H5N1

Vital Signs: Surveillance for acute flaccid myelitis — United States, 2018

Via MMWR, the CDC has published Vital Signs: Surveillance for Acute Flaccid Myelitis — United States, 2018 | MMWR. The summary and abstract:

Summary 

What is already known about this topic?  

Biennial U.S. outbreaks of acute flaccid myelitis (AFM) have been recognized since 2014. Most cases occur in children during late summer and early fall. 

What is added by this report?  

During 2018, 233 confirmed AFM cases were reported, the largest number since surveillance began in 2014. Upper limb involvement only was more prevalent in confirmed cases (42%), as was report of respiratory symptoms or fever (92%) within 4 weeks preceding limb weakness onset. Median intervals from onset of limb weakness to hospitalization, magnetic resonance imaging, and reporting to CDC were 1, 2, and 18 days, respectively.  

What are the implications for public health practice? 

Prompt recognition, early specimen collection, and rapid reporting will expedite public health investigations and help characterize AFM.

Abstract 

Background: 

Acute flaccid myelitis (AFM), a serious paralytic illness, was first recognized as a distinct condition in 2014, when cases were reported concurrent with a large U.S. outbreak of severe respiratory illness caused by enterovirus D-68 (EV-D68). Since 2014, nationwide outbreaks of AFM have occurred every 2 years in the United States; the cause for the recent change in the epidemiology of AFM in the United States, including the occurrence of outbreaks and a biennial periodicity since 2014, is under investigation. This report updates clinical, laboratory, and outcome data for cases reported to CDC during 2018.  

Methods: 

Clinical data and specimens from persons in the United States who met the clinical criterion for AFM (acute onset of flaccid limb weakness) with onset in 2018 were submitted to CDC for classification of the illnesses as confirmed, probable, or non-AFM cases. Enterovirus/rhinovirus (EV/RV) testing was performed on available specimens from persons meeting the clinical criterion. Descriptive analyses, laboratory results, and indicators of early recognition and reporting are summarized.  

Results: 

From January through December 2018, among 374 reported cases of AFM, 233 (62%) (from 41 states) were classified as confirmed, 26 (7%) as probable, and 115 (31%) as non-AFM cases. Median ages of patients with confirmed, probable, and non-AFM cases were 5.3, 2.9, and 8.8 years, respectively. Laboratory testing identified multiple EV/RV types, primarily in respiratory and stool specimens, in 44% of confirmed cases. Among confirmed cases, the interval from onset of limb weakness until specimen collection ranged from 2 to 7 days, depending on specimen type. Interval from onset of limb weakness until reporting to CDC during 2018 ranged from 18 to 36 days, with confirmed and probable cases reported earlier than non-AFM cases. 

Conclusion: 

Identification of risk factors leading to outbreaks of AFM remains a public health priority. Prompt recognition of signs and symptoms, early specimen collection, and complete and rapid reporting will expedite public health investigations and research studies to elucidate the recent epidemiology of AFM and subsequently inform treatment and prevention recommendations.

MMWR: Enterovirus D68–associated acute respiratory illness — New Vaccine Surveillance Network, United States, July–October, 2017 and 2018

MMWR has published Enterovirus D68–Associated Acute Respiratory Illness — New Vaccine Surveillance Network, United States, July–October, 2017 and 2018. The summary:

What is already known about this topic?  

A nationwide outbreak of enterovirus D68 (EV-D68), which is associated with acute respiratory illness (ARI), occurred in 2014. EV-D68 epidemiology is not fully understood because testing in clinical settings is limited and detections are not notifiable to CDC. 

What is added by this report?  

Based on active, prospective surveillance of ARI through the New Vaccine Surveillance Network, EV-D68 was detected in two (0.8%) patients in 2017 and 358 (13.9%) in 2018. Detections in 2018 peaked in September.  

What are the implications for public health practice? 

Continued active, prospective surveillance is needed to better understand trends in EV-D68 circulation.

Acute flaccid myelitis associated with enterovirus D68 in children, Argentina, 2016

Via Emerging Infectious Diseases: Acute Flaccid Myelitis Associated with Enterovirus D68 in Children, Argentina, 2016. The abstract:

After a 2014 outbreak of severe respiratory illness caused by enterovirus D68 in the United States, sporadic cases of acute flaccid myelitis have been reported worldwide. We describe a cluster of acute flaccid myelitis cases in Argentina in 2016, adding data to the evidence of association between enterovirus D68 and this polio-like illness.

