Dossier H5N8: Dutch outbreak (2014) linked to sequences of strains from Asia

Genetic analysis of influenza A(H5N8) virus from the Netherlands indicates that the virus probably was spread by migratory wild birds from Asia, possibly through overlapping flyways and common breeding sites in Siberia. In addition to the outbreak in the Netherlands, several other outbreaks of HPAI (H5N8) virus infections were reported in Europe at the end of 2014 after exponentially increasing deaths occurred in chicken and turkey flocks.

Genetic sequences submitted to the EpiFlu database indicated that the viruses from Europe showed a strong similarity to viruses isolated earlier in 2014 in South Korea, China, and Japan. An H5N8 virus isolated from a wigeon in Russia in September 2014 is located in the phylogenetic tree near the node of all sequences for H5N8 viruses from Europe.

In regard to time, this location fits the hypothesized route of H5N8 virus introduction into Europe. Furthermore, for several reasons, it is highly likely that the introduction of HPAI (H5N8) virus into the indoor-layer farm in the Netherlands occurred via indirect contact.

First, despite intensive monitoring, H5N8 viruses have never been detected in commercial poultry or wild birds in the Netherlands.

Second, when the virus was detected, the Netherlands had no direct trade contact with other European countries or Asia that might explain a route of introduction.

Third, because of the severity of disease in galliforms, outbreaks of H5N8 in the Netherlands before November 2014 would have been noticed.

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Dossier AI transmission: Wind-Mediated Spread of Avian Influenza Viruses

Avian influenza virus-infected poultry can release a large amount of virus-contaminated droppings that serve as sources of infection for susceptible birds. Much research so far has focused on virus spread within flocks. However, as fecal material or manure is a major constituent of airborne poultry dust, virus-contaminated particulate matter from infected flocks may be dispersed into the environment.

This study, demonstrates the presence of airborne influenza virus RNA downwind from buildings holding LPAI-infected birds, and the observed correlation between field data on airborne poultry and livestock associated microbial exposure and the OPS-ST model. These findings suggest that geographical estimates of areas at high risk for human and animal exposure to airborne influenza virus can be modeled during an outbreak, although additional field measurements are needed to validate this proposition. In addition, the outdoor detection of influenza virus contaminated airborne dust during outbreaks in poultry suggests that practical measures can assist in the control of future influenza outbreaks.

In general, exposure to airborne influenza virus on commercial poultry farms could be reduced both by minimizing the initial generation of airborne particles and implementing methods for abatement of particles once generated. As an example, emergency mass culling of poultry using a foam blanket over the birds instead of labor-intensive whole-house gassing followed by ventilation reduces both exposure of cullers and dispersion of contaminated dust into the environment, contributing to the control of influenza outbreaks.

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Dossier AI Transmission: Biosecurity and transmission through contact structure between farms

Contacts between people, equipment and vehicles prior and during outbreak situations are critical to determine the possible source of infection of a farm. Hired laborers are known to play a big role in interconnecting farms. Once a farm is infected, culling entire flock is the only option to prevent further spreading with devastating consequences for the industry.

In this paper, based on the HPAI outbreak in Holland 2003, the researchers found that 32 farms hired external labor of which seven accessed other poultry on the same day.

However, they were not the only ‘connectors’ as some (twelve) farmers also reported themselves helping on other poultry farms. Furthermore, 27 farms had family members visiting poultry or poultry-related businesses of which nine entered poultry houses during those visits. The other enhancing factor of farm interconnections was the reported ownership of multiple locations for ten of the interviewed farms and the reported on-premises sale of farm products on one pullet and eight layer farms. Also worth mentioning is the practice of a multiple age system reported on eight of the interviewed farms as this may increase the risk of infecting remaining birds when off-premises poultry movements occur.

AI viruses may be introduced into poultry from reservoirs such as aquatic wild birds but the mechanisms of their subsequent spread are partially unclear. Transmission of the virus through movements of humans (visitors, servicemen and farm personnel), vectors (wild birds, rodents, insects), air- (and dust-) related routes and other fomites (e.g., delivery trucks, visitors’ clothes and farm equipment) have all been hypothesized.

