A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012–14): a retrospective cohort study

Abstract

SUMMARY Background Enterovirus D68 (EV-D68) is implicated in a widespread 2014 outbreak of severe respiratory illness across the United States, and has also been sporadically reported in patients with acute flaccid myelitis (AFM). The association between EV-D68 infection and AFM remains unclear. Methods Here we report metagenomic and molecular epidemiological analyses of 25 AFM cases in California and Colorado from 2012−2014. Findings EV-D68 was detected in respiratory secretions from 7 of 11 (64%) patients comprising two temporally and geographically linked AFM clusters at the height of the 2014 outbreak, and from 12 of 25 (48%) investigated AFM cases overall. Phylogenetic analysis revealed that all AFM-associated EV-D68 sequences grouped into a single novel clade B1 strain that originally emerged in 2010. Out of six observed coding polymorphisms in the clade B1 EV-D68 polyprotein, 5 of 6 polymorphisms were shared between neuropathogenic poliovirus and/or EV-D70. One child with AFM and a sibling with only upper respiratory illness were both infected by identical EV-D68 strains, suggesting a potential role for host-specific factors in differential responses to EV-D68 infection. Notably, EV-D68 viremia was identified in a child experiencing acute neurologic progression of his paralytic illness. Deep metagenomic sequencing of CSF from 14 AFM cases failed to reveal evidence of an alternative infectious etiology to EV-D68. Interpretation Taken together, these findings strengthen the putative association between EV-D68 and AFM, as well as the contention that AFM is a rare yet severe clinical manifestation of EV-D68 infection in susceptible hosts.

The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus)

“…Rather than report as little as a single sequence read within a pool as evidence of viral presence, we established a percent of reads threshold to account for 'leakage' observed when multiple samples (here pools tagged with different barcodes) are sequenced on the same flow cell using Illumina technology. This phenomenon has been observed in our laboratory (data not shown) and by others (Greninger et al, 2015;Quail et al, 2014), and may occur due to cross-contamination during sample preparation and/or misclassification due to acquiring a barcode from another sample during bridge PCR to generate DNA clusters on the same Illumina flow cell. In order to establish a stringent threshold criterion for viral detection, we took advantage of the presence of known HIV-seropositive samples included in nine plasma pools.…”

Enterovirus D68 receptor requirements unveiled by haploid genetics

“…EV-D68 infections mostly cause mild respiratory disease but can also result in severe bronchiolitis or pneumonia, especially among children (4,5). In 2014, a nationwide EV-D68 outbreak in the United States was associated with severe respiratory disease and a cluster of acute flaccid myelitis and cranial nerve dysfunction in children, implicating EV-D68 as an emerging public health threat (8,9).…”

Human picornaviruses associated with neurological diseases and their neutralization by antibodies

“…One study undertaken in Finland addressed this question, reporting high titres of neutralizing responses to EV-D68 in 80 % of the studied individuals [168]. However, neutralization responses in this study were addressed against the prototype EV-D68 Fermon strain, which is antigenically very different from the currently circulating EV-D68 strains [91,167]. Therefore, neither EV-D68 antigenicity, nor the population protection levels are understood well at the moment.…”

“…Furthermore, EV-D68 has also been detected in four cases of AFP in Canada, two in Norway and one in France [87,89,90]. A recent retrospective study identified EV-D68 in respiratory secretions from 12 of 25 (48 %) patients with sporadic paralysis, strengthening the EV-D68 link to CNS disease [91]. Interestingly, all the EV-D68 strains identified in association with paralytic disease formed a distinct genetic cluster, suggesting the emergence of a novel clade and ongoing evolution of this virus [92].…”