CDC Acute Flaccid Myelitis Update

May 7, 2019

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CDC Acute Flaccid Myelitis Update, May 7, 2019

CDC Acute Flaccid Myelitis Update

Janell Routh, MD MHS
Medical Officer
Division of Viral Diseases
National Center for Immunization and Respiratory Diseases

Board of Scientific Counselors Meeting
May 7, 2019


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AFM reports to CDC by case status and month of onset, January 2018-April 2019

AFM reports to CDC by case status and month of onset, January 2018-April 2019

AFM reports to CDC by case status and month of onset, January 2018-April 2019
Classification 2018 2019
Confirmed 230 7
Probable 26 2
Non cases 108 12
Total classified 364 21

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2018 confirmed cases of acute flaccid myelitis (AFM) by state (Number=230)

2018 confirmed cases of acute flaccid myelitis (AFM) by state (N=230)*

*Confirmed AFM cases as of May 3, 2019. Patients under investigation are still being classified, and the case counts are subject to change. One of the confirmed cases is a foreign resident (based on the country of usual residence) and therefore not included in the state map.

More information about confirmed AFM cases in the United States


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CDC AFM laboratory testing, 2018–2019

CDC AFM laboratory testing, 2018–2019

  • Cerebrospinal fluid (CSF): remains low-yield (3%)
    • 1 for enterovirus-D68 (EV-D68)
    • 1 for enterovirus-A71 (EV-A71)
  • Stool: 13% tested positive
    • mix of enteroviruses/rhinoviruses (EV/RV) and parechoviruses
    • all negative for polio
  • Respiratory: 45% tested positive, consistent with other peak years
    • 25% of specimens positive for EV-D68
    • 20% of specimens positive for other EV/RV
  • 2019 testing has yielded only 1 positive respiratory sample (EV/RV untyped)

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CDC AFM Epidemiology Activities

CDC AFM Epidemiology Activities


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Advance understanding of the clinical presentation and outcomes of patients with AFM

Advance understanding of the clinical presentation and outcomes of patients with AFM

  • Abstracted clinical information from 2018 AFM patient medical records
    • Describe clinical phenotypes of confirmed cases
    • Compare clinical characteristics between cases and non-cases
    • Compare clinical data between peak and non-peak years
  • Long-term follow-up of AFM cases in progress
    • Interview 2018 confirmed and probable cases
    • Functional assessment at 2, 6 and 12 months post onset using a validated questionnaire

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Further interpret the temporal and geographical association between AFM cases and enteroviruses

Further interpret the temporal and geographical association between AFM cases and enteroviruses

  • Conduct modeling of AFM case and EV testing data in partnership with a commercial laboratory and AFM Task Force colleagues
  • Conduct enhanced AFM surveillance alongside active, prospective surveillance for gastroenteritis and respiratory illness in seven pediatric academic centers (WA, TX, MO, OH, TN, PA, NY)
    • Help to define baseline incidence of AFM
    • Compare monthly/seasonal incidence of AFM to viral circulation patterns detected by this surveillance system

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Describe the natural history of AFM and determine risk factors for illness

Describe the natural history of AFM and determine risk factors for illness

  • Collaborate in the NIH natural history study to better understand clinical presentation, etiologies, and outcomes of patients with AFM
  • Case-series investigation (hypothesis-generating) to identify potential exposures common to AFM patients
    • Interview of 2018 confirmed AFM cases in summer 2019
    • Variables include: medical and illness exposure history, care seeking behaviors for preceding illness and limb weakness, trauma, intra-muscular injections, vector exposure, genetic and environmental factors

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CDC AFM Laboratory Activities

CDC AFM Laboratory Activities


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Develop assays to look for indirect evidence of a viral infection

Develop assays to look for indirect evidence of a viral infection

  • Work with academic partners to examine EV-specific antibodies in CSF, which would provide additional support for a role of EV in AFM
  • Develop EV-D68 monoclonal antibodies to facilitate IgM and IgA assays to look for serum and intrathecal antibodies as evidence of exposure to virus
  • Investigate the immunophenotype of peripheral blood cells in AFM patients, to better understand what may be stimulating an immune response
  • Characterize cytokine/chemokine patterns in CSF and serum of confirmed AFM patients as potential hallmark biomarkers

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Explore the association between EV-D68 and AFM

Explore the association between EV-D68 and AFM

  • Understand the evolution of EV-D68
    • Generate complete genome sequences for viruses detected in AFM patient specimens and generate infectious clones
    • Use neuronal and respiratory cell models to understand EV-D68 infection and cytopathology
  • Further investigate the high seroprevalence to EV-D68 across all age groups in Kansas City by planning a similar study using more nationally representative samples
  • Develop assay for EV-D68 antibody-dependent disease enhancement

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CDC AFM Communications Activities

CDC AFM Communications Activities


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AFM Vital Signs Release (July 9, 2019)

AFM Vital Signs Release (July 9, 2019)

  • MMWR about 2018 cases, timing of care and reporting lags
  • Fact sheet targeting health care workers with specific messages on diagnosis and reporting
  • Emphasize distinction between patient diagnosis and public health surveillance
    • Diagnosis of AFM should be rapid for medical management and independent of the CDC case classification
    • CDC case classification is meant specifically for surveillance-to understand disease burden and illness trends over time

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Outreach to first-line pediatric responders and AFM parent group

Outreach to first-line pediatric responders and AFM parent group

  • Connect with primary care clinicians, urgent care and emergency provider organizations for ongoing AFM education and research on healthcare provider knowledge, attitudes, and behaviors
  • Communicate with AFM parent group through regular question and answer sessions and in-depth focus group discussions

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Conclusions

Conclusions

  • AFM cases continue to occur in seasonal, every-other-year outbreaks
  • Growing evidence suggests that enteroviruses, including EV-D68, are leading etiologic candidates; however other causes and mechanisms for disease should be explored
  • Robust surveillance and laboratory investigations will improve our understanding of the epidemiology and etiology of these outbreaks
  • Provider outreach through Vital Signs release should improve case recognition and reporting and encourage early specimen collection for improved pathogen detection

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Thank You

Thank You

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Page last reviewed: June 4, 2019