Highlights of the FAO and OIE International Scientific Conference on Avian Influenza and Wild Birds
2006年5月30－31日

意大利罗马

May 30 - 31, 2006, Rome, Italy

Ward Hagemeijer   
Introduction
At the end of the wild bird spring migration season 2006, more than 300 experts from around the world met to discuss the interface between avian influenza (AI), most notably highly pathogenic (HP) H5N1 or bird flu virus, and wild birds. The 2-day conference was sponsored by the Food and Agricultural Organization (FAO) of the United Nations and the World Organisation for Animal Health (OIE). The OIE, founded in 1924, is the international standard-setting body for animal health.

In his welcoming address, Dr. Gideon Bruckner[1] noted that the conference was bringing together representative experts from a variety of disciplines, including medical professionals, veterinarians, ornithologists, virologists, conservationists, and others. The stated purpose of the gathering was to share knowledge and expertise and to seek answers to the many unknown factors associated with AI, particularly those that are related to the role of wild birds in disease epidemiology. The transport of HPAI via migratory bird flyways, the sale of wild birds and other wildlife, and unmapped global trade were among some of the issues discussed by conference presenters and attendees.

The conference began with several overviews that set the scene for the more in-depth presentations that followed. Sessions were focused on the following aspects: ecology and virology; surveillance; sampling and risk analysis, including the risk transmission from wild birds to humans; and tools for disease management.

Abstracts and downloadable files of conference presentations are available at the FAO Web site.[2] This site also provides links to a number of background documents about AI. Additional information about FAO efforts to address the threat of AI can also be found at this Web site.[3]

The following report includes some of the most noteworthy information from a number of conference sessions.

AI — Global Overview
The meeting began with a historical perspective and an updated overview of the current global situation and developments in relation to HP H5N1. Calling it "an unprecedented crisis with complex epidemiological and socioeconomic impacts," Domenech[4] maintained that associated risks and impacts have extended beyond poultry systems to include the security of other foods and products, economic livelihood, and other zoonotic diseases.

The HPAI virus has been detected worldwide, with the exception of in the Americas. However, the situation overall seemed more stable at the end of May 2006, due to increased political and monetary support and to the increasing use of more efficient surveillance methods and tools for infection control.

The exception to the apparent current stability is the presence of HPAI in Africa, where poultry and/or wild birds in 8 countries are currently contaminated. Unlike other European, Asian, and Middle Eastern countries, most countries in Africa do not have sufficient resources to manage or eradicate the disease; thus, HP H5N1 could become endemic in areas of the continent.[4]

Wild birds have been strongly implicated in the spread of H5N1 westward from Asia and into the Middle East and Africa. However, how the spread has occurred remains unclear. More data are needed, particularly those that can be expressed through mapping of migratory routes. Furthermore, additional research is needed to determine whether wild birds are, or can become, permanent reservoirs of HPAI H5N1.[4]

FAO is concerned that international interest has been focused almost exclusively on the possibility of AI becoming epidemic in humans, with much less emphasis being placed on the potentially devastating impact on poultry (and subsequently, economic livelihoods) and other animals.[5] Domenech emphasized that the best way to protect people from AI is to control and try to eradicate the disease in animals.[4] Toward this end, an AI strategy developed by FAO/OIE includes targeted risk-based active surveillance, eradicating diseased animals, biosecurity, and movement control.

Surveillance and monitoring currently include poultry and other animals, followed by rapid reporting of any outbreaks to competent authorities and use of strict measures to limit disease spread. Limiting spread should entail the culling and secure disposal of sick poultry, and control of the movements of targeted poultry and related products.

Trade is considered the most frequent mechanism of spread of HPAI H5N1. This includes local, regional, and international trade of poultry and related products, and the trade of captive wild birds. Such activities take place both legally and illegally, with illegal trading being especially difficult to monitor.

Specifically, both movement of poultry to and from markets and the people involved in poultry production and marketing have been the main spreaders of disease to previously unaffected areas. Therefore, FAO is now urging farmers, traders, and others who come into close contact with poultry to be particularly careful to adhere to basic hygienic standards and for biosecurity measures in farm settings to be tightened.

