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.
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. 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.
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.
AI transmission risks: Analysis of biosecurity measures and contact structureHarm Kiezebrink
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.
Spatial, temporal and genetic dynamics of H5N1 in chinaHarm Kiezebrink
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.
Per contact probability of infection by Highly Pathogenic Avian InfluenzaHarm Kiezebrink
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.
H5N8 virus dutch outbreak (2014) linked to sequences of strains from asiaHarm Kiezebrink
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.
Outbreak of High Patogen Avian Influenza H5N8 in GermanyHarm Kiezebrink
Germany has reported an outbreak of highly pathogenic avian influenza, H5N8 in fattening turkeys in North East Germany
(Mecklenburg - Western Pomerania). Increased mortality was observed in one of the six sheds of 15 week old birds for fattening (total number of turkeys on the premises ~ 31,000 of which each shed contained 5,000).
The 3 P’s of avian influenza Prevent, Plan, PracticeHarm Kiezebrink
Avian Influenza has become endemic in many parts of the word. In it's current form it has been around since 1997 and although thy virus types have changed, emergency response, management & control are still a hot issue. In this article published in 2006 in the US magazine Poultry Perspectives, the subject what to do during crisis situations is presented. The conclusions are still valid today and may help to prevent large-scale outbreaks
Dossier transmission: Transmission of Avian Influenza Virus to DogsHarm Kiezebrink
Avian influenza was found in a dog on a farm in South Gyeongsang Province amid growing concerns that the disease could spread to other animals, officials the Ministry of Agriculture, Food and Rural Affairs said. The dog ― one of three at a duck farm in Goseong-gun, South Gyeongsang Province ― had antigens for the highly pathogenic H5N8 strain of bird flu, the Ministry of Agriculture, Food and Rural Affairs said. The disease affected the farm on Jan. 23.
Since the first case of a dog being infected with the poultry virus in March 2014, there have been 55 dogs found with antibodies to the bird flu virus. The antibody means the immune system of the dogs eliminated the virus. This is the first time bird flu has been found in a dog in Korea through the detection of antigens.
“None of these dogs had shown symptoms. No antigens or antibodies for the virus were found in the two other dogs, which means that dog-to-dog transmission is unlikely to have happened,” quarantine officials said.
The ministry suspected that the dog may have eaten infected animals at the farm. All poultry and dogs at the concerned farm were slaughtered as part of the preventive measures right after the farm was reported to have been infected with the disease, officials said.
Meanwhile, quarantine officials rejected the possibility of viral transmission to humans. According to the ministry’s report, about 450 workers at infected farms across the country had been given an antigen test, with none showing signs of infection. None of Korea’s 20,000 farm workers have reported any symptoms so far, officials added.
“It is thought that infected dogs do not show symptoms of the disease as they are naturally resistant to bird flu,” the ministry said. Meanwhile, the Agriculture Ministry has toughened the quarantine measures in Goseong-gun. The region is a frequented by migratory birds, which are suspected to have spread the viral disease.
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.
AI transmission risks: Analysis of biosecurity measures and contact structureHarm Kiezebrink
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.
Spatial, temporal and genetic dynamics of H5N1 in chinaHarm Kiezebrink
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.
Per contact probability of infection by Highly Pathogenic Avian InfluenzaHarm Kiezebrink
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.
H5N8 virus dutch outbreak (2014) linked to sequences of strains from asiaHarm Kiezebrink
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.
Outbreak of High Patogen Avian Influenza H5N8 in GermanyHarm Kiezebrink
Germany has reported an outbreak of highly pathogenic avian influenza, H5N8 in fattening turkeys in North East Germany
(Mecklenburg - Western Pomerania). Increased mortality was observed in one of the six sheds of 15 week old birds for fattening (total number of turkeys on the premises ~ 31,000 of which each shed contained 5,000).
The 3 P’s of avian influenza Prevent, Plan, PracticeHarm Kiezebrink
Avian Influenza has become endemic in many parts of the word. In it's current form it has been around since 1997 and although thy virus types have changed, emergency response, management & control are still a hot issue. In this article published in 2006 in the US magazine Poultry Perspectives, the subject what to do during crisis situations is presented. The conclusions are still valid today and may help to prevent large-scale outbreaks
Dossier transmission: Transmission of Avian Influenza Virus to DogsHarm Kiezebrink
Avian influenza was found in a dog on a farm in South Gyeongsang Province amid growing concerns that the disease could spread to other animals, officials the Ministry of Agriculture, Food and Rural Affairs said. The dog ― one of three at a duck farm in Goseong-gun, South Gyeongsang Province ― had antigens for the highly pathogenic H5N8 strain of bird flu, the Ministry of Agriculture, Food and Rural Affairs said. The disease affected the farm on Jan. 23.
Since the first case of a dog being infected with the poultry virus in March 2014, there have been 55 dogs found with antibodies to the bird flu virus. The antibody means the immune system of the dogs eliminated the virus. This is the first time bird flu has been found in a dog in Korea through the detection of antigens.
“None of these dogs had shown symptoms. No antigens or antibodies for the virus were found in the two other dogs, which means that dog-to-dog transmission is unlikely to have happened,” quarantine officials said.
The ministry suspected that the dog may have eaten infected animals at the farm. All poultry and dogs at the concerned farm were slaughtered as part of the preventive measures right after the farm was reported to have been infected with the disease, officials said.
Meanwhile, quarantine officials rejected the possibility of viral transmission to humans. According to the ministry’s report, about 450 workers at infected farms across the country had been given an antigen test, with none showing signs of infection. None of Korea’s 20,000 farm workers have reported any symptoms so far, officials added.
“It is thought that infected dogs do not show symptoms of the disease as they are naturally resistant to bird flu,” the ministry said. Meanwhile, the Agriculture Ministry has toughened the quarantine measures in Goseong-gun. The region is a frequented by migratory birds, which are suspected to have spread the viral disease.
In this paper various bird welfare aspects related to avian influenza and other contagious diseases are discussed.
Disease outbreaks will, apart from the obvious direct effects on bird health, and thereby their wellbeing, also indirectly influence the welfare of the birds. For example, restrictions on outdoor access for free-range poultry may be imposed, and vaccination or testing schemes may lead to handling or sampling procedures that are stressful to the birds.
At the same time, the immediate risk of a disease outbreak may lead to improved biosecurity measures on farms, which may in turn decrease the risk of other diseases entering the premises, thus resulting in improved bird health and welfare.
Different environmental drivers of H5N1 outbreaks in poultry and wild birdsHarm Kiezebrink
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.
Deadly H5N1 birdflu needs just five mutations to spread easily in peopleHarm Kiezebrink
Reference: Phys.org. 15 Apr 2014. Dutch researchers have found that the virus needs only five favorable gene mutations to become transmissible through coughing or sneezing, like regular flu viruses.
World health officials have long feared that the H5N1 virus will someday evolve a knack for airborne transmission, setting off a devastating pandemic. While the new study suggests the mutations needed are relatively few, it remains unclear whether they're likely to happen outside the laboratory.
Supplementary information wind mediated transmission HPAIHarm Kiezebrink
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 (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.
Modelling wind-borne spread of HPAI between farms (2012)Harm Kiezebrink
To understand the risks of spreading contaminated materials caused by stable gassing, 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.
The researchers Amos Ssematimba, Thomas J. Hagenaars, Mart C. M. de Jong of the Dutch Department of Epidemiology, Crisis Organization and Diagnostics, Central Veterinary Institute (CVI) part of Wageningen University and Research Centre, Lelystad, The Netherlands, and Quantitative Veterinary Epidemiology, Department of Animal Sciences, Wageningen University, Wageningen, The Netherland developed a model 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.
Spatio temporal dynamics of global H5N1 outbreaks match bird migration patternsHarm Kiezebrink
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.
Influenza in birds is caused by infection with viruses of the family Orthomyxoviridae placed in the genus influenza virus A. Influenza A viruses are the only orthomyxoviruses known to naturally affect birds. Many species of birds have been shown to be susceptible to infection with influenza A viruses; aquatic birds form a major reservoir of these viruses, and the overwhelming majority of isolates have been of low pathogenicity (low virulence) for chickens and turkeys. Influenza A viruses have antigenically related nucleocapsid and matrix proteins, but are classified into subtypes on the basis of their haemagglutinin (H) and neuraminidase (N) antigens (World Health Organization Expert Committee, 1980). At present, 16 H subtypes (H1–H16) and 9 N subtypes (N1–N9) are recognised with proposed new subtypes (H17, H18) for influenza A viruses from bats in Guatemala (Swayne et al., 2013; Tong et al., 2012; 2013). To date, naturally occurring highly pathogenic influenza A viruses that produce acute clinical disease in chickens, turkeys and other birds of economic importance have been associated only with the H5 and H7 subtypes. Most viruses of the H5 and H7 subtype isolated from birds have been of low pathogenicity for poultry. As there is the risk of a H5 or H7 virus of low pathogenicity (H5/H7 low pathogenicity avian influenza [LPAI]) becoming highly pathogenic by mutation, all H5/H7 LPAI viruses from poultry are notifiable to OIE. In addition, all high pathogenicity viruses from poultry and other birds, including wild birds, are notifiable to the OIE.
Overview of recent outbreaks of H5N8-High Pathogen Avian Influenza in Europe...Harm Kiezebrink
Updated outbreak assessment on Highly Pathogenic Avian Influenza: Europe, America and the Middle East. By the DEFRA, Veterinary & Science Policy Advice Team - International Disease Monitoring.
In 2007, USAID launched a worldwide program to battle outbreaks of Avian Influenza under the name STOP AI: Stamping Out Pandemic & Avian Influenza.
This program was one of the largest Training of trainer programs on Avian Influenza of its kind, with training programs conducted in more than 40 countries.
The training manual contains valuable training materials, presentations, background information and references on various subjects:
Module 1 – Overview of Avian Influenza
Module 2 – National Preparedness & Response Plans for HPAI
Module 3 – OIE Avian Influenza Standards and FAO Emergency Prevention System
Module 4 – Public Health and Occupational Safety
Module 5 – Animal Surveillance
Module 6 – Sample Collection and Transport
Module 7 – GIS and Outbreak Mapping
Module 8 – Biosecurity
Module 9 – Introduction to Outbreak Response
Module 10 – Depopulation, Disposal, and Decontamination
Module 11 – Recovery Options.
This training course was intended for animal and human health experts who have limited experience with avian influenza, but who do have field experience with other animal, zoonotic, or infectious diseases. This course includes modules on avian influenza virology, epidemiology, response, and recovery.
