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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Now showing 1 - 20 of 2025

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.
Molecular epidemiology and surveillance of imported dengue in travellers returning to Spain, 2022-2024.
(Elsevier, 2026) Sánchez-Mora, Patricia; Molero-Sanz, Francisca; Navascués, Ana; Zurita, Nelly Daniela; Zamarrón, Pilar; Lagarejos, Eduardo; Gómez, Sara; Cardona, Pere Joan; Carrasco, Blanca; López-Lomba, Marta; Escribano, Isabel; Martínez-Expósito, Óscar; Del Peso, Teresa; Herrero-Romero, Laura; Negredo, Anabel; Guillén-Calvo, Laura; Peña Gallego, Ana; Gutiérrez-López, Rafael; Labiod, Nuria; Vazquez, Ana; Sánchez-Seco, María Paz; Gutiérrez-López, Rafael; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Introduction: Dengue is the most significant vector-borne viral disease in global morbidity and mortality, and it is considered a re-emerging disease spreading into new regions. The risk of autochthonous dengue virus transmission in Spain remains high due to the increasing number of travellers returning from endemic areas and the presence of Aedes albopictus within our territory. Conducting epidemiological and molecular studies on returning travellers from endemic areas may be crucial to discern transmission patterns and track the global spread of the virus. This study focuses on the molecular characterization of suspected imported dengue cases from 2022 to 2024. Methods: We analysed 600 samples from 539 suspected dengue-infected travellers between 2022 and 2024. All samples were tested by a quantitative RT-PCR, and PCR-positive cases were confirmed by performing a non-overlapping nested RT-PCR, going under subsequent sequencing to identify viral diversity. Results: Of the 539 suspected cases, 183 were confirmed as DENV-positive, with Cuba as the most common travel origin associated with infections. Molecular analysis of positive samples identified all four DENV serotypes and ten genotype groups, with DENV-3 genotype III as the most predominant. Additionally, among confirmed cases reported from regions with Aedes albopictus presence, 73% (94/129) occurred during the vector's active season (May-November), increasing the risk of local transmission. Conclusion: Our results highlight the importance of returning travellers as sentinels for ongoing dengue outbreaks and epidemiology in endemic regions. Additionally, these emphasize the importance of early case identification through sentinel surveillance to prevent potential autochthonous transmission.
HIV/HCV prevalence and the retention paradox in marginalized populations in Madrid (2019-2023): A large-scale cross-sectional study.
(Elsevier, 2026-06) Valencia, Jorge; Ryan, Pablo; Codina Márquez, Helena; Cuevas, Guillermo; Manzano, Samuel; Estévez, Samuel; Martinez, Isidoro; Sepulveda-Crespo, Daniel; Resino, Salvador; Gilead Sciences (Spain); Instituto de Salud Carlos III; AbbVie; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Comisión Europea. NextGenerationEU
Objectives: Marginalized urban populations experience a high burden of HIV and HCV. We assessed the prevalence and risk factors for both infections and characterized the care cascades in a cohort of vulnerable individuals in Madrid, Spain. Methods: We conducted a cross-sectional study (2019-2023) of 4582 individuals via mobile units in high-risk hotspots, offering integrated rapid HIV/HCV testing with point-of-care HCV-RNA confirmation. Multivariable logistic regression identified independent HIV risk factors. Results: HIV prevalence was 6.3% (95% CI: 5.6-7.0). Among people with HIV (PWH), 17.0% of known cases were not receiving antiretroviral therapy; PrEP uptake was zero among HIV-negative individuals. A history of injecting drug use was the primary HIV risk factor (adjusted odds ratio[aOR] 6.6; 95% CI: 4.6-9.5), followed by age >50 years, Spanish origin, and alcohol/benzodiazepine misuse (all P < 0.05). Active HCV prevalence was 5.5% (95% CI: 4.9-6.2); 15.7% in PWH vs 4.8% in people without HIV (P < 0.001). Among confirmed cases, HCV linkage (≥95.2%) and treatment (≥88.6%) were high; however, 16.8% of all antibody-positive individuals (23.2% among PWH) missed confirmatory RNA testing. Conclusions: HIV and HCV remain prevalent, characterized by discontinuities in retention rather than diagnosis. Integrated, low-threshold strategies combining harm reduction with social support are required to address this syndemic.
