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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.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM) 1-6 . Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) 2 . CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM.

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) ( P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively). IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease., (Copyright © 2019 Mishra et al.)

Background: Acute flaccid myelitis (AFM), a serious paralytic illness, was first recognized as a distinct condition in 2014, when cases were reported concurrent with a large U.S. outbreak of severe respiratory illness caused by enterovirus D-68 (EV-D68). Since 2014, nationwide outbreaks of AFM have occurred every 2 years in the United States; the cause for the recent change in the epidemiology of AFM in the United States, including the occurrence of outbreaks and a biennial periodicity since 2014, is under investigation. This report updates clinical, laboratory, and outcome data for cases reported to CDC during 2018., Methods: Clinical data and specimens from persons in the United States who met the clinical criterion for AFM (acute onset of flaccid limb weakness) with onset in 2018 were submitted to CDC for classification of the illnesses as confirmed, probable, or non-AFM cases. Enterovirus/rhinovirus (EV/RV) testing was performed on available specimens from persons meeting the clinical criterion. Descriptive analyses, laboratory results, and indicators of early recognition and reporting are summarized., Results: From January through December 2018, among 374 reported cases of AFM, 233 (62%) (from 41 states) were classified as confirmed, 26 (7%) as probable, and 115 (31%) as non-AFM cases. Median ages of patients with confirmed, probable, and non-AFM cases were 5.3, 2.9, and 8.8 years, respectively. Laboratory testing identified multiple EV/RV types, primarily in respiratory and stool specimens, in 44% of confirmed cases. Among confirmed cases, the interval from onset of limb weakness until specimen collection ranged from 2 to 7 days, depending on specimen type. Interval from onset of limb weakness until reporting to CDC during 2018 ranged from 18 to 36 days, with confirmed and probable cases reported earlier than non-AFM cases., Conclusion: Identification of risk factors leading to outbreaks of AFM remains a public health priority. Prompt recognition of signs and symptoms, early specimen collection, and complete and rapid reporting will expedite public health investigations and research studies to elucidate the recent epidemiology of AFM and subsequently inform treatment and prevention recommendations., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.