Thursday, October 11, 2018

More AFM Reports & Recent Studies On AFM

CDC AFM Website


Over the past few days we've seen a rash of reports (see here, here, and here) of either suspected or confirmed AFM (Acute Flaccid Myelitis) - mostly in children - across the country.
Acute flaccid myelitis (AFM) is a rare illness that affects a person’s nervous system, specifically the spinal cord. AFM falls under a broader `umbrella' of syndromes called Acute Flaccid paralysis (AFP). AFM may be due to a variety of causes, including viral infection.
Overnight new reports have continued to come in, including from New York, Rhode Island, and the following statement Washington State.
News Release
For immediate release: October 10, 2018 (18-146)
Contact: Julie Graham, Strategic Communications Office 360-810-1628
Investigation into five possible AFM illnesses from four WA counties

OLYMPIA – The Washington State Department of Health and four local public health agencies are investigating reports of five children hospitalized for sudden onset of paralysis of one or more limbs. The Department of Health is working with experts in neurology from the Centers for Disease Control and Prevention (CDC) for confirmation of acute flaccid myelitis (AFM).

All cases are among infants and children under age six who all reportedly had symptoms of a respiratory illness in the week prior to developing symptoms of AFM. Four of the five had fever of 100.4 F or greater. The children are residents of King County (2), Pierce County (1), Lewis County (1), and Snohomish County (1).

The children are being evaluated for AFM, a rare condition that affects the nervous system, specifically the spinal cord. Symptoms typically include sudden weakness in one or more arms or legs, along with loss of muscle tone and decreased or absent reflexes. AFM can cause a range of types and severity of symptoms, but the commonality among them is a loss of strength or movement in one or more arms or legs. The cause of any individual case of AFM can be hard to determine, and often, no cause is found. CDC specialists will make the final determination if these cases are AFM.

“At this point there isn’t evidence that would point to a single source of illness among these cases,” said Dr. Scott Lindquist, state infectious disease epidemiologist at the Department of Health. “We’re working closely with medical providers and public health agencies. We’ll continue to investigate and share information when we have it.”

Some viruses and germs have been linked to AFM, including common germs that can cause colds and sore throats, and respiratory infections. It can also be caused by poliovirus and non-polio enteroviruses, mosquito-borne viruses (such as West Nile virus or Zika virus) and possibly by non-infectious conditions.

While there are no specific recommendations for avoiding AFM, you can help protect yourself from some of its known causes by: washing your hands often with soap and water, avoiding close contact with sick people, and cleaning surfaces with a disinfectant, especially those that a sick person has touched. Staying updated on recommended immunizations is also important to avoid vaccine preventable illnesses.

The Department of Health sent a notice to public health departments for distribution to healthcare providers across the state to be alert for other suspected AFM cases.

In 2016 there was a cluster of nine cases of AFM in Washington state. In 2017 there were three cases, and since the beginning of 2018 there has been one case in the state. For more information on AFM, visit the CDC website. From January 1st to September 30th, a total of 38 people in 16 states have been confirmed to have AFM. Most of these illnesses have been in children.

The last uptick in AFM cases in the United States was reported in the fall of 2016, and before that in the fall of 2014.  The exact cause of these outbreaks are still under investigation, although several normally mild enteroviruses (EV-D68, CV-A6 and EV-71) are high on the suspect list.

We've looked at research into the causes of AFM before, including:
EID Journal: Emerging Enteroviruses In China 2010-2016
Eurosurveillance Review: Association Between Acute Flaccid Myelitis (AFM) & Enterovirus D68 (EV-D68)

CDC Acute Flaccid Myelitis Update - January 2017

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

CDC Acute Flaccid Myelitis Update - January 2017

EID Journal Upsurge In EV-D68 In The Netherlands, 2016

Over the past month several new studies have been published, including last month's MMWR Notes from the Field: Enterovirus A71 Neurologic Disease in Children — Colorado, 2018.  Earlier this week Colorado announced 14 AFM cases, 11 of which tested positive for EV-71.

From the MMWR report:
EV-A71 can cause hand, foot, and mouth disease and neurologic disease, primarily among children aged < 5 years (2,3). Common manifestations include a febrile illness with lesions on the palms, soles, oral mucous membranes, or perineum; and aseptic meningitis. Severe CNS EV-A71 infection can cause brainstem encephalitis leading to cardiopulmonary collapse and polio-like AFM (4).
EV-A71 epidemics have occurred in the Asian-Pacific region since the late 1990s (5). Since the 1980s, the National Enterovirus Surveillance System has detected seasonal endemic EV-A71 activity in the United States; EV-A71 accounts for < 1% of typed EVs (3). Limited, regional U.S. outbreaks have occurred sporadically in an unpredictable pattern; factors causing year-to-year circulation have not been identified (3,6). Peak U.S. circulation of EVs, including EV-A71, usually occurs during June–October (3,6).
Although associated with neurologic disease, EV-A71 is uncommonly detected in CSF and is more frequently identified in respiratory and fecal specimens (7). In similar EV-A71 outbreaks in Colorado during 2003 and 2005, EV-A71 CNS infection was identified in 16 children (eight in each cluster); 11 children recovered fully, four had residual limb paralysis, and one child died (7). At this time, no other clusters of EV-A71 neurologic disease have been reported to CDC in 2018.