Dengue nanosensors: a roadmap for clinical viability.
(Elsevier, 2026-02-26) Codina Márquez, Helena; Quero-Delgado, Marta; Gómez, Rafael; Resino, Salvador; Martinez, Isidoro; Sepulveda-Crespo, Daniel; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Comisión Europea. NextGenerationEU; Centro de Investigación Biomédica en Red - CIBERBBN (Bioingeniería, Biomateriales y Nanomedicina)
Dengue nanosensors promise much but have failed in clinical application. This paradox stems from a focus on record sensitivity over real-world robustness. We propose a paradigm shift from materials discovery to product engineering, providing a translational roadmap to guide viable diagnostics from the lab bench to the patient.
Challenges in accurate HDV RNA quantification: inter-assay variability and the impact of thermal shock.
(American Society for Microbiology (ASM), 2026-02-11) Pérez-García, Felipe; Virseda-Berdices, Ana; Pita-Martínez, Carlos; Muñoz Monte, Mario; Sepulveda-Crespo, Daniel; Codina Márquez, Helena; Alonso, Roberto; Mesones, Lara; Rodrigo, Sandra; Macías, Juan; Real, Luis Miguel; Cuadros-González, Juan; Martinez, Isidoro; Resino, Salvador; Certest Biotech; Fundación para la Investigación Biomédica del Hospital Universitario Príncipe de Asturias; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Comisión Europea. NextGenerationEU; European Society of Clinical Microbiology and Infectious Diseases
Quantitative RT-PCR (qRT-PCR) is essential for monitoring hepatitis delta virus (HDV) RNA, yet assays lack standardization. We aimed to evaluate the performance of three qRT-PCR assays and to assess the impact of a pre-analytical thermal shock procedure. We conducted a comparative study using 206 samples (106 with anti-HDV antibodies and 100 anti-HDV-negative as a control group), which were tested in parallel with three qRT-PCR assays: Vircell, Certest, and Altona. Performance was evaluated for inter-assay agreement (kappa index), quantitative correlation (R²), and bias (Bland-Altman). Altona detected 56 HDV-RNA positive samples, whereas Vircell and Certest detected 55 positive samples. Inter-assay agreement was perfect comparing Vircell vs Certest (agreement = 100%, к = 1.000) and almost perfect comparing Altona with both Vircell and Certest (agreement = 99.5%, к = 0.988). Quantitatively, Vircell and Certest assays showed relevant systematic biases compared to Altona, overestimating viral loads by approximately 0.24 log International Units (IU)/mL (Certest) and 0.33 log IU/mL (Vircell). The correlation with Altona was strong for Certest (R² = 0.864) and moderate for Vircell (R² = 0.793), while the correlation between Certest and Vircell was weaker (R² = 0.720). Thermal shock improved sensitivity in one case (Certest vs Vircell) but increased quantitative variability, worsening the inter-assay correlation (R² = 0.684). In conclusion, all three assays were highly concordant for the qualitative diagnosis of HDV infection, but their quantitative biases prevent their interchangeable use for treatment monitoring. Thermal shock is not recommended for routine monitoring, as a significant compromise in quantitative accuracy and precision outweighs any potential gains in sensitivity.IMPORTANCEThis study evaluates three hepatitis delta virus (HDV) RNA quantitative real-time PCR (qRT-PCR) assays, crucial for managing the HDV infection, particularly in the setting of new therapies like Bulevirtide, where assessing viral load reduction and accurate monitoring is paramount. We reveal significant quantitative biases among widely used assays, precluding their interchangeable use and risking misinterpretation of treatment response. Furthermore, our systematic assessment of the thermal shock pre-analytical procedure highlights its detrimental impact on quantitative precision, despite modest sensitivity gains. This work provides essential evidence for clinicians and laboratories, guiding assay selection and standardization efforts to optimize HDV diagnosis and patient monitoring.
