Centro Nacional de Microbiología (CNM)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/19609

El Centro Nacional de Microbiología (CNM) es uno de los centros pertenecientes al Instituto de Salud Carlos III que proporciona apoyo científico-técnico a la Administración General del Estado, a las Comunidades Autónomas y al Sistema Nacional de Salud (SNS), tal y como se recoge en La Ley General de Sanidad (Ley 14/1986, de 25 de abril) y el Estatuto del Instituto de Salud Carlos III (RD 375/2001, de 6 abril y su posterior reforma, RD 1672/2009, de 6 de noviembre). La función específica del CNM es el control de las enfermedades infecciosas para lo que ofrece servicios de diagnóstico y referencia, manteniendo además programas de investigación, tanto básica como orientada, relacionados con la prevención, el diagnóstico y el tratamiento de estas enfermedades. Dispone de un sistema de gestión de calidad conforme a la norma UNE-EN ISO 9001, certificado por AENOR, para la recepción de muestras biológicas, así como varias técnicas y servicios acreditados por ENAC según la norma UNE-EN ISO 15189.

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Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study.
(Springer Nature, 2026-07-27) Pita-Martínez, Carlos; Rava, Marta; Virseda-Berdices, Ana; Martinez, Isidoro; Moreno, Santiago; Gómez Rodríguez, Carmen Elena; Armiñanzas, Carlos; Mena de Cea, Álvaro; Gisbert Pérez, Laura; Rodríguez-Rosado, Rafael; Jimenez-Sousa, Maria Angeles; Resino, Salvador; Martín-Escolano, Rubén; Instituto de Salud Carlos III; Agencia Estatal de Investigación (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Ministerio de Ciencia, Innovación y Universidades (España); Comunidad de Madrid (España)
Background: persistent immune dysregulation in people with HIV (PWH) on antiretroviral therapy (ART) contributes to an increased risk of skeletal-related events (SREs), serving as a critical paradigm for understanding accelerated aging and age-related diseases. We investigated the association between plasma biomarkers of immune regulation and senescence with incident SRE risk and evaluated potential effect modification by sex. Methods: in a case-cohort study nested within the Spanish CoRIS cohort (65 incident SRE cases; 252 subcohort, including 5 overlapping cases), we quantified 24 baseline biomarkers of immune checkpoints and senescence-associated secretory phenotype factors. We estimated adjusted hazard ratios (aHR) using Borgan II-weighted cause-specific Cox regression models adjusted for clinical confounders (age, region of origin, prior AIDS diagnosis, CD4 + T-cell count, coinfections, and lifestyle factors). Sex-biomarker interactions were assessed as exploratory endpoints. Results: nineteen biomarkers were independently associated with increased SRE risk (p < 0.05 & q < 0.10). Angiogenic factors (VEGF-A; aHR = 1.94; 95% CI, 1.40–2.68), immune checkpoints (PD-L2; aHR = 1.95; 95% CI, 1.09–3.49), and tissue remodeling markers (MMP-1; aHR = 1.91; 95% CI, 1.08–3.39) displayed independent associations, alongside consistent signals for TIM-3, PD-L1, and IL-8. Pairwise correlation analysis demonstrated clustering between checkpoints and inflammatory cytokines. Exploratory interaction analysis indicated that sex modified these associations; signals for seven markers (e.g., IL-1α, VEGF-A) were stronger in females, although the limited number of events warrants caution. Conclusions: circulating biomarkers of immune exhaustion, inflammation, and senescence are independently associated with incident SREs in PWH on long-term ART. Our findings indicate a systemic pro-inflammatory signature and suggest that females exhibit higher sensitivity to inflammatory damage.
Immunomics-guided biomarker discovery for human liver fluke infection and infection-associated cholangiocarcinoma.
(Springer Nature, 2025-07-01) Sadaow, Lakkhana; Rodpai, Rutchanee; Smout, Michael J; Nakajima, Rie; Boonroumkaew, Patcharaporn; Sotillo, Javier; Tedla, Bemnet A; Luvira, Vor; Kitkhuandee, Amnat; Paonariang, Krisada; Sukeepaisarnjaroen, Wattana; Yamasaki, Hiroshi; Suttiprapa, Sutas; Laha, Thewarach; Sripa, Banchob; de Assis, Rafael; Jain, Aarti; Ittiprasert, Wannaporn; Mann, Victoria H; Wong, Yide; Felgner, Philip L; Maleewong, Wanchai; Brindley, Paul J; Loukas, Alex; Intapan, Pewpan M; National Research Council of Thailand; Khon Kaen University (Tailandia); NIH - National Cancer Institute (NCI) (Estados Unidos); National Health and Medical Research Council (Australia)
Sensitive diagnostics are needed to improve management and surveillance of opisthorchiasis and opisthorchiasis-associated cholangiocarcinoma (CCA) throughout East Asia. Herein we generate and screen an Opisthorchis viverrini recombinant secreted proteome to identity antibody biomarkers of liver fluke infection and CCA with sera from study participants in endemic populations and evaluate their utility as point-of-care immunochromatographic tests (PoC-ICTs). We incorporate two of the most promising antigens from the proteome array screen, P1 and P9, into PoC-ICTs to further validate their diagnostic performance. The P9-IgG4 PoC-ICT is superior amongst the single recombinant antigen tests for diagnosing fluke infection as well as fluke-induced CCA, and out-performs parasite crude extract-IgG ICTs. Here we identify two biomarkers of O. viverrini infection and infection-associated CCA that could form the basis of novel antibody serodiagnostic tests for human liver fluke infection and associated cancer.
