High-pressure x-ray diffraction and ab initio study of Ni2Mo3N, Pd2Mo3N, Pt2Mo3N, Co3Mo3N, and Fe3Mo3N: Two families of ultra-incompressible bimetallic interstitial nitrides

We have studied by means of high-pressure x-ray diffraction the structural stability of Ni2Mo3N, Co3Mo3N, and Fe3Mo3N. We also report ab initio computing modeling of the high-pressure properties of these compounds, Pd2Mo3N, and Pt2Mo3N. We have found that the nitrides remain stable in the ambient-pressure cubic structure at least up to 50 GPa and determined their equation of state. All of them have a bulk modulus larger than 300 GPa. Single-crystal elastic constants have been calculated in order to quantify the stiffness of the investigated nitrides. We found that they should have a Vickers hardness similar to that of cubic spinel nitrides like gamma-Si3N4Comment: 25 pages, 6 figures, 3 table

Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016

Altres ajuts: We wish to thank I Bustillo, H del Pozo and P Higueras for their technical assistance. We also sincerely wish to thank all technical staff from microbiology departments and medical staff from paediatrics departments from all participating hospitals. Some of the samples are included in an ongoing project (PI15CIII-00020) which was supported by a grant by the Health Research System (AES).Introduction: Enterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions. Aim: Our objective was to investigate the epidemiology and clinical characteristics of the outbreak. Methods: We carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3'-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries. Results: Most EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported. Conclusion: An emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases

Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016

IntroductionEnterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions.AimOur objective was to investigate the epidemiology and clinical characteristics of the outbreak.MethodsWe carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3'-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries.ResultsMost EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported.ConclusionAn emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases.S

Incidence, clinical characteristics and management of inflammatory bowel disease in Spain: large-scale epidemiological study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100, 000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Annual Epidemiological Report: Acute Flaccid Paralysis Surveillance and Enterovirus Surveillance, Spain, 2019

Centro Nacional de Epidemiología y Centro Nacional de Microbiología. ISCIII. Plan de acción en España para la Erradicación de la Poliomielitis. Vigilancia de la Parálisis Flácida Aguda y Vigilancia de Enterovirus en España, año 2019. Madrid, 1 julio 2020.[ES]Los resultados de la vigilancia de parálisis flácida aguda (PFA) y de la vigilancia de enterovirus (EV) muestran que en España en el año 2019 no hubo casos de poliomielitis ni circulación de poliovirus. La sensibilidad del sistema está por debajo del objetivo establecido por la OMS–Europa de 1 caso de PFA al año por cada 100.000 menores de 15 años, al situarse en 0,55/104 hab (0,58/104 <15años en 2018 ). Sin embargo, su estudio una vez detectados es adecuado. El índice de vigilancia, que sintetiza la sensibilidad del sistema de vigilancia y su estudio en laboratorio, fue de 0,28, similar a otros años. Gracias a la vigilancia de EV se detectó un PV derivado de vacuna (PVDV) en un paciente excretor inmunodeprimido; además se hallaron diferentes EV-no polio, los serotipos identificados fundamentalmente fueron E-7, E-30, E-11, CV-A6 y E-13. En 2019 la OMS declaró la eliminación del PV salvaje tipo 3(PVS3) a nivel mundial, aunque resulta preocupante el aumento en la detección de PVS1 y PVDVc 2 tanto en muestras humanas como medioambientales. La Evaluación de la Comisión Regional de Certificación clasifica a España en 2018 como de riesgo bajo de transmisión de poliovirus. En Europa hay tres países con riesgo alto, debido fundamentalmente a la baja inmunidad de su población. Hay que mantener los sistemas ya establecidos de vigilancia de la circulación de EV -polio y no polio- (vigilancia de PFA, meningitis víricas y EV), de manera que permitan detectar a tiempo la circulación inesperada de un poliovirus o de otro tipo de EV clínicamente relevante. [EN]The results of acute flaccid paralysis (AFP) and enterovirus (EV) surveillance show that there were no cases of polio or poliovirus circulation in Spain in 2019. The sensitivity of the system is below the target set by WHO-Europe of 1 case of AFP per year per 100,000 children under 15 years, at 0.55/104 inhab (0.58/104 <15 years in 2018 ). However, their study once detected is adequate. The surveillance index, which synthesizes the sensitivity of the surveillance system and its laboratory study, was 0.28, similar to other years. Thanks to the surveillance of EV, a vaccine derived PV (PVDV) was detected in an immunosuppressed excretory patient; in addition, different non-polio-EV were found. The serotypes identified were mainly E-7, E-30, E-11, CV-A6 and E-13. In 2019 the WHO declared the elimination of wild PV type 3 (PVS3) worldwide, although the increase in detection of PVS1 and cVP2 in both human and environmental samples is of concern. The evaluation of the Regional Certification Commission classifies Spain in 2019 as having a low risk of poliovirus transmission. In Europe there are three countries at high risk, mainly due to the low immunity of their population. The already established systems for surveillance of the circulation of EV-polio and non-polio- (surveillance of AFP, viral meningitis and EV) must be maintained, so that the unexpected circulation of a poliovirus or other clinically relevant EV can be detected in time.N