Avian influenza is usually an inapparent or nonclinical
viral infection of wild birds that is caused by a group of
viruses known as type A influenzas. These viruses are maintained in wild birds by fecal-oral routes of transmission. This virus changes rapidly in nature by mixing of its genetic components to form slightly different virus subtypes. Avian influenza is caused by this collection of slightly different viruses rather than by a single virus type. The virus subtypes are identified and classified on the basis of two broad types of antigens, hemagglutinan (H) and neuraminidase (N); 15 H and 9 N antigens have been identified among all of the known type A influenzas.
FLI Seminar on different response strategies: Stamping out or NeutralizationHarm Kiezebrink
During this spring, American poultry producers are losing birds by the millions, due to the High Pathogenic Avian Influenza outbreaks on factory farms. USDA APHIS applied the stamping out strategy in an attempt to prevent the flu from spreading.
With stamping out as the highest priority of the response strategy, large numbers of responders are involved. With in average almost 1 million caged layers per farm in Iowa, there is hardly any room for a proper bio security training for these responders. And existing culling techniques had insufficient capacity, the authorities had to decide to apply drastic techniques like macerating live birds in order to take away the source of virus reproduction.
This strategy didn't work; on the contrary. Instead of slowing down the spreading of the virus, the outbreaks continue to reoccur and have caused death and destruction in 15 USA states, killing almost 50 million birds on mote than 220infected commercial poultry farms, all within a very small time frame.
The question is whether the priority of the response strategy should be on neutralizing the transmission routes instead of on stamping out infections after they occur. All indicators currently point out into the direction that the industry should prioritize on environmental drivers: the connection between outbreaks and wild ducks; wind-mediated transmission; pre-contact probability; on-farm bio security; transmission via rodents etc.
Once the contribution of each transmission route has been determined, a revolutionary new response strategy can be developed based on the principle of neutralizing transmission routes. Neutralizing risks means that fully new techniques need to be developed, based on culling the animals without human – to – animal contact; integrating detergent application into the culling operations; combining culling & disposal into one activity.
This new response strategy will be the main subject of the FLI Animal Welfare and Disease Control Seminar, organized at September 23, 2015 in Celle, Germany
Twenty-two researchers from labs across the world submitted a letter to Nature and Science yesterday detailing their proposed “gain-of-function” research on the avian influenza virus H7N9.
Their work would genetically engineer H7N9 to make it both more virulent and more readily transmissible person-to-person. The research sounds controversial, not the least because one of the scientists involved is Dr. Ron Fouchier, whose on gain-of-function work on H5N1 ingnited furious debate over what should research should and shouldn’t be published.
However, there is a very real possibility that H7N9 will naturally mutate to transmit effectively between people. We already know that the virus is just a single amino acid mutation away from becoming easily transmissible between people. Indeed, news of the first confirmed case of such transmission was published in the British Medical Journal this week.
With a 60% fatality rate and a completely naive global population, the results would be catastrophic. The proposed research would give us an idea of potential pandemic scenarios, giving us a head start on potential vaccine and antiviral development.
It may be controversial, but it’s absolutely necessary.
Influenza a emergency prepardness for healthcare facilitiesMoustapha Ramadan
The data presented are per 4th of March 2017 and subject to changes.
The presentation aims to provide the basic infection control requirement for healthcare facilities during large influenza epidemic or pandemic
In this paper various bird welfare aspects related to avian influenza and other contagious diseases are discussed.
Disease outbreaks will, apart from the obvious direct effects on bird health, and thereby their wellbeing, also indirectly influence the welfare of the birds. For example, restrictions on outdoor access for free-range poultry may be imposed, and vaccination or testing schemes may lead to handling or sampling procedures that are stressful to the birds.
At the same time, the immediate risk of a disease outbreak may lead to improved biosecurity measures on farms, which may in turn decrease the risk of other diseases entering the premises, thus resulting in improved bird health and welfare.
Different environmental drivers of H5N1 outbreaks in poultry and wild birdsHarm Kiezebrink
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.
Deadly H5N1 birdflu needs just five mutations to spread easily in peopleHarm Kiezebrink
Reference: Phys.org. 15 Apr 2014. Dutch researchers have found that the virus needs only five favorable gene mutations to become transmissible through coughing or sneezing, like regular flu viruses.
World health officials have long feared that the H5N1 virus will someday evolve a knack for airborne transmission, setting off a devastating pandemic. While the new study suggests the mutations needed are relatively few, it remains unclear whether they're likely to happen outside the laboratory.
Supplementary information wind mediated transmission HPAIHarm Kiezebrink
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 (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.
Modelling wind-borne spread of HPAI between farms (2012)Harm Kiezebrink
To understand the risks of spreading contaminated materials caused by stable gassing, 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.
The researchers Amos Ssematimba, Thomas J. Hagenaars, Mart C. M. de Jong of the Dutch Department of Epidemiology, Crisis Organization and Diagnostics, Central Veterinary Institute (CVI) part of Wageningen University and Research Centre, Lelystad, The Netherlands, and Quantitative Veterinary Epidemiology, Department of Animal Sciences, Wageningen University, Wageningen, The Netherland developed a model 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.
Spatio temporal dynamics of global H5N1 outbreaks match bird migration patternsHarm Kiezebrink
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.
Influenza in birds is caused by infection with viruses of the family Orthomyxoviridae placed in the genus influenza virus A. Influenza A viruses are the only orthomyxoviruses known to naturally affect birds. Many species of birds have been shown to be susceptible to infection with influenza A viruses; aquatic birds form a major reservoir of these viruses, and the overwhelming majority of isolates have been of low pathogenicity (low virulence) for chickens and turkeys. Influenza A viruses have antigenically related nucleocapsid and matrix proteins, but are classified into subtypes on the basis of their haemagglutinin (H) and neuraminidase (N) antigens (World Health Organization Expert Committee, 1980). At present, 16 H subtypes (H1–H16) and 9 N subtypes (N1–N9) are recognised with proposed new subtypes (H17, H18) for influenza A viruses from bats in Guatemala (Swayne et al., 2013; Tong et al., 2012; 2013). To date, naturally occurring highly pathogenic influenza A viruses that produce acute clinical disease in chickens, turkeys and other birds of economic importance have been associated only with the H5 and H7 subtypes. Most viruses of the H5 and H7 subtype isolated from birds have been of low pathogenicity for poultry. As there is the risk of a H5 or H7 virus of low pathogenicity (H5/H7 low pathogenicity avian influenza [LPAI]) becoming highly pathogenic by mutation, all H5/H7 LPAI viruses from poultry are notifiable to OIE. In addition, all high pathogenicity viruses from poultry and other birds, including wild birds, are notifiable to the OIE.
Overview of recent outbreaks of H5N8-High Pathogen Avian Influenza in Europe...Harm Kiezebrink
Updated outbreak assessment on Highly Pathogenic Avian Influenza: Europe, America and the Middle East. By the DEFRA, Veterinary & Science Policy Advice Team - International Disease Monitoring.
In 2007, USAID launched a worldwide program to battle outbreaks of Avian Influenza under the name STOP AI: Stamping Out Pandemic & Avian Influenza.
This program was one of the largest Training of trainer programs on Avian Influenza of its kind, with training programs conducted in more than 40 countries.
The training manual contains valuable training materials, presentations, background information and references on various subjects:
Module 1 – Overview of Avian Influenza
Module 2 – National Preparedness & Response Plans for HPAI
Module 3 – OIE Avian Influenza Standards and FAO Emergency Prevention System
Module 4 – Public Health and Occupational Safety
Module 5 – Animal Surveillance
Module 6 – Sample Collection and Transport
Module 7 – GIS and Outbreak Mapping
Module 8 – Biosecurity
Module 9 – Introduction to Outbreak Response
Module 10 – Depopulation, Disposal, and Decontamination
Module 11 – Recovery Options.
This training course was intended for animal and human health experts who have limited experience with avian influenza, but who do have field experience with other animal, zoonotic, or infectious diseases. This course includes modules on avian influenza virology, epidemiology, response, and recovery.
Avian influenza is usually an inapparent or nonclinical
viral infection of wild birds that is caused by a group of
viruses known as type A influenzas. These viruses are maintained in wild birds by fecal-oral routes of transmission. This virus changes rapidly in nature by mixing of its genetic components to form slightly different virus subtypes. Avian influenza is caused by this collection of slightly different viruses rather than by a single virus type. The virus subtypes are identified and classified on the basis of two broad types of antigens, hemagglutinan (H) and neuraminidase (N); 15 H and 9 N antigens have been identified among all of the known type A influenzas.
FLI Seminar on different response strategies: Stamping out or NeutralizationHarm Kiezebrink
During this spring, American poultry producers are losing birds by the millions, due to the High Pathogenic Avian Influenza outbreaks on factory farms. USDA APHIS applied the stamping out strategy in an attempt to prevent the flu from spreading.
With stamping out as the highest priority of the response strategy, large numbers of responders are involved. With in average almost 1 million caged layers per farm in Iowa, there is hardly any room for a proper bio security training for these responders. And existing culling techniques had insufficient capacity, the authorities had to decide to apply drastic techniques like macerating live birds in order to take away the source of virus reproduction.
This strategy didn't work; on the contrary. Instead of slowing down the spreading of the virus, the outbreaks continue to reoccur and have caused death and destruction in 15 USA states, killing almost 50 million birds on mote than 220infected commercial poultry farms, all within a very small time frame.
The question is whether the priority of the response strategy should be on neutralizing the transmission routes instead of on stamping out infections after they occur. All indicators currently point out into the direction that the industry should prioritize on environmental drivers: the connection between outbreaks and wild ducks; wind-mediated transmission; pre-contact probability; on-farm bio security; transmission via rodents etc.
Once the contribution of each transmission route has been determined, a revolutionary new response strategy can be developed based on the principle of neutralizing transmission routes. Neutralizing risks means that fully new techniques need to be developed, based on culling the animals without human – to – animal contact; integrating detergent application into the culling operations; combining culling & disposal into one activity.
This new response strategy will be the main subject of the FLI Animal Welfare and Disease Control Seminar, organized at September 23, 2015 in Celle, Germany
Twenty-two researchers from labs across the world submitted a letter to Nature and Science yesterday detailing their proposed “gain-of-function” research on the avian influenza virus H7N9.
Their work would genetically engineer H7N9 to make it both more virulent and more readily transmissible person-to-person. The research sounds controversial, not the least because one of the scientists involved is Dr. Ron Fouchier, whose on gain-of-function work on H5N1 ingnited furious debate over what should research should and shouldn’t be published.
However, there is a very real possibility that H7N9 will naturally mutate to transmit effectively between people. We already know that the virus is just a single amino acid mutation away from becoming easily transmissible between people. Indeed, news of the first confirmed case of such transmission was published in the British Medical Journal this week.
