Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role
ABSTRACT Enteroviruses are a common cause of respiratory and gastrointestinal illness, and multiple subtypes, including poliovirus, can cause neurologic disease. In recent years, enterovirus D68 (EV-D68) has been associated with serious neurologic illnesses, including acute flaccid myelitis (AFM), f...
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American Society for Microbiology
2019
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oai:doaj.org-article:c6f1e02cf148445cb90dd564caa672902021-11-15T15:55:14ZGenomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role10.1128/mBio.02262-182150-7511https://doaj.org/article/c6f1e02cf148445cb90dd564caa672902019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02262-18https://doaj.org/toc/2150-7511ABSTRACT Enteroviruses are a common cause of respiratory and gastrointestinal illness, and multiple subtypes, including poliovirus, can cause neurologic disease. In recent years, enterovirus D68 (EV-D68) has been associated with serious neurologic illnesses, including acute flaccid myelitis (AFM), frequently preceded by respiratory disease. A cluster of 11 suspect cases of pediatric AFM was identified in September 2016 in Phoenix, AZ. To determine if these cases were associated with EV-D68, we performed multiple genomic analyses of nasopharyngeal (NP) swabs and cerebrospinal fluid (CSF) material from the patients, including real-time PCR and amplicon sequencing targeting the EV-D68 VP1 gene and unbiased microbiome and metagenomic sequencing. Four of the 11 patients were classified as confirmed cases of AFM, and an additional case was classified as probable AFM. Real-time PCR and amplicon sequencing detected EV-D68 virus RNA in the three AFM patients from which NP swabs were collected, as well as in a fourth patient diagnosed with acute disseminated encephalomyelitis, a disease that commonly follows bacterial or viral infections, including enterovirus. No other obvious etiological causes for AFM were identified by 16S or RNA and DNA metagenomic sequencing in these cases, strengthening the likelihood that EV-D68 is an etiological factor. Herpes simplex viral DNA was detected in the CSF of the fourth case of AFM and in one additional suspect case from the cluster. Multiple genomic techniques, such as those described here, can be used to diagnose patients with suspected EV-D68 respiratory illness, to aid in AFM diagnosis, and for future EV-D68 surveillance and epidemiology. IMPORTANCE Enteroviruses frequently result in respiratory and gastrointestinal illness; however, multiple subtypes, including poliovirus, can cause severe neurologic disease. Recent biennial increases (i.e., 2014, 2016, and 2018) in cases of non-polio acute flaccid paralysis have led to speculations that other enteroviruses, specifically enterovirus D68 (EV-D68), are emerging to fill the niche that was left from poliovirus eradication. A cluster of 11 suspect cases of pediatric acute flaccid myelitis (AFM) was identified in 2016 in Phoenix, AZ. Multiple genomic analyses identified the presence of EV-D68 in the majority of clinical AFM cases. Beyond limited detection of herpesvirus, no other likely etiologies were found in the cluster. These findings strengthen the likelihood that EV-D68 is a cause of AFM and show that the rapid molecular assays developed for this study are useful for investigations of AFM and EV-D68.Jolene R. BowersMichael ValentineVeronica HarrisonViacheslav Y. FofanovJohn GilleceJosie DelisleBethany PattonJames SchuppKrystal SheridanDarrin LemmerScott OstdiekHarlori K. BainsJennifer HeimTammy SylvesterSiru PrasaiMelissa KretschmerNicole FowleKenneth KomatsuShane BradySusan RobinsonKathryn FitzpatrickGholamabbas Amin OstovarEric AlsopElizabeth HutchinsKendall JensenPaul KeimDavid M. EngelthalerAmerican Society for MicrobiologyarticleAFMEV-D68acute flaccid myelitisenterovirusgenomicsmetagenomicsMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
AFM EV-D68 acute flaccid myelitis enterovirus genomics metagenomics Microbiology QR1-502 |
| spellingShingle |
AFM EV-D68 acute flaccid myelitis enterovirus genomics metagenomics Microbiology QR1-502 Jolene R. Bowers Michael Valentine Veronica Harrison Viacheslav Y. Fofanov John Gillece Josie Delisle Bethany Patton James Schupp Krystal Sheridan Darrin Lemmer Scott Ostdiek Harlori K. Bains Jennifer Heim Tammy Sylvester Siru Prasai Melissa Kretschmer Nicole Fowle Kenneth Komatsu Shane Brady Susan Robinson Kathryn Fitzpatrick Gholamabbas Amin Ostovar Eric Alsop Elizabeth Hutchins Kendall Jensen Paul Keim David M. Engelthaler Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role |
