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In 2003, highly pathogenic avian influenza (HPAI) broke out in Southeast Asia. Until recently, HPAI only broke out in Indonesia, Viet Nam, Thailand, Laos, Cambodia and China and other eastern Asian countries. But from April to June, 2005, more than 6,000 migratory birds died of H5N1 in Qinghai Lake, China. In July 2005, H5N1 outbreaks also occurred in Russia and Kazakhstan. In August, 2005, a wild bird died of H5N1 in a lake area in northern Mongolia. In October 2005, poultry or wild birds infected with H5N1 were also detected in European countries such as Turkey, Romania, Greece, Sweden and Britain. The H5N1 avian influenza epidemic broke out in Anhui, Hunan and Liaoning. This worldwide outbreak of avian influenza has caused a large number of poultry to be killed and infected people. As of November 2, 2005, 122 people have been found to be infected with H5N1, of which 62 died [1]. The worldwide outbreak of H5N1 highly pathogenic avian influenza has caused great losses to agriculture and aquaculture, posed a serious threat to human life safety, and attracted worldwide attention. The worldwide outbreak of HPAI can easily remind people of the role of migratory birds in the spread of avian influenza, because migratory birds have the ability of long-distance migration across national boundaries, and they are regarded as a major carrier of avian influenza virus. However, based on the existing facts, it is still difficult to determine the role of migratory birds in the spread of avian influenza.The outbreak of avian influenza in 2005 showed some characteristics different from previous outbreaks. The research work is still going on. Although the role of wild birds in the spread of avian influenza is still controversial, it is urgent to establish a monitoring network for wild birds and conduct a dynamic study on the epidemiology of avian influenza virus.
1 influenza virus characteristics
Avian influenza virus belongs to Orthomyxoviridae. According to nuclear protein (NP) and membrane protein (M1), it can be divided into three types: A, B and C. According to hemagglutinin (HA) and neuraminidase (NA), influenza A virus is further divided into subtype 2. Up to now, 16 HA (H1-H16) and 9 NA (N1-N9) influenza virus subtypes have been found, and H5N1 is one of the virus subtypes 3.
According to the pathogenicity, avian influenza viruses can be divided into HPAI and LPAI (low pathogenicity avian influenza virus). LPAI is often parasitic in the respiratory and digestive systems of birds, and generally does not cause pathological reactions, or only causes mild pathological symptoms. However, HPAI can infect various tissues and cells of the host, causing various organs of the host to fail, leading to death, and its mortality rate is as high as 100%. Up to now, all the HPAI found are H5 and H7 subtype influenza viruses. LPAI can be transformed into HPAI4 through the change of amino acid site in HA0 cleavage region.
Influenza A virus has been isolated from many animals, including humans, pigs, horses, seals and wild birds. The phylogenetic study of influenza A virus found that influenza A virus has host interspecific relationship, and other animal influenza A viruses originated from waterfowl influenza A virus 5.
The wild migratory birds themselves are the natural reservoir of bird flu.
All virus subtypes of 16 kinds of HA and 9 kinds of NA have been found in aquatic bird populations. Stakkknecht and Shane isolated 2,317 strains of virus from 21,318 birds, with a carrying rate of 10.9%, including 14,303 birds of the order Animalia, and 2,173 strains of virus were detected (15.2%). Except for geese and ducks, the carrying rate of influenza virus in other birds was only (2.1%) 6. It is worth noting that influenza A virus seems to have achieved an ideal parasitic adaptation in the host of wild birds. LPAI is parasitic in the digestive or respiratory system of the host. LPAI isolated from most wild birds is nontoxic, and the host has no symptoms or only mild symptoms. The transmission between birds can be directly or indirectly through dust, water, food and other pollutants contaminated by feces. LPAI may be transmitted to poultry through contact between wild birds and poultry, and mutate in poultry population, leading to HPAI. Poultry infected with HPAI can lead to systemic infection. Clinical symptoms include decreased egg production, dyspnea, excessive tears, brain edema, diarrhea and neurological symptoms that eventually lead to death. But so far, there is no more evidence to prove that wild birds are natural reservoir of HPAI. Therefore, there is a theory of HPAI outbreak mechanism that only when LPAI in wild waterfowl spreads to poultry such as chickens or turkeys, and LPAI mutates into HPAI in poultry, will it lead to the outbreak of highly pathogenic avian influenza. Since 1959,There were 19 incidents in which LPAI from wild birds was transmitted to poultry and mutated into HPAI in poultry, which eventually led to the outbreak of the epidemic.