Sex and age-related differences in humoral and cellular responses to the recombinant zoster vaccine in people living with HIV.
(Elsevier, 2025-11) Díez, Cristina; Pita-Martínez, Carlos; Quero-Delgado, Marta; Gómez-Tórtola, Aurora; Fanciulli, Chiara; Marchan, Ana; Aldámiz-Echevarría, Teresa; Sepulveda-Crespo, Daniel; Tejerina, Francisco; Pérez-Latorre, Leire; Gutiérrez, Isabel; López, Juan Carlos; Martinez, Isidoro; Resino, Salvador; Agencia Estatal de Investigación (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Instituto de Salud Carlos III; Unión Europea. Comisión Europea. NextGenerationEU
Background: Data on the immunogenicity of the recombinant zoster vaccine (RZV) in people living with HIV (PLWH) are limited, despite their high risk for herpes zoster. This study aimed to characterize the humoral (Varicella-zoster virus (VZV)-specific IgG) and cellular (VZV-specific IFN-γ/IL-2 T-cell) immune responses to RZV in PLWH on suppressive antiretroviral therapy (ART), stratified by sex and age. Methods: This prospective study enrolled 207 PLWH on suppressive ART who received two doses of RZV. VZV-specific IgG antibody titers were quantified by in-house ELISA at baseline and post-vaccination and T-cell responses using FluoroSpot assays post-vaccination. We estimated geometric mean titers (GMTs), geometric mean fold rises (GMFRs), and adjusted arithmetic mean ratios (aAMRs) using generalized linear models. Results: RZV vaccination induced a significant humoral response, with an overall GMFR of 16.7 and a 71 % positive response rate (≥4-fold rise in IgG titers). Females < 60 years old exhibited a markedly higher GMFR (43.8) than all other subgroups (p < 0.05). The vaccine also induced robust VZV-specific T-cell responses, with GMTs being comparable across all groups. Notably, a strong positive association was found between humoral and T-cell responses, particularly with IL-2-secreting cells (aAMR=1.6, p < 0.001). This association was most pronounced in participants < 60 years, especially females, and was attenuated in older individuals. Conclusions: RZV vaccination effectively induces both humoral and T-cell immunity in PLWH. However, host factors, such as sex and age, critically modulate immunogenicity. Females < 60 years showed a superior humoral response and the strongest association between immune compartments, highlighting important variability in vaccine responsiveness.
Identification and functional insights into new phage tail-like bacteriocins targeting as new antimicrobials.
(American Society for Microbiology (ASM), 2026-03-24) Ibarguren-Quiles, Clara; Blasco, Lucía; López-Causape, Carla; Bleriot, Inés; Fernández-García, Laura; Arman, Lucia; Barrio-Pujante, Antonio; Ortiz-Cartagena, Concha; Aracil, Belen; Menéndez-Rodriguez, Olaya; Mariñas-Pardo, Luis; Cantón, Rafael; Oliver, Antonio; Tomás, María; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Ministerio de Ciencia, Innovación y Universidades (España); Unión Europea. Comisión Europea. NextGenerationEU; Xunta de Galicia (España)
The current health crisis caused by multidrug-resistant (MDR) pathogens is one of the health problems of most concern globally. Infections caused by these pathogens, such as , lead to high rates of complications, particularly in compromised patients such as cystic fibrosis (CF) patients. The need to counteract and minimize the forecast future impact has led to the rescue of phage therapy. The use of bacteriophages has important advantages, including highly specific targeting, self-amplification at the infection site, minimal disruption of the microbiome, safety, and biocompatibility. However, the capacity of bacteria to escape these entities results in a form of resistance that compromises the effectiveness of the therapy. This involves the search for potential alternatives, such as the phage tail-like bacteriocins (PTLBs), also named as tailocins. These high-molecular-weight particles resemble the tail structure of bacteriophages and are characterized by the absence of genetic material, avoiding the development of resistance, one of the