Seven Strains of Enterovirus D68 Detected in the United States during the 2014 Severe Respiratory Disease Outbreak.
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ABSTRACT:
SUBMITTER: Brown BA
PROVIDER: S-EPMC4239358 | biostudies-literature | 2014 Nov
REPOSITORIES: biostudies-literature
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Seven Strains of Enterovirus D68 Detected in the United States during the 2014 Severe Respiratory Disease Outbreak.
Brown B A BA Nix W A WA Sheth M M Frace M M Oberste M S MS
Genome announcements 20141120 6
Clusters of severe respiratory disease in the United States were reported to the CDC beginning in August 2014. Enterovirus D68 (EV-D68) was identified from 83% (30/36) of initial severe cases. Investigations in August and September found severe EV-D68 cases to be widespread across the United States. We report seven EV-D68 genomes from the outbreak. ...[more]
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Project description:BackgroundIn 2014, a nationwide outbreak of severe respiratory illness occurred in the United States, primarily associated with enterovirus D68 (EV-D68). A proportion of illness was associated with rhinoviruses (RVs) and other enteroviruses (EVs), which we aimed to characterize further.MethodsRespiratory specimens from pediatric and adult patients with respiratory illness were submitted to the Centers for Disease Control and Prevention during August 2014-November 2014. While initial laboratory testing focused on identification of EV-D68, the negative specimens were typed by molecular sequencing to identify additional EV and RV types. Testing for other pathogens was not conducted. We compared available clinical and epidemiologic characteristics among patients with EV-D68 and RV species A-C identified.ResultsAmong 2629 typed specimens, 1012 were EV-D68 (39%) and 81 (3.1%) represented 24 other EV types; 968 were RVs (37%) covering 114 types and grouped into 3 human RV species (RV-A, 446; RV-B, 133; RV-C, 389); and 568 (22%) had no RV or EV detected. EV-D68 was more frequently identified in patients who presented earlier in the investigation period. Among patients with EV-D68, RV-A, RV-B, or RV-C, the age distributions markedly differed. Clinical syndromes and intensive care unit admissions by age were largely similar.ConclusionsRVs were commonly associated with severe respiratory illness during a nationwide outbreak of EV-D68, and most clinical. Characteristics were similar between groups. A better understanding of the epidemiology of RVs and EVs is needed to help inform development and use of diagnostic tests, therapeutics, and preventive measures.
| S-EPMC11305614 | biostudies-literature
Project description:UnlabelledIn August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 outbreak. With these data in hand, we performed phylogenetic analyses of complete genome and VP1 capsid protein sequences. Notably, we observed considerable genetic diversity among EV-D68 isolates in Kansas City, manifest as phylogenetically distinct lineages, indicative of multiple introductions of this virus into the city. In addition, we identified an intersubclade recombination event within EV-D68, the first recombinant in this virus reported to date. Finally, we found no significant association between EV-D68 genetic variation, either lineages or individual mutations, and a variety of demographic and clinical variables, suggesting that host factors likely play a major role in determining disease severity. Overall, our study revealed the complex pattern of viral evolution within a single geographic locality during a single outbreak, which has implications for the design of effective intervention and prevention strategies.ImportanceUntil recently, EV-D68 was considered to be an uncommon human pathogen, associated with mild respiratory illness. However, in 2014 EV-D68 was responsible for more than 1,000 disease cases in North America, including severe respiratory illness in children and acute flaccid myelitis, raising concerns about its potential impact on public health. Despite the emergence of EV-D68, a lack of full-length genome sequences means that little is known about the molecular evolution of this virus within a single geographic locality during a single outbreak. Here, we doubled the number of publicly available complete genome sequences of EV-D68 by performing high-throughput next-generation sequencing, characterized the evolutionary history of this outbreak in detail, identified a recombination event, and investigated whether there was any correlation between the demographic and clinical characteristics of the patients and the viral variant that infected them. Overall, these results will help inform the design of intervention strategies for EV-D68.
| S-EPMC4733988 | biostudies-literature
Project description:To retrospectively investigate enterovirus D68 circulation in Senegal during the 2014 US outbreak, we retrieved specimens from 708 persons, mostly children, who had acute respiratory symptoms during September-December 2014. Enterovirus D68 was detected in 14 children (2.1%); most cases occurred in October. Phylogenetic analysis revealed that all strains clustered within subclade A1.
