Browsing by Author "Tarrago Asensio, David"
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Publication Brotes epidémicos y situaciones de alerta sanitaria de probable etiología vírica en el Centro Nacional de Microbiología durante el período 2012-2013.(Ministerio de Sanidad y Consumo (España), 2016-03-23) Echevarria, Jose Manuel; Avellón, Ana; Cabrerizo, Maria; Casas Flecha, Inmaculada; Echevarria, Juan Emilio; De Ory, Fernando de; Negredo, Anabel; Pozo Sanchez, Francisco; Sánchez-Seco, María Paz; Tarrago Asensio, David; Trallero, GloriaLos Planes Nacionales de erradicación o eliminación de la poliomielitis, el sarampión y la rubéola congénita establecen el papel a jugar por el Centro Nacional de Microbiología (CNM) en la vigilancia de esas enfermedades víricas. Además, el Sistema de Vigilancia de la Gripe en España el Real Decreto 1940/2004 sobre Vigilancia de las Zoonosis y el Plan de Contingencia contra la Rabia lo hacen también en lo relativo a la gripe y a las zoonosis víricas. Los resultados derivados de estas actividades se comunican con mayor o menor amplitud y regularidad.Publication Cytomegalovirus drug resistance mutations in transplant recipients with suspected resistance(BioMed Central (BMC), 2023-07-18) Recio Huertas, Vanessa; Gonzalez-Jimenez, Irene; Tarrago Asensio, David; Instituto de Salud Carlos III; Consejo Superior de Investigaciones Científicas (España); Conferencia de Rectores de las Universidades Españolas; Agencia Estatal de Investigación (España)Resistant CMV infections are challenging complications after SOT and HSCT. Prompt recognition of ARMs is imperative for appropriate therapy. 108 plasma samples from 96 CMV + transplant recipients with suspected resistance were analysed in CNM in a retrospective nationwide study from January 2018 to July 2022 for resistance genotyping. ARMs in UL97 and UL54 were found in 26.87% (18/67) and 10.60% (7/66) of patients, respectively. Patients' ARM distribution in UL97 was as follows: L595S n = 3; L595S/M460I n = 1; L595S/N510S n = 1; L595W n = 1; C603W n = 4; A594V n = 3; A594E n = 1; C607Y n = 1; L397R/T409M/H411L/M460I n = 1; L397I n = 1; H520Q n = 1; four patients showed ARMs in UL54 as well (F412C n = 1; T503I n = 2; P522S n = 1), whereas three patients exhibited ARMs in UL54 only (L501I/T503I/L516R/A834P n = 1; A987G n = 2). L516R in UL54 and L397R/I and H411L in UL97 have been found for the first time in a clinical sample. L595S/W was the most prevalent ARM found to lend resistance to GCV. In UL54 all ARMs lent resistance to GCV and CDV. In addition, A834P, found in one patient, also lent resistance to FOS. CMV load did not differ significantly in patients with or without ARMs, and no differences were found either between patients with ARMs in UL97 or in UL97 and UL54. Despite extensive use of classical antivirals for the treatment of CMV infection after HSCT and SOT, ARMs occurred mainly in viral UL97 kinase, which suggests that CDV and mostly FOS continue to be useful alternatives to nucleoside analogues after genotypic detection of ARMs.Publication Cytomegalovirus resistance in transplant patients Review(Peertechz Publications, 2023) Tarrago Asensio, DavidPublication Encephalitis associated with human herpesvirus-7 infection in an immunocompetent adult(BioMed Central (BMC), 2017-05-25) Parra, Mónica; Alcala, Adoración; Amoros, Cristina; Baeza, Anna; Galiana, Antonio; Tarrago Asensio, David; García-Quesada, Miguel Ángel; Sánchez-Hellín, VictoriaBACKGROUND: Primary Human herpesvirus-7 (HHV-7) infection usually occurs during childhood and causes several clinical manifestations: mainly exanthem subitum (roseola infantum), followed by a lifelong latent state with possible reactivation in case of immunodeficiency. Nevertheless, some considerably different approaches exist regarding the natural history of HHV-7 and the possible consequences of HHV-7 infection in immunocompetent adults. In particular, little is known about its pathogenic role in central nervous system (CNS) disease in nonimmunosuppressed adults. Specifically, in case of encephalitis, it is important to distinguish between infectious encephalitis and postinfectious encephalomyelitis for the management of patients CASE PRESENTATION: We describe here a case of encephalitis associated to human herpesvirus-7 with associated polymyeloradiculopathy in an immunocompetent patient which may contribute to the delineation of the approach to a patient profile with a similar clinical presentation and evolution to those presented in the literature. CONCLUSIONS: This case may alert clinicians to consider this specific etiology in the differential diagnosis of encephalopathy in patients with suspected infectious encephalitis who