Seroepidemiological and phylogenetic characterization of neurotropic enteroviruses in Ireland, 2005‐2014

Guerra, Jorge Abboud; Waters, Allison; Kelly, Alison; Morley, Ursula; O’Reilly, Paul; O'Kelly, Edwin; Dean, Jonathan; Cunney, Robert; O’Lorcain, P.; Cotter, Suzanne; Connell, Jeff; O’Gorman, Joanne; Hall, William W.; Carr, Michael J.; Gascun, Cillian F. De

doi:10.1002/jmv.24765

Cited by 11 publications

(7 citation statements)

References 52 publications

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“…Echovirus 6 is one of the most frequently identified EV types in Europe and worldwide and usually associated with outbreaks or sporadic cases of aseptic meningitis [34,37–41]. In the current study, E6 was the second most prevalent enterovirus overall and the most prevalent type in the years 2015 and 2017.…”

Section: Discussionmentioning

confidence: 50%

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Molecular epidemiology of enteroviruses in Cyprus 2008-2017

Richter¹,

Tryfonos²,

Christodoulou³

2019

PLoS ONE

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Enteroviruses (EVs) are associated with a broad spectrum of disease manifestations, including aseptic meningitis, encephalitis, hand, foot and mouth disease, acute flaccid paralysis and acute flaccid myelitis with outbreaks being reported frequently world-wide. The aim of this study was the molecular characterization of all enteroviruses detected in Cyprus in the ten-year period from January 2008 and December 2017 as well as a description of the circulation patterns associated with the most frequently encountered genotypes. For this purpose, serum, cerebrospinal fluid, nasal swab, skin swab and/or stool samples from 2666 patients with a suspected EV infection were analysed between January 2008 and December 2017. Enteroviruses were detected in 295 (11.1%) patients, which were then investigated further for epidemiological analysis by VP1 genotyping. Overall, 24 different enterovirus types belonging to three different species were identified. The predominant species was EV-B (209/295, 71%), followed by species EV-A (77/295, 26.1%). Only one virus belonged to species EV-D, whereas EV-C enteroviruses were not identified at all. The most frequent genotypes identified were echovirus 30 (26.1%), echovirus 6 (14.2%) and coxsackievirus A6 (10.9%). While Echovirus 30 and echovirus 6 frequency was significantly higher in patients older than 3 years of age, the opposite was observed for CV-A16 and EV-A71, which dominated in young children less than 3 years. Importantly, for the current study period a significant increase of previously only sporadically observed EV-A types, such as EV-A71 and CV-A16 was noted. A phylogenetic analysis of EV-A71 showed that the majority of the EV-A71 strains from Cyprus belonged to sub-genogroup C1 and C2, with the exception of one C4 strain that was observed in 2011. The data presented provide a comprehensive picture of enteroviruses circulating in Cyprus over the last decade and will be helpful to clinicians and researchers involved in the treatment, prevention and control of enteroviral infections by helping interpret trends in enteroviral diseases by associating them with circulating serotypes, for studying the association of enteroviruses with clinical manifestations and develop strategies for designing future EV vaccines.

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Section: Discussionmentioning

confidence: 50%

“…Coxsackievirus B5 is frequently reported in virus isolation and regularly appears in the top five commonly identified EV types in the United States, China and Europe being commonly associated with acute viral meningitis [37,49–51]. It was the fourth most frequent genotype detected and the predominant enterovirus in 2009 and 2016.…”

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of enteroviruses in Cyprus 2008-2017

Richter¹,

Tryfonos²,

Christodoulou³

2019

PLoS ONE

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“…Previous studies have determined that CSF is not a highly useful specimen type for EV-D68 detection (39). Despite detection from NP swabs, we did not detect EV-D68 in the CSF specimens from the AFM patients, an outcome that has been frequently reported (7, 11, 13, 40).…”