With a 60% fatality rate and a completely naive global population, the results would be catastrophic. The proposed research would give us an idea of potential pandemic scenarios, giving us a head start on potential vaccine and antiviral development.
It may be controversial, but it’s absolutely necessary.
Influenza a emergency prepardness for healthcare facilitiesMoustapha Ramadan
The data presented are per 4th of March 2017 and subject to changes.
The presentation aims to provide the basic infection control requirement for healthcare facilities during large influenza epidemic or pandemic
In light of the H7N9 , the Yale-Tulane ESF #8 Planning and Response Program has produced a special report on A(H7N9).The Yale-Tulane ESF #8 Program is a multi-disciplinary, multi-center, graduate-level, program designed to produce ESF #8 planners and responders with standardized skill sets that are consistent with evolving public policy, technologies, and best practices. The group that produced this summary and analysis of the current situation are graduate students from Yale and Tulane Universities. It was compiled entirely from open source materials. Please feel free to forward the report to anyone who might be interested.
Avian Influenza H7N9
Winnifred Brefo-kesse
Hlth 626
March 31, 2019
Professor Hughes
Part I: THE SITUATION ASSESSMENT
In February and March 2013, a novel influenza A (H7N9) virus emerged in China, causing an acute respiratory distress syndrome and occasionally multiple organ failure with high fatality rates in humans (Li et al., 2014). A total of 681 laboratory-confirmed cases and 275 deaths have been reported as of November 13th, 2015, with a fatality rate of 40% (http://www.who.int/influenza/human_animal_interface/HAI_Risk_Assessment/en/). H7N9 has been evolving and established amongst chickens in China over the past two years with occasional human infections (Lam et al., 2015; Su et al., 2015), thus posing a threat to public health. In the absence of an annually-updated effective vaccine, antiviral drugs constitute the first line of defense against H7N9 infections. H7N9 viruses already possess natural resistance to M2-ion channel blockers (amantadine and rimantadine) when it first emerged in 2013 (Gao et al., 2013). Therefore, neuraminidase inhibitors (NAIs), which include oseltamivir (TamifluH), zanamivir (RelenzaH) and peramivir constitute the main antiviral drugs against H7N9 infections (Hu et al., 2013; Wu et al., 2013). However, treatment with NAIs against H7N9 infections has resulted in the emergence of drug-resistant mutant viruses, as soon as 1~9 days after administration (Gao et al., 2013; Hu et al., 2013). Moreover, the first H7N9 isolate (A/Shanghai/1/2013(H7N9), SH-H7N9) was resistant to oseltamivir (Gao et al., 2013). Avian influenza A H7 viruses are a group of viruses that is mostly found amongst birds. The H7N9 virus is a subgroup of the H7 viruses and was recently discovered in China. There were three cases discovered in March of 2013 which ultimately increased in May by 132 cases. Of those cases, the 39 infected, died because of the virus (Peipei Song1, 2013). The clinical features described in the three patients with H7N9 virus infection, included fulminant pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), septic shock, multi-organ failure, rhabdomyolysis, and encephalopathy, are very troubling (Timothy M. Uyeki, 2013). As of now, this virus has reached stage two of three which is poultry passing the virus to humans. There is one more stage left which is human to human transmission which the Chinese health officials have confirmed it is not yet occurring. Creating an anti-virus takes a lot of time and until then public health officials should create new tactics in battling this epidemic.
Since there isn’t an anti-virus for the H7N9 virus, different health policies must be put in place to control the outbreak as well as preventative strategies from escalating. This vir.
Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus that regularly causes outbreaks of influenza in pigs. Swine flu viruses cause high levels of illness and low death rates in pigs. Swine influenza viruses may circulate among swine throughout the year, but most outbreaks occur during the late fall and winter months similar to outbreaks in humans. The classical swine flu virus (an influenza type A H1N1 virus) was first isolated from a pig in 1930.
Low Atmospheric Pressure Stunning is not a humane alternative to Carbon Dioxi...Harm Kiezebrink
I would like express gratitude to the HSA for their 20 years of tireless advocacy for improving pigs' welfare. Their efforts have empowered those seeking alternatives to carbon dioxide stunning. Over nearly 30 years, I've worked on animal welfare friendly stunning applications, particularly regarding stunning/slaughtering using nitrogen foam, and I believe I've found the definitive answer.
The industry originally adopted large-scale carbon dioxide stunning to optimize food production, reduce costs, and lower meat prices, which is only feasible with parallel processing (simultaneously stunning groups of pigs) rather than serial processing (stunning each pig individually). Electrocution is not viable for large-scale operations due to this need for parallel processing. Therefore, a replacement gas that lacks carbon dioxide's detrimental properties is needed, but only a few gases are suitable.
Additionally, the application of an alternative gas must adhere to several fundamental principles:
a) Applicability of the methods for stunning and killing pigs, including their scalability for large-scale application.
b) Description of the technical.
c) Animal welfare consequences associated with specific techniques, including welfare hazards (ABMs), animal-based indicators (ABIs), preventive and corrective measures, and the sufficiency of scientific literature in describing these consequences.
d) Applicability under field conditions.
Introducing a novel application for large-scale pig slaughter is complex and time-consuming before it can be expected, especially given the substantial economic and financial impact for the industry. However, there is hope on the horizon.
The alternative gas is nitrogen, and the application is based on using high-expansion foam filled with 100% nitrogen, applied in a closed container. Within a minute, all air is displaced by the foam, after which the container is sealed, and the foam is broken down with a powerful nitrogen pulse. This ensures that the foam does not affect the stunning process; the entire process can be visually and electronically monitored, and the residual oxygen level in the container is consistently below 2%. The container dimensions are identical to the gondolas used in the globally implemented carbon dioxide gondola system.
The integration of nitrogen foam technology into European regulation EU1099/2009 is nearing completion. All scientific and technical procedures have been submitted to the EU Commission, with finalization awaiting the presentation of EFSA's scientific opinion to the Commission and subsequent approval for inclusion. This final phase is anticipated to occur during the general meeting slated for June 2024.
This marks the first step toward replacing carbon dioxide in 25 years. Fingers crossed for the EU Commission's decision in June 2024!
Harm Kiezebrink
Independent Expert
Preventief ruimen bij vogelgriep in pluimveedichte gebieden en mogelijkheden ...Harm Kiezebrink
New Risk assessment model
The applications designed for farrow-to-weaner pig farms rely on a novel risk assessment model. This model, developed from a recent study, indicates that the likelihood of an undetected infection on nearby farms notably diminishes 7 to 14 days following the identification of the source farm.
This risk assessment model is based a Dutch study that is published by T.J. Hagenaars et al on June 30, 2023: “Preventief ruimen bij vogelgriep in pluimveedichte gebieden en mogelijkheden voor aanvullende bemonstering” (Preventive culling in areas densely populated with poultry, and possibilities for additional sampling).
According to this premise, instead of the standard depopulation approach of euthanizing pigs on-site, pigs beyond the immediate vicinity of infected farms are slaughtered.
Animal Health Canada is currently evaluating new strategies and technologies for managing large-scale emergency situations involving pigs. I have been actively involved in developing strategies and procedures aimed at implementing strict control measures for pig euthanasia during emergencies, with a focus on substantially reducing costs by avoiding unnecessary culling and destruction of healthy animals.
Opting for slaughtering over on-farm euthanasia not only reduces the operational burden on farms but also repurposes the pigs as a valuable protein source rather than considering them as animal waste. This approach assists in crisis management during widespread outbreaks, significantly reduces expenses, and simultaneously mitigates risks.
While this approach is influenced by the new EU regulations implemented since May 2022, it can be adapted for implementation within the context of any EU Member state, as well as in the USA and Canada.
Managing large-scale outbreaks at Farrow-to-Weaner FarmsHarm Kiezebrink
In the face of large-scale outbreaks of swine Influenza A Virus (swIAV), there's a call for exploring various strategies conducive to managing emergencies in field conditions.
Through subdivision, a customized approach can be embraced to enhance operational efficiency and effectiveness while mitigating the impact on individual farms. This tactic maximizes emergency deployment capacity and streamlines standard procedures. Moreover, leveraging the existing capacity of farming aids in alleviating scrutiny on animal welfare standards, presenting a notable advantage.
Nitrogen filled high expansion foam in open ContainersHarm Kiezebrink
On March 31, 2023 the US National Pork Board validated a study by Todd Williams, of Pipestone Veterinary Services, based on the use of high expansion nitrogen foam for the large-scale depopulation of all classes of swine, utilizing Livetec Systems Nitrogen Foam Delivery System (NFDS).
The high expansion foam produced by the Livetec Systems NFDS surrounds the animal in large bubbles filled with nitrogen with a base expansion ration of between 300 and 350 to 1, as mentioned on the information provided by the producer of the firefighting foam.
The Livetec technology, based on using Compressed Air Foam (CAF) filled with nitrogen instead of air for depopulating pigs, emerges within a critical landscape. The complexities of implementing effective emergency depopulation strategies for livestock, particularly swine, present multifaceted challenges. Livetec's approach relies on high expansion firefighting foam, aiming to euthanize pigs by submerging them in foam.
The Livetec system's claims about the effectiveness of nitrogen-filled high expansion foam for depopulating market pigs lack substantial evidence upon analysis. The discrepancy between the actual foam produced during field trials and the promised high expansion foam, coupled with the absence of concrete proof supporting the method's efficacy, discredits the technology's claims.
World bank evaluating the economic consequences of avian influenzaHarm Kiezebrink
Pandemics cause very serious loss of life, restrictions of freedom and serious economic damage. Potential pandemics all are related to our dealing with animals, both wild and domesticated.
In this Word Bank study of 2006, the effects of a severe HPAI pandemic (with a highly pathogenic avian influenza virus crossing the species barrier and infecting humans) predicted economic losses from 2-10% of the world economy.
The economic impact of the present COVID-19 crisis, caused by the SARS-CoV2 virus spreading from wild animals to humans, probably will reach the upper limits of this prediction even if the losses of life might be near the lower limits mentioned in the report (1,4 millions rather than 71 millions).
A common observation is that governments were late to react on the COVID-19 outbreak.
Pandemics are rare, so due to cost-benefit considerations emergency preparations do usually not get beyond an advisory (paperwork) phase. When an emergency eventually arises, the response is too late, too little, and with disastrous effects on animal and/or human welfare that could have been avoided. Relatively small, short-term financial savings result in big, long-term losses.
Protection against outbreaks cannot be achieved by political decisions during a crisis. Our dealing with animals, especially in animal production, must be inherently safe so that animal health and public health are protected.
This is recognized in the One Health strategy that has been adopted internationally.
An outbreak of animal disease occurs should be contained at a very early stage. This can only be realized if all farms have their own emergency plans, with equipment to deal with contagious diseases already present at the farm.
