Sunday, November 23, 2014

Netherlands Institutes New Bird Flu Control Measures

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"Map of restricted compartments Netherlands"

 

# 6365

 

The surprise arrival of avian H5N8 in European poultry farms just months after it emerged in South Korea has put agricultural interests (and to a lesser extent, public health) on alert.  The UK and Germany have each reported a single outbreak in poultry, although Germany yesterday reported an infected wild bird. 

 

The Netherlands has thus far been the hardest hit, with farms in three locations now reporting either confirmed or suspected H5N8 infections.

 

Although we tend to think of Asia when it comes to large avian flu outbreaks, in 2003 HPAI H7N7 was isolated from poultry on a farm in the Netherlands, marking the start of a large epizootic that also spilled into Germany and Belgium.

 

Before it was through, the virus had forced the culling of 30 million chickens across more than 1300 farms, along with infecting at least 89 people – killing one. Details on that cluster were reported in the December 2005 issue of the Eurosurveillance Journal (see Human-to-human transmission of avian influenza A/H7N7, The Netherlands, 2003).

 

Having already learned the hard way how devastating an avian flu outbreak can be, today the central government site for the Netherlands (Rijksoverheid.nl) has released an update on the farms currently affected, along with details of a new bird flu control plan.

 

Locations bird flu

After infection with a company in Hekendorp also been found on poultry farms in Ter Aar and around Kamperveen bird flu.

To combat the outbreak of bird flu in the Netherlands, have been taken on November 23, 2014 new measures . More information about bird flu can be found in the document  Frequently Asked Questions and Answers bird flu .

Bird flu Kamperveen

In Kamperveen (Overijssel) is November 21, 2014 to set a poultry bird flu (avian influenza, AI) . The infected farm is cleared as soon as possible. Also, bird flu is established in two other nearby businesses .

Bird flu Ter Aar

On a farm in Ter Aar is determined bird flu on November 20, 2014 . Because of the discovery apply again a nationwide transport ban for poultry and eggs.

Preventive culling Barneveld

In Barneveld on 22 November 8000 a company with ducks culled as a precaution . Research has shown that this company is visited by a truck that had done previously the infected ducks company Kamperveen. Secretary Dijksma wants given the location of the ducks in the poultry business rich Barneveld take any risks.

There are currently no suspected cases of bird flu in Barneveld.

Severe bird flu in Hekendorp

On November 16, 2014 determined that the bird flu is highly pathogenic virus at a poultry farm in Hekendorp (municipality Oudewater). The highly pathogenic strain of avian influenza is very contagious among poultry. For chicken, this version is deadly. Avian influenza is a zoonosis. That means that the infection from animals to humans can be transferred. Protective measures to be taken for that reason.

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New measures against bird flu

News item | 23-11-2014

To combat the outbreak of bird flu in the Netherlands, Secretary Dijksma takes a new package of measures. The national movement ban of 72 hours is replaced by a focused regional approach with additional measures for the coming weeks. Proclaimed zones around the infected farms in Hekendorp, Ter Aar and Kamperveen remain in force. All measures are designed to prevent bird flu can spread and are expected to remain 21 days in stand.

Four regions to avoid

Netherlands is divided into 4 regions, between which the contacts are kept to a minimum. These regions are structured so that the two poultry rich areas (Gelderland Valley and the Peel) are each in a different region. Also, the format so that these two poultry rich areas find themselves in a different region of the 3 and 10 km zones established around the places where an outbreak has occurred (Hekendorp, Ter Aar and Kamperveen). Thus spread of bird flu prevented.

Hygiene measures vital

The measures remain focused on the number of contacts between poultry and mixed (for example by means of transport or persons) to limit as much as possible. When transports are necessary hygiene measures very important. Per trip may be visited only one poultry farm, and the trolleys should be re-cleaned and disinfected. Moving poultry manure has a significant risk, and therefore remains prohibited.

No new supply chicks for poultry

In addition, it is not desirable that new poultry being supplied at present to companies. A larger quantity of poultry can lead to increased contamination of other poultry farms. Calculations of the CVI show that almost inevitable that the release of virus in regions with many poultry leading to an epidemic. Therefore, it remains forbidden to transport day-old chicks to poultry farms in the Netherlands.

The transport of day-old chicks has a very low health risk, as opposed to transporting other types of poultry. Therefore transport for export of day-old chicks of clean companies outside the 10 kilometer zones under strict conditions allowed.

PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2

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Photo Credit – FAO

 

# 9364

 

While the superstars of avian influenza tend to be those viruses that can infect, and sometimes kill, humans (H5N1, H7N9, H10N8) behind each of these deadly viruses is an obscure `parental’ virus called H9N2 that has lent a good deal of its backbone – it’s internal genes – to the creation of these emerging threats.

 

I’ve previously described H9N2 as the Professor Moriarty of avian flu viruses. 

 

Whenever something untoward happens with an avian flu strain – if you look deep enough – you often find clues that H9N2 was the viral `mastermind’ behind it all.

 

Last May, in EID Journal: H7N9 As A Work In Progress, we looked at a study that found the H7N9 avian virus continues to reassort with local H9N2 viruses, making the H7N9 viruses that circulated in wave 2 genetically distinct from those that were seen during the 1st wave.

 

Although categorized by their two surface proteins (HA & NA) Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).

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Shift, or reassortment, happens when two different influenza viruses co-infect the same host swap genetic material.  New hybrid viruses may be the result of multiple reassortments, with gene contributions coming from several parental viruses.

 

Of the three avian flu viruses we are currently watching with the most concern – H5N1, H7N9, and H10N8 – all  share several important features (see Study: Sequence & Phylogenetic Analysis Of Emerging H9N2 influenza Viruses In China):

 

    • They all first appeared in  Mainland China
    • They all  have come about through viral reassortment in poultry
    • And most telling of all, while their HA and NA genes differ - they all carry the internal genes from the avian H9N2 virus

 

This ubiquitous, yet fairly benign H9N2 virus is apparently very promiscuous, as we keep finding bits and pieces of it turning up in new reassortant viruses.  Last June, in Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission, we saw evidence of even more influence of H9N2 on the ongoing evolution of H7N9.

 

Last January, The Lancet carried a report entitled Poultry carrying H9N2 act as incubators for novel human avian influenza viruses by Chinese researchers Di Liu a, Weifeng Shi b & George F Gao that warned:

 

Several subtypes of avian influenza viruses in poultry are capable of infecting human beings, and the next avian influenza virus that could cause mass infections is not known. Therefore, slaughter of poultry carrying H9N2—the incubators for wild-bird-origin influenza viruses—would be an effective strategy to prevent human beings from becoming infected with avian influenza.

We call for either a shutdown of live poultry markets or periodic thorough disinfections of these markets in China and any other regions with live poultry markets.

 

In the past, we’ve looked at the propensity of the H9N2 virus to reassort with other avian flu viruses (see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses & PNAS: Reassortment Potential Of Avian H9N2) which have shown the H9N2 capable of producing `biologically fit’ and highly pathogenic reassortant viruses.

 

And in 2010 (see Study: The Continuing Evolution Of Avian H9N2) we looked at computer modeling (in silica) that warned the H9N2 virus has been slowly evolving towards becoming a `more humanized’ virus.

 

And while we have only seen a handful of human infections with this virus (see Hong Kong: Isolation & Treatment Of An H9N2 Patient), it is also true that in areas where this virus is most common, testing and surveillance for the virus is extremely limited.  Like so many other novel viruses, we can only guess at is true burden in the human population.

 

This week, we’ve a new study that finds a diverse set of H9N9 genotypes have been circulating in Chinese poultry between 2009-2013, with the majority sharing a remarkably stable internal-gene-combination”.  This internal gene structure has been `lent’ to the emerging H7N9 and H10N8 viruses as well.


Perhaps most surprising, of 35 viruses tested, all bound preferentially to alpha 2,6 receptor cells -  the type commonly found in the human upper respiratory tract, rather than to alpha 2,3 receptor cells which are found in the gastrointestinal tract of birds.


This is viewed as one of the crucial steps in the adaptation of an avian influenza virus to a mammalian host (see Nature Comms: Host Adaptation Of Avian Influenza Viruses). 

 

Additionally, six of nine viruses tested in ferrets transmitted via respiratory droplets (two being highly transmissible) and inoculated ferrets readily developing spontaneous viral mutations conducive to greater virulence and better transmission in mammals. 

 
For more details, follow the link below to read:

 

Genetics, Receptor Binding Property, and Transmissibility in Mammals of Naturally Isolated H9N2 Avian Influenza Viruses

Xuyong Li equal contributor, Jianzhong Shi equal contributor, Jing Guo equal contributor, Guohua Deng, Qianyi Zhang, Jinliang Wang,  Xijun He, Kaicheng Wang,  Jiming Chen,  Yuanyuan Li,  Jun Fan,  Huiui Kong, Chunyang Gu,  [ ... ], Hualan Chen mail

Abstract

H9N2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades. Because these viruses are of low pathogenicity in poultry, their eradication is not a priority for animal disease control in many countries, which has allowed them to continue to evolve and spread. Here, we characterized the genetic variation, receptor-binding specificity, replication capability, and transmission in mammals of a series of H9N2 influenza viruses that were detected in live poultry markets in southern China between 2009 and 2013.

