H5N1

Upsurge of enterovirus D68, the Netherlands, 2016

Via Emerging Infectious Diseases: Ahead of Print -Upsurge of Enterovirus D68, the Netherlands, 2016. The abstract:

In June and July 2016, we identified 8 adults and 17 children with respiratory enterovirus D68 infections. Thirteen children required intensive care unit admission because of respiratory insufficiency, and 1 had concomitant acute flaccid myelitis. Phylogenetic analysis showed that all of 20 sequences obtained belong to the recently described clade B3.

ECDC: Enterovirus associated with severe neurological symptoms

ECDC has published Enterovirus detections associated with severe neurological symptoms in children and adults in European countries. Click or tap through to download the PDF. The abstract:

​The timing of the current enterovirus outbreaks closely follows the usual increase in summer, but reports suggest that seasonal enterovirus activity in the EU/EEA Member States started earlier than in previous years. Some Member States also report an increased frequency of severe disease associated with enterovirus infection.   

While it is difficult to interpret these observations in the absence of robust historical data, Member States should consider raising awareness of the importance of including enterovirus infection in the differential diagnosis of neurological and severe respiratory illness. Reporting of enterovirus clusters and outbreaks through the Early Warning and Response System (EWRS) in EU/EEA countries is encouraged. ​

ECDC: Outbreak of enterovirus A71 in Catalonia, Spain

ECDC has published Outbreak of enterovirus A71 in Catalonia, Spain - rapid risk assessment. Excerpt from the summary:

​ECDC has published a rapid risk assessment due to a localised outbreak of neurological symptoms associated with enterovirus A71 (EV-A71) in Catalonia, Spain.  

Most EV infections, including EV-A71, result in asymptomatic infection. Most symptomatic EV-A71 infections manifest as a self-limiting hand, foot and mouth disease and only a very small proportion of patients develop severe and life-threatening disease. The current outbreak is notable in terms of its magnitude and the severity of symptoms of the reported cases. 

The outbreak with neurological complications caused by enterovirus has been ongoing in Catalonia since mid-April 2016, affecting children up to ten years of age. As of 7 June, 87 cases of enterovirus infection with neurological complications have been reported, most of which have evolved favourably, but 22 of the cases remain in hospital, including seven in intensive care units. According to the information received from regional authorities, there are no deaths related to this outbreak. The cases are widespread in Catalonia. 

Other EU Member States have not reported concomitant enterovirus outbreaks and ECDC is not aware of signals of other unusual enterovirus outbreaks in the EU. 

There is evidence to suggest that the epidemiological pattern of EV-A71 in Europe is going through a change, both due to virus molecular evolution, as well as an increasing likelihood of importation of new virus strains from outside the EU. 

The full characterisation of the isolates from the Spanish outbreak, and comparison of these to virus sequences from other countries and continents, should contribute to a better understanding of the changing pattern of EV-A71 epidemiology in Europe.

Eurosurveillance: Enterovirus D68 epidemiology in France and Germany

Via Eurosurveillance: A note from the editors: Enterovirus D68 epidemiology in France and Germany—food for thought. Excerpt:

Worldwide emergence of enterovirus (EV) D68 causing severe respiratory illness particularly in children, between 2008 and 2014, has been described in numerous articles. In 2014, EV-D68 gained particular attention when a large outbreak in children, associated with severe respiratory illness and possible neurological illness, occurred in the United States. This event triggered a number of surveillance activities in various countries, some of them published in Eurosurveillance. In our current issue we present investigations into the occurrence of EV-D68 in two European countries namely France and Germany. 

The articles present data from patients hospitalised or visiting hospital emergency departments with respiratory symptoms. Schuffenecker et al. report on samples collected by eleven laboratories of the French EV surveillance network from eight of 22 Regions over six months in 2014. These eleven laboratories represent about one-third of the laboratories participating in the French EV network. Böttcher et al. analysed samples during two entire years, 2013 and 2014, at three large tertiary hospital laboratories in Germany. These laboratories, situated mainly in the western part of the country, contribute ca 25% of the EV-positive samples in the nationwide RespVir surveillance. 

