Special Pathogens
Líneas de investigación
Content with Investigacion .
Virus entéricos
1. Vigilancia microbiológica y epidemiológica a nivel nacional de las infecciones causadas por enterovirus y parechovirus y de los casos de parálisis flácida aguda en menores de 15 años. Caracterización, asociación clínica y epidemiología molecular.
2. Investigación de los enterovirus y parechovirus que causan infecciones neurológicas y sistémicas severas en población pediátrica. Estudio de los factores virológicos implicados en la patogenicidad.
3. Estudio virológico de muestras ambientales (aguas residuales y tratadas para consumo) de la CAM.
4. Estudio virológico (diagnóstico y caracterización) de las infecciones gastrointestinales causadas por virus (norovirus, rotavirus y otros). Epidemiología molecular y caracterización de brotes.
Investigación y vigilancia de los poliovirus y la poliomielitis
El Laboratorio de Enterovirus (actualmente de Virus Entéricos) del CNM fue designado Laboratorio Nacional de Poliovirus en 1998 y desde entonces es certificado anualmente por la OMS, como parte del Plan Global de Erradicación de la Poliomielitis. Es responsable, junto a 3 laboratorios primarios en 3 CCAA, de la vigilancia de la poliomielitis a nivel nacional, estudiando e investigando (clínica, epidemiológica y virológicamente) todos los casos compatibles, incluidos los de parálisis flácida aguda en menores de 15 años (enfermedad de notificación obligatoria) para descartar la presencia y circulación de poliovirus en España.
Además, desde 1999 (y gracias a un convenio con el CYII) posee toda la infraestructura y metodología necesaria para realizar vigilancia medioambiental en aguas, tanto para medir la calidad de las aguas potables de ETAP, como para monitorizar la excreción de virus por parte de la población con el estudio de la presencia de poliovirus y otros enterovirus en aguas residuales de EDAR. Esto ha permitido que, a partir de marzo de este año, se estén realizando, además, ensayos de presencia de SARS-CoV-2 en las muestras procedentes de diferentes EDAR situadas en la CAM.
Investigación y referencia en infecciones por enterovirus y parechovirus
El Laboratorio también es Laboratorio de Referencia para las infecciones por Enterovirus y Parechovirus realizando: 1) el diagnostico virológico en muestras clínicas; 2) la caracterización de todos los enterovirus y parechovirus detectados (Programa de Vigilancia Microbiológica del CNM); 3) el desarrollo, mantenimiento y transferencia de métodos de diagnóstico y tipado, tanto moleculares como de cultivo viral; y 4) la investigación para profundizar en el conocimiento de aquellos virus implicados en casos de excepcional importancia clínica o epidemiológica. La larga experiencia del grupo en la propagación de cultivos virales de enterovirus y en técnicas celulares y moleculares de caracterización, ha permitido que el CNM posea una amplia colección de cepas, muy valiosa para la investigación de estos virus.
Investigación y referencia en infecciones gastrointestinales causadas por virus
Desde 2016, el laboratorio realiza: 1) el diagnostico virológico de Norovirus, Rotavirus, Adenovirus 40/41, Astrovirus y otros virus productores de gastroenteritis aguda en muestras clínicas; 2) el genotipado de los virus detectados y la caracterización de brotes; 3) el desarrollo y mantenimiento de métodos de diagnóstico y genotipado; y 4) la investigación básica y epidemiológica de aquellos virus de mayor importancia clínica.
Publicaciones destacadas
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus.
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus. Fungal Genet Biol. 2011 Apr;48(4):418-29. doi: 10.1016/j.fgb.2010.12.007. Epub 2010 Dec 22. PMID: 21184840.
PUBMED DOIImpact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.
Jiménez-Sousa MA (AC); Gómez-Moreno AZ; Pineda-Tenor D; et al. (1/9) Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 2019; 9(4).
DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA (AC); Jiménez JL; Fernández-Rodríguez A; et al. (1/10). DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study. Journal of Biomedical Science. 2019; 23;26(1):83. doi: 10.1186/s12929-019-0577-y.
TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine.
Resino S; Fernández-Rodríguez A; Pineda-Tenor D; et al; Jiménez-Sousa MA. (11/11). 2021. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine. 10-3, pp.483. ISSN 2077-0383. https://doi.org/10.3390/jcm10030483.
Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients
Salguero, Sergio; Rojo, David; Berenguer, Juan; et al; Jimenez-Sousa, Maria A. (AC) (15/15). 2020. Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients LIVER INTERNATIONAL. 40-9, pp.2215-2227. ISSN 1478-3223. https://doi.org/10.1111/liv.14580 3
Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals JOURNAL OF CLINICAL MEDICINE.
Molina-Carrion, Silvia; Brochado-Kith, Oscar; Gonzalez-Garcia, Juan; et al; Jimenez-Sousa, Maria Angeles. (12/12). 2020. Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals JOURNAL OF CLINICAL MEDICINE. 9. ISSN 2077-0383. https://doi.org/10.3390/jcm9082407.
Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018 Jul
Alastruey-Izquierdo A, Cadranel J, Flick H, Godet C, Hennequin C, Hoenigl M, Kosmidis C, Lange C, Munteanu O, Page I, Salzer HJF; on behalf of CPAnet. Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018 Jul 6:1-12. doi: 10.1159/000489474. [Epub ahead of print] Review. PMID: 29982245.
PUBMED DOIThe Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala. Open Forum Infect Dis. 2019 Dec
Samayoa B, Aguirre L, Bonilla O, Medina N, Lau-Bonilla D, Mercado D, Moller A, Perez JC, Alastruey-Izquierdo A, Arathoon E, Denning DW, Rodríguez-Tudela JL; “Fungired”. The Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala. Open Forum Infect Dis. 2019 Dec 15;7(1):ofz534. doi: 10.1093/ofid/ofz534. PMID: 31915715.
PUBMED DOIFungired. Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV. AIDS. 2020 Sep 1
Medina N, Alastruey-Izquierdo A, Mercado D, Bonilla O, Pérez JC, Aguirre L, Samayoa B, Arathoon E, Denning DW, Rodriguez-Tudela JL; Fungired. Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV. AIDS. 2020 Sep 1;34(11):1625-1632. doi: 10.1097/QAD.0000000000002631. PMID: 32694415.
PUBMED DOIPopulation-Based Program of filamentous fungi and Antifungal Resistance in Spain (FILPOP STUDY). Antimicrob Agents Chemother. 2013 Jul
Ana Alastruey-Izquierdo*, Emilia Mellado, Teresa Pelaez, Javier Pemán, Soledad Zapico, María Álvarez, Juan L Rodriguez-Tudela, Manuel Cuenca-Estrella Population-Based Program of filamentous fungi and Antifungal Resistance in Spain (FILPOP STUDY). Antimicrob Agents Chemother. 2013 Jul;57(7):3380-7. doi: 10.1128/AAC.01287-13. PMID: 28319466
PUBMED DOIThe global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017 Dec
Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017 Dec;17(12. doi: 10.1016/S1473-3099(17)30316-X. PMID: 28774698.
PUBMED DOISequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes.
Vega Y, Delgado E, de la Barrera J, Carrera C, Zaballos Á, Cuesta I, Mariño A, Ocampo A, Miralles C, Pérez-Castro S, Álvarez H, López-Miragaya I, García-Bodas E, Díez-Fuertes F, Thomson MM. Sequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes. PLoS One. 2016 Jun 29;11(6):e0158525.
PUBMED DOIY155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors
Perez-Sautu U, Pozo F, Cuesta I, Monzon S, Calderon A, Gonzalez M, Molinero M, Lopez-Miragaya I, Rey S, Cañizares A, Rodriguez G, Gonzalez-Velasco C, Lackenby A, Casas I. Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors. Euro Surveill. 2014 Jul 10;19(27):14-20.
PUBMED DOIComparison of two highly discriminatory typing methods to analyze Aspergillus fumigatus azole resistance
Garcia-Rubio R, Escribano P, Gomez A, Guinea J, and Mellado E. Comparison of two highly discriminatory typing methods to analyze Aspergillus fumigatus azole resistance. Frontiers in Microbiology 2018. Jul 20;9:1626.
PUBMED DOIEvaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia.
Rueda C, Puig-Asensio M, Guinea J, Almirante B, Cuenca-Estrella M, Zaragoza O. Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia. CANDIPOP Project from GEIH-GEMICOMED (SEIMC) and REIPI. Clin Microbiol Infect. 2017 Jan; 23(1):49.e1-49.e8.
PUBMED DOIDevelopment and Validation of a High-Resolution Melting Assay To Detect Azole Resistance in Aspergillus fumigatus.
Bernal-Martínez L, Gil H, Rivero-Menéndez O, Gago S, Cuenca-Estrella M, Mellado E, Alastruey-Izquierdo A. Development and Validation of a High-Resolution Melting Assay To Detect Azole Resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 2017 Nov 22;61(12). pii: e01083-17.
PUBMED DOICervicofacial lymphadenitis due Mycobacterium mantenii: rapid and reliable identification by MALDI-TOF MS.
Nebreda T, Andres AG, Fuentes S, Calleja R, Jimenez MS. Cervicofacial lymphadenitis due Mycobacterium mantenii: rapid and reliable identification by MALDI-TOF MS. New Microbes and New Infections .2018. March 22:1-3.
PUBMED DOIIn-depth analysis of the genome sequence of a clinical, extensively drug-resistant Mycobacterium bovis strain.
Sagasta S, Millan-Lou MI, Jiménez MS, Martin C, Samper S. In-depth analysis of the genome sequence of a clinical, extensively drug-resistant Mycobacterium bovis strain. Tuberculosis. 2016. Sep. 100:46-52.
PUBMED DOIGeneration and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection
Detalle L, Stohr T, Palomo C, Piedra PA, Gilbert BE, Mas V, et al. Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection. Antimicrob Agents Chemother. 2016;60(1):6-13.
PUBMED DOIContent with Investigacion .