Thirty-five viruses represented 17 genotypes on the basis of genomic diversity, and one specific “internal-gene-combination” predominated among the H9N2 viruses. This gene combination was also present in the H7N9 and H10N8 viruses that have infected humans in China.

All of the 35 viruses preferentially bound to the human-like receptor, although two also retained the ability to bind to the avian-like receptor. Six of nine viruses tested were transmissible in ferrets by respiratory droplet; two were highly transmissible. Some H9N2 viruses readily acquired the 627K or 701N mutation in their PB2 gene upon infection of ferrets, further enhancing their virulence and transmission in mammals.

Our study indicates that the widespread dissemination of H9N2 viruses poses a threat to human health not only because of the potential of these viruses to cause an influenza pandemic, but also because they can function as “vehicles” to deliver different subtypes of influenza viruses from avian species to humans.

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COCA Call Monday: Caring For Ebola Patients – A Nursing Perspective

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# 9363

 

While the United States is currently `Ebola-free’, that is a status that is unlikely to persist in the long run.  Additional Ebola cases will undoubtedly be evacuated to US facilities, and as we’ve already seen twice, infected individuals can also arrive in this country unaware that they have been infected.

 

While the US response wasn’t always perfect, it is nonetheless reassuring that neither unplanned introduction of the virus led to infections in the general public, and that our public health system was able to track, monitor, and manage hundreds of potential contacts.

 

As specialist treatment units like Emory University and the University of Nebraska Medical Center gain more experience, they continue to share it with others (see earlier CDC COCA Call : What U.S. Hospitals Can Learn From Emory & UNMC On Ebola).  Tomorrow afternoon, the CDC will present a new COCA Call presenting clinical management experiences of nurses who have worked with Ebola patients both at UNMC and Emory University.

 

Primarily of interest to clinicians and healthcare providers, COCA (Clinician Outreach Communication Activity) calls are designed to ensure that practitioners have up-to-date information for their practices.

 

 

Caring for Patients with Ebola in U.S. Hospitals: A Nursing Perspective

 

Image of Continuing Education Credits abbreviation. = No Continuing Education

Date: Monday, November 24, 2014

Time:2:00 – 3:00 PM (Eastern Time)

Participate by Phone:

  • 888-972-6898 (U.S. Callers)
  • 630-395-0194 (International Callers)

Passcode:5076538

Join by Live Audio Web Streaming: (Listen only)


http://event.on24.com/r.htm?e=897795&s=1&k=6DF1465EA1BB9109F0973F486C334C3C

Moderator

Mary Wakefield, PhD, RN
Administrator
Health Resources and Services Administration
U.S. Department of Health and Human Services

Presenter(s)

Clinical Team Member
Ebola Response
Centers for Disease Control and Prevention

Nurse Leaders
Emory Healthcare
Atlanta, Georgia

Nurse Leaders
University of Nebraska Medical Center
Omaha, Nebraska

Overview

Health care organizations across the country are preparing to respond to the possibility of Ebola cases in their communities. Several U.S. hospitals have treated patients with the disease and can provide important information to other health care workers related to personal protective equipment, staffing models, and critical care nursing. During this COCA Call, clinicians will learn about the clinical management experiences of nurses who cared for patients with Ebola at Emory Healthcare and Nebraska Medical Center.

Call Materials

Saturday, November 22, 2014

Saudi MOH: 1 MERS Case In Taif

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# 9362

 

After roughly 10 days without hearing of a case out of Taif, today the Saudi MOH announced that a 58 y.o. male is receiving treatment for the infection.

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You’ll recall that during September and October Taif was in the news nearly every day, with more than 20 MERS cases reported in that region, sparking several MOH press statements (see MERS Awareness Campaign).

Germany & Japan Both Report H5N8 In Wild Birds

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International Migratory Flyways

 

# 9361

 

On Tuesday, in H5N8: A Case Of Deja Flu?, I recounted the history of great H5N1 bird flu expansion of 2005-2007, where that virus jumped from only 9 Southeast Asia countries to 60+ nations across Europe and Asia.  While it is far from clear whether H5N8 will follow H5N1’s flight path, we continue to see evidence of its encroachment to other regions of the world.