Recent infections among newly diagnosed cases of HIV infection in Spain, 2015-2016. National estimates using cohort data.
(Taylor & Francis, 2021-06) Hernando Sebastian, Victoria; Cuevas, Maria Teresa; Perez-Olmeda, Mayte; Tasias, Maria; Vera, Mar; Jaen, Angels; Mena, Alvaro; Jarrin Vera, Inmaculada; Diaz Franco, Asuncion; CoRIS-HIV Biobank; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Background: To estimate the prevalence of recent infection (RI) among people newly diagnosed with HIV in Spain using a representative sample collected by the AIDS Research Network cohort (CoRIS) during 2015-2016. Methods: Stratified sampling of CoRIS data was used with proportional allocation by mode of transmission of new HIV diagnoses notified to National Surveillance System. Samples used were from patients in the CoRIS cohort with available stored plasma collected within 6 months after diagnosis. Weighted methods were used to estimate the prevalence of RI and multivariate logistic regression models were used to determine associated factors. Results: Of the 669 individuals included, 55.1% were men who had sex with men (MSM), 24.6% were heterosexual, and 20.3% were non-MSM non-heterosexual. The weighted prevalence of RI was 11.8% (95% Confidence interval [CI] 9.4-14.8%) overall, 15.5% (12.2-19.4%) among MSM, 6.3% (3.9-10.0%) among heterosexual, and 8.6% (3.2-20.9%) in non-MSM non-heterosexual persons. Factors associated with prevalence of RI were: MSM (OR 2.05; 95% CI 1.02-4.14) vs. heterosexual, being Spanish (OR 2.92; 1.36-6.26) or European (OR 3.42; 1.28-9.13) vs. Latin American, having a secondary or higher education level (OR 3.08; 0.95-1.00) vs. primary, and having a CD4 count of 350-499 (OR 3.26; 1.46-7.30) or >500 (OR 6.26; 2.92-13.39) vs. <350 cells/mm3. Conclusions: In the absence of direct data from surveillance systems, the use of cohort data is a very valuable option for identifying the prevalence of RI at national level. This is the first nationwide study carried out in Spain to determine the prevalence of RI using an avidity assay.
Comparison of three real-time polymerase chain reaction protocols for the diagnosis of imported schistosomiasis in a non-endemic setting.
(Springer Nature, 2025-12-29) Martínez-Vallejo, Patricia; Silgado, Aroa; Mediavilla, Alejandro; Rubio Maturana, Carles; Zarzuela, Francesc; Muixí, Marc; Goterris, Lidia; Rodríguez-Pérez, Esther; Vázquez-Ávila, Sara; Salvador, Fernando; Oliveira-Souto, Inés; Molina, Israel; Serre-Delcor, Núria; Sotillo, Javier; Sulleiro, Elena
Background: Schistosomiasis is a neglected tropical disease that mostly affects inhabitants of sub-Saharan Africa. With rising global migration, imported cases of schistosomiasis are increasingly being reported in non-endemic countries, where diagnosis is hindered by low parasite burdens and multiple Schistosoma species. Microscopy remains the gold standard, despite its limitations, whereas molecular techniques offer greater sensitivity. The aim of this study was to assess the performance of real-time polymerase chain reaction (PCR) protocols for the detection, at an international health centre in Barcelona, of imported cases of urogenital and intestinal schistosomiasis. Methods: This cross-sectional study included 75 adults from sub-Saharan Africa attending the Drassanes-Vall d'Hebron International Health Unit, Barcelona, between May 2023 and February 2024. Paired urine and stool samples were collected. Microscopy was performed on all samples. Urine was analysed by real-time PCR using the Dra1 target sequence. Stool was tested by three protocols targeting, respectively, Dra1, Sm1-7, and 28S rRNA. Schistosoma infection was confirmed by microscopic identification of eggs and/or parasite DNA detection by real-time PCR. Results: Schistosomiasis was confirmed in 12/75 patients (16%). Urogenital schistosomiasis was diagnosed in 3/75 cases; the performance values of real-time PCR in urine samples were not assessed. In stool, the pan-Schistosoma real-time PCR showed 55.6% sensitivity and 98.5% specificity, with a moderate agreement (κ = 0.631) with microscopy. The Sm1-7 assay fully matched microscopy for Schistosoma mansoni detection, and reached 100% sensitivity and specificity. A novel contribution of this study is the application of a real-time PCR assay targeting the Dra1 repetitive sequence in stool samples for the detection of Schistosoma intercalatum/Schistosoma guineensis. All of the microscopy-positive cases were real-time PCR positive, and one additional infection was detected by real-time PCR, which meant that 100% sensitivity and 98.6% specificity were achieved with this technique. Conclusions: Our findings underscore the need for accurate diagnostic tools for cases of imported schistosomiasis in non-endemic settings. Microscopy remains the reference standard, while the pan-Schistosoma real-time PCR showed limited sensitivity for stool samples. In contrast, the Sm1-7 and Dra1 assays demonstrated higher sensitivity and strong concordance with microscopy, with Dra1 also proving useful for the detection of S. intercalatum/S. guineensis in stool.