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María Cabrerizo Sanz
Tenure Scientist and Group Leader
ORCID code: 0000-0001-7054-5696
Doctor in Chemistry, specializing in Biochemistry and Molecular Biology, Universidad Autónoma de Madrid (2000). Except for a postdoctoral period of 2 years at the Hospital de La Princesa, in which her research was related to onco-hematological diseases, the rest of her scientific career has focused on the study of infectious diseases caused by viruses and their surveillance. She joined the Instituto de Salud Carlos III in 2003, first in the Laboratory of Arbovirus and Imported Viral Diseases, then in the Laboratory of Viral Hepatitis and finally, in the Laboratory of Enterovirus (which is accredited as a National Polio Laboratory -LNP- for the WHO since 1998). She obtained the position of Tenure Scientist in 2016, at the same time she assumed the responsibility of the laboratory, currently of Enteric Viruses: Poliovirus/Enterovirus, Parechovirus and Gastroenteritis-producing Viruses, of the CNM. She has 4 scientific sexennials and 4 quinquennials recognized.
She has been and is PI of 4 consecutive research projects and 3 service contracts, from 2012 to the present, participating, in addition, in other 20 projects. As head of the LNP, she is part of the Working Group of the National Plan for the Eradication of Poliomyelitis and of the WHO European Polio Laboratory Network. She is also a member of the European Non-Polio Enterovirus Network (ENPEN), and of the national cooperation networks CIBERESP and RITIP (IdiPAZ). Since 2023 she is a Council Member from Spain of the European Society.
In total she has published 98 articles in WoS indexed journals (23 Q1 and 22 D1), being first author, senior author or correspondence author in 43 of them (H=27). She has supervised 1 PhD Thesis (2017) and 12 TFM. She is currently supervising another doctoral thesis (IMIENS-UNED). She participates as a teacher in three university masters (UCM, UAH and UV), being coordinator of the subject H2 of the Master of Virology at UCM.
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Mª Dolores Fernández García
Tenure Scientist
ORCID code: 0000-0003-0336-6596
Degree in Pharmacy (2005) and PhD from the University VII Paris Diderot in Microbiology (2010). She completed her doctoral thesis at the Pasteur Institute in Paris characterizing the molecular and cellular basis of flavivirus entry into cells. Specialist in Public Health Microbiology (European Program EUPHEM coordinated by ECDC). She has worked 3 years for the French Ministry of Foreign Affairs as a researcher at the Pasteur Institute in Dakar (Senegal) carrying out microbiological surveillance activities and research on polioviruses and non-polio enteroviruses in West Africa. She has obtained two Miguel Servet contracts: one to work at IMIBIC in Cordoba (2019) and an intramural one to work at CNM (2020). Both were awarded for the study of neurotropic viruses applying massive sequencing for their diagnosis. In 2021 he joined the CNM-ISCIII as a Tenure Research Scientist at the Enterovirus and Viral Gastroenteritis Unit of the CNM-ISCIII. Since then, she combines her scientific activity with the assistance to the National Health System in the microbiological research of outbreaks and in the Genomic Surveillance of Enteroviruses and Gastroenteritis-producing Viruses.
She is a researcher in the Epidemiology and Public Health Area of the Centro de Investigación Biomédica en Red (CIBERESP-ISCIII). In addition, she is an evaluator and panelist for the HORIZON health program projects of the European Commission, the French National Agency ANRS-Emerging Infectious Diseases, R&D&I in HEALTH of the Strategic Action in Health (ISCIII) and the Andalusian Public Foundation Progreso y Salud. She has worked as scientific advisor to the Spanish Ministry of Health on Rotavirus and Polio. Since 2020 she has been teaching virology in different Spanish universities.
She has worked for WHO in the investigation of numerous outbreaks caused by viruses (Ebola, Zika, Yellow Fever, Dengue, etc.) in African and Asian countries strengthening laboratory capacities through technology transfer of diagnostic methods, training of laboratory personnel in these countries and scientific advisory tasks to the Ministries of Health. She has been the Health Coordinator of the START Project (Spanish Technical Aid Response Team) of the AECID, framed in the “Emergency Medical Teams” initiative of the WHO, participating in the establishment for Spain of a field hospital classified by the WHO as EMT Level 2 for interventions in humanitarian emergencies.
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Nerea García Ibáñez
Ayudante de Investigación de OPI. Técnico de laboratorio
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Vanesa Recio Huertas
Ayudante de Investigación de OPI. Técnico de laboratorio (apoyo)
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Ana Donoso Almenara
Contratada predoctoral pFIS
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Rubén González Sanz
Técnico Superior Especializado OPI
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Juan Camacho Padilla
Investigador predoctoral (PFIS)
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Clara Martín Martín
Investigador predoctoral (PFIS)
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Nazaret Díaz Sánchez
Técnico Superior Especializado OPI (apoyo)
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Carmen Serrano Risquez
Investigador predoctoral (CAM)
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Yasmin Biya Assiry
Técnico de laboratorio en formación (PEJ-CAM)
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Estrella Ruiz de Pedro
Técnico de laboratorio (PTA para Infraestructuras de I+D+I)
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.