| S-EPMC6590772 | biostudies-literature
Project description:In the late summer and the fall of 2014, the United States experienced an unprecedented outbreak of enterovirus D68 (EV-D68) infections. During the outbreak, we collected nasopharyngeal swab specimens from patients in the Lower Hudson Valley of New York. Here, we conduct a retrospective study on the genomic diversity of EV-D68 strains. We first employ a metagenomic shotgun sequencing protocol on a total of 93 clinical samples, including 21 negative controls, the results of which allow assembly of 20 EV-D68 genomes, six complete and 14 near-complete. We then investigate their genetic relationships, along with additional 20 EV-D68 strains having whole-genome sequences publicly available. Our comparative genomic analysis uncovers that the majority (26/29) of EV-D68 strains circulating in the 2014 outbreak differ significantly from prior ones, have a main feature of three variables, C1817T, C3277A, and A4020G, and belong to a new clade. C3277A causes amino acid substitution T860N in the protease 2A(pro) cleavage site between VP1 and 2A, whereas A4020G causes S1108G in a 3C(pro) cleavage site between 2B and 2C. The two functional mutations may alter the proteases' cleavage efficiency, leading to increased rate of viral replication and transmission. These provide insights into the evolution of epidemic EV-D68 strains.
| S-EPMC4606740 | biostudies-literature
Project description:In 2014 the United States experienced a nationwide outbreak of Enterovirus D68 (EV-D68) infection. There were no confirmed cases of EV-D68 in 2015 and CDC was only aware of limited sporadic EV-D68 detection in the US in 2016. In this report, we analyzed 749 nasopharyngeal (NP) specimens collected in 2015 and 2016 from patients in the Lower Hudson Valley, New York using a previously validated EV-D68-specific rRT-PCR assay. EV-D68 was detected in none of 199 NP specimens collected in 2015, and in one of 108 (0.9%) samples from January to May and 159 of 442 (36.0%) samples from July to October 2016. Complete EV-D68 genome sequences from 22 patients in 2016 were obtained using a metagenomic next-generation sequencing assay. Comparative genome analysis confirmed that a new EV-D68 strain belonging to subclade B3, with 3.2-4.8% divergence in nucleotide from subclade B1 strains identified during the 2014 US outbreak, was circulating in the US in 2016 and caused an outbreak in the Lower Hudson Valley, New York with 160 laboratory-confirmed cases. Our data highlight the genetic variability and capacity in causing outbreak by diverse EV-D68 strains, and the necessity of awareness and more surveillance on their active circulation worldwide.
| S-EPMC5430842 | biostudies-literature
Project description:Acute flaccid myelitis (AFM) is a serious neurologic condition that causes limb weakness or paralysis in previously healthy children. Since clusters of cases were first reported in 2014, nationwide surveillance has demonstrated sharp increases in AFM cases in the United States every 2 years, most occurring during late summer and early fall. Given this current biennial pattern, another peak AFM season is expected during fall 2020 in the United States. Scientific understanding of the etiology and the factors driving the biennial increases in AFM has advanced rapidly in the past few years, although areas of uncertainty remain. The Centers for Disease Control and Prevention and AFM partners are focused on answering key questions about AFM epidemiology and mechanisms of disease. This article summarizes the current understanding of AFM etiology and outlines priorities for surveillance and research as we prepare for a likely surge in cases in 2020.
| S-EPMC7510737 | biostudies-literature
Project description:During 2014, enterovirus D68 (EV-D68) outbreaks were described globally, causing severe respiratory diseases in children and, in some cases, subsequent paralysis. In this study, the type characterization of enterovirus (EV) detected in respiratory illnesses and the epidemiology and clinical association of EV-D68 infections in Spain over a five-year period were described. A total of 546 EV-positive samples from hospitalized patients with respiratory infections were included. EV-D68 was the most frequently detected type (46.6%, 191/410 typed EV). Other EV from species A (25.1%), B (27.8%) and C (0.5%) were also identified. EV-D68 infections were more associated with bronchitis while EV-A/B types were more frequent in upper respiratory illness (p < 0.01). EV-D68 was also detected in patients with neurological symptoms (nine meningitis/meningoencephalitis and eight acute flaccid paralysis cases). Phylogenetic analysis of 3'-VP1 region showed most Spanish EV-D68 sequences from 2014 to 2016 belonged to subclades B2/B3, as other American and European strains circulating during the same period. However, those detected in 2017 and 2018 clustered to the emerged subclade D1. In summary, different EV can cause respiratory infections but EV-D68 was the most prevalent, with several strains circulating in Spain at least since 2014. Association between EV-D68 infection and neurological disease was also described.
| S-EPMC6781473 | biostudies-literature
Project description:BackgroundEnterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness.MethodsWe collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel χ(2) tests were used to test for statistical significance.FindingsRegional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0·0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0·039).InterpretationIn 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden.FundingNone.
| S-EPMC5693332 | biostudies-literature
Project description: Not available
| S-EPMC8888215 | biostudies-literature
Project description:We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August-October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions.
| S-EPMC4412236 | biostudies-literature