Nippostrongylus brasiliensis and Heligmosomoides polygyrus exert anti-inflammatory effects through distinct immunomodulatory mechanisms in murine macrophages in vitro.
(Springer Nature, 2026-08-26) Varea, Covadonga; Martin-Galiano, Antonio Javier; Vázquez-Ávila, Sara; Montero-Calle, Ana Maria; Cesteros, Julia; Perteguer-Prieto, Maria Jesus; Peláez-García, Alberto; Barderas Manchado, Rodrigo; García-Rodríguez, Juan José; Sotillo, Javier; Ministerio de Ciencia, Innovación y Universidades (España); Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Hookworm infections affect hundreds of millions of people worldwide and rank among the most significant neglected tropical diseases in terms of morbidity. Due to the inverse correlation between hookworm infection and the incidence of immune-mediated inflammatory diseases, considerable research has focused on understanding how parasitic helminths modulate host inflammation. Heligmosomoides polygyrus and Nippostrongylus brasiliensis are two hookworm-like rodent models widely used to investigate fundamental aspects of immune regulation. However, no comparative study has yet analysed the distinct immunological pathways activated by these helminths in their hosts. In this study, we compared cytokine profiles and M1/M2 macrophage polarization markers induced by H. polygyrus and N. brasiliensis, alongside proteomic pathways involved in their activation, using the RAW 264.7 murine macrophage cell line. H. polygyrus downregulated proinflammatory cytokines such as TNF-α and MCP-1, whereas N. brasiliensis did not affect TNF-α expression. Both parasites upregulated Th2 and regulatory cytokines, including IL-4 and TGF-β. Furthermore, H. polygyrus predominantly polarized macrophages toward an M2 phenotype, while N. brasiliensis maintained a balanced M1/M2 profile. Proteomic analysis revealed that N. brasiliensis and H. polygyrus exert their anti-inflammatory effects through distinct mechanisms, with N. brasiliensis acting via peripheral pathways and H. polygyrus via central regulatory mechanisms.
Clinical significance of asymptomatic Leishmania infantum infection in people living with HIV_data set
(Instituto de Salud Carlos III (ISCIII). Centro Nacional de Microbiología (CNM), 2026-09-10) Barbiero, Anna; Moreno, Javier; Bernardo, Lorena; Lozano-Rendal, Marina; Solana, Jose Carlos; Sanchez Herrero, Carmen; Marco Vinuesa, Arantxa; Cuenca, Paula; San Martín, Juan Víctor; Lagi, Filippo; Zammarchi, Lorenzo; Spinicci, Michele; Bartoloni, Alessandro; Granozzi, Bianca; Bacchiega, Michele; De Pascali, Alessandra Mistral; Balducelli, Emma; Ortalli, Margherita; Zaghi, Irene; Varani, Stefania; Carrillo, Eugenia
This dataset contains demographic, clinical, immunological and molecular data from 204 people living with HIV (PLWH) recruited between 2013 and 2023 in Spain and Italy, all residing in Leishmania infantum-endemic areas. For each participant, the database includes age, sex, birthplace, cohort, CD4+ T-cell count, HIV viral load, antiretroviral treatment information, and the results of three complementary screening methods for asymptomatic Leishmania infection: kDNA real-time PCR, ELISA serology, and a whole blood stimulation assay (WBA) measuring parasite-specific cytokine responses (IFN-γ, IL-2 and IP-10). In addition, the dataset contains follow-up information for individuals with positive screening results, including repeated PCR, serological and immunological assessments and clinical monitoring for progression to visceral leishmaniasis. No cases of progression to overt VL were recorded during follow-up.
Impact of Nirsevimab on RSV and Non-RSV Severe Respiratory Infections in Hospitalized Infants.