Gas alternatives to carbon dioxide for euthanasia a piglet perspectiveHarm Kiezebrink
The use of nitrous oxide as an anesthetic/euthanasia agent may prove to be affordable, feasible and more humane than other alternatives.
The neonatal stage is a critical time in the life of a pig, when they are prone to become sick or weak. This is the stage at which most euthanasia procedures are required if the pig is judged unable to recover. Any euthanasia method should be humane, practical, economical and socially acceptable to be universally accepted.
They found that nitrous oxide in oxygen appeared to be less aversive than nitrous oxide, nitrogen, or argon all combined with low (30%) concentrations of carbon dioxide or 90% carbon dioxide by itself.
This study is the first to investigate the use of nitrous oxide at sufficiently high concentrations to cause anesthesia. Nitrous oxide, commonly referred to as laughing gas, has been widely used in human surgery and dental offices for its pain-relieving, sedative and anxiolytic effects. It is cheap, non-flammable, non-explosive, legally accessible and not classified as a drug in the U.S., and already commonly used in the food industry as a propellant for food products.
Development of its use into an automated procedure will allow producers to implement it with little effort. Thus its use as an anesthetic/euthanasia agent may prove to be affordable, feasible and more humane than other alternatives.
Anoxia: High expansion foam
The Anoxia method is unique for creating an environment without oxygen under atmospheric circumstances. High expansion foam is produced by mixing nitrogen and a mixture of water and specially developed high expansion detergent, with an expansion rate upto 1:1000, meaning that 1 litre of water/foam agent mix expands up to 1 m3 foam. Due to the specially designed foam generator, the high expansion foam bubbles are filled with a > 99% concentration of nitrogen. The oxygen level surrounding the animal drops from 21% in atmospheric air to < 1 % once the animal is submerged in the foam.
Anoxia: convulsions, but no stress or pain
The animals need a constant supply of oxygen to the brain. Applying Anoxia foam, the oxygen is replaced by nitrogen. As a result the nitrogen level is raised to > 99% and the oxygen level is lowered to < 1%. Considering the natural reaction to sudden lack of oxygen the animal is rendering quickly into unconsciousness. As a consequence, behavioral indicators like loss of posture and convulsions will appear. With this in mind, unconscious animals are insensitive to perceive unpleasant sensations like pain.
Anoxia: How Anoxia foam is created
A mixture of 97% water and 3% high expansion foam agent is sprayed into the Anoxia foam generator, creating a thin film on the outlet of the generator. At the same time, nitrogen is added with overpressure into the foam generator. The nitrogen expands when it exits the generator, creating robust high expansion foam. The high expansion foam bubbles are filled with > 99% nitrogen.
Anoxia: Single foam generator systems
In practice, one Anoxia foam generator creates a volume of up to 750 liter of high expansion foam per minute. This volume is more than sufficient to fill a wheelie-bin container within 30 seconds. The most common container volumes are: M size - 240 liter; L size - 340 liter; and XL size - 370 liter. The choice of the volume of the container depends of the size of the animal and/or the number of animals that need to be stunned/killed. A lid with a chiffon that seals the container. As soon as the foam exits the chiffon, the gas supply is stopped and the chiffon is closed. The nitrogen gas concentration in the container remains at 99%.
Although commonly used in other settings, defining animal welfare as part of a corporate CSR setting is not new.
There are many ways to define CSR. What they have in common is that CSR describes how companies manage their business processes to produce an overall positive impact on society. The phenomenon CSR is a value concept that is susceptible to particular ideological and emotional interpretations. Different organizations have framed different definitions - although there is considerable common ground between them.
Some important national players of the food chain at different steps (mainly food retailers and food services) have included animal welfare in their CSR.
The Anoxia technique is developed as alternative for existing animal stunning methods that are based on the use of CO2, electrocution, neck dislocation, captive-bolt, as well as killing methods like de-bleeding and maceration.
In the past 10 years, Wageningen University and University of Glasgow conducted several studies that proved that the technique could be applied successfully for culling poultry (Proof of Principle Anoxia Technique). This was the start of the development of several applications based on the Anoxia principle, using high expansion foam filled with >99% Nitrogen that are now introduced for:
1. Stunning and killing of sick and cripple killing piglets less than 5 kg
2. Stunning and killing of sick or cripple poultry (especially poultry > 3kg) who need to be killed on the farm by the staff for welfare purposes (avoiding unnecessary stress or pain)
3. Stunning and killing poultry that arrives on the slaughterhouse but that are unfit to be slaughtered (due to injuries occurred during transportation – providing signs of possible illness etc.)
4. Stunning and killing of male pullets at the hatchery
5. Stunning and killing of half-hatched chickens and embryos in partly-hatched eggs, before destruction
6. Stunning and killing parent stock poultry
7. Killing of animals that has been stunned (captive bolt – blow-on-the-head method, etc.) replacing killing by de-bleeding
8. Culling of ex-layers
9. Culling of poultry for disease control purposes
Last November we started the launch of the commercialization of the Anoxia applications in Holland, Germany and Sweden, focusing on the areas where a solution is most needed: piglets (< 5kg) and poultry (> 3kg) on farms.
Since November 2016, the introduction of these applications took place in Holland, Germany, Sweden and Denmark
World Health Organization director- general Margaret Chan Fung Fu-chun warns bird flu H7N9 is particularly worrying as it could be a flu pandemic strain. This is because H7N9 is unique as it does not make chickens sick but is deadly in humans. Sick birds could usually provide early warning for imminent outbreaks, Chan told The Standard. This comes as Macau reported its first human case of H7N9 yesterday. "The biggest challenge for the world is the next influenza pandemic," Chan said.
Laves presentation practical experiences in the culling of poultry in germanyHarm Kiezebrink
This presentation, based on the practical experiences in culling poultry in Germany, gives an overview of the culling techniques currently in use in Germany. It is presented by dr. Ursula Gerdes, dr. Josef Diekmann and ing. Rainer Thomes.
LAVES is the Lower Saxony State Office for Consumer Protection and Food Safety, located in Oldenburg, Germany. With around 900 employees they are entrusted with tasks in the areas of food and utensil inspection, feed inspection, meat hygiene, veterinary drug monitoring, eradication of animal diseases, disposal of animal by-products, animal welfare, ecological farming, market surveillance and technical process monitoring.
Berg et al. 2014 killing of spent laying hens using co2 in poultry barnsHarm Kiezebrink
September 2015: In Sweden, spent laying hens are killed either by traditional slaughter; on-farm with CO2 in a mobile container combined with a grinder; or with CO2 stable gassing inside the barn. The number of hens killed using the latter method has increased. During these killings a veterinarian is required to be present and report to the Swedish Board of Agriculture.
Data were registered during four commercial killings and extracted from all official veterinary reports at CO2 whole-house killings in 2008–2010. On-farm monitoring showed that temperature decreased greatly and with high variability. The time until birds became unconscious after coming into contact with the gas, based on time until loss of balance, was 3–5 min.
Veterinary reports show that 1.5 million laying hens were killed, in 150 separate instances. The most common non-compliance with legislation was failure to notify the regional animal welfare authorities prior to the killings. Six out of 150 killings were defined as animal welfare failures, eg delivery of insufficient CO2 or failure to seal buildings to achieve adequate gas concentration.
Eleven were either potentially or completely unacceptable from the perspective of animal welfare. We conclude that, on the whole, the CO2 whole-house gas killing of spent hens was carried out in accordance with the appropriate legislation. Death was achieved reliably.
However, there remain several risks to animal welfare and increased knowledge would appear vital in order to limit mistakes related to miscalculations of house volume, improper sealing or premature ventilation turn-off.
The latest outbreak of High Pathogen Avian Influenza in the USA and Canada in the spring of this year and the inability to avoid animal welfare catastrophes ultimately proves that new emergency response strategies are needed. Strategies that are based on taking away the source of infection instead of killing as many animals as possible within 24 hours, regardless the consequences.
The statement that “It’s possible that human infections with these viruses may occur” and that “these viruses have not spread easily to other people” is confusing. Humans can become infected without showing clinical signs. They can become the major carrier of the infection.
Especially during depopulation activities, viruses easily transmit through responders. Tasks like taking layers out of their cages and transport the birds manually through the narrow walkways between the cages, and disposal of infected animals are specific risks that need to be avoided. Simply switching of the electricity so that sick birds don’t have to be handled is not the solution.
Although humans are supposed to be less susceptible, they can become carrier of the virus. Only the highest level of biosecurity could prevent the transmission through the humans and materials that have been in direct contact with infected animals and materials.
Simply switching of the electricity so that sick birds don’t have to be handled is not the solution. Avoid killing animals is always the better option and in Germany, the discussion on the strategy based on neutralizing risks and is in the making. Avoiding situations demands a proactive role of the poultry industry.
Ventilation Shutdown: who takes the responsibility to flip the switch?Harm Kiezebrink
On September 18, 2015 the USA Government and the American egg producers announced that they would accept the Ventilation shutdown method as a method of mass destruction of poultry when other options, notably water-based foam and CO2, are not available for culling at the farm within 24-36 hours. This is actually the case on all caged layer farms in the USA, in particular in Iowa.
The Ventilation shutdown method consists of stopping ventilation, cutting off drinking water supply, and turning on heaters to raise the temperature in the poultry house to a level between 38 Celsius and 50 Celsius. Birds die of heat stress and by lack of oxygen in a process that easily takes over after a period of at least 3 days. Ventilation shutdown is a killing method without prior stunning of the birds, and as such is contrary to all international Animal Welfare standards.
Animal welfare specialists in disease control strongly oppose this introduction of the cruelest method of killing poultry that lost their economic value. The Humane Society (HSUS) described it as the “inhumane mass baking of live chickens”. With adequate preparation the alternative methods, like the water-based Anoxia foam method, can be available at each farm for immediate use in case of an outbreak. The ban of the Ventilation shutdown method should therefore be maintained and the Anoxia method should be further developed so that is suitable for application to caged layers and turkeys. In Germany, such a system is currently under development and will become commercially available soon.
The poultry industry in the USA ignores this development and asks for a formal approval of the Ventilation Shutdown method. Speaking on August 19, 2015, during the United Egg Producers (UEP) national briefing webinar, UEP President Chad Gregory explained that much research is being done concerning the feasibility of such a depopulation program.
“The government, the producers, the states and UEP, we all recognize that depopulation is going to have to happen faster and ideally within 24 hours.”
Quick depopulation of affected flocks is important, Gregory said, because the sooner a flock is depopulated, the risk of the virus going into fans and out into the atmosphere becomes smaller. Gregory said ventilation shutdown – if approved – would probably only be used in a worst-case scenario or when all other euthanasia options have been exhausted. Gregory did not elaborate on how to adequately prevent outbreaks and how to promote more animal-friendly methods.
