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

ABSTRACT: 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.

SUBMITTER: Gonzalez-Sanz R

PROVIDER: S-EPMC6381658 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

González-Sanz Rubén R Casas-Alba Didac D Launes Cristian C Muñoz-Almagro Carmen C Ruiz-García María Montserrat MM Alonso Mercedes M González-Abad María José MJ Megías Gregoria G Rabella Nuria N Del Cuerpo Margarita M Gozalo-Margüello Mónica M González-Praetorius Alejandro A Martínez-Sapiña Ana A Goyanes-Galán María José MJ Romero María Pilar MP Calvo Cristina C Antón Andrés A Imaz Manuel M Aranzamendi Maitane M Hernández-Rodríguez Águeda Á Moreno-Docón Antonio A Rey-Cao Sonia S Navascués Ana A Otero Almudena A Cabrerizo María M

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 20190201 7

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 ...[more]

PMID: 30782267

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Project description:BackgroundThe most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications.ObjectivesTo characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype.Study designWe performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses.ResultsWe amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community.ConclusionsThis is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.

Project description:Enterovirus A71 (EV-A71) is a non-polio enterovirus that currently represents a major public health concern worldwide. In Africa, only sporadic cases have been reported. Acute flaccid paralysis and environmental surveillance programs have been widely used as strategies for documenting the circulation of polio and non-polio enteroviruses. To date, little is known about the molecular epidemiology of enterovirus A71 in Africa where resources and diagnostic capacities are limited. To fill this gap in Senegal, a total of 521 non-polio enterovirus isolates collected from both acute flaccid paralysis (AFP) and environmental surveillance (ES) programs between 2013 and 2020 were screened for enterovirus A71 using real-time RT-PCR. Positive isolates were sequenced, and genomic data were analyzed using phylogeny. An overall rate of 1.72% (9/521) of the analyzed isolates tested positive for enterovirus A71. All positive isolates originated from the acute flaccid paralysis cases, and 44.4% (4/9) of them were isolated in 2016. The nine newly characterized sequences obtained in our study included eight complete polyprotein sequences and one partial sequence of the VP1 gene, all belonging to the C genogroup. Seven out of the eight complete polyprotein sequences belonged to the C2 subgenotype, while one of them grouped with previous sequences from the C1 subgenotype. The partial VP1 sequence belonged to the C1 subgenotype. Our data provide not only new insights into the recent molecular epidemiology of enterovirus A71 in Senegal but also point to the crucial need to set up specific surveillance programs targeting non-polio enteroviruses at country or regional levels in Africa for rapid identification emerging or re-emerging enteroviruses and better characterization of public health concerns causing acute flaccid paralysis in children such as enterovirus A71. To estimate the real distribution of EV-A71 in Africa, more sero-epidemiological studies should be promoted, particularly in countries where the virus has already been reported.

Dataset Information

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

Publications

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

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