Annual Epidemiological Report: Measles and Rubella Surveillance in Spain, 2019

Centro Nacional de Epidemiología (CNE). Centro Nacional de Microbiología (CNM). Instituto de Salud Carlos III (ISCIII), CIBERESP. Plan Nacional de Eliminación del Sarampión y de la Rubeola. Informe anual 2019. Madrid, España.[ES] En España en 2019 el sarampión presentó el perfil de la fase post-eliminación: importado, casos en adultos y asociado a los entornos sanitarios. Se notificaron 287 casos de sarampión-incidencia 6,1 casos por millón de habitantes- ligeramente superior a la de años anteriores. La incidencia de rubeola fue extremadamente baja, solo tres casos confirmados incidencia de 0,06 casos por millón de habitantes. No se notificó ningún Síndrome de Rubeola Congénita. El sarampión ocurrió en personas no vacunadas –niños menores de un año y adultos mayores de 30 años. Se registraron casos en adultos que habían recibido dos dosis de vacuna, la última dosis una media de 10 años antes de contagiarse de sarampión. La falta de refuerzos naturales de la inmunidad por ausencia de circulación del virus en la población facilita la evanescencia de la inmunidad, particularmente evidente en las personas más expuestas, sobre todo trabajadores del ámbito sanitario. En 2019 el sarampión en España fue importado. Las importaciones llegaron de diferentes zonas del mundo, pero sobre todo de países europeos que estaban registrando brotes y epidemias sostenidas de sarampión. El sarampión tuvo escasa difusión en la población generando brotes de pequeño tamaño <10 casos; solo dos brotes registraron en torno a los 100 casos y en estos la transmisión en el entorno sanitario mantuvo la circulación del sarampión. Se notificaron tres casos de rubeola en personas no vacunadas que se contagiaron en el seno de un brote importado -notificado a finales de 2018– ocurrido entre personas adultas que no habían nacido en España. El sistema de vigilancia es adecuado para investigar los casos sospechosos de sarampión o rubeola una vez que se notifican; sin embargo para mantener los estándares de calidad que requiere el proceso de verificación de la eliminación tienen que mejorarse la sensibilidad en la identificación de sospechas clínicas y la oportunidad de su notificación a los servicios de vigilancia epidemiológica. El sarampión sigue siendo una amenaza trasfronteriza y solo una fuerte inmunidad de la población evitará la aparición de epidemias. La rubeola es rara y ocurre en personas susceptibles nacidas fuera de España. Las claves para mantener interrumpida la transmisión del sarampión y rubeola en España: son: mantener altas coberturas con dos dosis de vacunación infantil, promover la vacunación oportunista de adultos, viajeros y personas nacidas en otros países y zonas del mundo, asegurar la inmunidad de los profesionales del ámbito sanitario, establecer medidas de aislamiento que reduzcan la transmisión en los entornos asistenciales y mantener la calidad del sistema de vigilancia y de los laboratorios. La pandemia de COVID-19 y las medidas de control establecidas han reducido drásticamente la importación y la transmisión de sarampión en España con los últimos casos notificados en marzo 2020. Algunas incertidumbres asociadas a la situación epidémica: las restricciones en la asistencia sanitaria durante las primeras semanas de confinamiento podrían haber afectado las coberturas de vacunación, particularmente con la segunda dosis de vacuna triple vírica. La sobrecarga generada en el sistema de salud podría afectar a la vigilancia, notificación e investigación de las sospechas de sarampión o rubeola. [EN] In Spain in 2019 measles presented the profile of the post-elimination phase: imported, cases in adults and transmission associated with health environments. 287 confirmed cases of measles were reported along the year 2019, incidence of 6.1 cases per million population - slightly higher than in previous years. The incidence of rubella was extremely low, with only three confirmed cases; the incidence was 0.06 cases per million population. None Congenital Rubella Syndrome was reported. Measles occured in unvaccinated persons - children under one year and adults over 30 years of age. Cases were reported in adults who had received two doses of vaccine, the last dose on average 10 years before getting measles. The lasted lack of virus circulation in the population reduces the natural booster of immunity and consequently facilitates the evanescence of immunity, what is is particularly evident in those most exposed, especially among health care workers. In 2019 measles in Spain was imported. Importations came from different areas of the world, mostly from some European countries experiencing sustained measles outbreaks and epidemics. In general measles spread little in the population generating small size outbreaks <10 cases; In the two outbreaks that recorded about 100 cases, transmission was documented in health care facilities and among health care workers, which likely sustained transmission longer. The surveillance system is adequate to investigate suspected cases of measles or rubella once they are reported,; however, in order to maintain the quality standards required by the WHO-Europe elimination verification process, the sensitivity in the identification of clinical suspicions and the timeliness of their notification to epidemiological surveillance services must be improved. Measles remains a transboundary threat and only strong immunity of the population will prevent epidemics. Rubella is rare and occurs in susceptible persons born outside Spain. The keys to maintaining interrupted transmission of measles and rubella in Spain are: maintaining high coverage with two doses of childhood vaccination, promoting opportunistic vaccination of adults, travelers and people born in other countries, ensuring the immunity of healthcare professionals, establishing isolation measures that reduce transmission in healthcare settings and maintaining the quality of the surveillance system and laboratories. The pandemic of COVID-19 and the control measures established have drastically reduced the importation and transmission of measles in Spain with the last cases reported in March 2020. Some uncertainties associated with the epidemic situation are: restrictions on health care during the first weeks of lockdown could have affected vaccination coverage, particularly with the second dose of MMR vaccine. The overload generated in the health system could affect surveillance, notification and investigation of suspected measles or rubella.1. Introducción. Planes de la OMS y su traslado a España. Estrategias para alcanzar la eliminación. 2. Evolución de las incidencia del sarampión y rubeola y las coberturas de vacunación. 3. Resultados de la vigilancia del sarampión y la rubeola en España, 2019. 4. Hospitalizaciones y complicaciones relacionadas con sarampión y rubeola. España, 2019. 5. Estudio de laboratorio de los casos sospechosos de sarampión y rubeola. España, 2019. 6. Brotes de sarampión y rubeola. España, 2019. 7. Sarampión en Europa y en el mundo, año 2019. 8. Clasificación de los casos sospechosos de sarampión y rubeola: incidencia y genotipos identificados en fase de post-eliminación. España 2013-2019. 9. Verificación de la eliminación del sarampión y la rubeola en OMS-Europa, 2019. 10. Informe Anual del Comité Regional para la Verificación (CRV) de la Eliminación del Sarampión y la Rubeola en OMS-Europa, 2018. 11. Indicadores de calidad de la vigilancia establecidos por la OMS-Europa, España, 2014-2019. 12. Conclusiones. ANEXO I. Modelo de notificación de los brotes de sarampión. Formato OMS-Europa.N

