Dossier Transmission: Animal-to-Human transmission of H7H7 in Holland 2003

The outbreak of highly pathogenic avian influenza A virus subtype H7N7 started at the end of February, 2003, in commercial poultry farms in the Netherlands. In this study, published in The Lancet in 2004, it is noted that an unexpectedly high number of transmissions of avian influenza A virus subtype H7N7 to people directly involved in handling infected poultry, providing evidence for person-to-person transmission.

Although the risk of transmission of these viruses to humans was initially thought to be low, an outbreak investigation was launched to assess the extent of transmission of influenza A virus subtype H7N7 from chickens to humans.

Most H7 cases were detected in the cullers. The attack rate (proportion of persons at risk that developed symptoms) of conjunctivitis was highest in veterinarians, and both cullers and veterinarians had the highest estimated attack rate of confirmed A/H7N7
infections.

453 people had health complaints—349 reported conjunctivitis, 90 had influenza-like illness, and 67 had other complaints. We detected A/H7 in conjunctival samples from 78 (26·4%) people with conjunctivitis only, in five (9·4%) with influenza-like illness and conjunctivitis, in two (5·4%) with influenza-like illness only, and in four (6%) who reported other symptoms. Most positive samples had been collected within 5 days of symptom onset.

A/H7 infection was confirmed in three contacts (of 83 tested), one of whom developed influenza-like illness. In three of these exposed contacts an A/H7N7 infection was confirmed. All three were household contacts.The first contact was the 13-year-old daughter of a poultry worker, who developed conjunctivitis approximately 10 days after onset of symptoms in her father.Six people had influenza A/H3N2 infection. After 19 people had been diagnosed with the infection, all workers received mandatory influenza virus vaccination and prophylactic treatment with oseltamivir. More than half (56%) of A/H7 infections reported here arose before the vaccination and treatment programme.

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Dossier H5N1: Spatial, temporal and genetic dynamics of H5N1 in China

The spatial spread of H5N1 avian influenza, significant ongoing mutations, and long-term persistence of the virus in some geographic regions has had an enormous impact on the poultry industry and presents a serious threat to human health.

This study revealed two different transmission modes of H5N1 viruses in China, and indicated a significant role of poultry in virus dissemination. Furthermore, selective pressure posed by vaccination was found in virus evolution in the country.

Phylogenetic analysis, geospatial techniques, and time series models were applied to investigate the spatiotemporal pattern of H5N1 outbreaks in China and the effect of vaccination on virus evolution.

Results showed obvious spatial and temporal clusters of H5N1 outbreaks on different scales, which may have been associated with poultry and wild-bird transmission modes of H5N1 viruses. Lead–lag relationships were found among poultry and wild-bird outbreaks and human cases. Human cases were preceded by poultry outbreaks, and wild-bird outbreaks were led by human cases.

Each clade has gained its own unique spatiotemporal and genetic dominance. Genetic diversity of the H5N1 virus decreased significantly between 1996 and 2011; presumably under strong selective pressure of vaccination. Mean evolutionary rates of H5N1 virus increased after vaccination was adopted in China.

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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 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: 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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Dossier wild ducks: Role wild ducks introducing LP Avian Influenza on free range farms in Holland

Lelystad, April 2015: According to a recently published study (in Dutch) by the University of Wageningen, wild ducks are are identified as a high risk factor for the introduction of Low Pathogen Avian Influenza viruses in free-range laying hens.

Through a case-control study investigated presumed risk factors for introduction of low-pathogenic avian influenza (LPAI) virus in poultry laying farms free range. Under a LPAI virus was defined in this study: an avian influenza virus of each subtype (H1 H16 tm), with the exception of the highly pathogenic avian influenza (HPAI) viruses.

In order to determine the potential risk factors for infection with LPAI virus, forty Dutch free range poultry farms where the introduction of Low Pathogen Avian Influenza virus has been confirmed in the past (cases) were compared with 81 free range poultry farms where no introduction has taken place (controls). Questions about the presence of potential risk factors through surveys submitted to the poultry farmers.

The analysis of the various factors shows that the risk of introduction of LPAI virus on free range laying farms 3.3 (95% CI: 1.2-9.7) times higher as mallards has identified by the farmer entering the free range area at least once a week, in comparison to free-range laying farms where wild ducks have been identified by the farmer once a month or less.

It seems logical that the regular presence of wild ducks in the free-range increases the risk exposure of the chickens LPAI virus since wild waterfowl are the natural reservoir of avian influenza viruses.

The study also revealed that the risk factor for free range layer farms located on clay is 5.8 (95% CI: 2.2-15.1) times have higher risk of introduction of LPAI virus then free range layer farms on sandy soil or a soil other than clay. The soil on which the free range farm is situated is probably an indirect risk factor (association and not causation): especially in case the farm is located near the coast or close to rivers.

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