Unraveling the Mysteries of Acute Flaccid Myelitis: Scientific Opportunities and Priorities for Future Research.

Since 2014, cases of acute flaccid myelitis (AFM) have been reported in the United States in increasing numbers biennially, occurring in the late summer and early fall. Although there is unlikely to be a single causative agent of this syndrome, non-polio enteroviruses (NPEV) including enterovirus D-68 (EV-D68) have had epidemiological and laboratory associations with AFM. Much remains to be known about AFM and AFM-associated enteroviruses, including disease pathogenesis and the best strategies for development of therapeutics or preventive modalities including vaccines. To catalyze research that addresses these scientific and clinical gaps, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop entitled "AFM Preparedness: Addressing EV-D68 and Other AFM-Associated Enteroviruses" on February 19-20, 2020.

[1]  M. Rossmann,et al.  Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease , 2020, Science Immunology.

[2]  J. Sejvar,et al.  Acute Flaccid Myelitis in the United States: 2015–2017 , 2019, Pediatrics.

[3]  M. Abzug,et al.  Acute Flaccid Myelitis Surveillance: A Signal Through the Noise , 2019, Pediatrics.

[4]  Rachel L. Marine,et al.  Pan-viral serology implicates enteroviruses in acute flaccid myelitis , 2019, Nature Medicine.

[5]  Rachel L. Marine,et al.  Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis , 2019, mBio.

[6]  Jennifer L. Konopka-Anstadt,et al.  Vital Signs: Surveillance for Acute Flaccid Myelitis - United States, 2018. , 2019, MMWR. Morbidity and mortality weekly report.

[7]  K. Tyler,et al.  Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid , 2019, Journal of Virology.

[8]  Xiao-Fang Yu,et al.  Current Understanding of Human Enterovirus D68 , 2019, Viruses.

[9]  J. Crowe,et al.  Current Understanding of Humoral Immunity to Enterovirus D68. , 2018, Journal of the Pediatric Infectious Diseases Society.

[10]  O. Brouwer,et al.  Twenty-nine Cases of Enterovirus-D68–associated Acute Flaccid Myelitis in Europe 2016 , 2018, The Pediatric infectious disease journal.

[11]  N. Grassly,et al.  Serotype-specific immunity explains the incidence of diseases caused by human enteroviruses , 2018, Science.

[12]  S. Samal,et al.  Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis , 2018, Journal of Virology.

[13]  N. Grassly,et al.  The seasonality of nonpolio enteroviruses in the United States: Patterns and drivers , 2018, Proceedings of the National Academy of Sciences.

[14]  V. Ruggieri,et al.  Enterovirus D68 infection in a cluster of children with acute flaccid myelitis, Buenos Aires, Argentina, 2016. , 2017, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[15]  T. Shiihara,et al.  Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August–December 2015 , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  D. Stuart,et al.  Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine , 2017, Nature Communications.

[17]  Audrey L. Warren,et al.  Neurotropism of Enterovirus D68 Isolates Is Independent of Sialic Acid and Is Not a Recently Acquired Phenotype , 2017, mBio.

[18]  Changgui Li,et al.  Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  J. Sejvar,et al.  Acute Flaccid Myelitis in the United States, August-December 2014: Results of Nationwide Surveillance. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  K. Tyler,et al.  Acute flaccid myelitis: A clinical review of US cases 2012–2015 , 2016, Annals of neurology.

[21]  J. Sejvar,et al.  Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014 , 2016, Emerging infectious diseases.

[22]  M. Rossmann,et al.  Enterovirus D68 receptor requirements unveiled by haploid genetics , 2016, Proceedings of the National Academy of Sciences.

[23]  Alexandra J. Lee,et al.  Genetic changes found in a distinct clade of Enterovirus D68 associated with paralysis during the 2014 outbreak , 2016, Virus evolution.

[24]  Xiao-Fang Yu,et al.  Analysis of Enterovirus 68 Strains from the 2014 North American Outbreak Reveals a New Clade, Indicating Viral Evolution , 2015, PloS one.

[25]  G. Aldrovandi,et al.  A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. , 2015, The Lancet. Infectious diseases.

[26]  D. Kihara,et al.  Structure and inhibition of EV-D68, a virus that causes respiratory illness in children , 2015, Science.

[27]  Jiansheng Liu,et al.  An inactivated enterovirus 71 vaccine in healthy children. , 2014, The New England journal of medicine.

[28]  Wenbo Xu,et al.  Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. , 2014, The New England journal of medicine.

[29]  Pei Liu,et al.  Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial , 2013, The Lancet.

[30]  A. Băicuș History of polio vaccination. , 2012, World journal of virology.

[31]  N. Nathanson,et al.  From Emergence to Eradication: The Epidemiology of Poliomyelitis Deconstructed , 2010, American journal of epidemiology.

[32]  M. Rossmann,et al.  Picornavirus-receptor interactions. , 2002, Trends in microbiology.

[33]  J. Crowe,et al.  Current Understanding of Humoral Immunity to Enterovirus D68. , 2018, Journal of the Pediatric Infectious Diseases Society.