Sunday, September 25, 2016

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

# 11,764

Enterovirus-D68 is one of dozens of non-polio enteroviruses (NPEVs) that circulate primarily during the summer and fall, and cause between 10 and 15 million (mostly) mild respiratory illnesses in the U.S. each year - primarily in children.

As the CDC explains:

Most people who are infected with non-polio enteroviruses do not get sick, or they only have mild illness, like the common cold. Infants, children, and teenagers are more likely than adults to get infected and become sick because they do not yet have immunity (protection) from previous exposures to the viruses. Adults can get infected too, but they are less likely to have symptoms, or their symptoms may be milder. Symptoms of mild illness may include:
  • fever
  • runny nose, sneezing, cough
  • skin rash
  • mouth blisters
  • body and muscle aches
Very rarely, some NPEVs (EV-71, EV-D68, etc.) can cause more serious illness, including:
  • viral conjunctivitis,
  • hand, foot, and mouth disease,
  • viral meningitis (infection of the covering of the spinal cord and/or brain)
  • viral encephalitis (infection of the brain)
  • myocarditis (infection of the heart)
  • pericarditis (infection of the sac around the heart)
  • acute flaccid paralysis (a sudden onset of weakness in one or more arms or legs)
  • inflammatory muscle disease (slow, progressive muscle weakness)

Perhaps most notorious is  EV-71, which has caused major outbreaks particularly in Asia and the South Pacific over the past couple of decades (see ECDC: Rapid Risk Assessment On Recent Enterovirus Outbreaks In Europe), and has been making inroads into Europe the past few years.

But in recent years another NPEV -  EV-D68 - has been on the rise as well. First discovered in 1962, this virus kept a relatively low profile until the middle of the last decade.

In 2011, in MMWR: Clusters Of HEV68 Respiratory Infections 2008-2010, we looked at a half dozen EV 68 associated clusters which occurred in Asia, Europe, and the United States during 2008--2010.  

In August of 2014, EV-D68  abruptly appeared in America’s heartland and quickly spread across the nation, causing a wide spectrum of respiratory illness, predominantly in young children and adolescents (see Kansas City Outbreak Identified As HEV 68).

Coincident with this outbreak doctors reported a rise in cases of neurological illness presenting with AFP (acute flaccid paralysis) or limb weakness – often associated with a recent respiratory illness – mostly in children.

While not conclusive, the evidence for a link between EV-D68 infection and AFP has grown stronger over the past couple of years (see EID Journal  Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014).

There are, however, many other viruses - including EV-71, West Nile Virus, cytomegalovirus and Epstein-Barr virus, and adenoviruses - that can cause similar neurological symptoms.  

After reporting no EV-D68 cases in 2015, the CDC is reporting sporadic cases again this summer across the United States, as announced on the CDC's  About EV-D68 page.

What is happening with EV-D68 in 2016?

Updated July 2016

CDC is aware of limited sporadic EV-D68 detections in the U.S. in 2016. There is no indication of unusual activity. Enteroviruses are ever-present in the community, and each year we expect to detect cases. As in previous years, CDC will continue to work in 2016 with states by testing specimens to determine virus type, supporting the identification and investigation of outbreaks, and monitoring seasonal activity.
Perhaps coincidentally, the CDC is also reporting an increase in AFP diagnoses over the past few months.  At least compared to 2015.  As of now we've no information definitively linking this increase to any specific cause. 

Late last month we also looked at a report out of Taiwan (see Taiwan CDC: 1st Case Of EV-D68 With Acute Flaccid Paralysis).

All of which brings us to a Rapid Communications published on Friday in the EID Journal on a marked increase in EV-D68 cases in the Netherlands over the summer, which they attribute to clade B3 of the virus.
EV-D68, like all viruses, continues to evolve

You'll want to follow the link below to read the full report, as I've only excerpted some highlights.
Volume 23, Number 1—January 2017
Upsurge of Enterovirus D68, the Netherlands, 2016

Marjolein KnoesterComments to Author , Elisabeth H. Schölvinck, Randy Poelman, Sylvia Smit, Clementien L. Vermont, Hubert G.M. Niesters, and Coretta C. Van Leer-Buter


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.

