what is known about the epidemiology of acute flaccid...
TRANSCRIPT
National Center for Immunization & Respiratory Diseases
What is known about the epidemiology of Acute Flaccid Myelitis
AFM SymposiumJune 5, 2020
Janell Routh, MD MHSAFM and Domestic Polio Team LeadDivision of Viral DiseasesNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention
Surveillance for AFM is challenging
Person with cough and fever
Laboratory test Case of influenza
Surveillance for AFM is challenging
Laboratory test Case of influenza
Person withLimb weakness Medical records and MRI images Case of AFM
Person with cough and fever
Case definition for AFM
2014 2015 2016 2017
Confirmed case of AFM –Acute onset of limb weakness and magnetic resonance image (MRI) showing a spinal cord lesion largely restricted to gray matter in a patient ≤21 years of age
Confirmed case of AFM –Acute onset of flaccid limb weakness, AND an MRI showing a spinal cord lesion largely restricted to gray matter and spanning one or more spinal segments. Probable case of AFM –Acute onset of flaccid limb weakness, AND cerebrospinal fluid (CSF) with pleocytosis(white blood cell count >5 cells/mm3).
2018 2019
June 2019: CSTE adopted revisions to case definition
Confirmed case of AFM – Acute onset of flaccid limb weakness, AND an MRI showing a spinal cord lesion largely restricted to gray matter and spanning one or more spinal segments* AND absence of clear alternative diagnosis attributable to a nationally notifiable condition. Probable case of AFM – Acute onset of flaccid limb weakness, AND an MRI showing spinal cord lesion where gray matter involvement is present* but predominance cannot be determined AND absence of clear alternative diagnosis attributable to a nationally notifiable condition. Suspect caseof AFM - Acute onset of flaccid limb weakness, AND an MRI showing a spinal cord lesion in at least some gra matter and spanning one or more spinal segments* AND available information is insufficient to classify as confirmed or probable.
* Excluding persons with gray matter lesions in the spinal cord resulting from physician diagnosed malignancy, vascular disease, or anatomic abnormality.
Confirmed case of AFM – Acute onset of focal limb weakness, AND an MRI showing a spinal cord lesion largely restricted to gray matter and spanning one or more spinal segments. Probable case of AFM –Acute onset of focal limb weakness, AND cerebrospinal fluid (CSF) with pleocytosis(white blood cell count >5 cells/mm3).
AFM surveillance processes involve clinicians and health departments
Clinician reports patient suspected
to have AFMto Health
Department
Health department (HD) verifies patient meets criteria and
reports to CDC
HD collectsmedical information, MRIs and coordinates specimens to send to
CDC
Neurology panel reviews information
and images and provides a case classification
Surveillance classification
communicated to HD and then
HD relays classification to
clinician
Clinical diagnosis and public health surveillance have different purposes
Public Health Surveillance Population-level Use of standardized case definitions Measures disease burden and
trends over time Delayed reporting and classification Balances sensitivity and specificity
Clinical Diagnosis Patient-level Used for individual clinical
management decisions Time-sensitive Diagnosis based on full clinical
presentation Aim for the most accurate
diagnosis
National increase in AFM cases every 2 years since 2014Number of confirmed reported AFM cases, Aug 2014 – May 2020 (n=625)
https://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.htmlData current as of June 1, 2020
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Month of onset
2014: 120 cases
2015: 22 cases
2016: 153 cases
2017: 38 cases
2018: 238 cases
2019: 46 cases
2020: 8 cases
Sept
Sept
Sept
Sept
Sept
Sept
AFM cases, 2005-2014, 5 sites combined, United States
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2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
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Jan-Jun Jul-Dec
Cortese MM, Kambhampati AK, Schuster JE, et.al. A ten-year retrospective evaluation of AFM at 5 pediatric centers in the US, 2005 – 2014. PLOS One. January, 2020.
