Thursday, July 20, 2017

MMWR: Cluster of Acute Flaccid Myelitis in Five Pediatric Patients - Arizona, 2016

Credit CDC AFM Surveillance Page


Acute flaccid myelitis (AFM) is a rare illness that affects a person’s nervous system, specifically the spinal cord. AFM is a subset of conditions that fall under a broader `umbrella' of syndromes called Acute Flaccid paralysis (AFP), which may include myelitis, peripheral neuropathy, myopathy, Guillain-BarrĂ© syndrome (GBS), toxic neuropathy, and other muscle disorders.
While the exact causes of Acute flaccid myelitis aren't fully understood, it has been linked to a number of viral infections, including West Nile Virus, Adenoviruses, and a number of (polio and non-polio) enteroviruses, including EV-71 and more recently, EV-D68.
In August of 2014 we saw a large increase in AFM cases tentatively linked to EV-D68, a relatively rare non-polio enterovirus that caused a nationwide outbreak of mild to moderate respiratory illness, mostly among children and teenagers (see Kansas City Outbreak Identified As HEV 68). 

While a circumstantial case has been made over the past couple of years (see EID Journal Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014), no definitive causal link to EV-D68 has been established. Some AFM cases have tested positive for EV-D68, while others have not.
AFM declined to low levels the U.S. in 2015 (see chart at top of this blog), but returned during the summer and fall of 2016. 
In response, last summer the CDC began publishing monthly updates on AFM as new cases began to surface. We also saw other reports from around the globe (see Taiwan CDC: 1st Case Of EV-D68 With Acute Flaccid Paralysis and EID Journal Upsurge In EV-D68 In The Netherlands, 2016), once again linking EV-D68 to at least some of these paralysis cases. 

The CDC is quick to point out what we know, and what we don't know about AFM.
What We Know

What we know about the AFM cases for which CDC has received information:

  • Most patients are children.
  • The patients’ symptoms have been most similar to complications of infection with certain viruses, including poliovirus, non-polio enteroviruses, adenoviruses, and West Nile virus. See a list of viruses associated with AFM.
  • Enteroviruses can cause neurologic illness, including meningitis. However, more severe disease, such as encephalitis and AFM, is not common. Rather, they most commonly cause mild illness.
  • CDC has tested many different specimens from the patients for a wide range of pathogens (germs) that can cause AFM. To date, we have not consistently detected a pathogen (germ) in the patients’ spinal fluid; a pathogen detected in the spinal fluid would be good evidence to indicate the cause of AFM since this illness affects the spinal cord.
  • The increase in AFM cases in 2014 coincided with a national outbreak of severe respiratory illness among people caused by enterovirus D68 (EV-D68). Among the people with AFM, CDC did not consistently detect EV-D68 in the specimens collected from them. In 2015 no cases of EV-D68 were detected. CDC did not receive information about large outbreaks of illness associated with EV-D68 detections in the United States in 2016. But information about sporadic cases of EV-D68 infections were sent during that time. Learn more about EV-D68.
What We Don’t Know

What we don’t know about the AFM cases for which CDC has received information:

  • Despite extensive testing, CDC does not yet know the cause of these AFM cases.
  • It is unclear what pathogen (germ) or immune response is causing the weakness and paralysis.
  • CDC has not yet determined who is at higher risk for developing AFM, or the reasons why they may be at higher risk.
  • See Prevention for information about how to protect your family from viral infections that may cause AFM.

All of which brings us to an MMWR report, published today, that describes a cluster of AFM pediatric cases in Maricopa County, Arizona in Aug- Sept of 2016. Once again, EV-D68 was detected in some, but not all, of the cases in this cluster.

Due to its length I've only included some excerpts.  Follow the link to read the full report.

Notes from the Field: Cluster of Acute Flaccid Myelitis in Five Pediatric Patients — Maricopa County, Arizona, 2016

Weekly / July 21, 2017 / 66(28);758–760
Sally A. Iverson, DVM1,2,3; Scott Ostdiek, MD4; Siru Prasai, MD2; David M. Engelthaler, PhD5; Melissa Kretschmer, MA2; Nicole Fowle2; Harlori K. Tokhie, MD4; Janell Routh, MD6; James Sejvar, MD7; Tracy Ayers, PhD6; Jolene Bowers, PhD5; Shane Brady, MPH3; Shannon Rogers, MS6; W. Allan Nix, PhD6; Ken Komatsu, MPH3; Rebecca Sunenshine, MD2,8; AFM Investigation Team

In 2016, CDC saw an increase in cases of acute flaccid myelitis (AFM); 144 persons in 37 states and the District of Columbia were confirmed to have AFM. After investigations in California (1) and Colorado (2) in 2014, CDC characterized AFM as an acute flaccid paralysis (AFP) distinguishable by magnetic resonance imaging (MRI) abnormalities of the gray matter of the anterior and posterior spinal cord segments, involving one or more spinal segments (3).

Although certain viruses (e.g., nonpoliovirus enteroviruses, adenoviruses, and West Nile virus) can cause rare cases of AFP, and findings from the 2014 outbreak investigations indicated that enterovirus D68 (EV-D68) was temporally associated with AFM, no viral etiology for AFM has been definitively established (3).
In September 2016, an acute care hospital in Arizona notified the Maricopa County Department of Public Health (MCDPH) of a suspected case of AFM and subsequent cluster of 11 children who were evaluated with similar neurologic deficits; differential diagnoses included transverse myelitis and AFM. The Maricopa County Department of Public Health, in cooperation with the Arizona Department of Health Services, CDC, the Translational Genomics Research Institute (TGen, Flagstaff, Arizona), and the acute care hospital, initiated an investigation to confirm AFM cases and identify an etiology. 

This cluster of AFM at one children’s acute care hospital is the largest cluster identified to date in Arizona and is part of a nationally identified increase in AFM cases. Although no statewide surveillance system specific to AFM is available, this cluster was detected by physician reporting, highlighting the need for physicians to remain vigilant for this emerging disease and to report cases that fit the AFM case definition to their local health department.
Metagenomic analyses identified EV-D68 in NP swabs from the three patients for whom specimens were available, along with a specimen from a patient who did not meet the AFM case definition; therefore, no single etiology or risk factor was associated with only confirmed cases.

Patient and family history of asthma was the most common comorbidity reported among confirmed AFM cases and should be considered in future case investigations. Expanded analysis of infectious, postinfectious, and noninfectious etiologies might provide further insight into the mechanism of AFM.

(Continue . . . )
For additional information on EV-D68, and/or AFM, you may wish to revisit these blogs:
CIDRAP On The Lancet EV-D68 Analysis
Molecular evolution and the global reemergence of enterovirus D68 by genome-wide analysis
Along with these resources from the CDC:
COCA Clinical Reminder (August 27, 2015) – Notice to Clinicians: Continued Vigilance Urged for Cases of Acute Flaccid Myelitis.

The 2014 investigation summary is available here: Acute Flaccid Myelitis in the United States—August – December 2014: Results of Nation-Wide Surveillance.

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