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Acute Flaccid Myelitis in the United States: 2015–2017 Tracy Ayers, Phd,A Adriana Lopez, MHS,B Adria Lee, MSPH,C Anita Kambhampati, MPH,C W

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Acute Flaccid Myelitis in the United States: 2015–2017 Tracy Ayers, Phd,A Adriana Lopez, MHS,B Adria Lee, MSPH,C Anita Kambhampati, MPH,C W Acute Flaccid Myelitis in the United States: 2015–2017 Tracy Ayers, PhD,a Adriana Lopez, MHS,b Adria Lee, MSPH,c Anita Kambhampati, MPH,c W. Allan Nix, PhD,b Elizabeth Henderson, BA,b Shannon Rogers, BS,b William C. Weldon, PhD,b M. Steven Oberste, PhD,b James Sejvar, MD,d Sarah E. Hopkins, MD, MSPH,e Mark A. Pallansch, PhD,b Janell A. Routh, MD, MHS,b Manisha Patel, MD, MSb BACKGROUND: Acute flaccid myelitis (AFM) is a neurologic condition characterized by flaccid limb abstract weakness. After a large number of reports of AFM in 2014, the Centers for Disease Control and Prevention began standardized surveillance in the United States to characterize the disease burden and explore potential etiologies and epidemiologic associations. METHODS: Persons meeting the clinical case criteria of acute flaccid limb weakness from January 1, 2015, through December 31, 2017, were classified as confirmed (spinal cord gray matter lesions on MRI) or probable (white blood cell count .5 cells per mm3 in cerebrospinal fluid [CSF]). We describe clinical, radiologic, laboratory, and epidemiologic findings of pediatric patients (age #21 years) confirmed with AFM. RESULTS: Of 305 children reported from 43 states, 193 were confirmed and 25 were probable. Of confirmed patients, 61% were male, with a median age of 6 years (range: 3 months to 21 years; interquartile range: 3 to 10 years). An antecedent respiratory or febrile illness was reported in 79% with a median of 5 days (interquartile range: 2 to 7 days) before limb weakness. Among 153 sterile-site specimens (CSF and serum) submitted to the Centers for Disease Control and Prevention, coxsackievirus A16 was detected in CSF and serum of one case patient and enterovirus D68 was detected in serum of another. Of 167 nonsterile site (respiratory and stool) specimens, 28% tested positive for enterovirus or rhinovirus. CONCLUSIONS: AFM surveillance data suggest a viral etiology, including enteroviruses. Further study is ongoing to better characterize the etiology, pathogenesis, and risk factors of this rare condition. cIHRC Inc. contracting agency to the Division of Viral Diseases, bDivision of Viral Diseases, National Center for WHAT’S KNOWN ON THIS SUBJECT: Acute flaccid Immunization and Respiratory Diseases, dDivision of High-Consequence Pathogens and Pathology, National Center myelitis (AFM) is a severe neurologic condition for Emerging and Zoonotic Infectious Diseases, and aEpidemic Intelligence Service, Centers for Disease Control characterized by flaccid limb weakness. The CDC e and Prevention, Atlanta, Georgia; and Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, began tracking AFM in 2014, when an outbreak of 120 Pennsylvania cases occurred. Most patients had symptoms of a viral The findings and conclusions in this report are those of the authors and do not necessarily illness shortly before weakness onset. represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services. WHAT THIS STUDY ADDS: This report provides the most comprehensive summary of clinical, laboratory, Drs Ayers, Routh, and Patel conceptualized and designed the study, coordinated and supervised radiologic, and epidemiologic data of AFM in the United data collection, drafted the initial manuscript, and reviewed and revised the manuscript; Ms Lopez, Ms Lee, and Ms Kambhampati designed the data collection instruments, collected data, conducted States to date, supporting the every-other-year peak in the initial analyses, and reviewed and revised the manuscript; Dr Nix, Ms Henderson, and Ms Rogers cases, pediatric predominance, and likely role of conducted laboratory testing and analysis on all samples and reviewed and revised the manuscript; viruses, including enteroviruses, in AFM pathogenesis. Drs Weldon, Oberste, and Pallansch supervised data collection and laboratory testing and critically reviewed the manuscript for important intellectual content; Drs Sejvar and Hopkins conducted To cite: Ayers T, Lopez A, Lee A, et al. Acute Flaccid fl fi acute accid myelitis case classi cations and critically reviewed the manuscript for important Myelitis in the United States: 2015–2017. Pediatrics. 2019; fi intellectual content; and all authors approved the nal manuscript as submitted and agree to be 144(5):e20191619 accountable for all aspects of the work. Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 144, number 5, November 2019:e20191619 ARTICLE Until the late 1950s, poliovirus was efforts at the CDC, public health collection of data for adult and amajorcauseofacuteflaccid paralysis departments, and academic centers to probable cases began in August 2015 (AFP) in the United States, with up to investigate a potential association and is reported in Supplemental 15 000 paralytic cases annually.1 between AFM and EV-D68.8,9 Despite Tables 5 and 6. Patients who met the Polioviruses can infect anterior horn these efforts, evidence to support clinical case criteria but could not be cells in the gray matter of the spinal asingleetiologicagentasthecauseof classified as confirmed or probable cord and cause paralysis in ∼0.1% of AFM remained inconclusive. cases were excluded from the primary all infections. After the introduction of analysis (Supplemental Table 7). In 2015, the CDC and the Council of effective vaccines in 1955, AFP cases State and Territorial Epidemiologists due to poliovirus were eliminated in Laboratory Testing established standardized surveillance the United States; the last endemic The CDC requested sterile-site (eg, for AFM in the United States to address case was reported in 1979, and the blood or serum and CSF) and numerous remaining questions, last imported case in 1993.1 However, nonsterile-site (eg, nasopharyngeal or including the burden of disease, nonpolio cases of AFP with similar oropharyngeal respiratory and stool) spectrum of clinical presentation, risk spinal cord involvement continue to specimens from each patient. We factors for paralysis, and etiologies.10 occur, albeit rarely, and have been tested for poliovirus using virus We describe characteristics of AFM associated with other enteroviruses isolation and molecular methods. cases reported in the United States (EVs), like coxsackieviruses (CVs), EV- During 2015 and 2016, the CDC – from 2015 through 2017. A71, and EV-C105.2 5 tested all specimens for EVs and rhinoviruses (EVs/RVs) using During late summer of 2014, several METHODS a qualitative real-time reverse cases of AFP among children were transcription–polymerase chain fi identified in Colorado.6,7 In response to Case Reporting and Classi cation reaction (RT-qPCR) pan-EV assay11 an increase in reports of children From January 1, 2015, to June 30, and an EV typing assay (species A–J) presenting similarly in other states, the 2017, a clinical case of AFM was by viral protein 1 reverse Centers for Disease Control and defined as a patient with acute onset of transcription-seminested PCR and Prevention (CDC) developed a case focal limb weakness. In June 2017, the Sanger sequencing.12 Specimens were definition for acute flaccid myelitis case definition was modified from also tested for parechoviruses (AFM), which included persons focal to flaccid to more accurately (species A–B) by using RT-qPCR.13 #21 years of age with acute limb describe the weakness associated with Respiratory specimens were further weakness and an MRI demonstrating AFM. After July 1, 2017, a clinical case tested by using an EV-D68–specific predominantly gray matter lesions of of AFM was defined as a patient with assay.14 Any respiratory specimens the spinal cord to differentiate this acute onset of flaccid limb weakness. that tested positive for EV-D68 by condition from other forms of AFP, Health departments and clinicians either viral protein 1 seminested such as Guillain-Barré syndrome submitted to the CDC demographic, sequencing or by the EV-D68–specific (GBS).8 A total of 120 confirmed cases clinical, epidemiologic, laboratory, and assay were considered EV-D68 were reported from August through radiographic information on patients positive. Because of wide availability December 2014, with a peak in late meeting the clinical case criteria. An of the pan-EV/RV RT-qPCR assay in summer and early fall. Most cases had AFM expert panel, consisting of the United States and in an effort to predominant anterior horn cell pediatricians and neurologists from preserve CSF specimen volume, the involvement, similar to poliomyelitis CDC and US academic centers, CDC modified its testing algorithm in lesions. The CDC performed an classified patients as confirmed or 2017 to perform only typing of EV/ extensive laboratory evaluation, probable on the basis of a thorough RV-positive specimens submitted including testing for poliovirus and review of all available data for each by external laboratories. We provide other EVs, parechoviruses, arboviruses, patient. A confirmed case was a patient results for the earliest specimen and herpesviruses, to identify possible who met the clinical case criteria and submitted if .1 specimen was etiologies. Poliovirus was conclusively had an MRI showing a spinal cord submitted per specimen site. Results ruled out as a causative agent, and lesion largely restricted to gray matter submitted to the CDC from other testing of hundreds of sterile-site and spanning $1 spinal segments. A laboratories are also summarized in specimens, including cerebrospinal probable case was a patient who met this report; diagnostic testing fluid (CSF)
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