arellano E, Sanchez-Lockhart M, Perteguer MJ, Bartlett M, Ortiz M, Campioli P, Hernández A, Gonzalez J, Garcia K, Ramos M, Jiménez-Clavero MÁ, Tenorio A, Sánchez-Seco MP, González F, Echevarría JE, Palacios G, Negredo A. First Evidence of Antibodies Against Lloviu Virus in Schreiber's Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain

Ramírez de Arellano E, Sanchez-Lockhart M, Perteguer MJ, Bartlett M, Ortiz M, Campioli P, Hernández A, Gonzalez J, Garcia K, Ramos M, Jiménez-Clavero MÁ, Tenorio A, Sánchez-Seco MP, González F, Echevarría JE, Palacios G, Negredo A. First Evidence of Antibodies Against Lloviu Virus in Schreiber's Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain. Viruses. 2019 Apr 19;11(4):360. doi: 10.3390/v11040360.

DOI

Meta-analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct-acting antivirals.

3. Sepúlveda-Crespo D, Treviño-Nakoura A, Bellon JM, Ardizone Jiménez B, Jiménez‑Sousa MA, Fernández-Rodríguez A, Martínez I (‡), Resino S (*‡). Meta-analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct-acting antivirals. Aliment Pharmacol Ther 2022; 56 (8): 1224-1234 (A; FI= 9.52; D1, Pharmacology & Pharmacy; JCR 2021).

PUBMED DOI

Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.

4. Martin-Vicente M, Carrasco I, Muñoz-Gomez MJ, Lobo AH, Mas V, Vigil-Vázquez S, Vázquez M, Manzanares A, Cano O, Alonso R, Sepúlveda-Crespo D, Tarancón-Díez L, Muñoz-Fernández MÁ, Muñoz-Chapuli M, Resino S#*, Navarro ML#, Martinez I#*. Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later. Birth. 2022 Jul 8:10.1111/birt.12667. doi: 10.1111/birt.12667. Online ahead of print. PMID: 35802776.

PUBMED

Hepatitis E virus seroprevalence is associated with neurodegenerative disorders in older people with dementia: a case-control study.

5. Pérez-García F, Vázquez-Morón S, Burgueño-García I, José Muñoz-Gómez M, Zea-Sevilla MA, Calero M, Martínez I#, Rábano A#, Resino S#. Hepatitis E virus seroprevalence is associated with neurodegenerative disorders in older people with dementia: a case-control study. J Infect Dis. 2022 Jun 27:jiac268. doi: 10.1093/infdis/jiac268. Online ahead of print. PMID: 35759220 (A; FI= 7.759; Q1 Microbiology; JCR 2021).

PUBMED

Negative impact of HIV infection on broad-spectrum anti-HCV neutralizing antibody titers in HCV-infected patients with advanced HCV-related cirrhosis.

6. Sepúlveda-Crespo D, Yélamos MB, Díez C, Gómez J, Hontañón V, Torresano-Felipe F, Berenguer J, González-García J, Ibañez-Samaniego L, Llop E, Olveira A, Martínez J, Resino S (‡ *), Martínez I (‡ *). Negative impact of HIV infection on broad-spectrum anti-HCV neutralizing antibody titers in HCV-infected patients with advanced HCV-related cirrhosis. Biomed Pharmacother 2022, 150: 113024. (A; FI= 7.42; D1, Pharmacology & Pharmacy; JCR 2021).

PUBMED DOI

. Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study.

7. Álvaro-Meca A, Goez MDC, Resino R, Matías V, Sepúlveda-Crespo D, Martínez I#, Resino S#. Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study. Environ Res. 2022 Sep; 212(Pt B):113319. doi: 10.1016/j.envres.2022.113319. PMID: 35447151. (A; FI= 8.431; D1 Public, Environmental & Occupational Health; JCR 2021).

PUBMED

Misdiagnosis rate of among negative COVID-19 patients in real-life with Panbio COVID-19 Antigen Rapid Test during 2021.

8. Ryan P, Pérez-García F, Torres-Macho J, Bibiano C, Ignacio Lazo J, Castaño-Ochoa G, Vidal-Alcántara EJ, Muñoz-Gómez MJ, Martínez I#, Resino S#. Misdiagnosis rate of among negative COVID-19 patients in real-life with Panbio COVID-19 Antigen Rapid Test during 2021. J Infect. 2022 May; 84(5):e42-e44. doi: 10.1016/j.jinf.2022.03.013. PMID: 35306106 (L; FI= 38.637; D1 Infectious Diseases; JCR 2021).