In order to become one step ahead of an outbreak of high pathogen diseases like the current H5N2, the veterinary authorities need to stop the outbreak immediately after the first signals occur. Strict and thorough biosecurity measures are the most fundamental feature to protect poultry flocks on farms.
Without functional culling techniques, the options to effectively and efficiently cull in average more than 925,000 chickens per farm (in Iowa, USA) are limited: either by macerating the chickens alive – or by ventilation shut-down (closing down all ventilation, placing heaters inside the house, and heat the entire house to a temperature higher than 600 C).
Although both methods cause death of the birds, it has not been proven to be effective nor efficient. The primary goal to slowdown outbreaks and bring it to a complete stop but macerating live birds and killing them by heat stress and lack of oxygen would be against all International Animal Welfare standards.
Animal welfare specialists in disease control strongly oppose against the introduction of these most cruel methods of killing poultry and argue that the ban on these methods should be maintained and alternative methods need to be considered.
Avian Influenza in the Netherlands 2003: comparing culling methodsHarm Kiezebrink
During the outbreak of H7N7 in Holland, 29,500.000 birds were killed at the farm. This presentation compares different culling techniques, such as stable gas, container gassing and electrocution.
Reseach on H9N2: evidence that link outbreaks in Eurasia, China, South Korea,...Harm Kiezebrink
In this study, 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.
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.”
The new study, led by the USGS, found low pathogenic H9N2 viruses 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, have 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. Non
Risk analysis on the role of wild ducks by the introduction of Avian Influenz...Harm Kiezebrink
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 determin the potential risk factors for infection with LPAI virus, forty Dutch free range poultry farms where the introduction of Low Pathogen Avian Ifluenza 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.
Anoxia presentation during the AI symposium in Taiwan, March 2015Harm Kiezebrink
During the Symposium on managing outbreaks of Avian Influenza in Taiwan, the main subject was managing the outbreaks without breaching animal welfare during the culling operations. Although it seams impossible, this can be done using the Anoxia method (see also www.N2GF.com for more information), under the condition that the entire process is been taking into account: killing of animals, carcass disposal, transport & logistic, Occupational Health & Safety, environmental issues, pest control, contact between animals and humans: all these factors contribute to the risks of spreading. If one factor fails, the virus can escape and infect the next flock, making it needed to kill more birds. For that reason, all factors are equally important to maintain animal welfare during outbreak situations.
In a number of recently published studies, Professor Stegeman (University of Utrecht, Holland) explains that serologic spreading of viruses is related to human contacts with contaminated infected animals, carcasses, manure and materials infected/suspected animals; movements of farm labourers, products, equipment etc. Most of these contacts (and movements) take place prior, during, and after the culling procedure, whereas the quantity and the intensity of the contacts - thus this human contact/materials are decisive factors for the serologic spreading of viruses to enter farms and most likely play an important role in spreading between farms. Suspicion/infection of farm animals inevitably leads to preventive culling of all farm animals within the direct proximity. For that reason, the serologic spread of viruses has become a major animal welfare indicator that has to be taken into consideration as such.
Each culling procedure features its own unique contact pattern between animals and humans and is based on applied culling, disposal and transport technique. These contact patterns related to the specific combination of applied methods, defines the major contribution factors for spreading of infections. Therefore should the potential risks of these procedures be evaluated and rated on the art and the intensity of the potential contact between animals and humans/materials, prior, during and after the procedure.
Therefore, the entire procedure of killing, disposal and transportation is therefore considered as Major Interest, in terms of animal welfare.
OIE terrestrial code killing of animals for disease preventionHarm Kiezebrink
The guidelines are intended to help countries identify priorities, objectives and the desired goal of disease control programmes.
Disease control programmes are often established with the aim of eventual eradication of agents at a country, zone or compartment level. While this approach is desirable, the needs of stakeholders may require a broader range of outcomes.
For some diseases, eradication may not be economically or practically feasible and options for sustained mitigation of disease impacts may be needed.
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‘वोटर्स विल मस्ट प्रीवेल’ (मतदाताओं को जीतना होगा) अभियान द्वारा जारी हेल्पलाइन नंबर, 4 जून को सुबह 7 बजे से दोपहर 12 बजे तक मतगणना प्रक्रिया में कहीं भी किसी भी तरह के उल्लंघन की रिपोर्ट करने के लिए खुला रहेगा।
role of women and girls in various terror groupssadiakorobi2
Women have three distinct types of involvement: direct involvement in terrorist acts; enabling of others to commit such acts; and facilitating the disengagement of others from violent or extremist groups.
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In a May 9, 2024 paper, Juri Opitz from the University of Zurich, along with Shira Wein and Nathan Schneider form Georgetown University, discussed the importance of linguistic expertise in natural language processing (NLP) in an era dominated by large language models (LLMs).
The authors explained that while machine translation (MT) previously relied heavily on linguists, the landscape has shifted. “Linguistics is no longer front and center in the way we build NLP systems,” they said. With the emergence of LLMs, which can generate fluent text without the need for specialized modules to handle grammar or semantic coherence, the need for linguistic expertise in NLP is being questioned.
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हम आग्रह करते हैं कि जो भी सत्ता में आए, वह संविधान का पालन करे, उसकी रक्षा करे और उसे बनाए रखे।" प्रस्ताव में कुल तीन प्रमुख हस्तक्षेप और उनके तंत्र भी प्रस्तुत किए गए। पहला हस्तक्षेप स्वतंत्र मीडिया को प्रोत्साहित करके, वास्तविकता पर आधारित काउंटर नैरेटिव का निर्माण करके और सत्तारूढ़ सरकार द्वारा नियोजित मनोवैज्ञानिक हेरफेर की रणनीति का मुकाबला करके लोगों द्वारा निर्धारित कथा को बनाए रखना और उस पर कार्यकरना था।
Human-to-Human transmission of H7H7 in Holland 2003
1. For personal use. Only reproduce with permission from The Lancet.
ARTICLES
Summary
Background An outbreak of highly pathogenic avian
influenza A virus subtype H7N7 started at the end of
February, 2003, in commercial poultry farms in the
Netherlands. 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.
Methods All workers in poultry farms, poultry farmers, and
their families were asked to report signs of conjunctivitis or
influenza-like illness. People with complaints were tested
for influenza virus type A subtype H7 (A/H7) infection and
completed a health questionnaire about type of symptoms,
duration of illness, and possible exposures to infected
poultry.
Findings 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. 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.
Diagnostic Laboratory for Infectious Diseases and Perinatal
Screening (M Koopmans DVM, B Wilbrink PhD, A Meijer PhD,
H van der Nat, H Vennema PhD), and Centre for Infectious
Diseases Epidemiology (M Conyn PhD, A Bosman MD), National
Institute of Public Health and the Environment, Bilthoven,
Netherlands; European Influenza Surveillance Scheme at
Netherlands Institute for Health Services Research, Utrecht
(A Meijer PhD); Virology Department, Erasmus Medical Centre,
Rotterdam (R Fouchier PhD, A Osterhaus DVM); National
Coordination Centre for Communicable Disease Control, Utrecht
(J van Steenbergen MD); and Municipal Health Centre, Arnhem
(G Natrop MD)
Correspondence to: Dr Marion Koopmans, Virology Section,
Diagnostic Laboratory for Infectious Diseases and Perinatal
Sceening, National Institute of Public Health and the Environment,
3720BA Bilthoven, Netherlands
(e-mail: marion.koopmans@rivm.nl)
Interpretation We noted an unexpectedly high number of
transmissions of avian influenza A virus subtype H7N7 to
people directly involved in handling infected poultry, and we
noted evidence for person-to-person transmission. Our data
emphasise the importance of adequate surveillance,
outbreak preparedness, and pandemic planning.
Lancet 2004; 363: 587–93
See Commentary page 582
Introduction
On March 1, 2003, the Dutch Ministry of Agriculture
announced a ban on the export of all poultry and poultry-
related products. This measure was taken in response to
outbreaks of a disease highly lethal to chickens on six farms
in the province of Gelderland, an area with a high density of
poultry farms. The infection spread to 255 farms, and the
Ministry’s order for the culling of all infected flocks led to
the killing of around 30 million chickens—about 28% of the
total chicken population in the Netherlands. The annual
export value of poultry and eggs contributes €284 million to
the Dutch economy every year.
The pathogen was identified as a highly pathogenic avian
influenza A virus (HPAI) subtype H7N7, and was related to
viruses detected in 2000 during routine surveillance of avian
influenza in ducks in the Netherlands. All internal genes of
the viruses were of avian origin.1
Epizootics and solitary
infections of A/H7N7 avian influenza virus in poultry have
been reported in surveillance studies, and humans were
thought to be at low risk of infection, although there have
been occasional reports of H7N7-associated conjunc-
tivitis.2–4
In 1996, influenza A/H7N7 virus (A/England/
268/96) was isolated from a 43-year-old duck owner with
mild one-sided conjunctivitis.4,5
In the week following the announcement of the avian
influenza outbreak, four independent anecdotal reports
suggested an increased incidence of health complaints,
particularly conjunctivitis, in people involved in the control
of the epizootic. Coincidentally, data from routine influenza
virus surveillance suggested a late seasonal increase in the
rate of human influenza viruses. With the almost
simultaneous confirmation of an influenza virus A/H7N7-
associated conjunctivitis and human influenza virus
A/H3N2 in two different veterinarians involved in control
measures for the HPAI epizootic, physical prevention
measures were reinforced and we began vaccination and
actively seeking out people with symptoms—ie, cases.
Here, we describe the epidemiological and virological
results of our case finding and the preventive measures
taken to control the outbreak in human beings.
Methods
Study organisation
After the first confirmation of chicken-to-human
transmission of influenza A/H7N7, an outbreak investi-
gation team was assembled at the RIVM (Rijksinstituut
Transmission of H7N7 avian influenza A virus to human beings
during a large outbreak in commercial poultry farms in the
Netherlands
Marion Koopmans, Berry Wilbrink, Marina Conyn, Gerard Natrop, Hans van der Nat, Harry Vennema, Adam Meijer,
Jim van Steenbergen, Ron Fouchier, Albert Osterhaus, Arnold Bosman
Articles
THE LANCET • Vol 363 • February 21, 2004 • www.thelancet.com 587
2. For personal use. Only reproduce with permission from The Lancet.
voor Volksgezondheid and Milieu [National Institute of
Public Health and the Environment]). The population at
risk was defined as the group of people living or working in
the Netherlands after February 28, 2003, who had direct
contact with poultry or poultry products that could have
been infected with H7, or who had close contact with an
H7-infected person. We set up a case register using
Microsoft Excel 97 to record and follow up all reports of
health complaints from people within the population at
risk. We designed a health questionnaire with questions
about symptoms, possible exposures, and background
demographic data to allow us to generate hypotheses on
risk factors for infection. Public-health nurses or doctors
from the Municipal Health Service (MHS) administered
questionnaires to all people in the case register. Workers
from the MHS offered to take eye swabs and nose/throat
swabs for diagnostic testing. Results from laboratory
testing and the trawling questionnaires were added to the
individual’s information in the case register.