do not respond to acyclovir or in patients who develop acute polymyeloradiculopathy, considering that HHV-7 may be a pathological factor and that a timely diagnosis is crucial for the early administration of specific treatment.Publication HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection(BioMed Central (BMC), 2022-06-20) Tarrago Asensio, David; Gonzalez-Jimenez, Irene; González-Escribano, Maria Francisca; Instituto de Salud Carlos IIIBackground: Congenital cytomegalovirus immunopathogenesis is largely unknown and multifactorial due to the complex interactions between viral, maternal, placental, and child factors. Polymorphisms in the HLA-E binding UL4015-23 peptide mimics HLA-E complexed peptides from certain HLA-A, -B, -C and -G alleles, which regulate the cellular immune response driven by natural killer-cells (NK) and CD8 + T cells. The aim of this study was to compare UL4015-23 peptides distribution in congenital CMV and the counterpart HLA Class I peptides in a healthy cohort to investigate risk factors and markers for cCMV disease. In this 10-year retrospective study, the UL40 gene was directly sequenced from 242 clinical samples from 199 cases of congenital CMV (166 children and 33 pregnant or breast feeding women). Distribution of HLA-E binding UL4015-23 peptides was analyzed and compared to those of HLA Class I observed in a cohort of 444 healthy individuals. Results: Nineteen different HLA-E binding UL4015-23 peptides were found. Three of them (VMAPRTLIL, VMAPRTLLL, VMAPRTLVL) were found in 88.3% of UL40 and 100% of HLA Class I of healthy individuals. In contrast, 15 of them (10.7%) were not found in HLA Class I. The VMAPRTLFL peptide was found in 1% of UL40 and all HLA-G alleles. Significant differences in peptide (VMAPRTLIL, VMAPRTLLL, VMAPRTLVL, other UL4015-23 peptides, other HLA Class I peptides) distribution between UL4015-23 from congenital CMV and HLA-A, -B, -C and -G from healthy individuals were found. Conclusions: Our findings suggest that a mismatch between UL4015-23 peptides and HLA Class I peptides between children and mothers might play a role in congenital CMV disease, and it may account for differences in outcome, morbidity and sequelae.Publication Human Herpesvirus 8-Associated Inflammatory Cytokine Syndrome(American Medical Association, 2018-02-01) Prieto-Barrios, Marta; Aragón-Miguel, Raquel; Tarrago Asensio, David; Lalueza, Antonio; Zarco-Olivo, CarlosPublication Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis(Springer, 2024-03-04) Launes, Cristian; Camacho, Juan; Pons-Espinal, Marina; López-Labrador, F Xavier; Esteva, Cristina; Cabrerizo, Maria; Fernandez-Garcia, Maria Dolores; Fogeda, Marta; Masa-Calles, Josefa; Lopez-Perea, Noemi; Echevarria, Juan Emilio; Muñoz-Almagro, Carmen; Tarrago Asensio, David; Conferencia de Rectores de las Universidades Españolas; Consejo Superior de Investigaciones Científicas (España); Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)Purpose: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). Methods: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. Results: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. Conclusion: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.Publication Molecular epidemiology of Kaposi sarcoma virus in Spain(Public Library of Science (PLOS), 2022-10-25) Gómez González, Inmaculada; Perez-Vazquez, Maria; Tarrago Asensio, David; Instituto de Salud Carlos IIIBackground: Since human herpesvirus 8 (HHV-8) infection may be underestimated and HHV-8 subtype circulation in Spain remains unknown, a molecular epidemiologic study is highly desirable. Objectives: This study aimed to analyse HHV-8 subtype diversity and their distribution in Spain. Study design: The study included 142 HHV-8 infected patients. A nested PCR was developed in order to permit Sanger sequencing of HHV-8 K1 ORF directly from clinical samples received at the CNM from 2013 to 2021. Phylogenetic characterization was performed. Results: Genotypes A and C comprised 55.6% and 42.3% of strains. Regarding subtypes, 25.4% of strains were C3, 19.7% were A3, 14.1% were A5, and C2, A1, A4, C1, A2, C7 were 11.3%, 11.3%, 8.5%, 4.2%, 2.1% and 1.4%, respectively. Subtype E1, E2 and B1 were found in only one patient each (0.7%). The Madrid region accounted for 52.1% of patients and showed a significantly different subtype distribution compared to the others (P = 0.018). Subtypes B1, E1, and E2 were observed to appear sporadically, although overall genotypes A and subtype C3 remained the most frequent and unwavering. Subtype A3 presented the highest diversity as displayed by the highest number of clusters in phylogenetic analysis. Non-significant differences in viral loads between