Since Tuesday, the Netherlands has reported several additional farms infected (see Netherlands: 2nd Farm At Kamperveen Showing Signs Of Bird Flu), and both Japan and Germany have found evidence of the virus in wild or migratory birds.

First stop, a report today from Reuters of a 2nd detection of H5N8 in Germany, this time in wild birds.

Germany reports second case of bird flu - H5N8 found in wild bird

BERLIN Sat Nov 22, 2014 10:51am EST

Nov 22 (Reuters) - German authorities on Saturday confirmed a second case of the H5N8 strain of bird flu in the eastern state of Mecklenburg-Vorpommern, with the virus found in a wild bird.

The strain is highly contagious among birds but has never been detected in humans.

"For the first time, the H5N8 virus has been confirmed in a wild bird in Mecklenburg-Vorpommern," Agriculture Minister Christian Schmidt said in a statement.

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Japan, which saw a brief incursion of the H5N8 virus last April while South Korea was battling against multiple outbreaks (see Japan’s Avian Flu Outbreak Identified As H5N8 ), and which reported a little more than a week ago H5N8 In Migratory Bird Droppings, has now reported to the OIE another detection of H5N8 in Chiba prefecture.

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According to a Japan News article earlier today (Bird flu detected in Chiba Prefecture), with this second detection, Japan will now raise its nationwide bird flu alert from 2 to 3, and dispatch an emergency wild bird survey team.


While none of this is absolute confirmation that the H5N8 virus arrived in Western Europe on the wings of migratory birds, when you combine these recent detections in birds, and the statement from the OIE: European H5N8 Strain `Closely Related’ To Korean Strain, the preponderance of evidence swings in that direction.

 

For more on this you may wish to revisit these recent related blogs:

FAO On The Potential Threat Of HPAI Spread Via Migratory Birds

Bird Flu Spread: The Flyway Or The Highway?

EID Journal: Subclinical HPAI In Vaccinated Poultry – China

Nature Comms: Host Adaptation Of Avian Influenza Viruses

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Flu Virus binding to Receptor Cells – Credit CDC

 

# 9360

 

More than a decade after it re-emerged in Vietnam, H5N1 continues to circulate widely in Asian and Middle Eastern poultry providing numerous opportunities to infect humans, and yet only a few more than 600 human infections have been identified.  

 

Similarly, the H7N9 virus which appeared 2 years ago in China appears well distributed in Asia’s domesticated poultry population, but only about 450 human infections have been reported.

 

While both viruses are capable of infecting and causing severe illness in humans, neither has taken off as a human-adapted pathogen.  Transmission has almost always been from bird to human, with secondary human-to-human transmission a rarity. 

 

Despite our concerns over the future of these influenza subtypes, both viruses remain primarily adapted to avian hosts.  The concern of course, is that over time, that may change.

 


Why some influenza viruses – like seasonal H1N1, H3N2, H2N2, and others through the years – have successfully adapted to humans, while others like H5N1, H7N9, H5N6, H10N8 haven’t remains a mystery, although researchers are making progress in figuring it out.  

 

Avian flu viruses are preferentially adapted to birds, where it is primarily a gastrointestinal infection. What scientists look for are `mammalian adaptations’;  those that favor the infection and respiratory transmission among mammals – including humans. 


Unlike solving a Rubik’s cube, there is probably more than just one `winning’ combination.  And a change in one part of the virus that favors adaptation may either be enhanced, or blocked, by a change somewhere else along the14,000 nucleotide chain of the influenza A virion.

 

Avian adapted flu viruses bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds. So the first barrier appears to be switching the RBS, or Receptor Binding Site (the area of its genetic sequence that allows it to attach to, and infect, host cells) to `fit’ the receptor cells commonly found in the human upper respiratory tract; the alpha 2,6 receptor cell (see Study: Dual Receptor Binding H5N1 Viruses In China)


But that, we are learning, isn’t enough on its own.

 

Birds run `hotter’ than mammals, with a normal body temperature  several degrees higher (and avian viruses replicate in the gut, which is warmer than the upper airway of humans).  Which means mammalian adapted viruses must be adapted to replicate at a lower temperature.

 

Researchers have determined the (E627K) substitution in the (PB2) protein - the swapping out of the amino acid Glutamic acid (E) at position 627 for Lysine (K) - makes the an influenza virus better able to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract (see Eurosurveillance: Genetic Analysis Of Novel H7N9 Virus).

 

These are just two examples of species barriers that must be overcome before an avian virus can successfully adapt to human (or mammalian) physiology.  There are more, some we know about, some we probably don’t

 

Complicating matters – influenza viruses constantly develop multiple amino acid changes – and their combined effects on the virulence, transmission, antiviral resistance, `fitness’, and host range of the virus are far from fully understood.