| description |
ABSTRACT Enteroviruses are a common cause of respiratory and gastrointestinal illness, and multiple subtypes, including poliovirus, can cause neurologic disease. In recent years, enterovirus D68 (EV-D68) has been associated with serious neurologic illnesses, including acute flaccid myelitis (AFM), frequently preceded by respiratory disease. A cluster of 11 suspect cases of pediatric AFM was identified in September 2016 in Phoenix, AZ. To determine if these cases were associated with EV-D68, we performed multiple genomic analyses of nasopharyngeal (NP) swabs and cerebrospinal fluid (CSF) material from the patients, including real-time PCR and amplicon sequencing targeting the EV-D68 VP1 gene and unbiased microbiome and metagenomic sequencing. Four of the 11 patients were classified as confirmed cases of AFM, and an additional case was classified as probable AFM. Real-time PCR and amplicon sequencing detected EV-D68 virus RNA in the three AFM patients from which NP swabs were collected, as well as in a fourth patient diagnosed with acute disseminated encephalomyelitis, a disease that commonly follows bacterial or viral infections, including enterovirus. No other obvious etiological causes for AFM were identified by 16S or RNA and DNA metagenomic sequencing in these cases, strengthening the likelihood that EV-D68 is an etiological factor. Herpes simplex viral DNA was detected in the CSF of the fourth case of AFM and in one additional suspect case from the cluster. Multiple genomic techniques, such as those described here, can be used to diagnose patients with suspected EV-D68 respiratory illness, to aid in AFM diagnosis, and for future EV-D68 surveillance and epidemiology. IMPORTANCE Enteroviruses frequently result in respiratory and gastrointestinal illness; however, multiple subtypes, including poliovirus, can cause severe neurologic disease. Recent biennial increases (i.e., 2014, 2016, and 2018) in cases of non-polio acute flaccid paralysis have led to speculations that other enteroviruses, specifically enterovirus D68 (EV-D68), are emerging to fill the niche that was left from poliovirus eradication. A cluster of 11 suspect cases of pediatric acute flaccid myelitis (AFM) was identified in 2016 in Phoenix, AZ. Multiple genomic analyses identified the presence of EV-D68 in the majority of clinical AFM cases. Beyond limited detection of herpesvirus, no other likely etiologies were found in the cluster. These findings strengthen the likelihood that EV-D68 is a cause of AFM and show that the rapid molecular assays developed for this study are useful for investigations of AFM and EV-D68. |
| format |
article |
| author |
Jolene R. Bowers Michael Valentine Veronica Harrison Viacheslav Y. Fofanov John Gillece Josie Delisle Bethany Patton James Schupp Krystal Sheridan Darrin Lemmer Scott Ostdiek Harlori K. Bains Jennifer Heim Tammy Sylvester Siru Prasai Melissa Kretschmer Nicole Fowle Kenneth Komatsu Shane Brady Susan Robinson Kathryn Fitzpatrick Gholamabbas Amin Ostovar Eric Alsop Elizabeth Hutchins Kendall Jensen Paul Keim David M. Engelthaler |
| author_facet |
Jolene R. Bowers Michael Valentine Veronica Harrison Viacheslav Y. Fofanov John Gillece Josie Delisle Bethany Patton James Schupp Krystal Sheridan Darrin Lemmer Scott Ostdiek Harlori K. Bains Jennifer Heim Tammy Sylvester Siru Prasai Melissa Kretschmer Nicole Fowle Kenneth Komatsu Shane Brady Susan Robinson Kathryn Fitzpatrick Gholamabbas Amin Ostovar Eric Alsop Elizabeth Hutchins Kendall Jensen Paul Keim David M. Engelthaler |
| author_sort |
Jolene R. Bowers |
| title |
Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role |
| title_short |
Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role |
| title_full |
Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role |
| title_fullStr |
Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role |
| title_full_unstemmed |
Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role |
| title_sort |
genomic analyses of acute flaccid myelitis cases among a cluster in arizona provide further evidence of enterovirus d68 role |
| publisher |
American Society for Microbiology |
| publishDate |
2019 |
| url |
https://doaj.org/article/c6f1e02cf148445cb90dd564caa67290 |
| work_keys_str_mv |
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