Plan Nacional de Eliminación del Sarampión y Rubeola en España. Informe anual 2020

Instituto de Salud Carlos III (ISCIII), CIBERESP y Ministerio de Sanidad. Plan de Eliminación del Sarampión y la Rubeola en España. Informe anual 2020. Madrid, 4 de marzo de 2022.[ES] OMS ha declarado la eliminación del sarampión y de la rubeola en España reconociendo que desde el año 2014 está interrumpida la transmisión endémica de los virus en el territorio. En España el sarampión y la rubeola son enfermedades importadas. Tras una importación se suelen producir brotes limitados, con afectación fundamentalmente de adultos no vacunados o que presentan evanescencia de la protección conferida por las vacunas que recibieron en su infancia. La transmisión del sarampión se concentra en los sitios de alta exposición, como son los centros de atención sanitaria. En los primeros años de la fase de post-eliminación (2014-2016) se registró una incidencia anual muy baja (2014-2016) se registró una incidencia anual muy baja (<0,1 casos por millón); entre 2017 y 2019 ocurrió un repunte del sarampión en España (6 casos por millón/año) coincidiendo con el resurgimiento de la enfermedad en Europa y en otras zonas del mundo; desde el primer trimestre del año 2020, coincidiendo con el establecimiento de las restricciones al movimiento de personas por la pandemia de Covid-19, la circulación de virus del sarampión se ha reducido drásticamente en todo el mundo. En España, la incidencia de sarampión en el año 2020 fue de 1,9 casos por millón de habitantes. Se notificó transmisión del sarampión en dos brotes activos durante el primer trimestre del año 2020 (último caso en estos brotes con fecha de exantema el 26 marzo 2020). Desde entonces y hasta febrero 2022 no se ha notificado transmisión del sarampión en España. En 2020, de los 159 casos sospechosos notificados, 88 se confirmaron y 71 se descartaron. Se identificó un caso importado, 84 casos secundarios a importación y tres casos para los que no se pudo determinar el origen; 86 casos ocurrieron asociados a brotes y dos fueron casos esporádicos. Se notificaron tres brotes de sarampión, dos de ellos iniciados a finales de 2019 y que se pudieron caracterizar molecularmente. En uno de ellos se identificó el caso índice procedente de Rumanía. El 71,6% de los casos de sarampión eran adultos de 20 o más años y el 12,5% niños menores de un año. La mayoría de los casos -61,4%- no estaban vacunados, el 9,1% había recibido una dosis de vacuna triple vírica y el 15,9% había recibido dos dosis. En el 13,6% de los casos se desconocía el estado de vacunación. En 2020, se notificaron tres sospechas de rubéola: una se confirmó por laboratorio y dos se descartaron. La rubeola confirmada fue importada y se diagnosticó en un adulto no vacunado que no había nacido en España. En 2020 no se notificó ningún caso de SRC. En cuanto a los indicadores de calidad de la vigilancia, la tasa de investigación de laboratorio, la proporción de casos con el origen de infección identificado y la puntualidad de la investigación fueron superiores al 80%. La tasa de casos descartados para sarampión fue de 0,20 por cada 100.000 habitantes, lejos del objetivo marcado por OMS de detectar, investigar y descartar al menos 2 casos de sarampión por cada 100.000 habitantes y año. El bajo número de sospechas de rubéola notificadas durante 2020 no permite obtener conclusiones sobre la calidad de la vigilancia para este año. En el estudio molecular de las cepas se encontraron los genotipos B3 y D8 del virus del sarampión. En el brote de Cataluña se identificó el haplotipo MVs/Barcelona.ESP/52.19/[B3], que tras el análisis filogenético se concluyó que formaba parte del clado filogenético de la variante MVi/Harare.ZWE/38.09/[B3] (B3-Harare). En el brote de Galicia importado de Rumania se identificó la variante MVs/Gir Somnath.IND/42.16/ [D8] ampliamente distribuida en Europa. En el caso importado de Mozambique, el análisis molecular confirmó este origen puesto que se identificó el haplotipo Mvs/Gaziantep.TUR/13.17/[D8] que estaba circulando en ese país. El patrón de genotipos y variantes no muestra circulación continua de ninguno de ellos y no