major handicaps associated with phage therapy. In this study, we detected 34 different PTLBs in 75 genomes, with different serotypes and sequence types, 11 of which were characterized as novel F-type PTLB subtypes (F13-F24). Furthermore, we report that four selected PTLBs (R1, F15, F19, and R3-F24) can deal with bacterial infection, with the R1 and the F15 PTLBs being the most efficient in clearing infection , yielding a survival rate of more than 75% in the larvae model. This reaffirms the potential of PTLBs to control infections, which can cause chronic infections in some patients, such as people with CF, due to its strong impact as a MDR bacterium.IMPORTANCEThe 75 genomes from people with cystic fibrosis in the study collection included at least one phage tail-like bacteriocins (PTLB) cluster. From the 34 different PTLBs detected in the study collection, 7 were R-type, 10 were complex (R- and F-type encoded), and 14 were F-type PTLBs. Eleven new F-type PTLBs were described in the collection under study. An association between the O-antigen present on the surface of the isolate and the encoded PTLB subtype was detected. The R1 and F15 PTLB subtypes display high antimicrobial activity both in vitro and in vivo (Galleria mellonella).
Advances in Nanotechnology-Enabled Optical Biosensors for Dengue Virus Detection: A Systematic Review.
(Wiley, 2025-07-29) Quero-Delgado, Marta; Codina Márquez, Helena; Gómez, Rafael; Terán, Francisco José; Muñoz-Fernández, M A; Jiménez, José Luis; Resino, Salvador; Sepulveda-Crespo, Daniel; Martinez, Isidoro; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Centro de Investigación Biomédica en Red - CIBERBBN (Bioingeniería, Biomateriales y Nanomedicina); Comunidad de Madrid (España)
The dramatic surge in dengue cases in early 2024, endangering half the global population, urgently necessitates faster diagnostic methods. Nanotechnology-enabled optical biosensors offer a promising avenue, leveraging nanomaterial properties for highly sensitive detection of dengue virus (DENV), potentially surpassing conventional techniques in terms of simplicity, speed, and cost-effectiveness. This systematic review analyzes recent advancements in these biosensors for DENV diagnosis. Following PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases (2010-June 1, 2025; OSF: https://osf.io/3gmey/). The methodological quality of the 98 included studies was assessed using a modified CASP checklist. Diverse nanotechnology-based optical biosensors were identified. SPR (36.7%) was the most common transducer, followed by fluorescence (24.5%), colorimetry (15.3%), and SERS (8.2%). Gold-based nanomaterials (35.7%) were most frequently employed, with silver nanomaterials (15.3%), quantum dots (15.3%), and graphene-based materials (15.3%) also showing promise. DENV NS1 protein was the primary target analyte (21.4%). Importantly, almost half of the studies (44.9%) used clinically relevant human samples. While many optical biosensors show promise, challenges hinder their demonstration of the true potential for point-of-care use in their current format; however, they offer high specificity and faster results, laying a strong foundation for cost-effective clinical diagnostics. Nanotechnology-driven optical biosensors offer a transformative approach for DENV detection. Advances in computational design and green synthesis of novel nanomaterials are key to addressing stability and field-deployment challenges. These innovations are crucial for developing robust, sensitive, and user-friendly tools to manage dengue and improve patient outcomes globally.
From Management to Cure: The Shifting Paradigm in HIV and Chronic Viral Hepatitis.
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-07-11) Sepulveda-Crespo, Daniel; Resino, Salvador
The management of human immunodeficiency virus (HIV) and chronic viral hepatitis (HBV, HCV, and HDV) infections continues to pose a significant global health challenge [...].
Prevalence and risk factors of active hepatitis C infection among at-risk migrant populations in Madrid, Spain, 2019 to 2023.