(Wiley, 2025-05) García-García, María Luz; Alonso-López, Patricia; Alcolea, Sonia; Arroyas, M; Pozo Sanchez, Francisco; Casas Flecha, Inmaculada; Iglesias-Caballero, Maria; Sánchez-León, Rocío; Hurtado-Gallego, Jara; Calvo, Cristina
Background: Nirsevimab, a monoclonal antibody providing passive immunity against RSV infections in infants, was introduced in Spain in October 2023 for children under 6 months and those born during the epidemic season. This study aimed to compare the clinical and virological characteristics of respiratory infections in hospitalized infants before and after nirsevimab introduction. Methods: We carried out a prospective study across two hospitals in Madrid during the 2022-2023 and 2023-2024 epidemic seasons. The study included infants under 12 months of age that were hospitalized with lower respiratory tract infections (LRTIs). Clinical, epidemiological, and virological data were analyzed and compared between the periods before and after the introduction of nirsevimab, as well as according to whether the infants had received this preventive treatment. Results: A total of 669 infants were included: 480 from October 2022 to March 2023 (S1) and 189 from October 2023 to March 2024 (S2). Respiratory infection-related admissions decreased by 62.5% in S2, with a 74.5% reduction in ICU admissions. RSV-related admissions decreased by 78%, HMPV by 36.6%, and adenovirus by 69.5%. Infants in S2 were older (p = 0.001) and had shorter hospital stays (p < 0.001) than in S1. Of 63 (33%) infants in S2 who received nirsevimab, 11 (17%) were diagnosed with RSV. High-flow oxygen use was less frequent among RSV patients treated with nirsevimab (p = 0.002). Conclusions: Nirsevimab introduction was significantly associated with reduced hospitalizations and severity of RSV and other respiratory infections. Its use was associated with fewer admissions and reduced need for intensive care, especially in RSV-infected infants but also in HMPV and adenovirus-infected infants.
Genomic Surveillance and Antigenic Characterization of Respiratory Syncytial Virus (RSV) in Spain During the 2023-2024 Season of Nirsevimab Administration.
(Oxford University Press, 2026-02-18) Iglesias-Caballero, Maria; Mas-Lloret, Vicente; Campoy, Albert; Calvo, Cristina; García, María Luz; Alcolea, Sonia; Moreno-Parrado, Laura; Reina, Jordi; Navascués, Ana; Antón, Andrés; Davina-Nunez, Carlos; Perez-Castro, Sonia; Costa, José; Fernández-González, Ana; Lepe, José Antonio; Gaona, Cristina; Pérez, Zulema; García-Martínez de Artola, Diego; Vázquez-Morón, Sonia; Camarero-Serrano, Sara; Cano, Olga; Pozo Sanchez, Francisco; Casas Flecha, Inmaculada; Instituto de Salud Carlos III; Unión Europea. Comisión Europea. Horizonte Europa
Respiratory Syncytial Virus (RSV) is a leading cause of respiratory infections in infants and older adults. In Spain, surveillance is supported by the SiVIRA system and the RELECOV genomic sequencing network. The 2023-2024 season marked the first nationwide administration of nirsevimab, a monoclonal antibody for preventing severe RSV in infants. This study analyzes the genomic evolution of RSV during this period, focusing on potential escape mutations in the F protein. RSV-A showed high genetic diversity with eleven circulating lineages, while RSV-B was dominated by lineage B.D.E.1. Phylogenetic analysis revealed three distinct B.D.4.1.1 groups, one sharing mutations with B.D.E.1 in the nirsevimab binding site. Despite these changes, neutralization assays confirmed that nirsevimab and other monoclonal antibodies remained effective. No significant antigenic drift compromising immunoprophylaxis was observed. These findings support the continued efficacy of nirsevimab and highlight the importance of genomic surveillance for tracking RSV evolution and informing future immunization strategies.
Second-season Impact of Nirsevimab: Clinical Outcomes of RSV Disease in Patients Immunized During Their First Season.
(Wolters Kluwer, 2025-10-01) González-Bertolín, Isabel; Alcolea, Sonia; Alonso, Patricia; Arroyas, María; Fernández Castiella, Isabel; Echavarren, Iciar; Iglesias-Caballero, Maria; Casas Flecha, Inmaculada; García-García, María Luz; Calvo, Cristina; Instituto de Salud Carlos III; Unión Europea. Comisión Europea. Horizonte Europa; Merck, Sharp & Dohme
Nirsevimab provides passive immunization against respiratory syncytial virus, yet concerns exist regarding its long-term impact. This study analyzed respiratory syncytial virus-associated lower respiratory tract infection severity in hospitalized children immunized with nirsevimab more than 6 months prior. No significant differences were found compared with nonimmunized children. Findings suggest no increased risk in the following season, supporting nirsevimab's safety as a preventive strategy.
Clinical and epidemiological changes in severe viral respiratory infections in pediatric patients after the COVID-19 pandemic in Spain.