genotypes were found, but significantly higher viral loads in subtype C2 compared to subtype C3 was found, while no significant subtype differences were observed between subtypes within genotype A. Infections with HHV-8 were detected in 94 (66.2%) patients without KS and compared to patients with KS non-significant differences in subtype distribution were found. Conclusions: Subtype prevalence and regional distribution followed a similar pattern compared to other western European countries. Our study is the first to report HHV-8 subtypes E1 and E2 circulating in Europe that might be reflective of migration of population from Caribbean countries. Our study suggests that infection by HHV-8 is underestimated, and wider screening should be recommended for risk groups.Publication Mpox, herpes, and enteroviruses: Differential diagnosis(Wiley, 2024-01) Guillén-Calvo, Laura; Negredo, Anabel; Sánchez-Mora, Patricia; Molero, Paqui; Vazquez, Ana; Cabrerizo, Maria; Orviz, Eva; Ledesma, Juan; Estrada, Vicente; Tarrago Asensio, David; Sánchez-Seco, María Paz; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Unión Europea. Comisión Europea. NextGenerationEU; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)Publication Mutations in Coding and Non-Coding Regions in Varicella-Zoster Virus Causing Fatal Hemorrhagic Fever Without Rash in an Immunocompetent Patient: Case Report(Springer, 2023-11) Camacho, Juan; Negredo, Anabel; Carrilero, Bartolomé; Segovia, Manuel; Moreno, Antonio; Pozo Sanchez, Francisco; Echevarria, Juan Emilio; Echevarria, Jose Manuel; Sánchez-Seco, María Paz; Tarrago Asensio, David; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)Introduction: We report the case of a fatal hemorrhagic varicella primary infection in an immunocompetent man and whole-genome characterization of the virus for the investigation of biomarkers of virulence. Case: A 38-year-old patient born in Nigeria presented to the emergency department with abdominal pain and subsequently developed fatal hemorrhagic disease without skin rash. Extensive laboratory tests including serology and PCR for arenaviruses, bunyaviruses and ebolaviruses were negative. Varicella-zoster virus (VZV) PCR of sera, liver and spleen tissue samples from autopsy revealed the presence of VZV DNA. Primary infection by varicella-zoster virus with hemorrhagic manifestations was diagnosed after virological testing. The VZV genome was sequenced using a mWGS approach. Bioinformatic analysis showed 53 mutations across the genome, 33 of them producing non-synonymous variants affecting up to 14 genes. Some of them, such as ORF11 and ORF 62, encoded for essential functions related to skin or neurotropism. To our knowledge, the mutations reported here have never been described in a VZV causing such a devastating outcome. Discussion: In immunocompetent patients, viral factors should be considered in patients with uncommon symptoms or severe diseases. Some relevant mutations revealed by using whole genome sequencing (WGS) directly from clinical samples may be involved in this case and deserves further investigation. Conclusion: Differential diagnosis of varicella-zoster virus in immunocompetent adults should be considered among patients with suspected VHF, even if the expected vesicular rash is not present at admission and does not arise thereafter. Whole genome sequencing of strains causing uncommon symptoms and/or mortality is needed for epidemiological surveillance and further characterization of putative markers of virulence. Additionally, this report highlights the recommendation for a VZV vaccination policy in non-immunized migrants from developing countries.Publication Pediatric parapneumonic empyema, Spain(Centers for Disease Control and Prevention (CDC), 2008-09) Obando, Ignacio; Muñoz-Almagro, Carmen; Arroyo, Luis A; Tarrago Asensio, David; Sanchez-Tatay, David; Moreno-Perez, David; Dhillon, Sahar S; Esteva, Cristina; Hernandez-Bou, Susanna; Garcia-Garcia, Juan J; Hausdorff, William P; Brueggemann, Angela B; Instituto de Salud Carlos III; RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España); GlaxoSmithKline; Fundación CajaSol; Regional Government of Andalusia (España)Pediatric parapneumonic empyema (PPE) has been increasing in several countries including Spain. Streptococcus pneumoniae is a major PPE pathogen; however, antimicrobial pretreatment before pleural fluid (PF) sampling frequently results in negative diagnostic cultures, thus greatly underestimating the contribution of pneumococci, especially pneumococci susceptible to antimicrobial agents, to PPE. The study aim was to identify the serotypes and genotypes that cause PPE by using molecular diagnostics and relate these data to disease