Furthermore, the MHS was asked to participate in
active case finding by visiting families and workers on all
poultry farms in the region. A medical post was set up at
the regional crisis centre in the most severely affected area,
to do the mandatory vaccination for human influenza and
to have close access to all workers involved in the culling of
poultry. People with confirmed A/H7 infection were
contacted by telephone for interviews on possible
symptoms in close contacts; symptomatic contacts were
then visited by staff from the MHS, or referred to the
medical post or their primary care physician for samples to
be taken. Rumours of possible illness in contacts (eg, from
discussions in the crews of poultry workers) were followed
up by one of the team members.
Patients gave written consent for nose and throat swabs
to be done.
Case register and case definition
Cases who were in close contact with poultry were
designated as primary cases. Cases who had had contact
with a poultry worker or farmer were designated as
secondary cases. Completed health questionnaires were
entered in the case register and linked by unique case
identifier to the laboratory information management
system of the RIVM virology laboratory. Test results were
uploaded daily at 1600 h to allow inclusion of the latest
laboratory results in the daily updates.
For conjunctivitis and influenza-like illness, probable
cases which tested positive for influenza A virus but could
not be subtyped were classified as probable cases.
Conjunctivitis—we defined a probable case of A/H7
conjunctivitis as a person who had possible close contact
with HPAI A/H7 (in poultry or human beings) in the
Netherlands on or after Feb 28, 2003, and who had two
or more of: red eyes, tearful eyes, itching eyes, painful
eyes, burning eyes, purulent fluid in eyes, or sensitivity to
light. A confirmed case of A/H7 conjunctivitis met
criteria as defined for a probable case of A/H7
conjunctivitis but also had at least one positive laboratory
result for their eye swab, or their nose/throat swab
Laboratory confirmation was by either RT-PCR for
influenza A virus followed by subtype H7 specific RT-
PCR, or by isolation of influenza virus in cell culture and
typing of the virus by haemagglutination inhibition assay.
Influenza—we defined a probable case of A/H7 influenza as
a person who had the opportunity of close contact with
HPAI A/H7 (in poultry or human beings) in the
Netherlands on or after Feb 28, 2003, with acute onset of
symptoms (prodromal phase maximum 4 days) and fever (if
measured, then у38·5º) and who had at least one of: cough,
rinorrhoea, sore throat, myalgia, or headache. A confirmed
case of A/H7 influenza was defined by the same criteria as
those for a probable case of A/H7 influenza, but also with at
least one positive laboratory result for influenza A/H7 virus.
Sampling collection
We distributed prepacked and labelled sampling kits and
instructions to the medical post at the regional crisis centre
and to all 39 MHS. Every kit contained two tubes with virus
transport medium, four cotton swabs, and a trawling
questionnaire. Swabs were collected from both eyes (by
protracting the lower eye-lid and rubbing the conjunctiva
with the swab), and from the oropharynx and nasopharynx.
Tubes and questionnaires were packed and labelled for
every patient with a unique LIMS number for matching of
epidemiological data and results from virus tests. After
sampling, the packages were stored at room temperature
and collected every day by courier or sent with the Dutch
postal service.
Virological analysis
We first tested swabs for the presence of influenza virus
using cell culture and RT-PCR. Influenza virus grown in
cell culture was typed and subtyped antigenically by
haemagglutination inhibition assays. After the first 25 cases
confirmed by cell culture, RT-PCR was used as the initial
screening method. Samples of the untreated fluid, and RNA
extracts of each specimen were packed in ice and sent to the
Erasmus Medical Centre for independent confirmation of
RT-PCR and for subtyping (H3, H7) by molecular
methods.
We unpacked and prepared samples for RNA extraction
and cell culture under BSL-2 conditions. Swabs were
vortexed in the virus transport medium, the fluid was
collected, and swabs were discarded. Samples were divided
into three aliquots of 750 L for testing by RT-PCR, cell-
culture methods, and confirmation at the second laboratory.
For RT-PCR, a negative control (virus transport
medium) was included for every four clinical samples. A
positive control sample (influenza A/Net/287/00, subtype
H3N2) was included in every RNA extraction and PCR
run. RNA was isolated with a high pure RNA isolation kit
(Roche Molecular Biochemicals) in accordance with
ARTICLES
588 THE LANCET • Vol 363 • February 21, 2004 • www.thelancet.com
Conjunctivitis Conjunctivitis+ILI Conjunctivitis total ILI only Other Total
Final laboratory results
Negative 198 (63·1%/66·9%) 39 (12·4%/73·6%) 237 (75·5%/67·9%) 27 (8·6%/72·9%) 50 (15·9%/74·6%) 314 (100%/69·3%)
A/H3 positive 2 (33·3%/0·7%) 3 (50·0%/5·7%) 5 (83·3%/1·4%) 1(16·7%/2·7%) 0 6 (100%/1·3%)
A/H7 positive 78 (87·6%/26·4%) 5 (5·6%/9·4%) 83 (93·3%/23·8%) 2 (2·2%/5·4%) 4 (4·5%/6·0%) 89 (100%/19·6%)
Influenza A positive, 8 (57·2%/2·7%) 2 (14·3%/3·8%) 10 (71·4%/2·9%) 2 (14·3%/5·4%) 2 (14·3%/3·0%) 14 (100%/3·1%)
no subtyping data
Not tested 10 (33·3%/3·4%) 4 (13·3%/7·5%) 14 (46·7%/4·0%) 5 (16·7%/13·5%) 11 (36·7%/16·4%) 30 (100%/6·6%)
Total 296 (65·3%/100%) 53 (11·7%/100%) 349 (77·0%/100%) 37 (8·2%/100%) 67 (14·8%/100%) 453 (100%/100%)*
ILI=influenza-like illness. Data are n (% of row total/% of column total). *322 men, 128 women, data missing for 3.
Table 1: Results of laboratory testing for influenza in people possibly exposed to HPAI A/H7 in the Netherlands, grouped by
presenting symptoms
3. For personal use. Only reproduce with permission from The Lancet.
manufacturer’s instructions, and with the addition of poly A
RNA as carrier. The RT-PCR screening for influenza A
virus was done essentially as described elsewhere.6
RNA
extraction, preparation of PCR mixtures, and addition of
RNA were done in a biosafety hood equipped with
ultraviolet germicidal lamps which were in separate,
dedicated, positive-pressure laboratories (>10 Pa) with
a negative-pressure-lock gate. Dedicated pipettes with
disposable filter tips, disposable gloves, disposable
laboratory coats, and non-reusable waste containers were
used in these rooms. Thermo cycling and amplicon
detection were done in a separate laboratory on a different
floor.
H3 genetic subtyping of samples positive for influenza A
virus was done at the Erasmus Medical Centre as
described.7
A real-time RT-PCR specific for the H7 virus
circulating in the Netherlands was developed at Erasmus
Medical Centre.1
At the RIVM, real-time RT-PCR specific
for H7 was developed with primers based on the
haemagglutinin gene of A/H7N7 avian isolates, provided by
G Koch (Central Institute for Animal Disease Control,
Lelystad, Netherlands) (forward H7-4 5ЈTTTGT
AATCTGCAGCAGTTC3Ј, reverse and RT primer H7-7
5ЈAGCAGGGC AGTAGGAAAATG3Ј). A more detailed
protocol is available from M Koopman.
A positive control sample (influenza A/Parrot/Northern
Ireland/VF-73-67/73 H7N1 provided by C van Maanen
[Animal Health Service, Deventer, Netherlands]) was
included in each PCR run. Since H1 molecular typing was
not operational at the EMC, samples that could not be
typed were assayed by cell culture and subtyped by
haemagglutination inhibition test.
For cell culture, transport medium was centrifuged
(10 min at 3000 g) and the supernatant was used for virus
isolation in accordance with standard protocols.7
We typed
and subtyped influenza viruses in haemagglutination
inhibition assays using turkey erythrocytes with standard
antisera against influenza A virus subtypes H1 and H3, and
influenza B virus, provided by the European Influenza virus
Surveillance Scheme.8,9
The antiserum used for H7 typing
was provided by C van Maanen; it had been obtained from
pathogen-free chickens injected with low pathogenic
influenza virus A/Parrot/Northern Ireland/VF-73-67/73
(H7N1).
Susceptibility testing
The susceptibility of the virus isolated from the clinical
sample of the first reported case was assessed, in
anticipation of the possible use of antivirals for the
prophylaxis and treatment of A/H7N7 in humans. This
stock virus was subtyped as H7 by haemagglutination
inhibition assays. The susceptibility of the virus for the
neuraminidase inhibitors oseltamivir (Roche Diagnostics,
Mannheim, Germany) and zanamivir (GlaxoSmithKline,
Zeist, Netherlands) was tested with a miniaturised format of
the fetuin based biochemical assay.10
We used a known
sensitive influenza virus (A/Chicken/Pennsylvania/21525/
83 H5N2) as positive control.
Statistical analysis
Data analysis for descriptive epidemiology was done with
MS-Excel 97. We used 2
test (with continuity correction)
to compare proportions of persons with symptoms in A/H7
positive and negative people.
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THE LANCET • Vol 363 • February 21, 2004 • www.thelancet.com 589
0
5
10
15
20
25
2003
Numberofcases
0
1
2
3
4
5
6
7
8
9
10
5-daymovingaveragenumberofcontaminatedfarms
Probable cases
A/H3 confirmed cases
A/H7 confirmed cases
Contaminated farms region 1
Contaminated farms region 2
1 2
3
Feb
16
Feb
23
M
ar2
M
ar9
M
ar16
M
ar23
M
ar30
Apr6
Apr13
Apr20
Apr27
M
ay4
M
ay11
M
ay18
M
ay25
June
1
Figure 1: Probable and confirmed cases of human conjunctivitis and influenza-like illness associated with HPAI H3 and H7 infection
during the avian influenza epizootic in the Netherlands, 2003
Green and red lines show 5-day moving average of newly diagnosed A/H7 contaminated farms in two regions. Arrows show start of active case finding (1),
start of prophylactic treatment with oseltamivir (2) and death of case with HPAI infection (3).