(Springer Nature, 2026-05-18) García-García, María Luz; Alonso-López, Patricia; Alcolea, Sonia; Arroyas, María; Iglesias-Caballero, Maria; Sánchez-León, Rocío; Hurtado-Gallego, Jara; Mas-Lloret, Vicente; Pozo Sanchez, Francisco; Casas Flecha, Inmaculada; Calvo, Cristina; Instituto de Salud Carlos III; Unión Europea. Comisión Europea. Horizonte Europa
The COVID-19 pandemic and associated public health measures disrupted the circulation of respiratory viruses worldwide. However, the long-term impact of these changes on pediatric respiratory tract infections (ARTIs) remains incompletely understood. We conducted a prospective study in children under 14 years hospitalized for ARTIs in Severo Ochoa Hospital (Spain) from January/2006 to September/2023. The cohort was divided into three periods: pre-pandemic (T1), pandemic (T2), and post-pandemic (T3). Clinical and virological results were compared. 6048 children were included (T1:5,101; T2:122; T3:825). Viral detection increased in T3 (91%) compared to T1 (78.7%) and T2 (69.5%), p < 0.001, with higher rate of coinfections, p < 0.001, and pneumonia diagnoses, p < 0.001. HRV and RSV were the most frequent viruses across periods, with HRV maintaining year-round circulation and RSV showing marked seasonal disruption in T2, followed by return to its typical winter pattern in T3. Detection of PIV and HMPV increased in T3, with altered seasonal peaks and a shift toward older age groups. Influenza infections, nearly absent in T2, re-emerged in T3 with delayed seasonal peaks and higher median ages. HBoV circulation declined and became more evenly distributed throughout the year. Clinically, children in T3 were older, with more hypoxia, radiological infiltrates, and pneumonia, while bronchiolitis cases decreased. Most pneumonia cases in T3 had a viral etiology, with HRV, RSV, HMPV, and PIV as the main contributors. Post-pandemic shifts in viral circulation and disease profiles among children with ARTIs highlight the ongoing impact of COVID-19 on pediatric respiratory health. The increased burden of viral pneumonia and the change in seasonal distribution of infections underscore the need for updated surveillance, diagnostic strategies, and prevention programs tailored to the post-pandemic context.
Datos actuales de la ENI en España.
(2026-09-03) Yuste, Jose Enrique; Domenech Lucas, Mirian
Ponencia sobre la actualización de la situación epidemiológica de la Enfermedad Neumocócica Invasiva (ENI) en España. En esta ponencia se muestran datos nacionales que abarcan tanto la situación pre-pandémica como la post-pandémica. Nuestros resultados confirman el aumento de casos de ENI tanto en población pediátrica como adulta en 2025. En esta presentación se observan diferentes patrones de distribución de serotipos en función de los diferentes grupos de edad y mostramos la importancia de algunos serotipos prevalentes.
Heat-inactivated Mycobacterium bovis and P22PI protein immunocomplex: Two candidates for use as immunostimulants of innate immune response.
(Elsevier, 2025-06) Agulló-Ros, Irene; Burucúa, Mercedes M; Cheuquepán, Felipe A; Dominguez-Rodriguez, Mercedes; Sevilla, Iker A; Martínez, Remigio; Plá, Natalia; Risalde, María A; Marin, Maia S; University of Córdoba (España); Ministerio de Ciencia, Innovación y Universidades (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación
Tuberculosis (TB), caused by members of the Mycobacterium tuberculosis complex, remains a critical global health challenge, affecting humans and a wide range of domestic and wild animals. Despite the availability of anti-TB drugs, cure rates remain suboptimal, exacerbated by the rise of multidrug-resistant TB strains. The Bacille Calmette-Guérin (BCG) vaccine, the only licensed vaccine against TB, has demonstrated efficacy in reducing lesion severity and bacterial burden in animals, as well as lowering TB-related and all-cause mortality in infants. However, BCG presents several safety concerns inherent to live vaccines. To overcome these limitations, exploring alternative vaccine candidates that do not incorporate live mycobacteria is crucial. This study aimed to evaluate and compare the immunostimulatory potential of two candidates based in mycobacteria inactivated or their derivatives, heat-inactivated Mycobacterium bovis (HIMB) and P22PI protein immunocomplex (P22PI), in bovine foetal lung cells. To assess the expression of innate immune components, including Toll-like receptors (TLRs), cathelicidins, and cytokines, bovine foetal lung were exposed to different concentrations of HIMB and P22PI immunostimulants, starting at 7.8 × 10⁶ CFU/ml and 10 µg/ml, respectively. These initial concentrations were subsequently diluted to 1/2 and 1/10 to evaluate dose-dependent effects. Our findings reveal that both HIMB and P22PI significantly stimulate innate immune mechanisms, as evidenced by the upregulation of TLR2 and TLR4, alongside the induction of BMAP28 cathelicidin, tumour necrosis factor alpha (TNFA) and interferons (IFNs). These results suggest their potential to orchestrate a robust innate immune response providing valuable insights into the immunological mechanisms underlying the protective effects of these immunostimulants. This underscores their potential role in in vivo studies as vaccine candidates. Furthermore, their ability to enhance antigen recognition via TLR and induce pro-inflammatory cytokines also indicates broader applications in immune modulation, potentially extending protection against heterologous pathogens through trained immunity.
Trends in Paediatric Viral Meningitis and Encephalitis With Unconfirmed Aetiology: A Spanish Population-Based Study, 2016-2020.