PUBMED

Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19.

11. Martín-Vicente M, Berenguer J, Muñoz-Gómez MJ, Díez C, Micán R, Pérez-Elías MJ, García-Fraile LJ, Peraire J, Suárez-García I, Jiménez-Sousa MÁ, Fernández-Rodríguez A, Vázquez M, Ryan P, González-García J, Jarrín I, Mas V, Martínez I#, Resino S#. Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19. J Infect. 2022 Mar;84(3):418-467. doi: 10.1016/j.jinf.2021.11.002. PMID: 34752819 (L; FI= 38.637; D1 Infectious Diseases; JCR 2021).

PUBMED

List of staff

Información adicional

1.- The study of non-gastrointestinal zoonoses, some of them transmitted by vectors and/or emerging, aims to: 

  • The development and validation of new diagnostic and genotyping techniques represent important scientific-technical support to the National Health System, acting as a reference laboratory. 
  • Research on the Molecular Epidemiology of Coxiella burnetii studies the circulating genotypes and their association with the different clinical presentations of Q fever. 
  • Discovery of new pathogens: especially relevant in the case of Francisella with the description of F. hispaniensis, as well as taxonomically unknown variants of Bartonella, Borrelia and Rickettsia, found in reservoirs, vectors and clinical samples. 
  • Surveillance in nature analyzes kinetics, transmission cycles and reservoirs. 

• Genotyping techniques allow traceability studies to be carried out in the case of natural outbreaks or intentional release. • Method accreditation: ISO15189 standard (clinical samples), ISO17025 (environmental). 

2.- The study of bacteria with potential use in bioterrorism through participation in European projects (Joint Actions: QUANDHIP, EMERGE, SHARP) allows us to respond appropriately to possible health alert situations. An important methodological development has been carried out for the detection of these agents and a Rapid Response System has been implemented.

The current director of CNM is Dr. José Miguel Rubio Muñoz.

Dr. José Miguel Rubio has a degree in Biological Sciences from the Universidad Autónoma de Madrid (1986) and a PhD in Biological Sciences from the same university (1992). He carried out his doctoral thesis at the Department of Genetics of the Universidad Autónoma de Madrid, as Associate Professor (1988-1989), and at the School of Biology of the University of East Anglia in Norwich, UK, as Senior Research Assistant (1989-1992).

During his postdoctoral period he obtained a grant from the European Commission within the Human Capital and Mobility Program to be carried out at the University of “La Sapienza” in Rome, Italy and the Institute of Molecular Biology and Biotechnology in Crete, Greece (1993-1994). Subsequently, he made a further stay funded by the WHO and the university itself at the Department of Entomology, Wageningen University, The Netherlands (1994-1996).

Since 1997 he has been a member of the Instituto de Salud Carlos III (ISCIII), where he joined the Department of Parasitology of the National Center of Microbiology, as an EU-INCO postdoctoral fellow and later with a grant from the Autonomous Community of Madrid (CAM). She was part of the founding group of the National Center for Tropical Medicine (2003-2006) and of the 24/7 Alerts and Emergencies Unit (2006-2018) and is currently Head of the Malaria and Emerging Parasitosis Unit of the National Microbiology Center and is part, as research staff, of the Center for Biomedical Research Network on Infectious Diseases (CIBERINFEC/ISCIII).

During his scientific career he has been Visiting Scientist at the Leonidas e Marie Dean Center (FIOCRUZ-AMAZONAS, Manaus, Brazil) and is an External Consultant of the Parasitology Departments of Cairo University (Egypt) and the Medical Research Center (MRC) of Kuala Lumpur (Malaysia).  He also belongs or has belonged to different national and international committees:  Member of the expert group for malaria control of the European Centre for Disease Control (ECDC) since 2011; Expert-Evaluator for health programs of the European Commission since 2004; Spanish Representative (commissioned by ISCIII and MSC) in the Technical Scientific Committee of the TDR (WHO) 2007-2008; Spanish Deputy Focal Point for microbiology at the European Centre for Disease Control (ECDC) from 2012 to 2020; and, member of the Research Ethics Committee of ISCIII until 2019.