Both reports are based on a considerable number of screened respiratory samples: 6,229 samples with 212 EV-D68 detections corresponding to 200 cases in France; 14,838 samples with 39 EV-D68-positive cases in Germany. 

In line with the literature, the German analysis suggests seasonality of EV-D68 infections, with most cases occurring between September and November (weeks 36‒48), and even though covering only six months, also the French analysis shows peaks in October (week 43) and November (week 48). Moreover, cases in both countries occurred mainly in children younger than five years, although French authors caution that a bias towards preferential sampling of children cannot be ruled out.

Atypical adult Guillain-Barré syndrome associated with EV-D68 in children

Via Eurosurveillance: Cluster of atypical adult Guillain-Barré syndrome temporally associated with neurological illness due to EV-D68 in children, South Wales, United Kingdom, October 2015 to January 2016.T The abstract:

We report a cluster of atypical Guillain–Barré syndrome in 10 adults temporally related to a cluster of four children with acute flaccid paralysis, over a 3-month period in South Wales, United Kingdom. 

All adult cases were male, aged between 24 and 77 years. Seven had prominent facial diplegia at onset. Available electrophysiological studies showed axonal involvement in five adults. Seven reported various forms of respiratory disease before onset of neurological symptoms. The ages of children ranged from one to 13 years, three of the four were two years old or younger. 

Enterovirus testing is available for three children; two had evidence of enterovirus D68 infection in stool or respiratory samples. 

We describe the clinical features, epidemiology and state of current investigations for these unusual clusters of illness.

Acute flaccid myelitis of unknown etiology in California, 2012-2015

Via JAMA: Acute Flaccid Myelitis of Unknown Etiology in California, 2012-2015. The abstract:

Importance  There has been limited surveillance for acute flaccid paralysis in North America since the regional eradication of poliovirus. In 2012, the California Department of Public Health received several reports of acute flaccid paralysis cases of unknown etiology. 

Objective  To quantify disease incidence and identify potential etiologies of acute flaccid paralysis cases with evidence of spinal motor neuron injury. 

Design, Setting, and Participants  Case series of acute flaccid paralysis in patients with radiological or neurophysiological findings suggestive of spinal motor neuron involvement reported to the California Department of Public Health with symptom onset between June 2012 and July 2015. Patients meeting diagnostic criteria for other acute flaccid paralysis etiologies were excluded. Cerebrospinal fluid, serum samples, nasopharyngeal swab specimens, and stool specimens were submitted to the state laboratory for infectious agent testing. 

Main Outcomes and Measures  Case incidence and infectious agent association. 

Results  Fifty-nine cases were identified. Median age was 9 years (interquartile range [IQR], 4-14 years; 50 of the cases were younger than 21 years). Symptoms that preceded or were concurrent included respiratory or gastrointestinal illness (n = 54), fever (n = 47), and limb myalgia (n = 41). Fifty-six patients had T2 hyperintensity of spinal gray matter on magnetic resonance imaging and 43 patients had cerebrospinal fluid pleocytosis. 

During the course of the initial hospitalization, 42 patients received intravenous steroids; 43, intravenous immunoglobulin; and 13, plasma exchange; or a combination of these treatments. Among 45 patients with follow-up data, 38 had persistent weakness at a median follow-up of 9 months (IQR, 3-12 months). Two patients, both immunocompromised adults, died within 60 days of symptom onset. Enteroviruses were the most frequently detected pathogen in either nasopharynx swab specimens, stool specimens, serum samples (15 of 45 patients tested). No pathogens were isolated from the cerebrospinal fluid. 

The incidence of reported cases was significantly higher during a national enterovirus D68 outbreak occurring from August 2014 through January 2015 (0.16 cases per 100 000 person-years) compared with other monitoring periods (0.028 cases per 100 000 person-years; P <.001). 

Conclusions and Relevance  In this series of patients identified in California from June 2012 through July 2015, clinical manifestations indicated a rare but distinct syndrome of acute flaccid paralysis with evidence of spinal motor neuron involvement. The etiology remains undetermined, most patients were children and young adults, and motor weakness was prolonged.

