Twenty-nine Cases of Enterovirus-D68–associated Acute Flaccid Myelitis in Europe 2016

Knoester, Marjolein; Helfferich, Jelte; Poelman, Randy; Leer-Buter, Coretta van; Brouwer, Oebele F.; Niesters, Hubert G. M.

doi:10.1097/inf.0000000000002188

Cited by 119 publications

(163 citation statements)

References 39 publications

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“…Considering the global distribution of EV-D68 (another member of EV species D) and its recurrent association with outbreaks with severe clinical manifestations (Esposito et al, 2015, Knoester et al, 2018, it is essential that the molecular epidemiology of this EV type be better investigated.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Identification of Enterovirus D111 in a Child with Acute Flaccid Paralysis in Nigeria

Faleye

Adewumi

et al. 2018

Preprint

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The WHO recommended cell-culture-based algorithm requires enterovirus (EV) isolates to produce reproducible cytopathic effect (R-CPE) in RD and/or L20b cell lines. Samples with nonreproducible CPE (NR-CPE) are considered negative for EVs. We investigated whether there could be EVs lurking in samples with NR-CPE.Fifty-nine (59) cell culture supernatants (CCS) (collected between 2016 and 2017) recovered from RD and L20b cell culture tubes with NR-CPE, were analyzed in this study. The tubes had been previously inoculated with stool suspension from children (<15 years) in Nigeria with acute flaccid paralysis (AFP). All CCS were screened for Enteric Adenoviruses and group A Rotavirus using a rapid immunochromatographic test kit. Subsequently, they were passaged in HEp-2 cell line. All isolates were subjected to RNA extraction, cDNA synthesis, three (5 l -UTR, VP1 and EV Species C [EV-C]) different PCR assays and sequencing of amplicons. EVs were further subjected to Illumina sequencing.All CCS were negative for Adenoviruses and group A Rotaviruses. Four CCS produced R-CPE in HEp-2 cell line, three of which were positive for the 5 l -UTR assay. Of the 3 isolates two and none were positive for the VP1 and EV-C assays, respectively. One of the two VP1 amplicons was successfully sequenced and identified as Echovirus 1(E1). Illumina sequencing of the three 5 l -UTR positive isolates confirmed the E1 isolate and typed the remaining two as EV-Ds (94 and 111).We describe the first EV-D94 and 111 isolates of Nigerian origin. We also show that NR-CPE could sometimes be caused by EVs that do not produce R-CPE in RD and L20b cell lines but do so in other cell lines like HEp-2.

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Section: Discussionmentioning

confidence: 99%

Isolation and Identification of Enterovirus D111 in a Child with Acute Flaccid Paralysis in Nigeria

Faleye

Adewumi

et al. 2018

Preprint

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“…Between 1970 and 2005, only 26 cases were reported to the CDC and the virus was generally associated with mild upper respiratory illness [8,9].In 2014, unprecedented outbreaks of EV-D68 associated with severe respiratory disease and acute flaccid myelitis emerged throughout the world [3,. Since 2014, there have been biannual patterns of severe disease associated with EV-D68 [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. This unique pattern of recurring outbreaks and severe pathology sheds light on the importance of understanding evolutionary changes in contemporary EV-D68 strains.…”

Section: Introductionmentioning

confidence: 99%

Contemporary Enterovirus D68 strains show enhanced replication and translation at 37°C

Smith

Pekosz

2020

Preprint

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Enterovirus D68 (EV-D68) emerged in 2014 as an important pathogen linked to severe lower respiratory disease and acute flaccid myelitis outbreaks. Historically associated with mild common-cold-like symptoms, clusters of severe disease attributed to EV-D68 appeared during a series of outbreaks in 2014, 2016, and 2018. Previous studies of historic EV-D68 strains demonstrated attenuated replication at temperatures of the lower respiratory tract (37°C), when compared to the upper respiratory tract (32°C). By testing a panel of historic and contemporary EV-D68 strains at 32°C and 37°C, we demonstrate that contemporary strains of EV-D68 undergo little to no attenuation at increased temperatures. Contemporary strains produced higher levels of viral proteins at 32°C and 37°C than historic strains, although both strains infected similar numbers of cells and had comparable amounts of replication complexes. IRES activity assays with dual-luciferase reporter plasmids demonstrated enhanced translation in recent EV-D68 strains mapped to regions of variability in the 5' UTR found only in contemporary strains. Using an infectious clone system, we demonstrate that the translation advantage dictated by the 5' UTR does not solely mediate temperature sensitivity. The strain-dependent effects of temperature on the EV-D68 life cycle gives insight into the susceptibility of the lower respiratory system to contemporary strains. IMPORTANCEEnterovirus-D68 (EV-D68) emerged in 2014 as a causative agent of biannual severe pediatric respiratory disease and acute flaccid myelitis (AFM). We show that recent EV-D68 viruses have gained the ability to replicate at 37⁰C. Enhanced virus protein translation seemed to correlate with enhanced virus replication at 37⁰C but other genetic factors are also contributing to this phenotype. An enhanced ability to replicate at core body temperature may have allowed EV-D68 to penetrate both lower in the respiratory tract and into the central nervous system, explaining the recent surge in severe disease associated with virus infection.

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“…However, enterovirus is not always found in cerebrospinal fluid,7 and other evidence suggests that the current outbreak is caused by enterovirus D68 13…”

mentioning

confidence: 97%

“…Enteroviruses A71 and D6878 have both been associated with acute flaccid myelitis, but D68 is emerging as the leading causal candidate. …”

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confidence: 99%

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Outbreaks of acute flaccid myelitis in the US

Stelzer-Braid

Rawlinson

2018

BMJ

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Twenty-nine Cases of Enterovirus-D68–associated Acute Flaccid Myelitis in Europe 2016

Abstract: Supplemental Digital Content is available in the text.

Cited by 119 publications

References 39 publications

Isolation and Identification of Enterovirus D111 in a Child with Acute Flaccid Paralysis in Nigeria

Isolation and Identification of Enterovirus D111 in a Child with Acute Flaccid Paralysis in Nigeria

Contemporary Enterovirus D68 strains show enhanced replication and translation at 37°C

Outbreaks of acute flaccid myelitis in the US

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