In this period he has published more than 100 articles in international indexed journals, 10 book chapters and has been co-editor of two books in the area of malaria, tropical medicine and neglected diseases. He has participated in 58 competitively funded research projects, 20 of them international, having been the principal investigator in 8 national and 11 international projects as PI of the project or WP leader. In addition, he has led five agreements with companies. Currently he has been awarded four sexenios of research, being presented this year 2025 to the fifth. In the teaching field, he participates in different postgraduate programs in the areas of microbiology and parasitology, having directed seven doctoral theses and more than 20 Master's or Degree final projects, both nationally and internationally. ​​​​​

El laboratorio de Referencia e Investigación en Resistencia a Antibióticos ofrece una amplia cartera de servicios al Sistema Nacional de Salud, las cuales pueden solicitarse en cnm-laboratorios.isciii.es. Jefe del Laboratorio: Jesús Oteo Iglesias (Punto focal Nacional de Resistencia antibiótica).

Dispone de dos programas de Vigilancia oficiales y gratuitos que engloban los ensayos ofertados ya sea como aislamientos individuales o mediante estudio de brotes. El Laboratorio utiliza asimismo técnicas de PCR en tiempo real para la detección de genes de resistencia, estas técnicas se han adaptado a un formato multiplex que permite detectar varios genes en la misma reacción. En los últimos años se han incluido metodologías basadas en la secuenciación de genomas completos para el análisis de bacterias multiresistentes (WGS).

Programa de vigilancia de Haemophilus influenzae. Responsables: María Pérez Vázquez (Punto focal Nacional de Haemophilus influenzae) y Belén Aracil. Laboratorio encargado de la identificación, estudio de sensibilidad y análisis genotípico de aislados de Haemophilus influenzae, centrándose esencialmente en la patología invasiva debida este patógeno. 

Programa de vigilancia de Resistencia a Antibióticos. Responsables: María Pérez Vázquez  y Belén Aracil (Punto focal Nacional de Resistencia antibiótica). Laboratorio encargado de la identificación, el estudio de sensibilidad antibiótica, y el diagnóstico fenotípico y genotípico de los diferentes mecanismos de resistencia a antibióticos fundamentalmente en enterobacterias y gram-negativos no fermentadores y Enterococcus spp.

Estudio de brotes. Responsables: Belén Aracil y María Pérez Vázquez. El programa incluye la caracterización de brotes nosocomiales y clones emergentes de alto riesgo mediante diferentes técnicas moleculares (tabla resumen). Éstas, nos permiten realizar estudios filogenéticos con el fin de obtener una información detallada acerca la relación entre los diferentes aislados y su trazabilidad. El objetivo final es generar datos que se transfieren a los hospitales como ayuda para la prevención o control de la propagación del brote.

Acreditación y Calidad. Responsable: Belén Aracil. El laboratorio Referencia e Investigación en Resistencia a Antibióticos ha sido de los primeros en el ISCIII en la utilización de técnicas acreditadas por la Entidad Nacional de Acreditaciones (ENAC). Este laboratorio consiguió la primera acreditación homologada de técnicas diagnósticas en 2012, programa que ha sido ampliado, de manera que en la actualidad más de la mitad de las técnicas ofrecidas al Sistema Nacional de Salud están debidamente acreditadas por ENAC.

Técnicos responsables de las técnicas realizadas en el Laboratorio: Noelia Lara Fuella y Verónica Bautista Sánchez.

En la siguiente imagen se resumen las técnicas ofrecidas al Sistema Nacional de Salud.

PROGRAMAS NOMBRE CARTERA SERVICIO PATÓGENO DETERMINACIÓN, DETECCIÓN, ANÁLISIS MÉTODOS

Programa de vigilancia de Haemophilus

Programa de vigilancia de resistencia a antibióticos.

 Identificación bacteriana

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus spp

 Identificación bacteriana

Bioquímicos

MALDI TOF

Secuenciación de RNAr
​ Identificación capsular

Haemophilus influenzae

 

 Identificación capsular fenotípica y genotípica

Aglutinación serológica en latex

PCR ind/multiplex
​ Determinación de Sensibilidad

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

 Determinación de Sensibilidad

Microdilución                

Tiras epsilon               

Kirby Bauer
​ Métodos fenotípicos de detección de mecanismos de resistencia

Enterobacterias, gram-negativos no fermentadores,

 

 Métodos fenotípicos de detección de mecanismos de resistencia

Discos y tabletas combinados con inhibidores                

Tiras combinadas     

Test de Hodge modificado

CabaNP                               

Inmunocromatografía CBP
​ Métodos genotípicos de detección de mecanismos de resistencia

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

 ADN, PCR y secuenciación

PCR ind/multiplex

Análisis comparativo de las secuencias
​ Tipificación molecular/análisis filogenéticos

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

Corte enzimas de restricción, electroforesis

ADN, PCR y secuenciación

Preparación de librerías y secuenciación y análisis de genomas completos

 

PFGE

 

MLST

 

WGS