It is therefore hypothesized that the risk of introducing the virus to a farm is determined by the farm’s neighborhood characteristics, contact structure and its biosecurity practices. On the one hand, neighborhood characteristics include factors such as the presence of water bodies (accessed by wild birds), the density of poultry farms (together with the number and type of birds on these farms) and poultry-related businesses and the road network. The use of manure in the farm’s vicinity is also deemed to be risky.

On the other hand, contact structure risk factors include the nature and frequency of farm visits. Therefore, a detailed analysis of the contact structure, including neighborhood risks, and biosecurity practices across different types of poultry farms and poultry-related businesses helps the improvement of intervention strategies, biosecurity protocols and adherence to these, as well as contact tracing protocols. Farmers’ perception of visitor- and neighborhood-associated risks of virus spread is also important due to its relevance to adherence with biosecurity protocols, to contact tracing and to communicating advice to them.

The between-farm virus transmission risks may be split into two categories:

1. Introduction
2. Onward-spread risks

The former entail the target farm’s exposure through incoming contacts (human and fomite), through inputs such as feed and egg trays and through neighborhood-related risks such as air-borne contamination. The latter can be through farm outputs (waste and non-waste), outgoing contacts (human and fomite) and contamination of the neighborhood (e.g., through emissions from the farm). Therefore, all day-to-day farm activities involving people and/or materials and/or equipment going in or out of the farm were systematically analyzed.

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Dossier Transmission: Potential transmission H7N9 between humans (Ro) ranges from 0,06 to 0,35

A new study suggests there have been multiple clusters of human-to-human transmission in recent outbreaks of the bird flu strain H7N9. There were around 400 human cases of H7N9 influenza and 177 deaths in 2013 and 2014, all of them in China. Most patients are believed to have caught the infection from close contact with birds, but the virus’s ability to spread between humans has been uncertain.

In a study published in Emerging Infectious Diseases, scientists from Imperial College London studied data from these outbreaks and used statistical methods to estimate how transmissible the virus is. The results suggest that around 70 cases were caused by an infection spread between people. However, the virus cannot spread easily enough in humans to cause sustained transmission at the level required for a pandemic.

The number of people one infected person will pass on the infection to, on average, is called the basic reproductive number. If the value is less than one, an outbreak would be expected to die out; while a value greater than one suggests an outbreak would grow.
“This study shows that H7N9 is currently short of the critical level of transmissibility required to cause a pandemic”, according to Dr Steven Riley of the MRC Centre for Outbreak Analysis and Modelling.

In the outbreaks studied, the reproductive number ranged from 0.06 to 0.35
. This means that once the virus infects a person, there is only a small risk of that person passing it to someone else. The researchers warned that H7N9 poses a continuing threat, and authorities must be vigilant in case the virus becomes more transmissible. Dr Steven Riley, senior author of the study, from the Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial, said: “This study shows that H7N9 is currently short of the critical level of transmissibility required to cause a pandemic. But even if the reproductive number is less than one, clusters of human transmission can occur. “In Zhejiang, the reproductive number increased between the first wave in 2013 and the second wave in 2014. We have to keep an eye on further outbreaks to see how the virus is evolving.”

The study also looked at the effectiveness of closing live bird markets, which are thought to be the main source of infections for humans. Closing the markets for short periods had little effect on the risk, but longer closures appeared to be more effective.

Dr Adam Kucharski, who worked on the study at Imperial before moving to the London School of Hygiene & Tropical Medicine, said: “Our findings suggest that prompt market closures for a sustained period can substantially reduce the number of infections.” The study was funded by the Wellcome Trust, the Medical Research Council, the National Institute of General Medical Sciences, the EU Seventh Framework Programme, the Fogarty International Center and the Research and Policy for Infectious Disease Dynamics programme.

Reference: Kucharski AJ, Mills HL, Donnelly CA, Riley S. Transmission potential of influenza A(H7N9) virus, China, 2013–2014. Emerg Infect Dis. 2015 May. http://dx.doi.org/10.3201/eid2105.141137

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Dossier AI transmission: After 5 month, transmission routes still unknown

By David Pitt, Associated Press: May 4,2015: Scientist work to answer questions about puzzling bird flu virus. It’s been five months since the H5N2 bird flu virus was discovered in the United States, and producers have lost 21 million birds in the Midwest alone. Yet researchers acknowledge they still know little about a bird flu virus that’s endangered turkey and egg-laying chicken populations that supply much of the nation.