(Wiley, 2025-09) Pons-Espinal, Marina; Lopez-Perea, Noemi; Masa-Calles, Josefa; Muñoz-Almagro, Carmen; Tarrago Asensio, David; Launes, Cristian; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)
Aim: The prevalence of meningitis and encephalitis of unknown aetiology in Spanish children has not been specifically documented before. The aim of this study is to describe the epidemiology and trends of these clinical conditions between 2016 and 2020. Methods: Retrospective study analysing hospitalised children < 15 years with meningitis and encephalitis/encephalomyelitis of unknown origin (ICD-10 codes) in Spain (2016-2020). Data from National Registry of Hospitalizations and National Institute for Statistics were used to calculate age-stratified hospitalisation rates (HR). Statistical analysis included Poisson regression to calculate hospitalisation rate ratios (HRR) by age groups and years and forecasting methods to predict 2020 HRs. Results: Four thousand six hundred childrens were hospitalised with viral meningitis and encephalitis-encephalomyelitis of unknown origin, resulting in a HR of 7.8/105 inhabitants. The highest HR was observed in children under 1 year (49.1/105) and those aged 5-9 (10.4/105). The global HR for viral meningitis (3.64/105) was lower than for encephalitis-encephalomyelitis (4.2/105). Hospitalisations decreased from 1475 (2016) to 452 (2020), attributed to enhanced pathogen detection methods and COVID-19 preventive measures. Conclusion: Undiagnosed central nervous system entities remain a significant cause of paediatric hospitalisations in Spain, despite a declining incidence. Enhanced diagnostic strategies, including expanded microbiological testing and molecular epidemiology surveillance, could prove beneficial.
Sustained circulation of enterovirus D68 in Europe in 2023 and the continued evolution of enterovirus D68 B3-lineages associated with distinct amino acid substitutions in VP1 protein.
(Elsevier, 2025-06) Hirvonen, Aurora; Johannesen, Caroline Klint; Simmonds, Peter; Fischer, Thea K; Harvala, Heli; Benschop, Kimberley S M; ENPEN study collaborators; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Unión Europea. Comisión Europea. NextGenerationEU; Helsinki University Hospital; The Slovenian Research and Innovation Agency; Rijksinstituut voor Ziekte- en Invaliditeitsverzekering; Cabrerizo, Maria; Fernandez-Garcia, Maria Dolores
Background: Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges. Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution. Study design: Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of EV samples tested, EV positive samples, EV-D68 positive samples and cases, and other EV positive samples detected in 2023. Information on sample types and surveillance system was recorded. Sequence data from the VP1 gene was used for phylogenetic and amino acid sequence analysis. Results: EV was detected in 13,585 out of 203,622 diagnostic samples tested (6.7 %), of which 402 (3.0 %) were determined as EV-D68, representing 386 cases. EV-D68 infections peaked in October 2023 (136/386; 35.2 %). 267/386 (69.2 %) of EV-D68 cases were captured through clinical EV surveillance, almost all of which (202/204 of positive samples with sample type information) were detected in respiratory specimens. Phylogenetic analysis performed on 99 VP1 sequences revealed a distinct B3-derived lineage with a previously undescribed residue change, D554E, in Europe. Conclusions: The study documents sustained circulation of EV-D68 in Europe in 2023, the evolution of B3-derived lineages, and appearance of previously undescribed amino acid substitutions in Europe. This stresses the need for continuous EV-D68 surveillance and harmonization of EV-D68 detection practices towards better data comparability across countries.
Extracellular vesicles derived microRNAs as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study.
(Elsevier, 2025-06) Cairoli, Victoria; Valle-Millares, Daniel; Ryan, Pablo; Dominguez, Lourdes; Martín-Carbonero, Luz; De Los Santos, Ignacio; De Matteo, Elena; Ameigeiras, Beatriz; De Sousa, Marcela; Briz, Veronica; Preciado, María V; Fernandez-Rodriguez, Amanda; Valva, Pamela; Instituto de Salud Carlos III; RETICS-Sida (RIS-ISCIII) (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Agencia Nacional de Promoción Científica y Tecnológica (Argentina); National Scientific and Technical Research Council (Argentina)
Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency Virus (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis C (CHC) progression. The objective of the study was to delve into the intricate EVs-miRNA profiles in CHC patients with different liver fibrosis stages, aiming to pinpoint non-invasive markers capable of distinguishing significant fibrosis. Plasma EV-miRNAs from 50 CHC patients (HCV+ and HCV+/HIV+) stratified in no significant (F < 2) and significant (F ≥ 2) fibrosis, were massively sequenced. General linear models (GLM) were used to identify significantly differential expressed (SDE) miRNAs according to liver fibrosis stages (F ≥ 2 and F < 2). Dysregulated biological pathways were subsequently analyzed for the following groups: i) all patients; ii) HCV+; and iii) HCV+/HIV+. Multiple-ordered logistic regression analysis was performed to develop a score to identify F ≥ 2 cases. The diagnostic potential of both the SDE miRNAs and the developed score was assessed using ROC curve analysis. With respect to all CHC patients, two SDE miRNAs (hsa-miR-122-5p and hsa-miR-92a-3p) were identified which regulate genes related to cytoskeleton organization. Regarding their diagnostic performance to discriminate F ≥ 2, both miRNAs individually demonstrated acceptable diagnostic values. However, their combined use in a new score enhanced their diagnostic performance (AUROC = 0.833). In the HCV+ subgroup, 8 SDE miRNAs (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), which regulate macrophage activity and cell growth/death regulation, were recognized. Among them, hsa-miR-3615 displayed the highest diagnostic performance to discriminate F ≥ 2 (AUROC = 0.936). With respect to HCV+/HIV+, 18 SDE miRNAs (hsa-miR-4508, hsa-miR-122-5p, hsa-miR-451a, hsa-miR-1290, hsa-miR-1246, hsa-miR-107, hsa-miR-15b-5p, hsa-miR-194-5p, hsa-miR-22-5p, hsa-miR-20b-5p, hsa-miR-142-5p, hsa-miR-328-3p, hsa-miR-335-3p, hsa-miR-125a-5p, hsa-miR-423-3p, hsa-let-7d-3p, hsa-miR-128-3p, hsa-miR-10a-5p) were recognized that regulate RNA silencing processes. In this case, hsa-miR-423-3p and hsa-miR-128-3p showed outstanding diagnostic performances (AUROC > 0.900). Distinct EVs-miRNA profiles were identified in patients with varying liver fibrosis stages, both in the overall CHC cohort and within HCV+ and HCV+/HIV+ subgroups. These specific miRNA signatures would allow the elucidation of potential mechanisms involved in clinical evolution and identification of specific biomarkers of unfavorable progression, plausible to be used in a diagnostic panel. Furthermore, the developed score demonstrates the ability to discriminate within the CHC group those individuals with significant fibrosis regardless of their HIV infection status.