The largest enterovirus D68 (EV-D68) outbreak occurred in the United States during the summer and fall of 2014. Approximately 1,100 respiratory EV-D68 infections were recorded, mostly in children, many of whom required intensive care unit (ICU) admission. Most diseases were of respiratory nature, but concurrent with the upsurge of EV-D68, the Centers for Disease Control and Prevention (Atlanta, GA, USA) recorded 120 cases of acute flaccid myelitis (AFM) (1). A Europewide study identified circulation of EV-D68 during the same period. Although numbers were lower, ICU admissions and 3 cases of AFM were reported (2). Before 2014, only a few small outbreaks of EV-D68 had been described worldwide, all with respiratory infections.

Our clinical virology laboratory (University Medical Center Groningen, Groningen, the Netherlands) reported an increase of EV-D68 infections in 2010 and again in 2014, in parallel with the US outbreak (3,4). Very limited activity of EV-D68 was observed in 2015. Since June 2016, we have again identified a substantial increase in respiratory EV-D68 infections in our hospital, just 2 years after the previous upsurge. To raise awareness of this upsurge and the severity of EV-D68 infections, we report on 25 cases. In addition, we show the phylogenetic relationship between the 2016 EV-D68 strains and those that circulated in 2014.


Evidence that EV-D68 might cause AFM is increasing after recent epidemiologic investigations (1,11,12). In patient 16, atypical Guillain-Barré syndrome initially was diagnosed; however, this diagnosis was later discarded because the electromyography results indicated motoric axon or anterior horn cell disease, and the clinical picture and MRI results were in favor of AFM (13). MRI findings were subtle, and radiologic diagnosis was made only after further review and discussion of the case with the neurologists. The absence of EV-D68 in CSF is consistent with previous reports (1,12).

Sequencing results showed that the strains in our study cluster in the recently described clade B3 (8). During the 2014 outbreak, most EV-D68 sequences belonged to clades B1 and B2, although A1 and A2 were also represented (2,14). Larger epidemiologic and genotyping studies are needed to evaluate whether the distinction within clade B is tenable and whether our clinical findings are typical for subclade B3.

This upsurge could indicate an active EV-D68 season, as highlighted by the epidemiologic curve, with a potential increase in AFM cases. Clinicians should be alert for EV-D68, its clinical implications, and the need for appropriate diagnostics, particularly in children who are admitted with respiratory failure to the ICU or with possible symptoms of AFM.
Dr. Knoester is an attending physician in clinical microbiology at the Division of Virology, University Medical Center Groningen. Her research focuses on clinical virology and epidemiology.

Saturday, September 24, 2016

FAO EMPRES: Risk Assessment For Spread Of H5N1 In The Middle East


A little over a decade ago, when HPAI H5N1 was the only avian flu virus of genuine concern, the virus began its diaspora out of China and Southeast Asia into Europe, the Middle East, and Western Africa.

In a matter of 24 months we went from 15 countries reporting the virus, to more than 60. 

Unexpectedly - and for reasons that aren't fully understood -  by 2008 the virus began to give up some of its new found territories, but remained firmly entrenched in Indonesia, India, Bangladesh, and Egypt.

This decline began to reverse itself in 2014, and over the past two years we've seen a resurgence of HPAI H5N1 in Western Africa, Eastern Europe, and parts of the Middle East (see Another Busy Bird Flu Summer).

Perhaps most ominously, over the spring and summer we saw reports of large outbreaks in Iraq - the first time we've seen confirmed reports out of that nation in a decade.
Today, H5N1 is no longer the only novel flu on our radar (see CDC: IRAT Evaluation Of Novel Avian & Swine Flu Risks), and H5N1 continues to mutate and evolve, potentially increasing its threat to public health.

All of which brings us to a recently published FAO/EMPRES Risk Assessment on the likelihood of further spread of HPAI H5N1 across the middle east. 

Highly pathogenic avian influenza (H5N1 HPAI) spread in the Middle East: risk assessment


This risk assessment provides an estimate of the likelihood of introduction of H5N1 HPAI from recently infected countries (Lebanon and Iraq) to other countries in the Middle East region and neighbouring territories as a result of the movement of live poultry (both legal and illegal), poultry-related products and the migration of wild birds.

The preliminary assessment based on the available information and uncertainties associated indicate that the risk of introduction of H5N1 HPAI for each of the nine regional and neighbouring countries or territories varies and is as follows:
  • High: Iran (Islamic Republic of), Israel, Jordan, the Syrian Arab Republic and Turkey
  • Medium: Gaza Strip, Kuwait, Saudi Arabia and The West Bank
  • Low: Armenia, Azerbaijan and Georgia
  • Negligible: Cyprus

The situation in the region is of concern given the existing poultry populations at risk and the potential for spread between countries. Given the presence of civil unrest and active civil war in some countries of the region, investment in agriculture and livestock is reduced, including limitations to public veterinary services.
Underreporting of animal disease events is a significant challenge given the lack of reporting systems in those areas with ongoing conflict. It is therefore possible that, in addition to Iraq and Lebanon, the disease is already present in the Syrian Arab Republic. The cause of the recent incursions into the region is currently unknown but a combination of wild birds seeding infection and trade with neighbouring countries is likely.