hay detección de genotipos endémicos. En 2020 no hay resultados del estudio molecular del único caso confirmado de rubeola por falta de muestras disponibles. En el año 2020 la cobertura nacional de la vacuna triple vírica fue del 96,3% con la primera dosis y del 93,9% con la segunda. [EN] The WHO has declared the elimination of measles and rubella in Spain, recognizing that since 2014 the endemic transmission of the viruses has been interrupted in the territory. Measles and rubella are imported diseases in Spain. Following importation, there are usually limited outbreaks, mainly affecting unvaccinated adults or adults who have lost the protection conferred by the vaccines they received as children. Measles transmission is concentrated in high-exposure sites, such as health care settings. In the first years of the post-elimination phase (2014-2016), a very low annual incidence (<0.1 cases per millón) was recorded; between 2017 and 2019 there was an upsurge of measles in Spain (6cases per million/year) coinciding wirth the resurgence of the disease in Europe and other áreas of the world; since the first quarter of 2020, coinciding with the establishment of restrictions on the movement of people due to the Covid-19 pandemic, measles virus circulation has been drastically reduced worldwide. In Spain, measles incidence in 2020 was 1.9 cases per million population. Measles transmission was reported in two active outbreaks during the first quarter of 2020 (last case in these outbreaks with an exanthema date of March 26th 2020). Since then and until February 2022, no measles transmission has been reported in Spain. In 2020, of the 159 suspected cases reported, 88 were confirmed and 71 were ruled out. Only one imported case was identified, 84 cases secondary to importation and three other cases for which the origin could not be determined; 86 cases occurred in association with outbreaks and two were sporadic cases. Three measles outbreaks were reported, two of which started in late 2019 and could be molecularly characterized. In one of them, the index case from Romania was identified. Of the measles cases, 71.6% were adults aged 20 years or older and 12.5% were children under one year of age. The majority of cases - 61.4% - were unvaccinated, 9.1% had received one dose of MMR vaccine and 15.9% had received two doses. Vaccination status was unknown in 13.6% of cases. In 2020, three suspected rubella cases were reported: one was laboratory confirmed and two were ruled out. The confirmed rubella was imported and diagnosed in an unvaccinated adult who was not born in Spain. No CRS cases were reported in 2020. In terms of surveillance quality indicators, the laboratory investigation rate, the proportion of cases with identified source of infection and the timeliness of investigation were above 80%. The rate of discarded cases for measles was 0.20 per 100,000 population, far from the WHO target of detecting, investigating and discarding at least 2 measles cases per 100,000 population per year. The low number of suspected cases of rubella reported during 2020 does not allow conclusions to be drawn on the quality of surveillance for this year. Measles virus genotypes B3 and D8 were found in the molecular study of the strains. In the outbreak in Catalonia, the haplotype MVs/Barcelona.ESP/52.19/[B3] was identified, which after phylogenetic analysis was concluded to be part of the phylogenetic clade of the variant MVi/Harare.ZWE/38.09/[B3] (B3-Harare). In the Galicia outbreak, imported from Romania, the MVs/Gir Somnath.IND/42.16/ [D8] variant widely distributed in Europe was identified. In the case imported from Mozambique, molecular analysis confirmed this origin as the haplotype Mvs/Gaziantep.TUR/13.17/[D8] was identified as circulating in that country. The pattern of genotypes and variants does not show continuous circulation of any of them without detection of endemic genotypes of measles virus. In 2020 there are no results of the molecular study of the only confirmed rubella case due to lack of available samples. In 2020, vaccination coverage of MMR vaccine was 96,3% for the first dose and 93,9% for the second dose.N