Until more data about wild birds are available, the OIE recommends that control efforts be focused at the animal source (poultry) rather than on wild bird populations in general.[5] Bruschke[6] described the new OIE standard for international trade and notification of disease, emphasizing that it is aimed at facilitating transparent reporting, including reporting of viruses in wildlife, while not creating unjustified barriers to trade. Standard recommendations include having mechanisms in place to encourage the reporting of sick animals at the local and regional levels. However, on the basis of the belief that a pandemic can be prevented if the viral load in poultry can be reduced, the standard does not recommend any measures that extend beyond poultry.

Early detection of HPAI H5N1 in poultry is therefore crucial, and the OIE standard stresses implementation of early warning systems in all countries. Only 4 countries in the European Union (EU) have seen outbreaks among poultry.[7] Brown contended that this containment was at least partly attributable to the use of early warning systems and to implementation of increased biosecurity standards.[7]

Lubroth[8] specifically focused on AI in wild birds, and acknowledged that both migratory behaviors and the effects of different environments on the spread of H5N1 are not completely understood. Although it is known that transmission from wild birds to poultry can occur, transmission between wild birds is still undocumented. Additionally, a positive antibody test result reflects exposure but not carrier status, and virus isolation does not necessarily indicate that the animal being evaluated is a reservoir for HPAI H5N1; both of these "knowns" make determinations that are related to AI transmission more difficult.

Other barriers to obtaining data that could describe potential transmission include:

Most identification of virus has been made only in dead or sick birds, rather than in healthy birds;

Limited expertise and funding to support wild bird research; and

Various logistic problems related to sampling exist.
AI knowns in wild birds include:

The Z genotype of H5N1 dominates, and has expressed increased virulence and increased host range; and

Morbidity and mortality seem to have increased over time in Mallard (Anas platyrhynchos); excretion of the virus has also increased.[8]
Ecology and Virology: What Is Known About How Low Pathogenic AI and HPAI Viruses Behave
More is known about low pathogenic (LP) influenza viruses in wild birds than is known about HPAI. Webster and colleagues[9] provided a review of findings specific to LPAI. These findings included the following:

Ducks and shorebirds appear to be the natural reservoir of LPAI viruses, which mainly occur in the intestinal tract in a limited number of species.

Differences have been observed between the Americas and Europe. In the Americas, shorebirds carry LPAI viruses north in spring; ducks carry the viruses south in the fall.

In Europe, waders (shorebirds) are not often infected with LPAI. Phylogenetic differences between the continents suggest limited mixing between the Americas and Eurasia.

LPAI viruses seem to follow the fecal-oral route in wild birds.

An intermediate host is necessary for LPAI viruses to be transmitted to humans.[9]
Differences Between LPAI and HPAI Viruses
There are indications that HP H5N1 behaviors differ from those of LP H5N1:

Most notably, direct transmission of HP H5N1 from wild birds to humans has been documented (Azerbaijan);

There is high lethality among water birds infected with HP H5N1, although this varies significantly among types;

Transmission of virus genes from poultry to wild birds and respiratory transmission and transmission to felids have also been documented;

HPAI H5N1 virus has also shown increased thermal stability[9]; and

Finally, the persistence of HP H5N1 in water appears to be shorter than for other AI viruses; persistence is longer in brackish than in fresh water.[10]
H5N1 Virus Genotypes
Isolates obtained from the first large-scale outbreak of HPAI H5N1 in wild birds provided important data about virus genotypes. The outbreak, which occurred in Qinghai Lake in China during the late spring of 2005, involved 6000 birds representing 6 species.[11] Sequencing results suggested that the original outbreak occurred in Bar-headed Geese (Anser indicus), a species that is found around the lake, which subsequently infected other wild bird species. Four different H5N1 genotypes were detected. Although the initial 2 viruses detected did not show this, most other isolates were found to possess a residue that is known to be associated with virulence in mice and adaptation to humans.[11]

Following this outbreak, virus that was isolated in Mongolia; Russia; and Liaoning Province, China, proved to be closely related to one of the genotypes identified in Qinghai. According to Chen,[11] this genotype has also been found in some countries in Europe and Africa. She contended that the apparent spread and dominance of this genotype underscore the need for more intensive surveillance.