 From The Neurologist (in German):
Neurological complications of infections with (novel) enteroviruses

Enterovirus (EV) infections are frequent and predominantly affect children. Neurological manifestations are rare but can induce severe consequences. Since 2014 a global rise in EV-D68 and EV-71 infections manifesting with neurological complications, namely rhombencephalitis (EV-71) and acute flaccid myelitis (EV-D68), has been observed with an increased distribution in Europe and isolated occurrences in Germany. 

Typically prodromes with respiratory infections and gastrointestinal conditions precede neurological symptoms. In these cases, an EV infection should be considered as the underlying cause and appropriate diagnostic tests should be performed. Other than the typical inflammatory signs in cerebrospinal fluid (CSF), the changes on magnetic resonance imaging (MRI) in particular are seminal; however, confirmation of the virus is often not possible in the CSF so that other specimens from, e.g. feces or the respiratory tract are required. 

To date there are no causal therapies for either of these EV infections; therefore, a comprehensive supportive therapy is of major significance. In Taiwan some beneficial effects could be observed by administration of intravenous immunoglobulins; however, a reliable study has not yet been published.

And from The Pediatric Infectious Disease Journal.

Twenty-Nine Cases of Enterovirus-D68 Associated Acute Flaccid Myelitis in Europe 2016; A Case Series and Epidemiologic Overview

Knoester, Marjolein, MD, PhD1; Helfferich, Jelte, MD2; Poelman, Randy, MSc1; Van Leer-Buter, Coretta, MD, PhD1; Brouwer, Oebele F., MD, PhD2; Niesters, Hubert G.M., MD, PhD1 on behalf of the 2016 EV-D68 AFM Working Group
The Pediatric Infectious Disease Journal: September 18, 2018 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/INF.0000000000002188

BACKGROUND: Enterovirus D68 (EV-D68) is a respiratory virus within the genus Enterovirus and the family of Picornaviridae. Genetically, it is closely related to rhinovirus that replicates in the respiratory tract and causes respiratory disease. Since 2014, EV-D68 has been associated with the neurologic syndrome of acute flaccid myelitis (AFM).

METHODS: In October 2016, questionnaires were sent out to a European network including 66 virologists and clinicians, to develop an inventory of EV-D68 associated AFM cases in Europe. Clinical and virologic information of case patients was requested. In addition, epidemiologic information on EV-testing was collected for the period between March and October 2016.

RESULTS: Twenty-nine cases of EV-D68 associated AFM were identified, from 12 different European countries. Five originated from France, 5 from Scotland and 3 each from Sweden, Norway and Spain. Twenty-six were children (median age 3.8 years), 3 were adults. EV-D68 was detected in respiratory materials (n=27), feces (n=8) and/or cerebrospinal fluid (n=2).

Common clinical features were asymmetric flaccid limb weakness, cranial nerve deficits and bulbar symptoms. On magnetic resonance imaging, typical findings were hyperintensity of the central cord and/or brainstem; low motor amplitudes with normal conduction velocities were seen on electromyography. Full clinical recovery was rare (n=3), and 2 patients died.

The epidemiologic data from 16 European laboratories showed that of all EV-D68 positive samples, 99% was detected in a respiratory specimen.

CONCLUSIONS: For 2016, 29 EV-D68 related AFM cases were identified in mostly Western Europe. This is likely an underestimation, since case identification is dependent on awareness among clinicians, adequate viral diagnostics on respiratory samples, and the capability of laboratories to type EVs.  
There appear to be a number of possible causes of AFM, including infection by West Nile Virus, some adenoviruses, and the NPEVs (Non-polio Enteroviruses) mentioned above. There are likely others factors that haven't yet identified.
Since AFM can present days or weeks after infection, often by the time testing is done, no traces of a virus can be found.
Whether this recent uptick in AFM across the country is the result of a single virus or factor - or more than one - remains unknown.  The condition remains very rare, with the CDC estimating only 1 person in 1 million likely to experience it in any given year.

 For information on how to reduce the chances of infection for you or your children, the CDC recommends:

Possible Causes of AFM

AFM or similar neurologic conditions may have a variety of possible causes such as viruses, environmental toxins, and genetic disorders.
Certain viruses that can cause AFM or similar neurologic conditions are
Oftentimes, despite extensive lab tests, the cause of a patient’s AFM is not identified.
Poliovirus and West Nile virus may sometimes lead to AFM.
  • You can protect yourself and your children from poliovirus by getting vaccinated.
  • You can protect against bites from mosquitoes, which can carry West Nile virus, by using mosquito repellent, staying indoors at dusk and dawn (when bites are more common), and removing standing or stagnant water near your home (where mosquitoes can breed).
While we don’t know if it is effective in preventing AFM, washing your hands often with soap and water is one of the best ways to avoid getting sick and spreading germs to other people. Learn about when and how to wash your hands.
For more information on what CDC is doing, see our AFM Investigation page.

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