Scientists at the U.S. Department of Agriculture, the Centers for Disease Control and Prevention and other federal agencies are puzzled by the H5N2 virus’s spread — even amid heightened biosecurity measures — and apparent lack of widespread deaths in largely unprotected backyard flocks. “At this point, we don’t know very much about these viruses because they’ve only recently been identified,” Dr. Alicia Fry, the CDC’s leader of the influenza prevention and control team, said. “We’re following the situation very closely because this is something we’re continuing to understand.”

The current H5N2 virus surfaced last winter in Canada and was first identified in the United States in early December, when it was found in a wild bird on the West Coast. This spring, the virus was found in poultry operations in eight Midwest states, forcing commercial producers to kill and compost millions of turkeys and chickens in Iowa, Minnesota and elsewhere.

Scientists speculate that perhaps rodents or small birds, seeking food, tracked the virus into barns. Maybe it’s the work of flies, as the bird flu virus has been found on the insects in a Pennsylvania outbreak in 1983 and in Japan in 2004. The USDA’s chief veterinarian even has floated the idea that wind may be blowing dust and feathers carrying the virus from the barnyard into buildings through air vents. “To me, the main concern is the disease is moving even with heightened biosecurity,” said Richard French, a professor of animal health at Becker College in Worcester, Massachusetts. “Ideally we’ve got to try and figure out the way it’s most likely moving and try to put controls in place to stop that.”

Poultry farms’ biosecurity measures include changing clothes and boots before entering barns, disinfecting equipment and vehicles before they approach barns, and assigning workers to specific barns. As new operations are infected almost daily, USDA epidemiologists also are trying to determine whether the virus came from a wild bird or could have spread from poultry in another barn or a nearby farm.
“We are continuing to evaluate how facilities become positive because we also want to be cognizant of any potential risk of lateral spread from farm to farm,” said Dr. T.J. Myers, the USDA associate deputy administrator of veterinary services. “We are doing those evaluations as we speak, and we really don’t have enough data to report on that yet.”

Another puzzling question has been why there hasn’t been a surge in infections of backyard flocks. The USDA has identified 12 cases including five in Washington in January and February, plus others in Idaho, Kansas, Minnesota, Montana, Oregon and Wisconsin.
Cases might not be reported, French said, noting that commercial operations have a financial incentive to immediately report illnesses because the government pays them for each live bird that must be destroyed. Plus, French said, outdoor chickens could have been exposed over time to low pathogenic versions of bird flu and have developed stronger immunity.

One belief held by researchers will soon be tested: whether the virus will die as temperatures warm and ultraviolet light increases. With temperatures this week in the 70s in many of the affected states and even warmer weather expected soon, infections should decline if that assumption is true.

But David Swayne, director of the Southeast Poultry Research Laboratory in Athens, Georgia, acknowledged it’s hard to predict what will happen. “It’s pretty complex. It involves the climate, the temperature itself, the amount of humidity there,” he said.
Scientists expect the virus to return in the fall along with cooler temperatures and wild birds migrating south, but Swayne says the virus could burn itself out and disappear for a while before that.

Amid all the questions is one about the human element: Could the virus spread to people? So far, it hasn’t, but significant efforts are underway to develop a vaccine just in case. “We’re cautiously optimistic that we will not see any human cases, but there certainly is a possibility that we may,” Fry said.

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Dossier AI Transmission: Per-Contact Probability of Infection by Highly Pathogenic Avian Influenza

Estimates of the per-contact probability of transmission between farms of Highly Pathogenic Avian Influenza virus of H7N7 subtype during the 2003 epidemic in the Netherlands are important for the design of better control and biosecurity strategies.

We used standardized data collected during the epidemic and a model to extract data for untraced contacts based on the daily number of infectious farms within a given distance of a susceptible farm.
With these data, the ‘maximum likelihood estimation’ approach was used to estimate the transmission probabilities by the individual contact types, both traced and untraced.