(European Centre for Disease Prevention and Control (ECDC), 2025-07) Ryan, Pablo; Valencia, Jorge; Pérez-García, Felipe; Quero-Delgado, Marta; Cuevas, Guillermo; Manzano, Samuel; Estévez, Samuel; Martinez, Isidoro; Sepulveda-Crespo, Daniel; Resino, Salvador; Gilead Sciences (Spain); Instituto de Salud Carlos III; AbbVie; Asociación Española para el Estudio del Hígado; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Background: Hepatitis C virus (HCV) microelimination among at-risk migrants supports global elimination goals.AIMTo evaluate risk factors, prevalence and trends of active HCV infection among at-risk migrants screened for HCV in Madrid from 2019-23. Methods: At-risk migrants (born outside Spain, living in country < 10 years regardless of legal status), were screened for HCV via mobile units with rapid antibody testing, and confirmed by RNA testing. Recruitment of this convenience sample focused on migrant centres, shelters, harm reduction centres and social service sites. Primary outcome was active HCV prevalence. Risk factors analysed included origin, alcohol use, no stable income, drug use and sexual behaviour. Data were analysed using general linear models with negative binomial distribution and p values adjusted for multiple comparisons (q values). Results: TSAmong 2,288 migrants, 6.5% (149/2,288) had anti-HCV antibodies, 47.0% (70/149) of whom tested positive for HCV-RNA; 81.4% (57/70) began antiviral therapy. Overall prevalence of active HCV infection was 3.1% (70/2,288). Injection drug use (non-active vs never used (aIRR: 7.3; 95% CI: 2.7-12.7) and active (aIRR: 14.7; 95% CI: 6.7-32.1)), European origin (vs non-European; aIRR: 5.8; 95% CI: 2.7-12.7) and alcohol misuse (vs no misuse; aIRR: 1.8; 95% CI: 1.1-2.9) were main risk factors. Prevalence showed no significant change during 2019-23 in the overall population and across risk groups. Conclusion: At-risk migrants screened in Madrid had a high prevalence of active HCV infection. This is higher than reported estimates for the general Spanish population and supports the need to enhance targeted HCV prevention, screening and treatment strategies among migrant populations.
Persistent Low Anti-HIV Neutralizing Antibody Titers in HIV/HCV Coinfection Despite HCV Cure: A 5-Year Longitudinal Analysis.
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-05-19) Sepulveda-Crespo, Daniel; Sánchez-Merino, Víctor; Amigot-Sánchez, Rafael; Rubio-Pérez, Almudena; Díez, Cristina; Hontañón, Víctor; Berenguer, Juan; González-García, Juan; García, Felipe; Martinez, Isidoro; Yuste, Eloísa; Resino, Salvador; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Background: Anti-HIV neutralizing antibodies (anti-HIV-nAbs) play a critical role in the immune defense against HIV by preventing viral entry and limiting replication. This study longitudinally evaluated the titers and variability of anti-HIV-nAbs in individuals coinfected with HIV and HCV. Samples were collected at three time points: before starting HCV treatment, one year after completion, and five years post-treatment. Methods: A retrospective analysis was conducted on 71 HIV/HCV-coinfected patients who achieved a sustained virologic response following antiviral therapy for HCV. A control group of 41 HIV-monoinfected individuals was also included. Anti-HIV-nAb titers were evaluated by HIV neutralization assays using a panel of six recombinant HIV viruses representing multiple genetic subtypes. Generalized Linear Mixed Models and Generalized Linear Models were used for statistical analysis. p-values were adjusted using the Benjamini-Hochberg procedure (q-value). Results: HIV-neutralizing antibody responses in HIV/HCV-coinfected individuals remained stable over five years following HCV therapy without significant changes (q-value > 0.05). The mean neutralization scores remained stable, with baseline scores of 6.1 (95% CI: 5.4-6.7), 6.2 (95% CI: 5.5-6.8) at one year post-HCV therapy, and 6.0 (95% CI: 5.3-6.7) at five years post-HCV therapy. HIV/HCV-coinfected individuals consistently showed lower neutralization scores compared to the control group throughout the follow-up (q-value < 0.05). Regression analyses adjusted for age, gender, nadir CD4+, and baseline CD4+ counts confirmed that the observed differences between HIV-monoinfected and HIV/HCV-coinfected individuals persisted (q-value < 0.05) at both the baseline and after HCV therapy completion. Conclusions: Successful HCV eradication in HIV/HCV-coinfected individuals did not normalize anti-HIV-nAb titers, which remained consistently lower than those in HIV-monoinfected controls over five years.