The sulfur-related metabolic status of during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target.
(Taylor & Francis, 2025-12) Alharthi, Reem; Sueiro-Olivares, Monica; Storer, Isabelle; Bin Shuraym, Hajer; Scott, Jennifer; Al-Shidhani, Reem; Fortune-Grant, Rachael; Bignell, Elaine; Tabernero, Lydia; Bromley, Michael; Zhao, Can; Amich, Jorge; Agencia Estatal de Investigación (España); Wellcome Trust
Sulfur metabolism is an essential aspect of fungal physiology and pathogenicity. Fungal sulfur metabolism comprises anabolic and catabolic routes that are not well conserved in mammals, therefore is considered a promising source of prospective novel antifungal targets. To gain insight into sulfur-related metabolism during infection, we used a NanoString custom nCounter-TagSet and compared the expression of 68 key metabolic genes in different murine models of invasive pulmonary aspergillosis, at 3 time-points, and under a variety of conditions. We identified a set of 15 genes that were consistently expressed at higher levels than , suggesting that they may be particularly relevant for intrapulmonary growth and thus constitute promising drug targets. Indeed, the role of 5 of the 15 genes has previously been empirically validated, supporting the likelihood that the remaining candidates are relevant. In addition, the analysis of gene expression dynamics at early (16 h), mid (24 h), and late (72 h) time-points uncovered potential disease initiation and progression factors. We further characterized one of the identified genes, encoding the cytosolic serine hydroxymethyltransferase ShmB, and demonstrated that it is an essential gene of , also required for virulence in a murine model of established pulmonary infection. We further showed that the structure of the ligand-binding pocket of the fungal enzyme differs significantly from its human counterpart, suggesting that specific inhibitors can be designed. Therefore, transcriptomics is a powerful tool for identifying genes crucial for fungal pathogenicity that may encode promising antifungal target candidates.
Sur8/Shoc2 como nuevo actor en envejecimiento y fragilidad (SENFRA-5). Data Management Plan V1.0.
(Instituto de Salud Carlos III (ISCIII). Centro Nacional de Microbiología (CNM), 2026-07-03) Fernandez-Rodriguez, Amanda; Instituto de Salud Carlos III
El presente Plan de Gestión de Datos (PGD) define las estrategias, procedimientos y responsabilidades relacionadas con la generación, almacenamiento, acceso, difusión y protección de los datos derivados del proyecto COOPERA-ISCIII. Se alinea con los criterios de evaluación del ISCIII (calidad, viabilidad e impacto) y con los principios FAIR (Findable, Accessible, Interoperable, Reusable), tal como requieren las convocatorias de la Acción Estratégica en Salud.
Bidirectional Interaction Between Liposomal Amphotericin B Pharmacokinetics and Parasite Dynamics in Patients With Post-Kala-Azar Dermal Leishmaniasis: Potential Implications for Optimal Dosing.
