Severe enterovirus 68 respiratory illness in children requiring intensive care management

Schuster, Jennifer E; Miller, Jenna; Selvarangan, Rangaraj; Weddle, Gina; Thompson, Marita; Hassan, Ferdaus; Rogers, Shannon; Oberste, M. Steven; Nix, W. Allan; Jackson, Mary Anne

doi:10.1016/j.jcv.2015.07.298

Cited by 55 publications

(57 citation statements)

References 38 publications

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“…Patients, aged 0 to 17 years, admitted to Children's Mercy Hospital from 1 August to 15 September 2014 with a positive test result for enterovirus/rhinovirus by FilmArray respiratory panel assay (Biofire LLC, Idaho) were retrospectively tested for the presence of EV-D68 by real-time PCR (37). EV-D68-positive patients admitted to the pediatric intensive care unit (ICU) were age matched with two patients not requiring ICU care.…”

Section: Methodsmentioning

confidence: 99%

“…The 2014 outbreak of EV-D68 was the largest outbreak recorded in North America, with more than 1,153 confirmed EV-D68 cases in 49 U.S. states and the District of Columbia (35). The majority of cases were associated with severe respiratory illness in children (36,37) leading to hospitalization. In addition, there was a surge in EV-D68 infections associated with AFM and encephalitis (36,38,39).…”

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confidence: 99%

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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: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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“…EV-D68 caused more severe disease in patients with history of asthma and reactive airway disease. Less than 50% of patients were febrile, and it is possible that milder cases of respiratory illness caused by EV-D68 were being underreported [35]. Co-detection of other pathogens was rare.…”

Section: Emerging Enteroviruses and Associations With Acute Flaccid Mmentioning

confidence: 99%

Enteroviruses in the early 21st century

Lugo¹,

Krogstad

2016

Current Opinion in Pediatrics

127

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Purpose of review Enteroviruses cause a wide variety of diseases with neurologic, respiratory, skin, and gastrointestinal findings. The purpose of this review is to clarify changes in the classification of enteroviruses, provide information about recent disease outbreaks, and to summarize progress toward treatment and prevention of these infections. Recent findings Enteroviruses are now classified into 4 distinct species. New variants of Coxsackievirus B1, Enterovirus-A71, and Enterovirus-D68 (EV-D68) have emerged as causes of recent outbreaks in the United States and other countries, including more severe disease manifestations than previously described. EV-D68 now commonly circulates in the United States, and has been linked to severe respiratory disease and associated with acute flaccid myelitis. Overcoming enormous political and logistical challenges, fewer than 100 cases of polio have been reported in 2015, and the initiation of “endgame” strategies appears imminent. Unfortunately treatment for enterovirus infections remains supportive, although the recently completed pleconaril trial in newborns suggests that antiviral therapy may reduce mortality in neonatal disease. Summary Clinicians should be aware of the respiratory and neurological manifestations associated with EV-D68 and the potential for severe disease seen with other recently described enterovirus variants. Healthcare professionals should recognize the utility of rapid diagnostic methods and progress toward prevention and treatment of enterovirus infections.

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“…8 A study from Alberta compared patients with EV-D68 to those with other enterovirus strains to determine whether the former group of patients was more likely to have respiratory illness. 9 Although the researchers found an association between asthma and EV-D68, the results were based on information from administrative and surveillance databases, and therefore the full clinical spectrum on disease severity and outcomes was not available.…”

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confidence: 99%

“…Schuster and colleagues did document statistically significant increased odds of asthma or recurrent wheeze in patients admitted to intesive care with EV-D68. 8 Therefore, although it is important to consider that history would have been dependent on parental self-report and provider documentation, it seems reasonable to hypothesize that EV-D68 may be a more virulent pathogen in patients with preexisting atopic disease when compared with rhinoviruses and other enteroviruses.…”

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confidence: 99%

Enterovirus D68 and disease severity: more questions than answers

Allen

2015

CMAJ

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Severe enterovirus 68 respiratory illness in children requiring intensive care management

Cited by 55 publications

References 38 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

Enteroviruses in the early 21st century

Enterovirus D68 and disease severity: more questions than answers

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