Risk for Introduction of HPAI H5N1 to the EU by Migrating Birds
Pfeiffer[12] described a recently published risk assessment conducted by the European Food Safety Authority that focused on the probability of introduction of HPAI H5N1 to the EU by migrating birds and the probability of transmission to other wild birds and poultry. In this qualitative assessment, risks were expressed in terms of probability, which varied, and as associated uncertainty, which was uniformly high. Findings included:

High probability of HPAI H5N1 being released into the EU by higher risk species of migratory birds;

Low probability of HPAI H5N1 being released into the EU by other species of migratory birds;

Low-to-high probability of HPAI H5N1 being transmitted from wild birds to poultry in free-range and backyard flocks in Europe or in indoor flocks without high biosecurity standards; and

Low-to-medium probability of HPAI H5N1 being transmitted to indoor poultry flocks kept under conditions of a high biosecurity standard in a high-density poultry population area.
However, Pfeiffer[12] noted that this type of modeling requires a better understanding of the infection dynamics in wild bird populations.

AI: Humans, Wild Birds, and Poultry
The risk for a human AI pandemic spread by wild birds was addressed by Brown,[13] who described characteristics of the cases of human infection that have occurred in the European region. During February and March 2006, deaths from H5N1 in wild swans heralded the spread of virus, and measures to prevent transmission to poultry were instituted. However, she noted that 34 of 52 countries in the region have confirmed HPAI H5N1 in poultry or wild birds (as of May 19, 2006).

Out of a total of 218 human cases documented (as of May 26, 2006), there have been 124 deaths worldwide — a case fatality rate of 57%. Twelve deaths occurred in Turkey, 2 in Iraq, and 8 in Azerbaijan, with most other documented deaths occurring in Southeast Asia. An important finding is that greater geographic diversification among humans was seen after the Qinghai Lake outbreak in wild birds during the summer of 2005. Prior to this, cases of HPAI were confined to 2 countries; this number increased to 10 after the Qinghai outbreak.

Azerbaijan, Turkey, and Iraq: Differences in Human Cases. The human infections in Azerbaijan were the first documented cases of direct infection from wild birds to humans. It is believed that transmission occurred through the plucking of feathers of dead swans. It is not clear whether this happened indoors or outdoors, whether there was exposure to carcasses before or after defeathering, and whether the carcasses were consumed.

In contrast, investigators believe that exposures for the human cases in Turkey and Iraq occurred following contact with poultry. Exposures took place through slaughtering and preparation for consumption, and exposure risks were most likely amplified (at least in Turkey) because poultry had been brought indoors due to cold weather. Caring for sick chickens and playing with parts of dead chickens may also have been factors.

The ratio of male:female infection was 4:5 in Turkey, 2:6 in Azerbaijan, and 1:1 in Iraq. The average age of those infected was 9.5 years in Turkey, 16.5 years in Azerbaijan, and 27 years in Iraq. The low average age of infected individuals in Turkey is possibly related to children using poultry as pets and the fact that adolescents are often responsible for slaughtering of poultry (and may also be more likely to pick feathers from wild swans). However, the possibility that children and adolescents are more susceptible to AI has not been excluded.[13]

Family clusters of human cases have been found in all 3 countries, but these are most likely due to common source(s) of exposure. To date, 2 families in Turkey had 2 and 3 family members with AI, respectively; 1 family had 2 infected members in Iraq. In Azerbaijan, the 6 cases from 5 families were cousins.

The outbreak in Azerbaijan was the most complex with respect to transmission, because affected families had healthy poultry and denied contact with wild birds. It is possible that contact with wild birds was denied for fear of punishment (eg, illegal harvesting of swans). Furthermore, the families who were involved did not initially believe that their children had AI. Throat cultures and blood specimens were obtained from 18 household contacts; no H5N1 virus was detected and all individuals were antibody-negative. Specimens from a mother in close contact with 2 patients with AI were also negative. Of interest, 3 asymptomatic cases were detected through surveillance that extended beyond affected households.

Human Cases: Implications for Clinical Interventions, Surveillance, and Infection Control. Although it is currently believed that family clustering has been due to a common exposure, the possibility of human-to-human transmission cannot be excluded. The current recommendation is that family members receive antiviral prophylaxis as quickly as possible following identification of a case, because of the same (high) risk for common exposure.

Although many strains of H5N1 viruses have been detected, virus seen in humans has been 100% avian. Brown showed how H5N1 isolates from humans and animals in Europe and the Middle East have a phylogenetic relationship. These isolates have segregated from earlier Asian isolates and demonstrate antigenic differences.[13] In relation to human risks, Kida[14] pointed out that any subtype of AI could contribute genes to the generation of reassortants in pigs, and can therefore be a candidate for future pandemic strains. This possibility stresses the importance of surveillance of both AI and swine influenza.