3 Debate about Wild Birds as Spreaders of HPAI
It is precisely because wild birds are the natural reservoir of avian influenza virus, and the migratory route of migratory birds can obviously connect Asian countries with the outbreak points of H5N1 avian influenza in Siberia, Kazakhstan and Europe. Therefore, when HPAI was raging, some people suspected that migratory birds were spreading the bird flu virus. But so far, no clear source of H5N1 HPAI that ravaged Asia in 2005 has been found. It is speculated that before the outbreak of HPAI in domestic chickens in Hong Kong in 1997, LPAI, the predecessor of this kind of HPAI, might parasitize the wild waterfowl population in southern China and spread and evolve, and then contact with poultry in Hong Kong through some channels. LPAI mutated into HPAI and broke out in 2003. The Hong Kong government controlled the outbreak of bird flu by killing 1.5 million poultry. Then, in December 2003, the virus once again ravaged Korean chicken farms. Outbreaks in Japan and Vietnam in January 2004; An epidemic was discovered in Indonesia in February; It soon led to outbreaks in Thailand and China.
But many ornithologists doubt the hypothesis that wild birds infect avian influenza. First, since the late 1990s, the United States Department of Agriculture has detected tens of thousands of migratory birds migrating from Asia to Alaska, and Hong Kong researchers have also sampled thousands of inbound migratory birds, but none of these tens of thousands of wild bird samples have detected H5N1 subtype. Up to now, the research results show that the H5N1 strain that causes high mortality of poultry is also pathogenic to wild birds. Wild birds infected with HPAI will also get sick and die. When the host dies, the spread of the virus stops, and the spread chain of the virus is interrupted. Secondly, the transmission path and outbreak time of avian influenza are not very consistent with the migration path and migration time of migratory birds. Although wild birds are the natural reservoir of avian influenza, it is not entirely accurate to blame wild birds for the outbreak of HPAI. Because in addition to the migration of migratory birds, bird flu may be spread, the backward feeding methods of mixing livestock and poultry with wild birds provide an ideal environment for the mutation and breeding of bird flu virus, and human activities such as frequent poultry trade and wildlife smuggling may play an unimaginable role in the spread of the virus. For example, in January 2004, an outbreak of H5N1 occurred in Lhasa, Xizang, which was finally found to be caused by selling a batch of sick poultry from Lanzhou, Gansu, 1500 kilometers away to Lhasa. An even more surprising incident occurred in Brussels. In October 2004, two crested eagles smuggled into Belgium from Bangkok Bird Market were seized at Brussels Airport.And detected that it has been infected with H5N1 virus. Therefore, many biologists are skeptical about the hypothesis that migratory birds spread avian influenza virus.
While people are arguing about the role of wild birds in the spread of avian influenza, the H5N1 outbreak in 2005 showed several aspects different from previous epidemics. Until the spring of 2005, there had not been any death of wild birds infected with H5N1 virus. However, in April 2005, the H5N1 outbreak in Qinghai Lake killed more than 6,000 migratory birds. At present, researchers are still investigating the causes and possible consequences of the outbreak of H5N1 in Qinghai Lake.
Then in August, 2005, wild birds in Lake Irkher in Mongolia also died of H5N1 infection. There are few poultry farms in Lake Irhull. It is likely that wild birds infected with H5N1 brought the virus to Lake Irhull, and the US Department of Agriculture only detected H5N1 strains in dead birds, but not in other living ducks, gulls, geese and swans. It is not known which kind of birds spread the virus, which may be very difficult, because there is very little research work on avian influenza virus in other birds except waterfowl. While the research work is still in progress, in October 2005, several European countries in Caspian Sea, Black Sea and Mediterranean Sea broke out one after another, which made more and more people believe that wild birds played a role in the spread of avian influenza.
In October 2005, an outbreak of avian influenza occurred in Hunan, Anhui and Liaoning, and the state took decisive measures to control the epidemic. Some experts said that the epidemic focus may come from migratory birds 9.
