Enterovirus D68–Associated Severe Pneumonia, China, 2014

Zhang, Tiegang; Ren, Lili; Luo, Ming‐Cheng; Li, Aihua; Cheng, Gong; Chen, Meng; Yu, Xiaoyan; Wu, Jiang; Deng, Ying; Huang, Fang

doi:10.3201/eid2105.150036

Cited by 40 publications

(35 citation statements)

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“…One of the most striking features of the 2014 outbreak was that most EV-D68 infections were associated with severe respiratory diseases in children (36,40,41,(60)(61)(62)(63)(64)(65)69). However, we found no association between age, gender, or clinical symptoms and different viral subclades in our Kansas City population.…”

Section: Discussioncontrasting

confidence: 53%

“…In line with our subclade definition, subclades A1 and B2 were endemic and found in many countries before the (16,19,30). During the 2014 outbreak, a novel subclade, B1, seems to have rapidly emerged and was dominant during the U.S. outbreak (38,60,61). During the same period, subclades A1 and B2 continued to be isolated in European countries (40,41,(62)(63)(64)(65).…”

Section: Discussionmentioning

confidence: 60%

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Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Tan

Hassan

Schuster

et al. 2016

J Virol

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In 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.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 60%

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Tan

Hassan

Schuster

et al. 2016

J Virol

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“…In particular, EV-D68 outbreaks in the United States in 2014 have raised concerns of a pandemic789. Similarly, between 2006 and 2014 EV-D68 infections in China were also detected in children and adults with respiratory infections410111213. In contrast to the symptoms caused by EV-D68 and the prevalence observed in the United States, none of the cases in China had nervous system dysfunction and no notable outbreak was reported.…”

mentioning

confidence: 99%

“…To understand the prevalence of EV-D68 in China, we analyzed 64 Chinese EV-D68 sequences including 54 sequences, which were previously identified410111213, two sequences submitted directly to Genbank, and eight sequences that were detected from children hospitalized in Beijing Children’s Hospital between 2007 and 2014. Our results revealed sequence differences in the 3′-UTR and puff region of VP2 as well as six coding polymorphisms that are associated with neurovirulence7.…”

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confidence: 99%

Genetic divergence of enterovirus D68 in China and the United States

Zou

Xie

Liu

et al. 2016

Sci Rep

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The largest outbreak of human enterovirus 68 (EV-D68) infections associated with severe respiratory illness and neurological complications emerged from the United States in 2014. China reported the circulation of EV-D68 since 2006, but these cases were sporadic and did not display neurological symptoms. Yet viral determinants responsible for the difference in prevalence between China and the U.S. were not clear. We analyzed the genome of 64 reported Chinese EV-D68 strains and found that genogroup replacement has occurred in China since 2006. The six coding mutations (M291T, V341A, T860N, D927N, S1108G and R2005K) associated with neurovirulence reported in American strains were not found in Chinese strains. Moreover, 2014 Chinese strains had a unique R220A mutation in the puff region of VP2 while R220E mutation occurred in other strains. Like other enteroviruses, the loop sequences of the domain X and Y in the 3′-UTR of the Chinese strains are complementary. However, the X loop sequences of the 2014 American strains were not complementary but identical to Y loop sequences. These results indicate that different EV-D68 strains circulated in China and America and the mutations might be responsible for different prevalence. Our findings also provide new evidence for the sequence diversity of EV-D68.

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“…The viral genome also revealed 2 deletions at the 5?-UTR spacer region between the end of the internal ribosome entry site and the beginning of the polyprotein open reading frame. These same deletions have been found in EV-D68 isolated in South Africa (29), China (30), and the United States (28). Whether these deletions affect the initiation of translation and virulence will require further investigation.…”

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confidence: 78%

Prevalence and Phylogenetic Characterization of Enterovirus D68 in Pediatric Patients with Acute Respiratory Tract Infection in Thailand

et al. 2016

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SUMMARY: Enterovirus D68 (EV-D68) is associated with severe lower respiratory tract infection and neurological abnormalities including acute myelitis and cranial nerve dysfunction. To determine whether an increased incidence of EV-D68 occurs in Southeast Asia, we retrospectively tested specimens collected from Thai pediatric patients who were less than 5 years of age and presented with acute respiratory tract infections between 2012 and 2014. Reverse transcription-polymerase chain reaction and nucleotide sequencing of the 5 ? -UTR/VP2 region were used to identify EV-D68. We also examined the epidemiological pattern of EV-D68 since 2009, when it was first identified in Thailand, and compiled records of clinical manifestations in children with confirmed EV-D68 infection. From 837 samples, 5 samples (0.6z) tested positive for EV-D68. All patients presented with viral pneumonia and required hospitalization. Phylogenetic analysis of the VP4/VP2 regions revealed that EV-D68 strains circulating in Thailand between 2012 and 2014 were closely related to strains reported in Japan, United Kingdom, China, and France. Continued surveillance of probable EV-D68-associated severe respiratory tract infection and the development of a rapid diagnostic test for EV-D68 are essential in supporting awareness and facilitating disease prevention and control.Enterovirus D68 (EV-D68) is a subtype of Enterovirus enterovirus D within the family Picornaviridae. It was first isolated in the United States in 1962 from respiratory specimens obtained from 4 pediatric patients with pneumonia and bronchiolitis (1). Since then, EV-D68 infections have occurred in small numbers and accounted for only 26 reports among enteroviruses detected in the United States during the 36-year surveillance period from 1970-2005 (2). Between 2008-2010, clusters of EV-D68 emerged in the Philippines, Japan, the Netherlands, and the United States (3). EV-D68 infections have

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Enterovirus D68–Associated Severe Pneumonia, China, 2014

Cited by 40 publications

References 4 publications

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Genetic divergence of enterovirus D68 in China and the United States

Prevalence and Phylogenetic Characterization of Enterovirus D68 in Pediatric Patients with Acute Respiratory Tract Infection in Thailand

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