(Wiley, 2026-02) Chu, Wan-Yu; Singh, Om Prakash; Sundar, Shyam; Mondal, Dinesh; Pandey, Krishna; Das, Pradeep; Roseboom, Ignace C; Raja, Sheeraz; Torres Garcia, Ana Maria; Carrillo, Eugenia; Huitema, Alwin D R; Alves, Fabiana; Dorlo, Thomas P C; Dutch Research Council (Holanda); Swedish Research Council
Post-kala-azar dermal leishmaniasis (PKDL) involves a high macrophage burden in which the Leishmania parasites reside. Liposomal amphotericin B (LAmB) plays a key role in the treatment of PKDL. The mononuclear phagocyte system (MPS) is crucial in the distribution of liposomal drugs as well as the leishmaniasis pathophysiology. This study focused on characterizing the interaction between LAmB pharmacokinetics, the MPS, and parasite dynamics for optimal dosing of LAmB in PKDL. Clinical trial data from the Indian subcontinent, involving short-course LAmB administered alone or with miltefosine, were analyzed using nonlinear mixed-effects modeling. The pharmacokinetics of LAmB were best described by a two-compartment model with a saturable LAmB uptake by the MPS. The maximum MPS uptake capacity was modeled with a baseline component and an additional disease-related component relative to the parasite burden. As treatment progressed, MPS capacity decreased with declining parasite load, resulting in a median 54% increase in the systemic LAmB exposure (AUC) by the end of treatment. Simulations suggested that a similar parasite clearance could be achieved with a 50% lower total LAmB dose, supporting the potential efficacy of reduced dosing regimens. Combining LAmB and miltefosine further accelerated parasite clearance compared to LAmB alone. This study highlights the importance of understanding the bidirectional interactions between LAmB pharmacokinetics and parasite infection for interpreting systemic exposure and optimizing treatment approaches. If confirmed in clinical trials, reduced LAmB dosing strategies could enable more rational and cost-effective management of PKDL and other dermal leishmaniases.
Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection.
(Microbiology Society, 2026-03) Martín-Martín, Clara; Ruiz-Rico, María; Barat, José Manuel; García-Ríos, Estéfani; Pérez-Romero, Pilar; Instituto de Salud Carlos III; Agencia Estatal de Investigación (España); Generalitat Valenciana (España); University of Notre Dame
Human cytomegalovirus (HCMV) poses serious health risks, particularly for immunocompromised individuals. However, the current FDA-approved anti-HCMV drugs face challenges such as drug resistance and significant side effects, underscoring the need for alternative treatment options. Essential oil components (EOCs), including eugenol, thymol and vanillin, are recognized for their therapeutic potential. This study evaluates their antiviral effects against HCMV in epithelial (ARPE-19) and fibroblast (MRC-5) cell lines. Among the EOCs, vanillin demonstrated the highest efficacy, characterized by low toxicity and a high selectivity index in both cell types. Mechanistic differences were noted between the cell lines. In ARPE-19 cells, eugenol showed virucidal activity, inhibited viral entry and suppressed early gene expression (IE-1). Conversely, in MRC-5 cells, eugenol mainly blocked viral entry and exhibited virucidal effects. Thymol was most effective in ARPE-19 cells, where it completely suppressed IE-1 expression as a result of both inhibition of viral entry and a direct disruptive effect on IE-1 expression. In addition, thymol showed an effect on viral replication. In MRC-5 cells, thymol primarily inhibited viral entry and attachment. Vanillin exhibited dual inhibitory activity in both cell lines, blocking viral attachment and entry. In MRC-5, vanillin also appears to affect intermediate processes. Notably, combining EOCs with ganciclovir resulted in synergistic effects. The eugenol/ganciclovir combination was particularly effective in ARPE-19 cells, while thymol/ganciclovir showed enhanced efficacy in MRC-5 cells. These findings suggest that EOCs have significant potential as adjunct therapies to improve antiviral outcomes and address drug-resistant HCMV strains.
Detection and genetic characterization of Crimean-Congo hemorrhagic fever virus in ticks from western Spain (2017, 2020-2024).
(Frontiers Media, 2026-04-01) Sánchez-Mora, Patricia; Habela, Miguel A; Del Peso, Teresa; Grande Ávila, Ana Candela; García López, Ana María; Mata García Soldado, Jennifer; Tapia, María M; Molero-Sanz, Francisca; Herrero-Romero, Laura; Olmeda, A Sonia; Valcárcel, Félix; Estrada-Peña, Agustín; Negredo, Anabel; Sánchez-Seco, María Paz; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Comisión Europea. NextGenerationEU
Introduction: Crimean-Congo hemorrhagic fever virus (CCHFV) was first detected in Spain in ticks collected from red deer in southwestern Cáceres. Since then, this region, established as endemic, has been the focus of several surveillance studies. However, updated data on viral circulation in this area remain limited. Materials and methods: We conducted a retrospective surveillance study to assess the presence and genetic diversity of CCHFV in ticks collected in central and southern Cáceres over multiple years (2017 and 2020-2024). A total of 3,183 ticks, grouped into 1,569 pools, were collected from wild ungulates, livestock, domestic animals and vegetation, and analyzed by two PCR methods. Positive pools were characterized by Sanger sequencing. Results: CCHFV was exclusively detected in Hyalomma lusitanicum ticks, with an overall infection rate of 1.54% (95% CI: 1.14-2.03). Most positive pools originated from wild ungulates, particularly red deer. Genetic analysis revealed the circulation of two CCHFV genotypes, predominantly genotype III. Discussion: The detection of CCHFV in ticks collected over multiple years supports the sustained circulation of the virus in southwestern Cáceres. Our findings also reinforce the key role of H. lusitanicum as the main vector maintaining the virus in wild ungulates and underscore the genetic diversity of circulating strains and the importance of using multiple molecular methods. These results emphasize the need for continuous surveillance in endemic areas to monitor viral circulation and assess animal and public health risks.

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