Antibody Response Against SARS-CoV-2 Spike Protein in People with HIV After COVID-19 Vaccination.
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-04-29) Muñoz-Gómez, María José; Ryan, Pablo; Quero-Delgado, Marta; Martin-Vicente, Maria; Cuevas, Guillermo; Valencia, Jorge; Jiménez, Eva; Blanca-López, Natalia; Manzano, Samuel; Lazo, Juan Ignacio; Mas, Vicente; Vázquez, Mónica; Sepulveda-Crespo, Daniel; Torres-Macho, Juan; Martinez, Isidoro; Resino, Salvador; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
People with HIV (PWH) often have a suboptimal response to vaccines, raising concerns regarding the efficacy of coronavirus disease 2019 (COVID-19) vaccines in this population. We aimed to evaluate the humoral immune response to the B.1 lineage and Omicron variant in PWH on antiretroviral therapy (ART) following COVID-19 vaccination. : We conducted a prospective study of 19 PWH on ART who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. Participants without HIV infection (n = 25) were included as a healthy control (HC) group. The humoral response to the COVID-19 vaccine (anti-SARS-CoV-2 S IgG levels and ability to block ACE2-S interaction) against both the original B.1 lineage and the Omicron variant was assessed using immunoassays. : The humoral response in PWH was very strong (geometric mean fold rise, GMFR > 8) after the second dose and strong (GMFR > 4) after the booster dose for both the B.1 lineage and the Omicron variant. We found comparable humoral responses to the B.1 lineage and Omicron variant between PWH and HC groups after the second and booster doses (q-value > 0.05). The COVID-19 vaccine generated a significantly weaker humoral response against the Omicron variant compared to the B.1 lineage in both groups (q-value < 0.05). However, this response improved after the booster dose, although it remained weaker in PWH. : PWH showed a strong humoral response to the COVID-19 vaccine against B.1 and Omicron, though the Omicron response was weaker than B.1. Booster doses in PWH improved the Omicron response, but it stayed lower than B.1. Findings confirm vaccine effectiveness in PWH, stressing the critical role of boosters and potential need for updated vaccines for variants like Omicron.
Diagnostic performance of dried blood spot hepatitis C virus core antigen testing for hepatitis C screening: A systematic review and meta-analysis.
(Wiley, 2024-10) Treviño-Nakoura, Ana; Sepulveda-Crespo, Daniel; Bellon, José M; Codina, Helena; Amigot-Sánchez, Rafael; Quero-Delgado, Marta; Ryan, Pablo; Martinez, Isidoro; Resino, Salvador; Instituto de Salud Carlos III; Gilead Sciences (Spain); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Dried blood spot (DBS) sampling is increasingly used for hepatitis C virus (HCV) screening. HCVcAg testing offers a faster and more streamlined approach to diagnosing HCV infection. We conducted a systematic review and meta-analysis to assess the diagnostic performance of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection using DBS samples. Eight studies (n = 1229) were selected among all published studies available up to October 4, 2024, in different databases with a search strategy registered (PROSPERO: CRD42022363975). The gold standard method was the HCV PCR test. Data were analyzed using the MIDAS module in STATA with a random effects model. Combined diagnostic accuracy measures were as follows: sensitivity 85%, specificity 100%, positive likelihood ratio (PLR) 233.1, negative likelihood ratio (NLR) 0.15, and summary receiver operating characteristic (SROC) 0.99. Likelihood ratios and Fagan's nomogram suggested that the HCVcAg assay with DBS samples can confirm or rule out active HCV infection with over 92% accuracy in high-prevalence settings (≥5%). However, in low-prevalence settings (≤1%), a confirmatory test must be required for positive results. The ability of the test to identify people without HCV infection was high regardless of HCV prevalence, with an error rate of less than 3%. This meta-analysis is subject to limitations, particularly due to the number of included studies and significant heterogeneity among them. HCV screening using the Abbott ARCHITECT HCV Ag assay with DBS samples showed excellent diagnostic performance, but its external validity may be limited when HCV prevalence is low (≤1%).