Poultry and poultry-related trade and movements play an important role in national and cross-border spread. The overall risk for the region in terms of potential spread to uninfected countries ranges from negligible to high depending on the country with Iran (Islamic Republic of), Israel, Jordan, the Syrian Arab Republic and Turkey being at highest risk of incursion.  The current H5N1 HPAI epizootic is expected to have a potential impact on food security, human health and poultry-dependent livelihoods in a region which is already suffering from political unrest and deteriorated public and animal health services.
       (Continue . . . )

You'll want to download and read the entire, data-rich 8 page risk assessment.   

As discussed earlier this week, and from another FAO document (see FAO/EMPRES: H5N8 Clade Detected Over Summer In Russia), the H5N8 virus has proven itself to be an excellent traveler as well, making its way to Europe, North America, and Taiwan within a year of emerging in South Korea.

Over the summer we've seen some evidence that H5N8 might threaten again this winter, and there are concerns what would happen if it should turn up in areas (like the Middle East or Western Africa) where H5N1 is already well established. 

And of course, we continue to watch H7N9, H5N6 along with a longer list of (presumably) less concerning novel flu strains, for signs of geographic spread of enhanced transmission.


Friday, September 23, 2016

WHO: 6 Candidates Announced For Director-General


After 10 years Dr. Margaret Chan will turn over the reigns of the World Health Organization to another Director-General next year.  Six countries have submitted candidates for the position, but we won't know who gets the nod until next May.

The following statement was emailed to journalists earlier today, and is now on the WHO website.

23 September 2016 | Geneva: Six candidates have been proposed by Member States of the World Health Organization (WHO) for the position of WHO Director-General.

Member States proposed the following candidates:

·         The Government of Ethiopia has submitted the nomination of Dr Tedros Adhanom Ghebreyesus;
·         The Government of Italy has submitted the nomination of Dr Flavia Bustreo;
·         The Government of France has submitted the nomination of Professor Philippe Douste-Blazy;
·         The Government of the United Kingdom of Great Britain and Northern Ireland has submitted the nomination of Dr David Nabarro;
·         The Government of Pakistan has submitted the nomination of Dr Sania Nishtar;
·         The Government of Hungary has submitted the nomination of Dr Miklós Szócska.


The deadline for proposals closed on 22 September 2016. Since 22 April 2016, WHO's 194 Member States have had the opportunity to propose candidates.
The Director-General is WHO’s chief technical and administrative officer and oversees WHO’s international health work. The current Director-General, Dr Margaret Chan, was appointed  in 2006 and will complete her second term on 30 June next year.

On 1-2 November, a forum will be held for candidates to present their visions to WHO Member States, and the public, and answer questions from Member States on their candidacy. The forum will be webcast in all UN languages on the WHO website: Arabic, Chinese, English, French, Russian and Spanish.

In January 2017, WHO’s Executive Board will draw up a shortlist with a maximum of 5 candidates. Executive Board members will then interview these candidates and nominate up to 3 to go forward for consideration by the World Health Assembly in May 2017, when Member States will vote in a new Director-General. Previously, just 1 nomination was submitted by WHO’s Executive Board to the World Health Assembly, which then made the final appointment.

The new Director-General will take office on 1 July 2017.

Eurosurveillance: Lack Of Evidence For Continued Circulation Of HPAI H5N8 In The Netherlands

H5N8 December 2014 - Credit DEFRA


Although they were not hit nearly as hard as was North America, Western Europe saw multiple outbreaks and isolated detections of HPAI H5N8 during the fall-winter of 2014-15.

By the spring of 2015, however, reports in Europe ended.

Like in North America, the virus was fully expected to return in the fall of 2015, but did not.  Since then, researchers have been trying to figure out why the virus seemingly vanished.

Yesterday the journal Eurosurveillance published a lengthy research article on virological and serological surveillance of wild birds in the Netherlands before, during, and after 2014's outbreak. 

And, just as we've seen in North America, there's been little or no evidence of active H5N8 infection in any of the birds sampled since their outbreaks ended. 