The outcomes were validated against literature data on virus genetic sequences for outbreak farms. The findings highlight the need to

1) Understand the routes underlying the infections without traced contacts and
2) To review whether the contact-tracing protocol is exhaustive in relation to all the farm’s day-to-day activities and practices.

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Dossier AI Transmission: Supplementary information wind-mediated transmission HPAI

A comparison between the transmission risk pattern predicted by the model and the pattern observed during the 2003 epidemic reveals that the wind-borne route alone is insufficient to explain the observations although it could contribute substantially to the spread over short distance ranges, for example, explaining 24% of the transmission over distances up to 25 km.

In this generic overview, you will find the date used in the publication “Modelling the Wind-Borne Spread of Highly Pathogenic Avian Influenza Virus between Farms”, published February 2012 (see also http://n2gf.com/?p=2377). For the outbreak of avian influenza A(H7N7) in the Netherlands in 2003, much data are available. The overview gives a description of the data used in the analyses of the mentioned publication:

Epidemiological data

There were 5360 poultry farms in the Netherlands in 2003, for all of which geographical information x is available. For 1531 farms the flocks were culled, for all of these the date of culling Tcull is known. For 227 of the 241 infected farms the date of infection tinf has been estimated, based on mortality data. The remaining 14 farms are hobby farms, defined as farms with less than 300 animals, for which no mortality data are available.

The geographic and temporal data together have previously been used to estimate the critical farm density, i.e. above what density of farms outbreaks are can occur.

Genetic data
The HA, NA and PB2 genes of viral samples from 231 farms have previously been sequenced. Sequence data RNA can be found in the GISAID database under accession numbers EPI ISL 68268-68352, EPI ISL 82373-82472 and EPI ISL 83984-84031. These data have previously been used to give general characteristics of the outbreak, to reconstruct the transmission tree and to assess the public health threat due to mutations of the virus in the animal host.

Meteorological data

Available meteorological data include wind speed wv and direction wdir (with a ten degree precision) and the fraction of time r without precipitation for every hour of every day of the outbreak, measured at five weather stations close to the infected farms. These data are available from the Royal Dutch Meteorological Institute at www.knmi.nl.

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Dossier AI Transmission: Modelling the Wind-Borne Spread of Highly Pathogenic Avian Influenza Virus between Farms

The mechanisms of HPAI virus spread between farms are poorly understood; it has been hypothesized that the indirect between-farm contacts play a role [9,14–17].

The frequency and the transmission effectiveness of these contacts determine their virus transmission rates. Here we perform a quantitative assessment of the contribution of indirect contacts to the spread of the virus between farms during the 2003 HPAI epidemic in the Netherlands.

During this epidemic, potentially infectious contacts to both infected and escaping farms were traced. In this paper, the collected data is used to quantify the per-contact probability of virus transmission between farms.

A quantitative understanding of the spread of contaminated farm dust between locations is a prerequisite for obtaining much-needed insight into one of the possible mechanisms of disease spread between farms.

A model was developed to calculate the quantity of contaminated farm-dust particles deposited at various locations downwind of a source farm and apply the model to assess the possible contribution of the wind-borne route to the transmission of Highly Pathogenic Avian Influenza virus (HPAI) during the 2003 epidemic in the Netherlands.

The model is obtained from a Gaussian Plume Model by incorporating the dust deposition process, pathogen decay, and a model for the infection process on exposed farms. Using poultry- and avian influenza-specific parameter values we calculate the distance-dependent probability of between-farm transmission by this route.

A comparison between the transmission risk pattern predicted by the model and the pattern observed during the 2003 epidemic reveals that the wind-borne route alone is insufficient to explain the observations although it could contribute substantially to the spread over short distance ranges, for example, explaining 24% of the transmission over distances up to 25 km.

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Dossier AI Transmission: Public statements about infectiousness H5N2 is only half the story

The risk that a highly infectious strain of avian flu virus named H5N2 will infect humans is “low at this time,” CDC officer Alicia Fry said during a press conference on April 22, 2015. The virus, which infects turkeys and chickens, is different from previous flu strains that have been able to infect humans, she said. So far, it has “not caused infections in humans anywhere in the world.”