IL7RA rs10491434 polymorphism is related to spontaneous HIV infection control in naïve HIV-infected patients: A retrospective study.
(Wiley, 2023-11) Sepulveda-Crespo, Daniel; Jimenez-Sousa, Maria Angeles; Fernandez-Rodriguez, Amanda; Muñoz-Fernández, María A; Jiménez, José L; Caraciolo, Begoña B; Reus Bañuls, Sergio; Vilchez, Helem; Mothe, Beatriz; Martinez, Isidoro; Benito, José M; Rallón, Norma; Resino, Salvador; Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Redes Temáticas de Investigación Cooperativa en Salud (RETICS) (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Comisión Europea. NextGenerationEU
Interleukin 7 receptor (IL7R) is vital in the adaptive immune response against human immunodeficiency viruses (HIV). We assessed IL7RA polymorphisms (SNPs) in antiretroviral therapy (ART)-naïve HIV patients for their association with spontaneous HIV infection control. We conducted a retrospective cohort study involving 667 ART-naïve patients categorized by HIV progression (ordinal variable): 150 rapid progressors, 334 moderate/typical progressors, 86 long-term nonprogressors elite controllers (LTNPs-EC), and 97 LTNPs-non-EC. We genotyped three IL7RA SNPs using Agena Bioscience's MassARRAY platform. The association between IL7RA SNPs and spontaneous HIV infection control was evaluated using ordinal logistic regression. Individuals carrying the rs10491434 G allele have a higher likelihood of spontaneous HIV infection control (adjusted odds ratio [aOR] = 1.33; p = 0.023). Moreover, the IL7RA GCT haplotype, consisting of three specific SNPs (rs6897932, rs987106, and rs10491434), demonstrated an association with the control of untreated HIV infection (aOR = 1.34; p = 0.050). Remarkably, the rs10491434 SNP and the IL7RA GCT haplotype exhibited similar aOR values, suggesting that rs10491434 may be primarily responsible for the observed effect of the haplotype. IL7RA rs10491434 G allele is associated with a higher likelihood of spontaneous HIV infection control, indicating its significant role in the pathogenesis of HIV, possibly influencing infection course and viral replication control.
IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination.
(Springer Nature, 2024-06) Muñoz-Gómez, María José; Martin-Vicente, Maria; Vigil-Vazquez, Sara; Carrasco, Itziar; Lobo, Alicia Hernanz; Mas, Vicente; Vázquez, Mónica; Manzanares, Angela; Cano, Olga; Zamora, Clara; Alonso, Roberto; Sepulveda-Crespo, Daniel; Tarancon-Diez, Laura; Muñoz-Fernández, María Ángeles; Muñoz-Chapuli, Mar; Resino, Salvador; Navarro, Maria Luisa; Martinez, Isidoro; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Centro de Investigación Biomédica en Red - CIBERBBN (Bioingeniería, Biomateriales y Nanomedicina)
Purpose: We aimed to assess IgG antibodies against the SARS-CoV-2 spike protein (anti-SARS-CoV-2 S IgG) in vaccinated mothers and their infants at delivery and 2-3 months of age. Methods: We conducted a prospective study on mothers who received at least one dose of the COVID-19 vaccine (Pfizer-BNT162b2, Moderna mRNA-1273, or Oxford-AstraZeneca ChAdOx1-S) during pregnancy and on their infants. The baseline was at the time of delivery (n = 93), and the end of follow-up was 2 to 3 months post-partum (n = 53). Serum anti-SARS-CoV-2 S IgG titers and ACE2 binding inhibition levels were quantified by immunoassays. Results: Mothers and infants had high anti-SARS-CoV-2 S IgG titers against the B.1 lineage at birth. However, while antibody titers were maintained at 2-3 months post-partum in mothers, they decreased significantly in infants (p < 0.001). Positive and significant correlations were found between anti-SARS-CoV-2 S IgG titers and ACE2-binding inhibition levels in mothers and infants at birth and 2-3 months post-partum (r > 0.8, p < 0.001). Anti-S antibodies were also quantified for the Omicron variant at 2-3 months post-partum. The antibody titers against Omicron were significantly lower in mothers and infants than those against B.1 (p < 0.001). Again, a positive correlation was observed for Omicron between IgG titers and ACE2-binding inhibition both in mothers (r = 0.818, p < 0.001) and infants (r = 0.386, p < 0.005). Previous SARS-CoV-2 infection and COVID-19 vaccination near delivery positively impacted anti-SARS-CoV-2 S IgG levels. Conclusions: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.