US: Parents of children with AFM warn about rare polio-like condition

Via The Washington Post: Parents of children with AFM warn about rare polio-like condition. Excerpt:

It started with a sinus infection. Then 4-year-old Camdyn Carr couldn’t move the right side of his face or lift his arm to scratch his nose. 

His parents decided to take him a couple of hours away to see doctors who might be able to figure out what had afflicted their young boy. But as they drove from their Roanoke home to the University of Virginia, Carr’s whole body seized up and he was suddenly paralyzed.  

Many tests later, Carr was diagnosed with the rare polio-like condition acute flaccid myelitis, or AFM. He is now a patient at Kennedy Krieger Institute, where his father, Christopher Carr, brought him for physical therapy and other treatment to try to get his son moving again.  

AFM affects the gray matter in the spinal cord and can lead to paralysis, but is so rare that fewer than 1 in 1 million people, mostly children, contract it. 

But a recent uptick in cases in the United States has put public health officials on alert and freaked out parents because of the severe symptoms that sometimes accompany it. Doctors don’t know exactly what is causing the mystery illness and there is no official treatment for it, raising the fear factor for some. 

“So much of this doesn’t make sense to me,” said Christopher Carr, who is staying with Camdyn at Kennedy Krieger while the rest of the family remains at home. “I am hoping the physical therapy can help improve my son’s condition.” 

The Centers for Disease Control held a teleconference Tuesday expressing concern about the disease, which has sickened 62 children this year and killed one. The CDC is investigating an additional 65 cases, including five children with the symptoms reported in Maryland. 

Public health officials have not identified a common link among cases, but there seems to be a surge every couple of years. 

The International Center for Spinal Cord Injury at Kennedy Krieger Institute has treated many cases from around the country, including six patients who are there now. 

“Until we figure out if this is an infection or if this is an autoimmune process, until we figure out how to prevent it, then the effort to bring awareness to it and develop timely interventions is appropriate even if it is 1 in a million,” said Cristina L. Sadowsky, the center’s clinical director.

The most recent mention of AFM on the website of the Public Health Agency of Canada is this note from early 2016, which lists it as a possible consequence of an EV-D68 infection. The Washington Post story cites enteroviruses but doesn't specify them.

CIDRAP: CDC, partners probe 127 polio-like cases in 22 states

Via CIDRAP, Lisa Schnirring writes: CDC, partners probe 127 polio-like cases in 22 states. Excerpt:

The US Centers for Disease Control and Prevention (CDC) said today that officials are investigating a spike in acute flaccid myelitis (AFM) cases, mostly in children, that looks similar to increases they saw in the late summer and fall of 2014 and 2016, with 127 cases under investigation in 22 states. 

So far 62 of the cases—marked by sudden onset of limb weakness and decreased muscle tone—have been confirmed, Nancy Messonnier, MD, director of the CDC's National Center for Immunization and Respiratory Diseases, said today at a media briefing. More than 90% have been in children, and the average age is 4 years.  

She emphasized the AFM cases are very rare, affecting 1 in 1 million people, and the condition is not caused by poliovirus, though symptoms can be similar to polio. In addition, unlike with polio, most children recover, though some require ongoing treatment. Only one death has been reported, which involved an AFM illness reported in 2017. 

Messonnier urged parents to seek care right away if children experience AFM symptoms.  

Cause still a mystery 

In 2014, a large AFM epidemic coincided with a national outbreak of severe respiratory illness caused by enterovirus D68 (EV-D68), but in-depth testing of patient samples hasn't consistently found a common cause. 

Messonnier said the search for a cause is frustrating, and so far, no particular pathogen or immune response has been identified that would explain the big AFM peaks. Some patients have tested positive for enterovirus or rhinovirus. 

Other countries have reported AFM cases, but not the same seasonal pattern the United States has experienced. Messonnier added that health officials are considering other potential causes, such as West Nile virus and environmental toxins, though none of the cases have involved them.  

So far, the CDC hasn't seen any geographic patterns based on reporting from states. 