Last July, we looked at a similar study (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl)
which concluded while migratory waterfowl can briefly carry HPAI H5, they are not a good long-term reservoir for highly pathogenic avian flu viruses.

HPAI viruses appear to burn out fairly quickly in aquatic waterfowl populations, likely due to their immunity to LPAI viruses, and would have to be reintroduced periodically. 

Another study, published last month in Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1, suggests that waterfowl pick up new HPAI viruses in the spring (likely from poultry or terrestrial birds) on their way north to their summer breeding spots.

The following fall enough of the virus may still be circulating among them - due in part to immunologically naive hatchlings born over the summer - to be spread during their southbound migration.

At least that's the theory.

Since HPAI H5N8 has recently been detected in both Alaskan and Russian wild birds, its possible we'll see that theory tested again this winter.   Poultry producers in Europe, and in North America are being urged to beef up their biosecurity . . . just in case.

The abstract and some excerpts from yesterday's Eurosurveillance report follow.

Eurosurveillance, Volume 21, Issue 38, 22 September 2016
Research article

Lack of virological and serological evidence for continued circulation of highly pathogenic avian influenza H5N8 virus in wild birds in the Netherlands, 14 November 2014 to 31 January 2016

MJ Poen 1 2 , JH Verhagen 1 2 , RJ Manvell 3 , I Brown 3 , TM Bestebroer 1 , S van der Vliet 1 , O Vuong 1 , RD Scheuer 1 , HP van der Jeugd 4 5 , BA Nolet 4 6 , E Kleyheeg 4 5 , GJDM Müskens 7 , FA Majoor 8 , C Grund 9 , RAM Fouchier 1

Correspondence: Ron A M Fouchier (

Citation style for this article: Poen MJ, Verhagen JH, Manvell RJ, Brown I, Bestebroer TM, van der Vliet S, Vuong O, Scheuer RD, van der Jeugd HP, Nolet BA, Kleyheeg E, Müskens GJDM, Majoor FA, Grund C, Fouchier RAM. Lack of virological and serological evidence for continued circulation of highly pathogenic avian influenza H5N8 virus in wild birds in the Netherlands, 14 November 2014 to 31 January 2016. Euro Surveill. 2016;21(38):pii=30349. DOI:
Received:05 April 2016; Accepted:21 July 2016

In 2014, H5N8 clade highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage emerged in poultry and wild birds in Asia, Europe and North America. Here, wild birds were extensively investigated in the Netherlands for HPAI H5N8 virus (real-time polymerase chain reaction targeting the matrix and H5 gene) and antibody detection (haemagglutination inhibition and virus neutralisation assays) before, during and after the first virus detection in Europe in late 2014.

Between 21 February 2015 and 31 January 2016, 7,337 bird samples were tested for the virus. One HPAI H5N8 virus-infected Eurasian wigeon (Anas penelope) sampled on 25 February 2015 was detected. Serological assays were performed on 1,443 samples, including 149 collected between 2007 and 2013, 945 between 14 November 2014 and 13 May 2015, and 349 between 1 September and 31 December 2015. 

Antibodies specific for HPAI H5 clade were absent in wild bird sera obtained before 2014 and present in sera collected during and after the HPAI H5N8 emergence in Europe, with antibody incidence declining after the 2014/15 winter. Our results indicate that the HPAI H5N8 virus has not continued to circulate extensively in wild bird populations since the 2014/15 winter and that independent maintenance of the virus in these populations appears unlikely.


In conclusion, our results provide evidence that clinically unaffected long distance migratory and local wild birds sampled in the Netherlands during the H5N8 outbreak late 2014 and early 2015, and again late 2015, have been exposed to HPAI H5N8 or closely related HPAI H5 clade viruses and seroconverted upon exposure. 

Since HPAI H5N8 virus has not been detected in Europe since early 2015 and because HPAI H5 clade antibody incidence decreased in time, we conclude that the virus has not circulated extensively at the breeding grounds in summer and upon the return of the birds to their wintering areas in the 2015/16 winter. 

As a consequence, the newly emerging HPAI H5N8 clade virus subtype appears to have already disappeared from European wild birds indicating that sustained transmission and independent maintenance may be less likely.
This is an important consideration in the ongoing evolution and ecology of these viruses in wild birds and the potential risks they pose for introduction to poultry and the pathways through which they might spread. Finally we recommend that serological tools be further optimised, harmonised, and validated for avian influenza surveillance studies in wild birds.

Saudi Arabia Reports 2 New MERS Cases


Although the link on the Saudi MOH's website somewhat confusingly reads MOH: '4 New Confirmed Corona Cases Recorded', today's report only shows 2 new cases, and 1 recovery. 