4. For personal use. Only reproduce with permission from The Lancet.
Role of the funding source
The Dutch Ministry of Health was informed of all activites
but had no decisive role in study design, data collection,
data analysis, data interpretation, writing of the report, or
the decision to submit the paper for publication.
Results
Case finding
On March 5, 2003, a veterinarian who visited several farms
with HPAI-infected poultry flocks developed acute con-
junctivitis. The symptoms in the first eye started 30 h after
his last farm visit; within the next 24 h, similar problems
arose in the other eye. Eye swabs collected about 60 h after
the onset of symptoms were positive for influenza A/H7 by
RT-PCR and tissue culture. On the basis of these findings,
active case finding was started from March 10, 2003.
By June 9, 2003, 453 people who might have been
exposed to avian influenza virus A/H7 reported illness of
some kind. Of these, 349 (77%) met the probable case
definition for conjunctivitis (279 primary and 70 secondary
cases) and 90 (20%) the probable case definition for
influenza-like illness (77 primary and 13 secondary cases)
(table 1). A/H7 was detected by RT-PCR, virus isolation,
or both in 82 primary cases (two with influenza-like illness
only, 75 with conjunctivitis only, and five who had both),
three secondary cases (all with conjunctivitis, of whom one
also had influenza-like illness), and in two people with “red
eyes” only (ie, they did not fit any case definition). A/H7
was also detected in two people for whom we did not
receive a trawling questionnaire and, therefore, who could
not be categorised by symptoms.
Of the two primary A/H7-cases with influenza-like illness
only, one had a previous eye injury, precluding evaluation
for conjunctivitis, the other was a veterinarian with chronic
blepharitis who developed a respiratory distress syndrome
and died.
The veterinarian, who had previously been healthy,
developed high fever and severe headache without signs
of respiratory or ocular diseases 2 days after visiting a
farm with infected chickens. He had not used antiviral
prophylactic treatment. He consulted a general practitioner
for persisting fever and headache, and 1 week after his farm
visit, samples were taken to test for avian influenza. Results
of RT-PCR tests done in two laboratories were negative for
avian influenza virus and for a range of other respiratory
pathogens. 9 days after exposure, he was admitted with
pneumonia. His condition deteriorated despite treatment
with antibiotics, and on day 12, he developed multi-organ
failure. On day 15, he died of respiratory insufficiency. A
bronchio-alveolar lavage sample collected on day 11, and
lung tissue taken during autopsy tested positive for A/H7
with RT-PCR and cell culture. Histopathology of the lung
tissue showed extensive diffuse alveolar damage.
We estimate that about 4500 people were exposed to
A/H7-infected poultry in the Netherlands. The 553 people
reporting health complaints represent 12·3% of this group.
The attack rate of conjunctivitis was 7·8%, whereas
influenza-like illness was reported in 2%.
The mean age of people included in the case register
was 32·8 years (SD 16·4, [range 0–103]). In confirmed
A/H7 cases the average age was 30·4 years (12·3, [13–59]).
The peak incidence was between March 8, and March 20,
2003 (figure 1). Most H7 cases were detected in workers
who were culling chickens (table 2). The attack rate
(proportion of persons at risk who developed symptoms) of
conjunctivitis was highest in veterinarians, and cullers and
veterinarians had the highest estimated attack rate of
confirmed A/H7 infections.
Symptoms in people who had been in contact with
people with confirmed A/H7 infection were assessed via the
health questionnaires. Of those exposed to 83 primary
cases of confirmed A/H7 infection, 70 people reported
conjunctivitis, 13 influenza-like illness, and 14 other illness.
Three exposed contacts had confirmed A/H7 infection
(table 3). All of these secondary cases shared a household
with a poultry worker or farmer. The first contact was the
13-year-old daughter of a poultry worker, who developed
conjunctivitis about 10 days after the onset of symptoms in
her father. Eye swabs from the child tested positive for
A/H7. 2 days later, she also developed moderate influenza-
like illness, and A/H7 was noted in one of the eye swab
samples submitted for diagnostic testing. 4 days after the
onset of illness in her daughter, the 37-year-old mother
developed conjunctivitis, and RT-PCR showed samples
taken from eyes and throat swabs were positive for
A/H7. Both patients were given a therapeutic course of
neuraminidase inhibitor, and recovered uneventfully.
The third contact was the 44-year-old father of an
infected poultry worker with conjunctivitis, who developed
conjunctivitis 1 day after onset of symptoms in his son.
Contacts of the deceased veterinarian with symptoms were
subjected to a broader panel of diagnostic tests but A/H7
was not detected. Two of the 19 people with symptoms
were positive for Chlamydophila pneumoniae infection, and
one person was positive for rhinovirus.
Symptoms of influenza-like illness were reported less
often by A/H7-positive cases than by people who tested
negative for the viruses (table 4).
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590 THE LANCET • Vol 363 • February 21, 2004 • www.thelancet.com
Cases Negative* H3 H7 Positive; no Unknown Estimate of number % cases/% H7
subtype at risk positive (estimate)
Poultry farmer/family 109 77 (70·6%) 1 (0·9%) 16 (14·7%) 3 (2·8%) 12 (11·0%) 1400 7·8%/1·1%
Cullers 131 60 (45·8%) 1 (0·7%) 54 (41·2%) 8 (6·1%) 8 (6·1%) 1800 7·2%/2·9%
Veterinarians 19 12 (63·2%) 1 (5·3%) 5 (26·3%) 1 (5·3%) 0 180 10·6%/2·8%
Medical personnel† 12 12 (100%) 0 0 0 0 60 20%/0%
Others 182 153 (84·1%) 3 (1·6%) 14 (7·7%) 2 (1·1%) 10 (5·5%) NK NA
Total 453 314 (69·3%) 6 (1·3%) 89 (19·6%) 14 (3·1%) 30 (6·6%) >3410 NA
NK=not known; NA=not applicable. Data are n or n (%). *% are proportion of cases in risk group. †Staff from hospitals involved in care of patient who died.
Table 2: Reported cases by risk group and laboratory result
Conjunctivitis Conjunctivitis + ILI Conjunctivitis total ILI Other Total
A/H3 positive 1 (33·3%/1·7%) 2 (66·7%/20%) 3 (100%/4·3%) 0 0 3 (100%/3·4%)
A/H7 positive 2 (66·7%/3·3%) 1 (33·3%/10%) 3 (100%/4·3%) 0 0 3 (100%/3·4%)
Negative 57 (74·0%/95·0%) 5 (6·5%/50%) 62 (80·5%/88·6%) 3 (3·9%/100%) 12 (15·6%/85·7%) 77 (100%/88·5%)
Not tested 0 2 (50%/20%) 2 (50%/2·9%) 0 2 (50%/14·3%) 4 (100%/4·6%)
Total 60 (69%/100%) 10 (11·5%/100%) 70 (80·5%/100%) 3 (3·4%/100%) 14 (16·1%/100%) 87 (100%/100%)
ILI=influenza-like illness. Data are n (% of row total/% of column total).
Table 3: Results of laboratory testing by category of symptoms in contacts from cases with confirmed A/H7 infection
5. For personal use. Only reproduce with permission from The Lancet.
Virological analysis
The proportion of samples positive for A/H7 was highest in
the first 4 days from the onset of illness, and eye swabs were
more frequently positive than were throat swabs. Maximum
detection rates were 44% of eye swabs collected on the
second day of illness, and 12% for throat swabs taken on
the second day of illness (figure 2). 39 eye swabs shown to
be positive by RT-PCR were cultured. 31 (79%) of these
yielded infectious A/H7 virus. 13 RT-PCR-negative eye
swabs were all culture negative. Characterisation of the
viruses found in the index case, the fatal case, and the
three contact cases was done to exclude the possibility of
spread of a reassorted influenza virus variant. All viruses
characterised were completely of avian origin.1
Susceptibility to antivirals
The 50% inhibitory concentration of oseltamivir for the
H7N7 virus was 1·29 nmol/L (95%CI 1·19–1·40 nmol/L)
and of zanamivir 3·94 nmol/L (3·61–4·29). A known
sensitive control virus (A/Chicken/Pennsylvania/21525/83
H5N2) had a 50% inhibitory concentration of 0·33 nmol/L
(0·30–0·36) for oseltamivir, results which are similar to
previous findings in our laboratories. These values were
well within the range of 50% inhibitory concentrations for
sensitive H1N1 and H3N2 clinical isolates (0·2–6·8 nmol/L
for oseltamivir and 0·3–13·1 nmol/L for zanamivir,
dependent on isolate and assay).11
90 people in the case
registry reported that they had had prophylactic treatment.
Avian influenza virus infection was detected in one of
38 (2·6%) people who used oseltamivir, compared with
five of 52 (9·6 %) who reported that they had not taken
prophylactic medication (p=0·38).
Overview of control measures taken
On March 3, 2003, following confirmation that A/H7N7
was the cause of the avian influenza outbreak, the outbreak
management team advised all workers who screen and cull
poultry to wear protective eye glasses and mouth and nose
masks to reduce contact with avian influenza virus. People
with symptoms of influenza-like illness were exempted
from work. When the first case of A/H7-confirmed
conjunctivitis was diagnosed on March 7, 2003, and in
view of the concomitant increase in the number of
influenza virus cases, on March 9, 2003, the outbreak
management team recommended mandatory vaccination
with inactivated influenza virus vaccine be offered to all
poultry workers who handle, screen, or cull potentially
infected chickens. This policy aimed to reduce the risk of a
possible genetic mixing or reassortment of avian and
human influenza virus in one person through prevention of
infection with human influenza virus. As of March 10,
2003, all workers had agreed to be vaccinated. Based on
the virology update of March 14, 2003, when 19 confirmed
cases of A/H7 were discussed, as well as the first confirmed
contact transmission, preventive measures were stepped
up. The need for personal protection was emphasised, and
the importance of washing hands after leaving the
workplace and personal hygiene at home was stressed.
Immediate treatment with oseltamivir
was recommended for all new
conjunctivitis cases, and a prophylactic
regimen of oseltamivir (75 mg daily)
was started for all people handling
potentially infected poultry, to be
continued for 2 days after last
exposure. The recommendation for
vaccination was extended to all poultry
farmers and their families in a 3 km
radius of infected poultry farms, and
those suspected of having the infection.
Discussion
We describe a large outbreak of avian
influenza A/H7 in human beings, with
89 infected people, of whom 85 fitted
case definitions of conjunctivitis or
influenza-like illness. Conjunctivitis was
noted as the prevailing symptom in
three secondary cases, confirming the
predilection of these viruses for the eye.