And for now, it's hard to say if 2018 will equal or surpass spikes seen in 2014 and 2016, Messonnier said, adding that state and federal health officials haven't finished the whole diagnostic algorithm for many of the cases reported over the past several weeks. Also, she said there can be lags in reporting because of the time it takes to review a patient's clinical syndrome and radiographic findings. 

To give parents, healthcare workers, and public health officials a look at what to expect, she said the CDC will report suspected cases this year, as well as confirmed ones. The agency had a teleconference with health providers slated for later today, and it provided a toolkit for diagnosing AFM, along with instructions for reporting suspected cases.

Enterovirus D68 and acute flaccid myelitis—evaluating the evidence for causality

Via The Lancet Infectious Diseases: Enterovirus D68 and acute flaccid myelitis—evaluating the evidence for causality. The full article is behind a paywall; here is the summary:

Increased circulation of enterovirus D68 in 2014 and 2016 temporally and geographically coincided with increases in cases of acute flaccid myelitis, an uncommon condition of paralysis due to lesions in the anterior horn of the spinal cord. The identification of enterovirus D68 in respiratory specimens from cases of acute flaccid myelitis worldwide further supports an association, yet the absence of direct virus isolation from affected tissues, infrequent detection in cerebrospinal fluid, and the absence, until recently, of an animal model has left the causal nature of the relationship unproven. 

In this Personal View we evaluate epidemiological and biological evidence linking enterovirus D68 and acute flaccid myelitis. We applied the Bradford Hill criteria to investigate the evidence for a causal relationship and highlight the importance of comprehensive surveillance and research to further characterise the role of enterovirus D68 in acute flaccid myelitis and pursue effective therapies and prevention strategies.

Enterovirus D68 shown to be likely cause of mystery polio-like illness

Via Science Daily, a report from the University of New South Wales: Virus shown to be likely cause of mystery polio-like illness. Excerpt:

A major review by UNSW Sydney medical researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.  

The study, by a team led by UNSW Professor Raina MacIntyre, Director of the NHMRC Centre for Research Excellence in Epidemic Response, is published in the journal Eurosurveillance. 

"In 2014, children in the US began to be diagnosed with a mystery illness that caused a polio-like paralysis," says Professor MacIntyre. 

"More than 120 children developed the condition, known as acute flaccid myelitis, in the US alone but experts were baffled as to the cause."  

That same year there were also unusually large outbreaks of infection with Enterovirus D68, or EV-D68 -- a virus known since the early 1960s to cause runny noses, coughs, muscle aches, fever and difficulty breathing.  

About 2280 people in the US, Canada and Europe were infected with the virus, many of them children, and their respiratory symptoms were more severe than usual.  

Clusters of the paralysing illness, also mostly in children, were reported in the same regions.  

"This raised the possibility of a link between EV-D68 and acute flaccid myelitis. However, the virus had never been known to cause paralysis before," says Professor MacIntyre. 

For the new study, the UNSW team analysed the scientific literature on acute flaccid myelitis. They applied the Bradfield Hill criteria -- a set of nine principles developed to determine causality that are named after the two researcher who used them to settle the debate about smoking causing lung cancer. 

"The scientific method Bradfield and Hill used to prove that smoking caused cancer is now an accepted tool to determine causality," says Professor MacIntyre.  

"We are first to use his approach to analyse the relationship between EV-D68 and acute flaccid myelitis. Our results show that it is very likely that EV-D68 is the cause of the mystery illness and the paralysis of children."

ECDC: CDTR, week 44

ECDC has published Summary of Public health threats, CDTR week 44/2016. Click or tap through to download the full report and use the links. The summary:

​The ECDC Communicable Disease Threats Report (CDTR) is a weekly bulletin for epidemiologists and health professionals about active public health threats. This issue covers the period 30 October to 5 November 2016 and includes updates on West Nile virus, enteroviruses and influenza. 

West Nile virus 

This week, one new case of West Nile fever has been reported from Bucharest, Romania.   

During the June-to-November transmission season, ECDC monitors the situation in EU Member States and neighbouring countries in order to inform the blood safety authorities of areas affected by West Nile fever and changes in the epidemiology of the disease.  

Enteroviruses 

In early November, Sweden confirmed eight cases with symptoms similar to acute flaccid myelitis whereof 4 with confirmed enterovirus D68.   

