what is known about the epidemiology of acute flaccid...

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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2014: 120 cases

2015: 22 cases

2016: 153 cases

2017: 38 cases

2018: 238 cases

2019: 46 cases

2020: 8 cases

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Sept

Sept

Sept

AFM cases, 2005-2014, 5 sites combined, United States

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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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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

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-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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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