 

All of which serves as prelude to a study recently published in Nature Communications, that finds another PB2 amino acid substitution (K526R) enhances the effects of the E627K mutation mentioned above.

 

First the link and abstract with the daunting title of:

 

The K526R substitution in viral protein ​PB2 enhances the effects of E627K on influenza virus replication

Wenjun Song, Pui Wang, Bobo Wing-Yee Mok, Siu-Ying Lau, Xiaofeng Huang, Wai-Lan Wu, Min Zheng, Xi Wen, Shigui Yang, Yu Chen, Lanjuan Li, Kwok-Yung Yuen & Honglin Chen

Host-adaptive strategies, such as the E627K substitution in the ​PB2 protein, are critical for replication of avian influenza A viruses in mammalian hosts. Here we show that mutation ​PB2-K526R is present in some human H7N9 influenza isolates, in nearly 80% of H5N1 human isolates from Indonesia and, in conjunction with E627K, in almost all seasonal H3N2 viruses since 1970.

Polymerase complexes containing ​PB2-526R derived from H7N9, H5N1 or H3N2 viruses exhibit increased polymerase activity. ​PB2-526R also enhances viral transcription and replication in cells. In comparison with viruses carrying 627K, H7N9 viruses carrying both 526R and 627K replicate more efficiently in mammalian (but not avian) cells and in mouse lung tissues, and cause greater body weight loss and mortality in infected mice. ​PB2-K526R interacts with nuclear export protein and our results suggest that it contributes to enhance replication for certain influenza virus subtypes, particularly in combination with 627K.

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Simply put, an influenza virus carrying both the E637K and K526R mutation in it’s PB2 protein replicates more efficiently in mammalian hosts. 

 

Interestingly, the H3N2 seasonal flu virus – which traditionally produces more severe flu seasons than does seasonal H1N1 – has also carried this dynamic duo of amino acid substitutions since the early 1970s.

 

HKU (Hong Kong University) – which did this study – published a press release (excerpts below) with a summary of their findings:

 

HKU medical research team finds host adaptation strategies of avian influenza A viruses for better replication in human

20 Nov 2014

(EXCERPT)

Research findings
In a recent study reported in the Nature Communications, a research team led by Dr. Honglin Chen, Associate Professor, and Professor Kwok-yung Yuen, Henry Fok Professor in Infectious Diseases, Chair Professor of Infectious Diseases from the Department of Microbiology, Li Ka Shing Faculty of Medicine, and State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong, found that avian influenza A H5N1 and H7N9, and seasonal H3N2 viruses may gain the ability to replicate in mammal and human cells through various adaptation changes in the viral replication enzyme complex called the PB2 subunit. 

They found that H7N9 avian influenza A virus is able to utilize multiple adaptive strategies to replicate in human cells, which may explain why H7N9 is distinct in causing human infections; This study identified a novel adaption marker, PB2-526R among some H7N9 viruses and almost exclusively among all H5N1 human cases from Indonesia.  It has been a puzzle why there is no known PB2 adaptation marker in the H5N1 virus from Indonesia human cases and the finding from HKU nicely explained how this Indonesian subclade of avian H5N1 virus may have adapted for human infections. 

This study also found PB2-526R is able to enhance replication and pathogenicity of other types of PB2 adaptations, such as previously known PB2-627K, in H7N9 and H3N2 viruses.  Since the human pandemic H3N2 virus emerged in 1968, it has gained an additional PB2-526R adaptation marker since 1970s and the PB2-526R-627K virus replicates better than the solely PB2-627K virus.  It is likely that the impression of more severe disease burden caused by H3N2  than that of H1N1 may be partly attributed to the better replication ability of PB2-526R-627K virus. 

These findings by HKU provided new insight for the understanding of cross species transmission and replication in human cells by avian influenza viruses.  The study provides a new genetic marker for the surveillance of avian influenza A virus with potential for human infection.

While this study provides us with a new genetic marker by which to track the evolution of avian flu viruses, it alone is obviously not the only barrier to seeing H7N9, H5N1, or any other novel flu virus become a pandemic. 


But given its sloppy replication habits, and promiscuous `mating habits (reassortment)’, influenza viruses get billions of throws of the genetic dice each and every day.

 

So the odds (and history) suggest that given enough time the `right’ combination will come up, and another novel virus will strike mammalian host gold.  We’ve seen that happen four times in the past century (2009, 1968, 1957, and 1918), and there is no reason to doubt it will happen again.