Since April 2016, Denmark, the Netherlands, Spain, Sweden and United Kingdom (Wales) have reported various severe Enterovirus infections and some have also increased enterovirus detections (the Netherlands and Germany) compared to previous years. The increased detections of enteroviruses associated with neurological symptoms in EU/EEA countries are notable in terms of the severity of symptoms of the reported cases.   

ECDC published a rapid risk assessment on 8 August 2016.   

Influenza 

Activity remained low in the region, with few samples testing positive for influenza viruses (2% of sentinel samples). Levels are similar to those observed for the same period in recent seasons.   

Influenza transmission in Europe shows a seasonal pattern, with peak activity during winter months. ECDC monitors influenza activity in Europe during the winter season.   

ECDC publishes its weekly report on the Flu News Europe website.

CIDRAP: CDC probes rise in AFM cases as Washington reports cluster

Via CIDRAP, Lisa Schnirring writes: CDC probes rise in AFM cases as Washington reports cluster. Excerpt:

The Centers for Disease Control and Prevention (CDC) is investigating a national increase in acute flaccid myelitis (AFM) this year, with a surge in recent months, a pattern that may be linked to a recent cluster of suspected cases in Washington state. 

Though this year's cases of AFM—marked by sudden onset of limb weakness associated with spinal cord inflammation—haven't reached levels seen in 2014 when the condition first appeared on the national radar with 120 cases reported, the CDC said it is worried about the recent uptick.  

No common cause identified 

In an update on its AFM page yesterday, the CDC said as of Sep 30, 89 AFM cases have been confirmed in 33 states, mostly in children. The rise in cases from across the country began in August, and the CDC said it has been actively investigating the illness since then. 

For comparison, in 2015 the agency received reports of 21 confirmed AFM cases from 16 states. 

Despite extensive testing, the CDC hasn't yet determined what's causing the AFM cases. A long list of viruses can cause AFM symptoms, including poliovirus and adenoviruses. The 2014 outbreak coincided with a national outbreak of severe respiratory illnesses caused by enterovirus D68 (EV-D68).  

CDC scientists have tested many specimens from patients, but so far they haven't consistently detected a pathogen in spinal fluid, which it said would likely yield good evidence about the cause, given that the illness affects the spinal cord. 

The CDC said it's hard to sort out trends with AFM data, because reporting began only in 2014 and is voluntary for most states. Initial years of reporting might contain data variability that makes it hard to compare cases from year to year. "One possible reason for differences in annual reporting is more awareness among and reporting by healthcare providers and health departments," it said. 

Washington's cluster rises to 9 

Meanwhile, the Washington State Department of Health (WSDH) said in an Oct 28 media statement that it is leading a joint investigation that includes the CDC into a cluster of eight suspected AFM cases, all of them involving children admitted to Seattle Children's Hospital with acute neurologic illness.

Dr. Racaniello on Zika and enterovirus D68

On his blog Zika Diaries, Dr. Vincent Racaniello writes: Zika and enterovirus D68. Excerpt:

Enterovirus D68 is classified in the picornavirus family, and shares features with both polioviruses (which cause paralysis but not respiratory disease) and rhinoviruses (which cause respiratory disease but not paralysis). Like human rhinoviruses, EV-D68 initiates infection in the the respiratory tract, but not the intestinal mucosa like poliovirus. Transmission of EV-D68 is by respiratory aerosols (like rhinoviruses), not faecal-oral contamination as for poliovirus. Unlike poliovirus, EV-D68 has not been found in the stool of infected patients. 

Although EV-D68 infection has been associated with paralysis in young children, it is not clear if the virus is responsible for this condition. Therefore it is important to determine if EV-D68 is neurovirulent—if it is able to replicate in and destroy neural cells. Until recently we had no clear path to answering this question.  

Our work on Zika virus has lead to the establishment of two different systems in our laboratory for studying viral neurovirulence. I previously described our finding that Zika virus can replicate in human cortical neurons produced from human embryonic stem cells. I’ve also described our use of embryonic mice to determine if Zika virus can infect the brain. Both systems could be used to study EV-D68 neurovirulence.  

That’s how a research laboratory should work: progress made on one project (Zika virus) can be used to advance our understanding of a different virus (EV-D68). Even though our laboratory is small, we can work on two very different viruses because the experimental approaches are similar.