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

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.


Dossier H5N1: Spreading patterns global H5N1 outbreaks match bird migration patterns

The global spread of highly pathogenic avian influenza H5N1 in poultry, wild birds and humans, poses a significant pandemic threat and a serious public health risk.

An efficient surveillance and disease control system relies on the understanding of the dispersion patterns and spreading mechanisms of the virus. A space-time cluster analysis of H5N1 outbreaks was used to identify spatio-temporal patterns at a global scale and over an extended period of time.

Potential mechanisms explaining the spread of the H5N1 virus, and the role of wild birds, were analyzed. Between December 2003 and December 2006, three global epidemic phases of H5N1 influenza were identified.

These H5N1 outbreaks showed a clear seasonal pattern, with a high density of outbreaks in winter and early spring (i.e., October to March). In phase I and II only the East Asia Australian flyway was affected. During phase III, the H5N1 viruses started to appear in four other flyways: the Central Asian flyway, the Black Sea Mediterranean flyway, the East Atlantic flyway and the East Africa West Asian flyway.

Six disease cluster patterns along these flyways were found to be associated with the seasonal migration of wild birds. The spread of the H5N1 virus, as demonstrated by the space-time clusters, was associated with the patterns of migration of wild birds. Wild birds may therefore play an important role in the spread of H5N1 over long distances.

Disease clusters were also detected at sites where wild birds are known to overwinter and at times when migratory birds were present. This leads to the suggestion that wild birds may also be involved in spreading the H5N1 virus over short distances.


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.


Dossier H5N1: Different environmental drivers of outbreaks in poultry and wild birds

Different environmental drivers operate on HPAI H5N1 outbreaks in poultry and wild birds in Europe. The probability of HPAI H5N1 outbreaks in poultry increases in areas with a higher human population density and a shorter distance to lakes or wetlands.

This reflects areas where the location of farms or trade areas and habitats for wild birds overlap. In wild birds, HPAI H5N1 outbreaks mostly occurred in areas with increased NDVI and lower elevations, which are typically areas where food and shelter for wild birds are available.

The association with migratory flyways has also been found in the intra-continental spread of the low pathogenic avian influenza virus in North American wild birds. These different environmental drivers suggest that different spread mechanisms operate.

Disease might spread to poultry via both poultry and wild birds, through direct (via other birds) or indirect (e.g. via contaminated environment) infection. Outbreaks in wild birds are mainly caused by transmission via wild birds alone, through sharing foraging areas or shelters. These findings are in contrast with a previous study, which did not find environmental differences between disease outbreaks in poultry and wild birds in Europe.


Dossier Anoxia Method: The sensible culling method for the use on organic farms

Organic poultry farming is the most responsively production system to produce healthy, good quality poultry meat and eggs in an ecologically way. It’s designed to avoid the need for agrochemicals and to minimize damage to the environment and wildlife.

Still, also organic poultry production is not free from the danger becoming infected by contagious diseases, like the current H5N2 outbreak in Canada and the USA.

All currently commercially available depopulation techniques focus on stamping out the virus, in an attempt to stop the spreading, not on maintaining animal welfare standards: methods like macerating birds alive; using CO2 in containers or throughout the entire poultry house; by electrocution; or by occlusion of the trachea with firefighting foam. This makes these techniques irreconcilable with the principle of organic farming, because the culling process with he current methods leave little room for the animal’s welfare rights in the last day of its existence.

Since June 2015, a new sensible culling technique is commercially available that serves both the goal to bring an outbreak to a stop and to maintain a high level of animal welfare during the process of culling for disease control purposes.

The Anoxia method is the most humane method to euthanize animals that are in severe pain or suffer severely seems to be the use of nitrogen gas foam. By this method the animals will be unconscious within a short time through an abundance of nitrogen. The animals die in a short time, without regaining consciousness.

The method of nitrogen gas foam uses a barrel, filled up with a layer of high expansion foam (big bubbles) completely filled with pure nitrogen. The animal will be placed in the foam and covered with a layer of foam of at least 60 centimetres. The animal will breathe 98 per cent nitrogen. The amount of oxygen in the blood diminishes very quickly and the animal will very soon be unconscious. Because of the extreme oxygen deficiency (anoxia) the animal dies within one and a half to two minutes. The animal will not regain consciousness and won’t notice that it dies.

The animal will be unaware that it breathes in pure nitrogen and it will not be harmful or painful for the animal because the normal air an animal breathes consists already of 78 per cent nitrogen. Inhalation of nitrogen is therefore not stressful, whereas for example with high concentrations of carbon dioxide the animal will try not to breathe.

The Anoxia method is not physically demanding on the farmer and his employees. The animals almost instantly lose consciousness after being dipped through the foam. Fixation of the animal to avoid them to hurt themselves during stunning is not needed, as necessary in most other methods. Because of the thick nitrogen foam layer and the amount of 98 per cent nitrogen it is certain that the animal will die. The chance that the method fails and the animal regain consciousness and won’t die, are next to zero.


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.


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.


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.


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.


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.