I posted a few news stories about these cases, including this item on March 20, 2014. 

A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA

Via The Lancet: A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA. The summary:

Background 

Clusters of acute flaccid paralysis or cranial nerve dysfunction in children are uncommon. We aimed to assess a cluster of children with acute flaccid paralysis and cranial nerve dysfunction geographically and temporally associated with an outbreak of enterovirus-D68 respiratory disease. 

Methods 

We defined a case of neurological disease as any child admitted to Children's Hospital Colorado (Aurora, CO, USA) with acute flaccid paralysis with spinal-cord lesions involving mainly grey matter on imaging, or acute cranial nerve dysfunction with brainstem lesions on imaging, who had onset of neurological symptoms between Aug 1, 2014, and Oct 31, 2014. We used Poisson regression to assess whether the numbers of cases during the outbreak period were significantly greater than baseline case numbers from a historical control period (July 31, 2010, to July 31, 2014). 

Findings 

12 children met the case definition (median age 11·5 years [IQR 6·75–15]). All had a prodromal febrile illness preceding neurological symptoms by a median of 7 days (IQR 5·75–8). Neurological deficits included flaccid limb weakness (n=10; asymmetric n=7), bulbar weakness (n=6), and cranial nerve VI (n=3) and VII (n=2) dysfunction. Ten (83%) children had confluent, longitudinally extensive spinal-cord lesions of the central grey matter, with predominant anterior horn-cell involvement, and nine (75%) children had brainstem lesions. Ten (91%) of 11 children had cerebrospinal fluid pleocytosis. Nasopharyngeal specimens from eight (73%) of 11 children were positive for rhinovirus or enterovirus. Viruses from five (45%) of 11 children were typed as enterovirus D68. Enterovirus PCR of cerebrospinal fluid, blood, and rectal swabs, and tests for other causes, were negative. Improvement of cranial nerve dysfunction has been noted in three (30%) of ten children. All ten children with limb weakness have residual deficits. 

Interpretation 

We report the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of enterovirus-D68 respiratory illness. Our findings suggest the possibility of an association between enterovirus D68 and neurological disease in children. If enterovirus-D68 infections continue to happen in an endemic or epidemic pattern, development of effective antiviral or immunomodulatory therapies and vaccines should become scientific priorities.

‘Polio-like’ strain of enterovirus D68 may be responsible for mystery paralysis, study says

Via The Washington Post: ‘Polio-like’ strain of enterovirus D68 may be responsible for mystery paralysis, study says. Excerpt:

Genetic sequencing of a virus found in respiratory secretions of children in California and Colorado who suffered from paralysis or muscle weakness last fall reveals that they were infected with a mutated strain of enterovirus D68 that is closer to polio than other strains common in previous years. 

The study, published Monday in Lancet Infectious Diseases, sheds new light on one of the most troubling medical mysteries of recent years. Amid a nationwide outbreak of severe respiratory illness, doctors at hospitals nationwide began to report that they were seeing an alarming number of children with unexplained weakness in an arm or a leg to complete paralysis that required them to be put on ventilators. 

Treating physicians noted that many of the children appeared to be infected with enterovirus D68, but researchers were cautious about drawing a causal link because virus had been bouncing around the world since the 1960s and had typically only caused breathing issues such as coughing and wheezing. 

While the research does not provide a definitive link -- that would only be established if the virus were  found in the spinal fluid and it was not -- it provides the strongest evidence to date of the link between enterovirus D68 and paralysis. The researchers theorize that the reason the virus was not found in the spinal fluid could be because the samples were taken too late. Scientists also tested the children for the presence of other pathogens capable of causing the symptoms but didn't find other viruses, bacteria, fungi or parasites. 

The new research reveals that the children had a novel strain of the virus, called B1, which emerged about four years ago. That strain has only five to six coding differences from previous strains that were commonly found in the United States but each of those are mutated in the direction of polio or another nerve-damaging virus known as EV-D70. 

"These are changes that may have made the virus more polio-like," said Charles Chiu, an associate professor at the University of California-San Francisco who worked on the study. 