AFM has multiple causes
InfectionsEnteroviruses
(EV-D68, EV-A71)Flaviviruses (WNV, JEV)
AdenovirusesHerpesviruses
OtherNeuro-inflammatory (TM, ADEM, NMOSD,
anti-MOG, MS)Spinal stroke/embolism
AFM
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Month of limb weakness onsethttps://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.htmlData current as of June 1, 2020
U.S. surveillance shows a consistent baseline rate of AFM Number of confirmed reported AFM cases, Aug 2014 – May 2020 (n=625)
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Month of limb weakness onsethttps://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.htmlData current as of June 1, 2020
What is causing the biennial peaks in AFM?Number of confirmed reported AFM cases, Aug 2014 – May 2020 (n=625)
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Month of limb weakness onset
2018
https://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.htmlData current as of June 1, 2020
2018 was the most recent peak year for AFMNumber of confirmed reported AFM cases, January – December, 2020 (n=238)
5.3 years(IQR: 3.3—8.2)
94% <18 years
Median Age
58% male
Sex
42 states
Geography Race
53% White20% Hispanic
9% Black4% Asian
Demographic characteristics of confirmed AFM cases, 2018
Data current as of June 1, 2020Icon Credits: Juan Pablo Bravo; Marie Van de Broeck; DT Design; MRFA
No geographic clustering of AFM among 238 cases in 42 states
https://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.htmlData current as of June 1, 2020
98%(54% ICU)
Hospitalization
87%WBC count 94 cells/mm3
(IQR: 43–163)Lymphocyte predominance
CSF Pleocytosis Limbs affected
47% upper only16% lower only
1 limb: 37%2 limbs: 30%3 limbs: 6%4 limbs: 27%
Number of Limbs
Clinical Characteristics of confirmed AFM cases, 2018
Data current as of June 1, 2020Icon credits: Aldric Rodriguez; ProSymbols; Tawny Whatmore
Symptoms consistent with a viral illness precede limb weakness
10%
22%
37%
46%
77%
80%
92%
97%
RashGI illness
HeadacheNeck/back pain
FeverURI
Fever or URIAny
Proportion of cases
Days from symptom onset to limb weakness
Median (IQR)
6
6
6
3
1.5
2
2
4
-9 -6 -3 0
CSFN=74
StoolN=100
RespiratoryN=123
Total*
N=151
54 (44%)
13 (13%)
2 (3%)
71 (47%)
EV/RV positive
*Some patients had multiple positive specimens
AFM diagnostic testing remains low yieldCDC testing results, 2018
Lopez, et al. Vital Signs: Surveillance for Acute Flaccid Myelitis – US, 2018, MMWR 2019
0% 20% 40% 60% 80% 100%
EV-D68 EV-A71 Other EV/RV EV/RV negative
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Month of limb weakness onsethttps://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.htmlData current as of June 1, 2020
What is causing the biennial peaks in AFM?
AFM case characteristics in peak years differ from those in non-peak years
86%
33%
78%
38%
54%
13%
3%
5.2 y
60%
16%
43%
16%
0%
32%
18%
8.3 y
CSF pleocytosis
Upper extremity weakness only
Preceding respiratory illness
EV/RV positive
EV-D68 positive
Lower extremity weakness only
More severe disease
Older age
Peak years (2016, 2018) Non-peak years (2015, 2017)
McLaren, et.al. Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015 – 2018. EID, Vol 26; February 2020.
AFM case characteristics also differ between peak years
6%
37%
70%
76%
6%
0%
19%
45%
80%
17%
Severe illness
Cranial nerve involvement
EV-D68 positive
Preceding respiratory illness
EV-A71 positive
2016 2018
McLaren, et.al. Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015 – 2018. EID, Vol 26; February 2020.
Summary Causes of AFM in peak years appear different from those in non-peak years,
but even in peak years there may be multiple causes Differences in EV and EV-D68 detection support an association in peak years
– Detection of two main EV types in 2018 emphasize need for clinical surveillance plus laboratory surveillance to understand the full spectrum of AFM
Underlying mechanism of disease remains the critical unknown – If EV-D68 is the primary driver in peak years, why does paralysis develop rarely?– Do different case characteristics give clues about disease mechanism?– Understanding disease mechanisms for AFM will allow for treatment and
prevention strategies to move forward
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Month of limb weakness onsethttps://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.htmlData current as of June 1, 2020
What do we expect for AFM in 2020?
Current number of suspect AFM cases reported to CDC is typical of both peak and non-peak years for this time period
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Average reports peak years Average reports non-peak years 2020
Thank you!
AcknowledgmentsSarah Kidd Steve Oberste Mark Pallansch
Adriana Lopez Will Weldon Glen Abedi
Adria Lee Jennifer Anstadt Cate Otten
Manisha Patel Alan Nix Brian Emery
Susannah McKay Shannon Rogers Jessica Ciomperlik
Margaret Cortese Sue Tong AFM Response Team
Eileen Yee Grace Gombolay Kim Hetzler
Sue Gerber and the EV team
State and local health depts.
External AFM collaborators
Dan Pastula Heather Jost Anita Kambhampati
Sarah Hopkins
What is known about the viruses involved in AFM
Charles Chiu, MD, PhD.
Professor, Laboratory Medicine and Medicine Division of Infectious Diseases
Director, UCSF-Abbott Viral Diagnostics and Discovery CenterAssociate Director, UCSF Clinical Microbiology Laboratory
University of California San Francisco