Yes, she is absolutely correct: at this moment, H5N2 doesn’t pose a threat to human health. The general public doesn’t have to fear that the Spanish flu will repeat itself, and that is probably the reason CDC organized this press conference, so the public can go on with their life as if nothing has happened. But the risk of human infection is only half of the story: H5N2 is like EBOLA to poultry, especially to turkeys. Therefore the public should be careful when they enter wildlife areas, and farmers should mistrust each and every visitor to their farm, because the public is not aware of these risks. And this unawareness of the public poses an absolute risk for the poultry industry. To demonstrate this, I would like to share the story how in 2003 Belgium farms most likely got infected during the European outbreak of H7N7:

The news media was trying to cover an outbreak of AI in Holland, and in order to get a better view on what was happening on the farm, the film crew went (without protective clothing) over the barrier, on to the farmland, close to the barn. Halfway they’re filming, the local police, who spotted the film crew in the possible infected field, stopped them and ordered them to leave the area immediately. Because they had to deliver their material before a specific deadline, they crossed the nearby border between Holland and Belgium, and finished their film on a similar looking farm, 40 km into Belgium, were there were no outbreaks of AI at that time. They managed to end their reportage in time for the 8 O’clock, but with the result that soon after that, the first outbreak occurred in Belgium at the farm where the crew had finished their reportage. Later on, in search of what caused the virus to jump from Holland to Belgium, this event was mentioned as the most likely route.

The moral of this story is that the message that H5N2 poses little risk on human infections, but that the infection risks for poultry are extremely high: avoid the risk of spreading contaminated materials to farm areas!

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Dossier AI Transmission: Evidence that link outbreaks in Eurasia, China, South Korea, USA and Canada

In a new study published in the Journal Virology on March 31, 2015, scientists from the U.S. Geological Survey and U.S. Fish and Wildlife Service harnessed a new type of DNA technology to investigate avian influenza viruses in Alaska. Using a “next generation” sequencing approach, which identifies gene sequences of interest more rapidly and more completely than by traditional techniques, scientists identified low pathogenic avian influenza viruses in Alaska that are nearly identical to viruses found in China and South Korea. This publication provides even more evidence of this intercontinental avian influenza exchange program.
The viruses were found in an area of western Alaska that is known to be a hot spot for both American and Eurasian forms of avian influenza. “Our past research in western Alaska has shown that 70 percent of avian influenza viruses isolated in this area were found to contain genetic material from Eurasia, providing evidence for high levels of intercontinental viral exchange,” said Andy Ramey, a scientist with the USGS Alaska Science Center and lead author of the study. “This is because Asian and North American migratory flyways overlap in western Alaska.”

In this study, led by the USGS, low pathogenic H9N2 viruses were found in an Emperor Goose and a Northern Pintail. Both of the H9N2 viruses were nearly identical genetically to viruses found in wild bird samples from Lake Dongting, China and Cheon-su Bay, South Korea.
“These H9N2 viruses are low pathogenic and not known to infect humans, but similar viruses have been implicated in disease outbreaks in domestic poultry in Asia,” said Ramey. “There is no commercial poultry production in western Alaska and highly similar H9N2 virus strains have not been reported in poultry in East Asia or North America, so it is unlikely that agricultural imports influenced this result.”
The finding provides evidence for intercontinental movement of intact avian influenza viruses by migratory birds. The USGS recently released a publication about the detection of a novel highly pathogenic H5N8 virus in the U.S. that is highly similar to the Eurasian H5N8 viruses. This suggests that the novel re-assortment may be adapted to certain waterfowl species, enabling it to survive long migrations. That virus, and associated strains, has now spread from early detections in wild and domestic birds in Pacific states to poultry outbreaks in Minnesota, Missouri and Arkansas.

“The frequency of inter-hemispheric dispersal events of avian influenza viruses by migratory birds may be higher than previously recognized,” said Ramey. While some of the samples for the project came from bird fecal samples collected from beaches at Izembek National Wildlife Refuge, most of the samples came from sport hunters.

“For the past several years, we’ve worked closely with sport hunters in the fall to obtain swab samples from birds and that has really informed our understanding of wildlife disease in this area,” said Bruce Casler, formerly a biologist with the USFWS Izembek National Wildlife Refuge and a co-author of the study.

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