While the study identified D68 as a possible trigger of the paralysis, it was not able to shed any light on another key question: Why have some children been affected so severely while others have been fine?

The study included a pair of siblings with a 100 percent genetically identical strain of the virus. One experienced muscle weakness and paralysis while the other only experienced upper respiratory symptoms.

Mystery childhood paralysis stumps researchers

Via Nature News & Comment: Mystery childhood paralysis stumps researchers. Excerpt:

Since August 2014, more than 100 children and young adults in the United States have developed a mysterious paralysis. Many of them had fevers before losing strength in one or more limbs, and the cases coincided with a wider epidemic of a little-known respiratory pathogen. That virus, enterovirus D68 (EV-D68), is the leading candidate for the cause of the paralysis, which few children have recovered from. 

Yet researchers have not definitively linked the two, or determined how the virus could cause the children’s symptoms. A study published on 28 January in The Lancet that describes a cluster of cases from Denver, Colorado, strengthens the link, but falls short of providing a 'smoking gun'. Here is what we know about the virus — and what scientists are trying to find out. 

What is EV-D68? 

It belongs to the enterovirus family, which includes poliovirus and the pathogens that cause common colds; it is most similar to the rhinoviruses that cause respiratory infections. Although EV-D68 was first isolated in the 1960s, it is relatively uncommon among enteroviruses circulating worldwide. 

However, since August 2014, the virus has been linked to more than 1,000 respiratory infections in the United States, some of them severe, and France has seen cases, too. John Watson, a medical epidemiologist at the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, says that last year, EV-D68 was the predominant type of enterovirus circulating in the country. “That’s a first,” he says. Genome sequencing of viruses recovered from respiratory cases in St Louis, Missouri, shows that the EV-D68 strain circulating in the United States is most closely related to viruses that caused a pneumonia-like illness in three children in Thailand in 2011. 

What is the evidence that links EV-D68 to the cases of paralysis? 

It has mostly to do with the timing: the cases of paralysis appeared during a wider outbreak of EV-D68, says Watson, whose team at the CDC’s Division of Viral Diseases is investigating the link. Researchers detected EV-D68 in nasal swabs from 8 out 41 people with paralysis who were tested, and another 9 people tested positive for related viruses.

US: The mysterious polio-like illness that has afflicted more than 100 children

Via The Washington Post: The mysterious polio-like illness that has afflicted more than 100 children. Excerpt:

Since last summer, public-health officials have been trying to figure out why more than 100 children in dozens of states have suffered from a polio-like weakness in their limbs. 

And while authorities have not found a direct link to the severe respiratory illness that affected children across the country last year, they are exploring whether that nationwide outbreak may be tied to this mysterious situation. 

There have been 103 confirmed reports of children who have developed the illness, which is called “acute flaccid myelitis,” according to the Centers for Disease Control and Prevention. These cases, which span 34 states, have almost all led to the hospitalization of the affected children, with some of them put on breathing machines.  

Last fall, the CDC began testing cases that occurred after Aug. 1. They had tested 88 cases by mid-November and found some possible trends, but the ultimate cause of the illnesses were still unclear. A handful of cases involved children who had been affected by the enterovirus D68 outbreak, but the CDC cautioned that no causal relationship between the illness could be confirmed by that time. There are also other viruses that can cause illnesses with symptoms like the ones currently being seen, the CDC noted. 

The possible tie to the enterovirus D68 (or EV-D68) outbreak is particularly worrisome, given how widespread this virus became. More than 1,100 people — again, most of them children — have been affected since last August. 

This number is likely severely underestimating how many were infected, as the CDC says there were presumably “millions” of mild infections in people who did not get tested. The virus was ultimately confirmed in 49 states and the District of Columbia. 

In September, as the enterovirus outbreak continued, health officials in Colorado explored a cluster of nine children suffering from weakness and paralysis. Some of these children tested positive for the enterovirus. 

Still, another concern in this latest illness is how many children have not seen any improvement since developing symptoms. Two out of three have said they had some improvement, compared to one in three who showed none. So far, only one child with the illness had fully recovered, the CDC says.