Almudena Otero

Enteroviruses in Spain over the decade 1998-2007: virological and epidemiological studies.

BACKGROUND Human enteroviruses (HEV) are the commonest cause of viral meningitis as well as other pathologies, therefore HEV characterization is important both in patient management and epidemiological investigation. OBJECTIVES A 10-year study of patients with enteroviral infection was carried out in Spain to determine the underlying etiology. STUDY DESIGN HEV were fully typed by microneutralisation tests and/or molecular methods. RESULTS A collection of 86404 clinical samples were studied in several Spanish laboratories. These were collected from patients with different syndromes, mainly aseptic meningitis (AM), fever, respiratory diseases and acute flaccid paralysis. Of these, 6867 HEV were obtained. At the National Poliovirus Laboratory 2814 were serotypically characterised. Among non-polio enteroviruses, the eight main serotypes were Echovirus 30 (25%), Echovirus 6 (12.4%), Echovirus 13 (8.3%), Echovirus 11 (7.4%) and Echovirus 9 (4.7%), followed by Coxsackievirus B5 (4.2%) and Echovirus 7 and Coxsackievirus A9 (3.7%) each. In AM cases, Echovirus 30 was identified in 39% of them, followed by Echovirus 6 (14%). However, Echovirus 6 was mainly associated with respiratory disease (17%), followed by Echovirus 11 (10%). On the other hand, Echovirus 30, Echovirus 11 and Echovirus 6 contributed equally with 12% of each serotype in the cases of fever. CONCLUSIONS The present report complements previous data (Trallero et al.(13)), with the results of HEV incidence in Spain from 1998 to 2007. The surveillance described in this study provided valuable information as to which serotypes are in circulation, the emergence of new HEV and association with clinical manifestations.

Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand, foot and mouth disease in Spain

Hand, foot and mouth disease (HFMD) is a childhood illness frequently caused by genotypes belonging to the enterovirus A species, including coxsackievirus (CV)-A16 and enterovirus (EV)-71. Between 2010 and 2012, several outbreaks and sporadic cases of HFMD occurred in different regions of Spain. The objective of the present study was to describe the enterovirus epidemiology associated with HFMD in the country. A total of 80 patients with HFMD or atypical rash were included. Detection and typing of the enteroviruses were performed directly in clinical samples using molecular methods. Enteroviruses were detected in 53 of the patients (66%). CV-A6 was the most frequent genotype, followed by CV-A16 and EV-71, but other minority types were also identified. Interestingly, during almost all of 2010, CV-A16 was the only causative agent of HFMD but by the end of the year and during 2011, CV-A6 became predominant, while CV-A16 was not detected. In 2012, however, both CV-A6 and CV-A16 circulated. EV-71 was associated with HFMD symptoms only in three cases during 2012. All Spanish CV-A6 sequences segregated into one major genetic cluster together with other European and Asian strains isolated between 2008 and 2011, most forming a particular clade. Spanish EV-71 strains belonged to subgenogroup C2, as did most of the European sequences circulated. In conclusion, the recent increase of HFMD cases in Spain and other European countries has been due to a larger incidence of circulating species A enteroviruses, mainly CV-A6 and CV-A16, and the emergence of new genetic variants of these viruses.

Enterovirus 75, un nuevo virus patógeno en nuestro medio

Introduccion Los miembros del genero Enterovirus generalmente se investigan por su papel etiologico en procesos neurologicos. Sin embargo, a menudo se han asociado a otros sindromes, como sindrome febril, infeccion respiratoria aguda y enfermedad exantematica. En este trabajo hemos analizado los datos clinicos y epidemiologicos de 5 casos de infeccion causada por el recientemente descrito enterovirus 75 en la provincia de Granada. Metodos El diagnostico a nivel de genero se realizo por cultivo viral en lineas celulares MRC-5 y rabdomiosarcoma (RD). El serotipo de los aislados se determino mediante retrotranscripcion-PCR (RT-PCR) de un fragmento de la region de la proteina viral 1 (VP1) y posterior secuenciacion de los productos de PCR. Resultados De los cinco enterovirus 75 aislados, 2 se detectaron en ninos con meningitis aseptica (de 1 mes y 12 anos de edad), y 3 en sujetos con procesos no neurologicos, que fueron infeccion respiratoria aguda, sindrome febril y gastroenteritis (todos menores de 1 ano). Los 5 casos se detectaron entre diciembre de 2005 y mayo de 2006. Todos los pacientes se recuperaron sin secuelas. Conclusion Estos datos demuestran la circulacion de enterovirus 75 en el sur de Espana, e indican que este serotipo puede estar implicado en procesos no neurologicos menos graves, especialmente en ninos pequenos, y sobre todo, durante los meses frios del ano.

Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4‐year period in Spain

The epidemiology and clinical association of enterovirus (EV) and parechovirus (HPeV) infections, as well as the type‐distribution‐according‐to‐age, were determined during a 4‐year study period in Spain. During 2010–2013, a total of 21,832 clinical samples were screened for EV and the detection frequency was 6.5% (1,430). Of the total EV‐negative samples, only 1,873 samples from 2011 to 2013 were available for HPeV testing. HPeV was detected in 42 (2%) of them. Positive samples were genotyped using PCR and sequencing. EV infections occurred in all age groups of patients: neonates (17%), children 28 days to 2 years (29%), children 2–14 years (40%), and adults (14%). Thirty‐four different EV types were identified. HPeV infections were detected exclusively in infants <8 m (70% neonates, P < 0.05). All but one HPeV were HPeV‐3. Differences in type frequency detection were found according to age and clinical manifestation. Coxsackievirus (CV)‐B4 (61%), CV‐B5 (83%), and HPeV‐3 (64%) were more frequent in neonates than in older patients (P < 0.05). Echovirus (E)‐3 (60%), E‐18 (47%), E‐25 (62%), CV‐A6 (61%), CV‐A16 (72%), and EV‐71 (75%) were mainly detected in children 28 days to 2 years (P < 0.05), whereas, E‐6 (79%), E‐20 (88%), and E‐30 (85%) were predominant in children >2 years and adults (P < 0.05). Clinically, meningitis was associated with EV (P < 0.01) whereas, encephalitis was more frequent in HPeV‐infected patients. CV‐B types were associated with myocarditis (90%; P < 0.05) and EV species A with hand–foot–mouth‐disease/atypical exanthema (88%; P < 0.05). J. Med. Virol. 89:435–442, 2017.

Red de Laboratorios del Plan de Erradicación de la Poliomielitis (1998-2003): 6 años de vigilancia de parálisis flácida aguda en España

Introduccion La Organizacion Mundial de la Salud (OMS) planteo como objetivo la erradicacion de la poliomielitis en 1988, basandose fundamentalmente en alcanzar y mantener alta cobertura de inmunizacion e implantar sistemas eficaces de vigilancia de las infecciones por poliovirus. Metodos En Espana, el sistema de vigilancia se basa en la busqueda activa de casos de paralisis flacida aguda (PFA), mediante una red de 9 laboratorios coordinados por el Laboratorio Nacional de Poliovirus (LNP) del Centro Nacional de Microbiologia y apoyados por epidemiologos de cada comunidad autonoma. Adicionalmente, la red envia datos de aislamiento de enterovirus en cualquier sindrome clinico. En los laboratorios de la red se realiza el estudio virologico primario, mientras que en el LNP se caracterizan todos los poliovirus y los enterovirus no polio de mayor importancia epidemiologica. Resultados El total de muestras estudiadas por la red ha sido de 54.533, con un rendimiento de enterovirus del 9%. Todos los poliovirus aislados (n = 196) se caracterizaron como Sabin-like (vacunales) y entre los enterovirus no polio, Echovirus 30 fue el dominante. El 3% de las muestras estudiadas correspondian a pacientes con PFA o sus contactos (268 casos). Discusion Espana puede ser considerada como libre de polio, pero por su situacion geografica, puede ser puerta de entrada de poliovirus salvaje y dar lugar a casos importados. Por ello, debe participar activamente en todas las estrategias propuestas por la OMS, manteniendo en especial la infraestructura creada en el plan de la erradicacion de la poliomielitis y continuando con la vigilancia e inmunizacion.

Características epidemiológicas y clínicas de los lactantes hospitalizados por infecciones por parechovirus humanos. Estudio prospectivo en España

INTRODUCTION Human parechovirus (HPeV) is one of the recently described picornaviridae viruses that have been associated with fever of unknown origin (FUO), clinical sepsis, gastroenteritis, meningitis, or encephalitis in very young infants. The aim of this study is to describe the epidemiology and clinical features of these viruses. PATIENTS AND METHODS A prospective multicentre 3-year study was conducted in 12 hospitals in Spain. Out of 850 specimens examined, 47 were positive (5.52%), with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae. RESULTS Out of 850 specimens examined, 47 were positive (5.52%) for HPeV, with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae CONCLUSIONS: HPeV circulates in our country, mainly during spring and summer, and affects young infants with a FUO and clinical sepsis. Molecular diagnostic techniques in all hospitals could help in improving the management of patients with these infections.