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Commentary

Novel Enterovirus D68 Sub-Clade Linked to Flaccid Paralysis
Recombinomics Commentary
November 10, 2014 22:00

University of California San Francisco researchers have released a series of enterovirus D68 sequences from 2014 cases in California and Colorado.  The title on the characterization sheet for these sequences, “Genomic Analysis Uncovers a Novel Circulating Enterovirus D68 Strain in Association with Cases of Acute Flaccid Paralysis from 2012-2014” suggests that the recent sequences are from Acute Flaccid Paralysis (AFP) cases.  The sequences are closely related to an earlier series of 2013-2014 sequences from cases in California, which were released under the tile “Whole-genome deep sequencing of enterovirus D68 strains in cases of acute flaccid paralysis in California”.

Earlier this year researchers from UCSF and Stanford described five cases from California in 2012 or 2013.  Enterovirus D68 was identified in two of these cases, and a search of cases reported to California’s Neurologic and Surveillance Testing program identified 20-25 cases reported from  August 2012 to July 2013.  That report was followed by a CDC alert on a large number of hospitalized children who tested positive for D68 in Chicago, Illinois and Kansas City, Missouri.  The CDC subsequently issued a HAN on paralytic cases in Colorado, raising concerns that a subset of the D68 cases was linked to AFP.

Although D68 was first described in California in 1962, detection of this Enterovirus group was relatively rare.  Increased attention to this group has led to a large number of recent sequences, including a partial sequence (339 BP representing positions 133 to 471 of the VP1 region of the Fermon strain) from over 100 cases, including a 2014 cohort from the Netherlands as described in Eurosurveillance.

The recent paper in Eurosurveillance noted that in the Netherlands all three major clades (A, B, & C) which were designated as Group 3, 1,& 2, respective in the Eurosurveillance paper were found in 2014 cases.  In contrast, the US sequences were concentrated in clade B (or Group 1), which could be designated as two distinct sub-clades.  Two of the US sequences (US/KY/14/18951 and US/IL/14/18952) along with a large number of sequences from the Netherlands from 2012-2014 formed one sub-clade. 

However, the second sub-clade had all of the US AFP cases, raising concerns that this sub-clade represents a novel sub-clade with a significantly higher frequency of AFP cases.  This sub-clade has a 2013 AFP case, CA/AFP/11-1767, at its base.  This sub-clade then breaks into two branches.  One is dominated by 2011 sequences from Asia (four China sequences, CQ-5584, CQ-5585, CQ-5735, CQ-5759 and five Thailand sequences, CU134, CU171, TH_CU101, TH_CU124, TH_CU134).  This branch also has one 2012 sequence  from the Netherlands, 4311200780_NL12.  The other branch is dominated by US sequences.  It has one 2012 sequence from Italy, ITA/20528/12, and 2013/2014 sequences from the Netherlands (4311300117_NL13 & 4311400698_NL14). 

However, the remainder includes 2013/2014 AFP sequences from California (CA/AFP/v12T00346, CA/AFP/12T04950, CA/AFP/v14T04344) released earlier, as well as recent sequences from California (US/CA/14-6092, US/CA/14-6100, US/CA/14-6103SIB) and Colorado (US/CO/14-60, US/CO/14-94), as well as identical or virtually identic al sequences from Missouri (US/MO/14-18947, US/MO/14-18948, US/MO/14-18949, US/MO/14-18950, EV-D68_STL-2014-12).

These data raise concerns that the sub-clade on the second branch produce a higher frequency of AFP cases, and this sub-clade is widespread in the United States.

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