A network of macrophages supports mitochondrial homeostasis in the heart

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte’s autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function

A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. Video Abstract: [Figure presented] A system of macrophages in the heart supports cardiomyocyte health by phagocytosing exopher particles ejected from cardiomyocytes that contain defective mitochondria, among other cellular contents.This study was supported by Intramural grants from the Severo Ochoa program (IGP-SO); grants SAF2015-71878-REDT and SAF2014-56819-R from the Ministerio de Ciencia e Innovacion (MICINN) to A.C.; European Research Council grant EU-rhythmy (ERC-ADG-2014-ID:669387) to S.G.P., and MATRIX (ERC-COG-2018-ID: 819775) to B.I.; L.G.N. is supported by SIgN core funding from A∗STAR; grant BFU2016-75144-R from the Ministry of Science and Innovation to J.A.B,; grants PGC2018-096486-B-I00 and RD16/0011/0019 (ISCIII) from MICINN, TNE-17CVD04 from the Leducq Foundation, and S2017/BMD-3875 from the Comunidad de Madrid to M.T; intramural grant TPC/O-SO and grants SAF2015-65633-R, RTI2018-099357-B-I00, and HFSP (RGP0016/2018) to J.A.E.; intramural grant IGP-SO to J.A.-C. and A.H.; BIO2017-83640-P and RYC-2014-16604 to J.A-C; grants PRB3 (IPT17/0019-ISCIII-SGEFI/ERDF, ProteoRed) from the Carlos III Institute of Health and Fondo de Investigaciones Sanitarias, BIO2015-67580-P and PGC2018-097019-B-I00 from MICINN to J.V.; RTI2018-096068 from MICINN, AFM, MDA, LaCaixa-HR17-00040, UPGRADE-H2020-825825, and European Research Council (ERC-741538) to P.M.C.; S2017/BMD-3867 RENIM-CM from the Comunidad de Madrid and cofunded with European structural and investment funds to M.D.; 120/C/2015-20153032 from Fundació la Marató de TV3, SAF2015-65607-R and RTI2018-095497-B-I00 from MICINN, HR17_00527 from La Caixa Foundation, and TNE-18CVD04 from the Leducq Foundation to A.H.; C.V.R. is a Howard Hughes Medical Institute Faculty Scholar; J.A.N-A is supported by fellowship SVP-2014-068595, A.V.L.-V. by SVP-2013-068089, L.E.-M. by FJCI-2016-29384, and A.R.-P. by BES-2016-076635, all from MICINN; and the CNIC International Postdoctoral Program (EU grant agreement 600396 to D.J.S.). The CNIC is supported by the MICINN and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MICINN award SEV-2015-0505)

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field