In humans, virus infection acquired from wild birds has not been different from infection acquired from poultry. However, there is a difference between wild birds and poultry with respect to potential transmission. Most importantly, risks associated with close human contact with wild birds are far less than contact with poultry. This means that virus from wild birds will have less chance to reassort, and therefore adapt to humans. Consequently, wild birds most likely constitute a lower risk to humans due to less overall intensive exposure.

According to the World Health Organization, evidence indicates that the principal source of human infection with H5N1 is close contact with sick or dead birds. High-risk behaviors for transmission include slaughtering, butchering, or other preparation for consumption of infected birds. The European Center for Disease Control categorizes risk as follows:

Group 1 — low but real risk: The risk is confined to those who have close and intense contact with sick poultry; and

Group 2 — theoretical risk (precautions required): This group includes individuals in places where H5N1 may be present — healthcare workers, cullers, farm workers, and individuals having close contact with infected wild birds (eg, hunters and ornithologists).
Brown concluded that with respect to prevention, emphasis should be on identification and education of vulnerable human populations, including hunting communities.[13]

Vulnerable populations also include individuals who may be exposed via the wildlife trade.[15] This trade is a huge industry, involving an estimated 350 million live animals annually, with a worth of $20 billion. At least 25% (and perhaps more) of this trade happens illegally, thus involving unregulated, untested wildlife. In contrast to the distribution of beef, pork, and chicken worldwide, even the flow of legal wildlife trade remains largely uncharacterized.

Karesh[15] described both legal and illegal wildlife trading, including implications for the spread of AI. He asserted that in addition to having the potential to infect humans, such trade threatens rural livelihood, native wildlife populations, and overall ecosystem health. Highly pathogenic stains of AI and Newcastle's disease have been detected in traded nondomestic birds. Traded birds also have the potential to harbor parasites, bacteria, and viruses that are typically not a threat to a host, yet could pose a threat when introduced into a new geographic location or to a new species. Examples of Ebola virus transmission in central Africa and the spread of severe acute respiratory syndrome (SARS) were used to demonstrate previous connections between wild animals and humans. Karesh also provided insight into the myriad of ways in which wild animals are used worldwide, including use as food, traditional medicines, entertainment (eg, cockfighting), and pets. He contended that reducing contact among species, including humans, at hubs created by the wildlife trade would be more a more efficient and cost-effective approach than attempting to eradicate viruses among wild birds.

Conclusion
Consensus of those attending the conference was that migrating wild birds have had, and will continue to have, an epidemiologic role in transporting HPAI.[16] According to the concluding document, "Several presentations at the conference, some supported by recent publications in peer-reviewed scientific journals, implicated wild birds in the introduction of HPAI H5N1 virus at considerable geographical distance from known H5N1 outbreaks in poultry.[16]" The specifics of how wild birds have contributed to the spread of HPAI to more than 50 countries on 3 continents and whether wild birds are reservoirs of virus remain undetermined.

It was also concluded that poultry farming systems and associated trade have a larger role in the spread of HP H5N1 than migratory wild birds. Participants appeared united in the conviction that the key to controlling disease is early detection and eradication among poultry.

A concerted global effort is required to monitor and contain HPAI outbreaks, whether in humans or other animals. Better understanding of the role of wild birds though strengthened monitoring and increased mapping of migration, improved surveillance methods and tools, and an increased multidisciplinary focus will all be required to prevent further consequences related to the HP H5N1 virus.

References
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International Scientific Conference on Avian Influenza and Wild Birds Web site. Available at: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/conference/index_en.html Accessed August 2, 2006.
Food and Agricultural Organization (FAO). Avian influenza control and eradication — FAO's proposal for a global programme. March 2006. Available at: http://www.fao.org/ag/againfo/subjects/documents/ai/Global_Programme_March06.pdf Accessed August 2, 2006.
Domenech J, Lubroth J, Martin V. Avian influenza: global situation. Program and abstracts of the FAO and OIE International Scientific Conference on Avian Influenza and Wild Birds; May 30-31, 2006; Rome, Italy. Available at: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/conference/
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