Plan de Acción en España para la erradicación de la poliomelitis: Vigilancia de la Parálisis Flácida Aguda y Vigilancia de Enterovirus en España. Informe 2020

Centro Nacional de Epidemiología y Centro Nacional de Microbiología. ISCIII. Plan de acción en España para la Erradicación de la Poliomielitis. Vigilancia de la Parálisis Flácida Aguda y Vigilancia de Enterovirus en España, Informe año 2020. Madrid, 5 de noviembre de 2021.[ES] En España la situación libre de polio se monitoriza con la vigilancia de Parálisis Flácida Aguda (PFA) en niños menores de 15 años, como recomienda la Organización Mundial de la Salud (OMS). La vigilancia la realizan los servicios de vigilancia autonómicos y la red de laboratorios de PFA y a nivel nacional se coordina en el Centro Nacional de Epidemiología (CNE, ISCIII) y en el Laboratorio de Poliovirus del Centro Nacional de Microbiología (CNM, ISCIII). En el año 2020 en España no hubo casos de poliomielitis. Se notificaron 0,17 casos de PFA por 100.000 niños menores de 15 años, por debajo del objetivo de sensibilidad establecido por la OMS de un caso de PFA al año por cada 100.000 menores de 15 años. Solamente se detectaron enterovirus no-polio (EVNP) en las muestras de dos casos (EV-D68 y EV-B, respectivamente). En España también se realiza la vigilancia de EVNP en otros síndromes neurológicos para complementar el sistema de vigilancia de PFA. En las muestras investigadas en 2020 no se identificó ningún poliovirus y los EVNP más frecuentemente identificados fueron E-18, CV-A6 y E-21. Mientras haya circulación de poliovirus en el mundo hay que mantener activos los sistemas de vigilancia para detectar a tiempo cualquier importación de poliovirus. [EN] Spain monitors its polio-free status by conducting surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age, as recommended by the World Health Organization (WHO). The AFP surveillance is performed by the 19 Regional Epidemiological Surveillance Units and the AFP Surveillance Laboratory Network, coordinated at national level by the National Centre for Epidemiology (CNE. ISCIII) and the National Poliovirus Laboratory at Nacional Center of Microbiology (CNM. ISCIII) respectively. In 2020, no cases of poliomyelitis were reported from clinical surveillance; Spain reported 0.17 non-polio AFP cases per 100,000 children, below the WHO's performance criterion for a sensitive surveillance system (1 non-polio AFP cases per 100,000 children). The non-polio enteroviruses EV-D68, EV-B were identified from clinical specimens collected from AFP cases. Spain also performs enterovirus surveillance to complement the clinical system In 2020, non poliovirus were identified; The non-polioviruses E-18, CV-A6 y E-21 were the most frequently identified serotypes. As long as poliovirus is circulating in the world, surveillance systems must remain active to detect any importation of poliovirus in a timely manner.1. Resumen. 2. Introducción. 3. Resultados de la vigilancia de Parálisis Flácida Aguda (PFA) en España, 2020. 4. Resultados de la vigilancia de enterovirus, España 2020. 5. Resultados de la vigilancia medioambiental de poliovirus. España, 2020. 6. Sistema de Información Microbiológica (SIM). Meningitis por enterovirus. Tendencia. 7. Conclusiones.N

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Characterisation of SARS-CoV-2 lineages during June 2020 in Aragon, Spain

Trabajo presentado al 31st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), celebrado online del 9 al 12 de julio de 2021.Peer reviewe