Recently acquired hepatitis C: Epidemiological characteristics and treatment response in a large cohort of MSM living with HIV in Madrid.
(Elsevier, 2024-10) Martín-Carbonero, Luz; Gutierrez, Ángela; Bisbal, Otilia; Vergas, Jorge; González-Baeza, Alicia; Rodríguez Martín, Carmen; Vivancos, María Jesús; Sanz, José; Álvarez, Beatriz; Palomar, Marina; de Los Santos, Ignacio; Sepulveda-Crespo, Daniel; Resino, Salvador; Berenguer, Juan; Cano-Smith, Joanna; González-García, Juan; Ryan, Pablo; Instituto de Salud Carlos III
Introduction: We analyzed epidemiological, clinical characteristics, and the response to treatment in people living with HIV (PLHIV) who recently acquired hepatitis C (RAHC) in a multicentre study in Madrid (Spain). Methods: Multicenter, ambispective, observational study of RAHC in men who have sex with men (MSM) infected with HIV. Clinical, epidemiological, and RAHC evolution were recorded prospectively in 2019 and 2020 and retrospectively in 2017 and 2018. In patients who received HCV treatment, sustained virological response (SVR) was provided 12 weeks after the end of treatment in an intention to treat analysis (ITT): all treated patients were included; and in analysis per-protocol (PP): missing patients were excluded. Results: Overall, 133 patients were included. Median (IQR) age was 40 (34.3-46.1) years, 90.9% had at least one previous sexual transmission disease (STD), and 33.6% had previously hepatitis C. More than half of the prospective sample included patients using chemsex related drugs (57.3%), 45.7% of them intravenously. The most prevalent genotype was G1a (66.2%), followed by G4 (11.3%). Ten of 90 patients evaluated for spontaneous cure (11%) cured the infection spontaneously, and 119 had treatment after a median time of 1.8 (0.7-4.6) months: sustained virological response (SVR) was achieved in 90.7% in the ITT and 94.7% in the PP analysis, with no differences regarding the direct-acting antiviral agents (DAA) combination used. Conclusions: MSM infected by HIV with a RAHC were exposed to high-risk sexual behavior. Spontaneous cure rate was low, while SVR after treatment was achieved by more than 90%.
IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.
(Wiley, 2023-06) Sepulveda-Crespo, Daniel; Jimenez-Sousa, Maria Angeles; Fernandez-Rodriguez, Amanda; Muñoz-Fernández, María A; Jiménez, José Luis; Moreno, Santiago; Garcia, Felipe; Martinez, Isidoro; Benito, José M; Rallón, Norma; Resino, Salvador; Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Plan Nacional de I+D+i (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Comisión Europea. NextGenerationEU; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Redes Temáticas de Investigación Cooperativa en Salud (RETICS) (España)
IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4 ≥ 500 cells/mm , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.

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