That influenza-like symptoms were
reported less often by A/H7-positive
cases than other cases suggests that the
influenza A/H7 viruses do not cause
influenza-like illness. Alternatively, the
detection methods we used could have
been less suitable for virus detection in
infected people without conjunctivitis—
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THE LANCET • Vol 363 • February 21, 2004 • www.thelancet.com 591
0·05
0·10
0·15
0·20
0·25
0·30
0·35
0·40
0·45
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Day of illness
Proportionofpositivetests
0
10
20
30
40
50
60
70
80
90
Numberofpatientstested
Eye swabs
Throat swabs
Tested patients
Figure 2: Proportion of eye swabs and nose/throat swabs positive for influenza
by RT-PCR
13 patients were tested between days 19 and 61 of illness, but no eye swabs or nose/throat swabs
were positive for influenza.
H7 positive (%) H7 and H3 p
(n=89) negative (%)
(n=314)
Ocular symptoms
Red eyes 82 (92%) 184 (59%) <0·001
Tearful eyes 67 (75%) 165 (53%) <0·001
Burning eyes 55 (62%) 192 (61%) 1·000
Painful eyes 27 (30%) 133 (42%) 0·055
Itching eyes 50 (56%) 148 (47%) 0·166
Pus in eyes 41 (46%) 109 (35%) 0·067
Photophobia 28 (31%) 97 (31%) 1·000
Influenza-like symptoms
Fever 8 (9%) 75 (24%) 0·004
Cough 13 (15%) 125 (40%) <0·001
Rhinorrhoea 25 (28%) 129 (41%) 0·036
Sore throat 9 (10%) 110 (35%) <0·001
Headache 13 (15%) 114 (36%) <0·001
Myalgia 7 (8%) 79 (25%) <0·001
Table 4: Symptoms in A/H7 positive, and A/H7 and A/H3-
negative cases
6. For personal use. Only reproduce with permission from The Lancet.
a suggestion lent support by the negative results for swabs
collected 5 days after symptom onset from the veterinarian
who subsequently died. However, such differences in rate of
detection have not been noted for human influenza A
viruses, and, therefore, are not likely.
It has been postulated that the detection of influenza A
virus in eye swabs by RT-PCR may be the result from
mechanical contamination by virus-containing dust.
However, virus was detected more frequently in people who
had recently developed symptoms. Since all poultry workers
were still working at the time samples were taken, simple
contamination would be expected to occur more randomly.
The association of positive virus tests with recent onset of
illness, and the finding that contacts had ocular shedding,
led us to conclude that the conjunctivitis was caused by
replicating avian influenza A viruses.
Three household contacts in our survey had avian
influenza virus A/H7, which may have been attributable to
person-to-person transmission. This finding raised concerns
of possible viral adaptation or reassortment. Birds, and
especially waterfowl, can serve as a reservoir for a wide
range of genes of influenza A viruses, thus contributing to
the potential risk of generation of a novel pandemic
influenza virus strain.12
A prerequisite for reassortment is
simultaneous infection of a susceptible host (such as a pig or
human being) with both avian and human influenza viruses,
resulting in viral offspring that has a mixture of the genome
segments derived from both parental strains. Essential
contributing factors, such as the transmission of influenza
viruses from birds to pigs, and from pigs to humans, have
been noted on several occasions.12–18
Full details of the virological characterisation in this
outbreak will be published elsewhere, but to date, all
viruses examined had internal gene segments from avian
influenza A viruses and not from circulating human
influenza A viruses. This work builds on previous findings
that avian influenza viruses have pathogenic potential for
humans.19–22
Whether the behaviour of the A/H7/N7 viruses in this
outbreak was very different from that of other avian
influenza viruses in humans is unclear. During a recent
A/H7N1 outbreak in chickens in Italy, virological analysis
and serologic tests did not yield evidence of infection in
human beings. However, during the Italian outbreak
disease reporting was passive, and the absence of a
serological response has been documented for people with
H7N7 infection.2,3,23
By contrast, the avian influenza
virus A subtype H5N1 has caused illnesses ranging from
mild respiratory disease to influenza-like illness with
pneumonia and a high case-fatality rate. Yet, follow-up
investigations after the 1997 outbreak of the H5N1 virus
in Hong Kong showed anti-H5 antibodies in poultry
workers and health-care workers, which suggests that
transmission is much more widespread and that the case-
fatality rate is lower than previously supposed.24–27
In 1999, direct transmission of avian influenza A virus
subtype H9N2 occurred, again in Hong Kong, and the two
identified patients did seroconvert. Furthermore, screening
for antibodies to H9 showed evidence of widespread
exposure to the avian viruses in blood donors but not
health-care workers.21,28
These data illustrate the need for a
better understanding of the extent of transmission of the
avian viruses to humans, to help assess the potential risk of
emerging variants in times of outbreaks. Data suggesting a
common background to some of the genes found in both
viruses (H9N2, H5N1) that have caused significant human
disease are intriguing in this respect.29,30
Based on our data, veterinarians and people who cull
infected poultry have had the highest risk of A/H7
infection. The veterinarian who died had spent a few
hours screening flocks that were later confirmed to be
positive for HPAI. Yet, poultry farmers did not have high
rates of infection. Cohort studies are underway to explain
these differences in infection rates between workers.
Comparisons of transmission rates will be done after
serological tests are complete.
On Friday April 4, 2003, the outbreak of HPAI
expanded to two different regions of the Netherlands
(North Brabant and Limburg), where there were about
62 million chickens (figure 1). The data in the case
register suggest that before April 4, 2003, at least eight
people reported health complaints during the culling in
Gelderland, but lived in North Brabant and Limburg.
Two had confirmed A/H7 infection, and it is possible that
humans have contributed to the spread of A/H7 outside of
Gelderland. Veterinary control of the outbreak high-
lighted the importance of movement restrictions for
animals, vehicles, and humans beings, but several
breaches of practice were detected. Also, the size of the
outbreak meant that there was a shortage of experienced
poultry workers. In addition, we have at least four reports
of confirmed A/H7 illness in poultry workers from other
countries, who travelled back to their country of origin
during the time when they were likely to be shedding the
virus. The need for coordination of international
responses during outbreak control is an important lesson
for pandemic preparedness planning: at present, all
control measures in Europe stop at national borders.
A challenging aspect of any outbreak of an emerging
disease is the translation of findings into control measures,
since there may be very few data available on which to
base decisions. During the course of the HPAI outbreak,
measures were gradually increased in stringency, because
the initial assessment had been that, although A/H7N7
might be a threat to human health, the risk was thought to
be low. Treatment of all people involved in handling
infected poultry was only started in the middle of
March, after confirmation of several cases of A/H7 and
the first secondary case. The rationale was to reduce the
probability of coinfection of individuals by the avian virus
and any fortuitously circulating human influenza virus.
A difficulty faced by health planners was the paucity of
data about widespread and lengthy use of oseltamivir for
prophylaxis. Arguments against widespread use of
oseltamivir were: (1) the ethical dilemma of prescribing a
drug with possible side-effects to healthy people so as to
protect others; (2) mass prescription of drugs without
individual medical guidance could negatively affect the
national policy of restricted drug use; (3) potential for
development of resistance; (4) implementation and
improvement of personal protection measures might be as
effective as drug treatment; and (5) the rate of non-
adherence to oseltamivir might be as high as that for
personal protection. At first, people were slow to accept
antiviral medication; however, the uptake rate increased
after the fatal case.
Our experience with the largest documented outbreak
of avian influenza A virus of subtype H7N7 in human
beings provided important new data on the potential for
transmission of these viruses to humans. Attack rates far
exceeded those reported previously, but it remains unclear
whether this finding was due to unique properties of the
viruses, the type of poultry work taking place during this
outbreak, or a consequence of active case finding
including assessment of people with mild illness. A follow-
up cohort study is underway to assess the extent of
transmission to poultry workers (as measured by testing
for anti H7 antibodies) and potential risk factors.
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592 THE LANCET • Vol 363 • February 21, 2004 • www.thelancet.com
7. For personal use. Only reproduce with permission from The Lancet.
The size of the outbreak, which coincided with the peak
activity of human influenza virus, reinforced the message
that emergence of new pandemic influenza viruses might
arise via the mixing of genes from avian and human viruses
in humans, and that tracking and containment of these
viruses might be very difficult. Although we launched a large
and costly outbreak investigation (using a combination of
pandemic and bioterrorism preparedness protocols), and
despite decisions being made very quickly, a sobering
conclusion is that by the time full prophylactic measures
were reinforced (1 week after the first confirmation of
human infection), more than 1000 people from all over the
Netherlands and from abroad had been exposed. Therefore,
if a variant with more effective spreading capabilities had
arisen, containment would have been very difficult. We see
this outbreak as providing strong support for the need for
pretested pandemic preparedness plans, including the
stockpiling of essential control components such as vaccines
and antivirals.
Contributors
M Koopmans, A Bosman, and M Conyn designed the outbreak
investigation and the case registry; designed questionnaires; organised
logistics, data aggregation and transfer, and daily updates for all groups.
M Koopmans and A Bosman prepared the body of the manuscript.
B Wilbrink, H van der Nat, and A Meijer ran the lab logistics at RIVM,
including preparation of sampling kits, virological analyses, and coordination
of shipments and data for subtyping. H Vennema developed and
implemented H7 realtime typing in the course of the investigation;
J van Steenberg coordinated activities between the outbreak team and other
parties such as the municipal health services, medical microbiology
laboratories, and the ministries. G Natrop did the medical examination of
possible cases at the regional crisis centre; R Fouchier and A Oosterhaus
confirmed avian influenza virus infections as National Reference laboratory
for Influenza viruses. M Koopmans, M Conyn, J van Steenberg, and
A Osterhaus served as members of the (National) outbreak management
team, and helped formulate guidelines for control of the outbreak.
Conflict of interest statement
None declared.
Acknowledgments
We thank Carolien de Jager, Winette van den Brandhof, Petra Brandsema,
Myrna du Ry Holle van Beest, and Nienke Bruinsema for helping us handle
the large amount of patient data and processing laboratory results in the case
register; Bas van der Veer, Erwin de Bruin, Louise Beens,
Esther van de Kamp, Gert-Jan Godeke, Paul Bijkerk, Ron Alterna,
Tineke Herremans, Jacintha Bakker, Mariam Bagheri, Fleur Twisk,
Erwin Duizer, Theo Bestebroer, Vincent Munster, Martin Schutten,
Gerard van Doornum, Ruud van Beek, Chantal Baas, Judith Guldemeester,
Annelies Albrecht, Jeroen Kellermann for assistance with virological analysis
of patient samples and preparation of the logistics for the outbreak
investigation; Loek Timmermans for programming the interface to enable
the link between laboratory data and the case register.
This study was funded through public health budgets available for outbreak
management from the ministry of health.
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