Wednesday, November 08, 2017

PAHO Epi Alert: AFM Associated With EV-D68 Infection


Acute flaccid myelitis (AFM) is a rare polio-like illness that affects a person’s nervous system - specifically the spinal cord - and is characterized by sudden weakness in one or more arms or legs, along with loss of muscle tone and decreased or absent reflexes.

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-Barré 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, but returned during the summer and fall of 2016 (see chart below).
Credit CDC - AFM Surveillance Page

Meanwhile we've seen other AFM cases around the world (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. 
Last July, in MMWR: Cluster of Acute Flaccid Myelitis in Five Pediatric Patients - Arizona, 2016, we looked at a case report that described 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.
All of which brings us to an Epidemiological Alert, issued by PAHO (Pan-American Health Organization) and WHO, regarding a recent cluster of AFM cases reported in Argentina which they associate with a concurrent outbreak of EV-D68.

Epidemiological Alert
Acute Flaccid Myelitis associated with enterovirus D68 in the context of Acute Flaccid Paralysis surveillance

1 November 2017


In 2016, the European Center for Disease Control and Prevention (ECDC) informed that Denmark, France, the Netherlands, Spain, Sweden, and the United Kingdom reported clusters and isolated cases of severe neurological syndromes in children and adults associated with enterovirus infection among which EV-D68 was detected.1 

In October 2017, the Argentina International Health Regulations National Focal Point reported a cluster of acute flaccid myelitis (AFM) associated with EV-D68 infection. Between epidemiological week (EW) 13 and EW 21 of 2016, 15 cases of AFM were identified in residents of the provinces of Buenos Aires (13) and Chubut (1 case) and the Autonomous City of Buenos Aires (CABA per acronym in Spanish; 1 case). 

All cases were in children under 15 years, since the detection occurred in the context of acute flaccid paralysis (AFP) surveillance. This event coincided with the increase in AFP cases in children under 15 years of age observed at the national level between EW 16 and EW 21 of 2016. In 6 of the 15 reported AFM cases, the Regional Poliovirus Reference Laboratory - INEI - ANLIS ”Dr. Carlos G. Malbrán” detected the presence of EV-D68. 

Positive results were obtained in samples of nasopharyngeal aspirate and in one case the same result was also obtained in a cerebrospinal fluid (CSF) sample. In addition, human EV B and human EV C were detected in stool samples of two of the AFM cases; rhinovirus C in one case and coxsackie virus A13 in one case (7).

Considering the context of polio eradication, 2 the switch from trivalent oral polio vaccine (OPV) to the bivalent OPV since April 2016, that AFM is a type of AFP, and the need to increase knowledge about the role of enteroviruses in the epidemiology of neuroinvasive diseases, the Pan American Health Organization / World Health Organization (PAHO / WHO) reminds Member States that enterovirus is part of the differential diagnosis of AFP.
The following is a series of advice to health authorities regarding surveillance, including laboratory detection.
Recommendations for national authorities

Case management
A patient with suspected AFM shall have timely access to health services that manage neurological syndromes. The capacity to make a differential diagnosis is key for defining complementary tests, treatments to follow, guiding rehabilitation and, finally, determining the prognosis.

AFM surveillance associated with enteroviruses is a component of AFP surveillance and, as such, a support for polio eradication efforts. The quality of this surveillance is measured based on the usual performance indicators of AFP surveillance 

The following is recommended:
  • Investigate all AFP cases in children under 15 or of any age where polio3 is suspected within 48 hours of notification.4
  • If there is a strong presumption of AFM, a respiratory sample (necessary for the detection of enterovirus D68) should be obtained and a spinal nuclear magnetic resonance should be considered.
  • Investigate any increase or cluster of AFP. In this situation, if cases have clinical characteristic of AFM, a respiratory sample in addition to the stool sample should be obtained.
  •  Follow up cases, 60 days after the beginning of the paralysis, to determine if they have residual paralysis.
(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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