Section: Discussionmentioning

confidence: 99%

“…EV-D68 has been documented in CSF in limited cases, including (i) a fast-progressing, fatal case of meningomyeloencephalitis (41), (ii) an undescribed case of acute flaccid paralysis in 2005 (42), (iii) a hematopoietic stem cell transplant recipient on mild immunosuppressants (43), (iv) a single patient in an Argentinian cluster (30), and (v) a CSF specimen contaminated with blood cells (limiting conclusions as to the nature of the viral infection) (14). Other neuropathic enteroviruses are also rarely detected in CSF (39, 44), including poliovirus (https://www.cdc.gov/polio/us/lab-testing/diagnostic.html; 45); therefore, testing recommendations for suspect viral neurologic illness typically include collection of stool and/or NP swabs (46, 47). EV-D68 viremia is an exceedingly rare finding; a recently developed EV-D68 mouse model suggests viral dissemination occurs via a direct neural pathway rather than via a hematogenous route (33), although Greninger et al did report EV-D68 in the blood of one child diagnosed with AFM (7).…”

Section: Discussionmentioning

confidence: 99%

Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role

Bowers

Valentine

Harrison

et al. 2019

mBio

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Enteroviruses frequently result in respiratory and gastrointestinal illness; however, multiple subtypes, including poliovirus, can cause severe neurologic disease. Recent biennial increases (i.e., 2014, 2016, and 2018) in cases of non-polio acute flaccid paralysis have led to speculations that other enteroviruses, specifically enterovirus D68 (EV-D68), are emerging to fill the niche that was left from poliovirus eradication. A cluster of 11 suspect cases of pediatric acute flaccid myelitis (AFM) was identified in 2016 in Phoenix, AZ. Multiple genomic analyses identified the presence of EV-D68 in the majority of clinical AFM cases. Beyond limited detection of herpesvirus, no other likely etiologies were found in the cluster. These findings strengthen the likelihood that EV-D68 is a cause of AFM and show that the rapid molecular assays developed for this study are useful for investigations of AFM and EV-D68.

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“…EVs have traditionally been serotyped by assessment of neutralizing antibody responses in cultured cells; however, since 2000, DNA sequence-based genotyping approaches have become standard practice, with a “type” rather than a serotype name, e.g., Echovirus type 30 rather than Echovirus serotype 30. In recent years, the genetic typing of specimens has grown due to the more rapid and simpler PCR testing for EV detection [15,16], while use of cultured cells are also increasingly being supplanted by molecular approaches due to their low isolation rates. For the identification of the viral type by nucleotide sequence analysis, the VP4-VP2 partial region of the capsid region and the analysis by amplifying the VP1 partial region (CODEHOP RT-semi-nested PCR) are widely used.…”

Section: Enterovirus Amentioning

confidence: 99%

Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World

González

Carr

Kobayashi

et al. 2019

IJMS

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Enteroviruses (EVs) are responsible for extremely large-scale, periodic epidemics in pediatric cohorts, particularly in East and Southeast Asia. Clinical presentation includes a diverse disease spectrum, including hand-foot and mouth disease (HFMD), aseptic meningitis, encephalitis, acute flaccid paralysis, and acute flaccid myelitis. HFMD is predominantly attributable to EV-A types, including the major pathogen EV-A71, and coxsackieviruses, particularly CV-A6, CV-A16, and CV-A10. There have been multiple EV-A71 outbreaks associated with a profound burden of neurological disease and fatal outcomes in Asia since the early 1980s. Efficacious vaccines against EV-A71 have been developed in China but widespread pediatric vaccination programs have not been introduced in other countries. Encephalitis, as a consequence of complications arising from HFMD infection, leads to damage to the thalamus and medulla oblongata. Studies in Vietnam suggest that myoclonus is a significant indicator of central nervous system (CNS) complications in EV-A71-associated HFMD cases. Rapid response in HFMD cases in children is imperative to prevent the progression to a CNS infection; however, prophylactic and therapeutic agents have not been well established internationally, therefore surveillance and functional studies including development of antivirals and multivalent vaccines is critically important to reduce disease burden in pediatric populations.

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Seroepidemiological and phylogenetic characterization of neurotropic enteroviruses in Ireland, 2005‐2014

Cited by 11 publications

References 52 publications

Molecular epidemiology of enteroviruses in Cyprus 2008-2017

Molecular epidemiology of enteroviruses in Cyprus 2008-2017

Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role

Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World

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