Both cases are listed as `primary', which only tells us these cases had no known exposure to an identified MERS case or a recent visit to a health care facility. 

Since both cases are listed has having no recent camel exposure, we don't currently know how they may have acquired the virus.

Estimates suggest that only about 40% of Saudi cases are identified and isolated (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016), which leaves open the possibility of limited community transmission by unidentified cases.

Another Monkeypox Outbreak In The Central African Republic

Credit Wikipedia


For the second time in 2016 we are seeing reports of an outbreak of Monkeypox in the Central African Republic. The first outbreak, which started in late December of 2015, was reported in early January (see Monkeypox Outbreak Reported In Central African Republic), and was followed a month later Reports Of A Large Monkeypox Outbreak In The DRC.

If it seems as if we are seeing more frequent outbreaks in recent years, there is some evidence to back that up.

A 2016 study (see EID Journal:Extended H-2-H Transmission during a Monkeypox Outbreak) looked at a large 2013 outbreak of Monkeypox in the DRC and suggests that the virus's epidemiological characteristics may be changing (possibly due to the waning smallpox vaccine derived immunity in the community).

In 2013, the DRC reported a 600% increase in cases over both 2011, and 2012.  The authors also cite a higher attack rate, longer chains of infection, and more pronounced community spread than have earlier reports.

First a report from on this latest outbreak, then I'll return with more. 

Basse-Kotto prefecture / Sub-prefecture of Mingala

Health: An epidemic of smallpox Monkey (Monkey Pox) was reported in four villages in the Sub-prefecture of Mingala. According to the National Health Cluster, the first case was recorded August 17, 2016, and 14 cases with 1 death were reported on 15 September. According to the same source, 10 cases of unsolved deaths were reported by the community during the same period in these villages.  

Some cases are supported at the health post Irra Banda (about 50 km from Mingala, Bria Mingala-axis), while others are referred to the District Alindao hospital. A consultation is underway in Bangui, between the Ministry of Health and health sector partners, to respond to this epidemic through communication activities, capacity building and staffing support for inputs . At Alindao, health partner has initiated outreach activities in villages in the sub-prefecture of Mingala.

Recall that a first outbreak in the Prefecture of Mbomou (and Bakouma Bangassou), was declared December 29, 2015 by the Ministry of Health. The latter was supported by end January 2016.

Human monkeypox was first identified in 1970 in the DRC, and since then has sparked small, sporadic outbreaks in the Congo Basin and Western Africa.

The name `monkeypox’ is a bit of a misnomer. It was first detected (in 1958) in laboratory monkeys, but further research has revealed its host to be rodents or possibly squirrels.

It produces a remarkably `smallpox looking'  illness in humans, albeit not as deadly.  The CDC's Monkeypox website states:

The illness typically lasts for 2−4 weeks. In Africa, monkeypox has been shown to cause death in as many as 1 in 10 persons who contract the disease

Humans can contract it in the wild from an animal bite or direct contact with the infected animal’s blood, body fluids, or lesions, but consumption of under cooked bushmeat is also suspected as an infection risk.

Human-to-human transmission is also possible.  This from the CDC’s Factsheet on Monkeypox:

The disease also can be spread from person to person, but it is much less infectious than smallpox. The virus is thought to be transmitted by large respiratory droplets during direct and prolonged face-to-face contact. In addition, monkeypox can be spread by direct contact with body fluids of an infected person or with virus-contaminated objects, such as bedding or clothing.

According to the CDC there are two distinct genetic groups (clades) of monkeypox virus—Central African and West African. West African monkeypox is associated with milder disease, fewer deaths, and limited human-to-human transmission.

Somewhat famously, the United States saw an outbreak (of the milder, West African clade) in 2003 that affected 47 confirmed and probable cases across six states—Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin - all of whom had contact with infected prairie dogs purchased as pets.
These pets became infected when an animal distributor imported hundreds of small animals from Ghana, which in turn infected prairie dogs that were subsequently sold to the public (see MMWR Update On Monkeypox 2003).

While still considered a geographically limited threat, in 2010 a study that appeared in PNAS warned that the incidence of human monkeypox infection was increasing, and that it posed a potential risk well beyond localized outbreaks in Africa.

Although monkeypox outbreaks tend to burn themselves out fairly quickly, and rarely spread very far, those were the same qualities we attributed to Ebola two years ago.  So we'll keep an eye on this outbreak, in the unlikely event it should spread beyond Mingala.