incidence and severity. A total of 208 children with PPE were prospectively enrolled; blood and PF samples were collected. Pneumococci were detected in 79% of culture-positive and 84% of culture-negative samples. All pneumococci were genotyped by multilocus sequence typing. Serotypes were determined for 111 PPE cases; 48% were serotype 1, of 3 major genotypes previously circulating in Spain. Variance in patient complication rates was statistically significant by serotype. The recent PPE increase is principally due to nonvaccine serotypes, especially the highly invasive serotype 1.Publication Pneumococcal serotypes in children in 4 European countries(Centers for Disease Control and Prevention (CDC), 2010-09) Hanquet, Germaine; Kissling, Esther; Fenoll, Asuncion; George, Robert; Lepoutre, Agnes; Lernout, Tinne; Tarrago Asensio, David; Varon, Emmanuelle; Verhaegen, Jan; Instituto de Salud Carlos III; GlaxoSmithKline; SanofiAfter heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non-PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999-2002 (prevaccine) and 2005-2006 (postmarketing). Vaccine coverage increased to approximately 32%-48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3-4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9-16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends.Publication Shotgun metagenomics to investigate unknown viral etiologies of pediatric meningoencephalitis(Public Library of Science (PLOS), 2023) Castellot, Andrea; Camacho, Juan; Fernandez-Garcia, Maria Dolores; Tarrago Asensio, David; Instituto de Salud Carlos IIIIntroduction: Meningoencephalitis in children poses a diagnostic challenge, as etiology remains unknown for most of patients. Viral metagenomics by shotgun sequencing represents a powerful tool for investigating unknown viral infections related to these cases. Patients and methods: In a two-year, reference-centre, retrospective study, we investigated the usefulness of viral metagenomics of cerebrospinal fluid (CSF) for the diagnosis of viral infectious meningoencephalitis in forty seven pediatric patients, forty of them previously tested negative with a routine neurologic panel of viral targets that included herpesvirus 1-3 and enterovirus. We enhanced the detection by targeting viral sequences by hybrid capture. Raw sequence data was analysed using three bioinformatics pipelines. Results: Out of forty remaining children with meningoencephalitis of unknown viral etiology, a significant detection of viral nucleic acid by shotgun sequencing was found in twenty one, which was confirmed in ten of them by specific PCR: seven human endogenous retrovirus K113 (HER K113), one parechovirus 3, one human herpesvirus 5 (HHV5); one enterovirus B (Echovirus 9). The remaining eleven CSF were not confirmed by PCR: three rotavirus, one human herpesvirus 7 (HHV7), one influenza A, one mastadenovirus C, one sindbis virus, one torque teno virus, one human immunodeficiency virus 1 (HIV-1), one human alphaherpesvirus 3 (HHV3), one human alphaherpesvirus 2 (HHV2). Conclusions: Underutilization of currently available meningitis-encephalitis diagnostic techniques such as BioFire® FilmArray® is the main cause of undiagnosed cases of meningoencephalitis. However, in this study we detected uncommon viruses that should be considered, including virus, rotavirus, sindbis virus, influenza A virus and HHV7. No other viral sequences that could be readily linked to CNS inflammation were detected. Some findings may stem from reagent or sample contamination, as seen with papillomavirus; for others, the clinical relevance of the virus remains uncertain and should be substantiated by further studies, as is the case with endogenous retrovirus K113 virus. Online bioinformatics pipeline CZID represents a valuable tool for analysing shotgun sequencing data in cases of neurological conditions with unknown etiology. Altogether, this study highlights the potential of shotgun sequencing in identifying previously unknown viral neuropathogens and sheds light on the interpretation issues related to its application in clinical microbiology.Publication Varicella-zoster virus clades circulating in Spain over two decades(Elsevier, 2019-01) González, Irene; Molina-Ortega, Alejandro; Perez-Romero, Pilar; Echevarria, Juan Emilio; He, Lante; Tarrago Asensio, David; Instituto de Salud Carlos IIIBACKGROUND: Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain. OBJECTIVES: To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016. STUDY DESIGN: In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs. RESULTS: Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001). CONCLUSIONS: Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population.