4. Establish a wild bird influenza virus monitoring network and strengthen
Protection of wild bird resources
While the role of wild birds in the transmission of avian influenza is still controversial, Europe has begun to establish a European-wide investigation and monitoring network for wild birds. Researchers in the Netherlands have collected more than 6,000 bird samples on the migration routes of European migratory birds. The monitoring network is not only to study the role of wild birds in the spread of avian influenza, but also to monitor the changing direction of avian influenza epidemic, study the variation law of avian influenza virus, and provide valuable data for preventing the outbreak of avian influenza.
Because all the influenza strains in the history of human influenza outbreaks are new strains formed by the recombination of avian influenza strains and human influenza strains, it is difficult for human immune system to play a role in the face of this new strain, and it is difficult for vaccines based on unchanged strains to play a role in the new strain, so it is easy to trigger human influenza outbreaks, resulting in significant economic losses and human death. The wild bird influenza epidemic monitoring network can not only be used as an early warning network for human influenza outbreaks, but also monitor the variation direction of viruses, providing reliable data for vaccine development, and developing vaccine strains that may cause influenza outbreaks before influenza outbreaks, thus changing the previous practice that vaccines can only be developed after influenza outbreaks. In addition, this monitoring network can also monitor the changes of antiviral drug resistance of viruses for a long time to ensure the effectiveness of antiviral drugs in the emergency of influenza outbreak. At present, it has been found that avian influenza virus has developed resistance to interferents based on hemagglutinin (such as amantadine); The interferents developed based on neuraminidase mainly include Tamiflu produced by Roche and Rekenza produced by Gkaxo Smith Kkine. Recent studies have found that influenza virus has produced a few resistance to Tamiflu, while Rekenza has not found any record of resistance because of its low dosage. Therefore, governments around the world should pay attention to the problem of drug resistance while stockpiling antiviral drugs. Use the monitoring network to monitor the virus for a long time,The problem of drug failure caused by drug resistance can be found in time.
Therefore, it is of great significance to establish an influenza surveillance network for wild birds. In the face of severe avian influenza epidemic, China should immediately set up its own wild bird monitoring network, study the role of wild birds in the outbreak of avian influenza, find key hosts, study the transformation and variation law between LPAI and HPAI, monitor the direction of virus variation, and provide reference for vaccine development, and monitor the change of virus resistance, so as to provide reference for the development and storage of antiviral drugs.
5 conclusion
The role of wild birds in the spread and outbreak of avian influenza is still controversial. By analyzing the existing evidence, it is still impossible to confirm the role played by wild migratory birds in the spread of avian influenza. After more than one year’s molecular epidemiological investigation of avian influenza, although it has not been confirmed that wild birds are natural reservoir of HPAI, it can be confirmed that wild birds can be infected with HPAI H5N1 virus, not only migratory birds but also resident birds. All kinds of facts remind us that the outbreak and epidemic of HPAI H5N1 in the world may include the repeated transmission link of "wild birds → poultry → wild birds → poultry", and each host transfer and repetition may enhance the toxicity of the virus.
LPAI can mutate cyclically in poultry and wild birds until the HPAI epidemic occurs. HPAI virus is fatal to poultry and wild birds that originated in the first place. Infected wild birds are often dying or dying, which may affect their ability to spread the virus over a long distance. The fact that migratory birds in Qinghai Lake are infected with avian influenza reveals that H5N1 virus can spread among wild birds. However, these viruses are collected from dead or dying individuals, and they are the ultimate hosts. The further monitoring results of migratory birds that survived the bird flu control in Qinghai Lake will prove whether it is possible for migratory birds in Qinghai Lake to spread the virus with migration. At present, before we fully understand the role of migratory bird migration in the process of bird flu transmission, we should not blindly assume that HPAI has nothing to do with migratory bird migration, nor should we ignore the role of migratory bird migration in bird flu transmission. In addition, a very important point is often overlooked by everyone, that is, keeping birds. Previous studies mainly focused on migratory birds, and recently HPAI virus was detected in resident birds. If HPAI H5N1 can be isolated from a large number of healthy birds, it will be the biggest threat for human beings to prevent and control avian influenza.
From the perspective of logistics, environment and biodiversity, it is difficult to control avian influenza infection in wild birds at this stage. Indiscriminately killing wild birds is ineffective in preventing the spread of avian influenza, and it is likely to cause the extinction of wild birds.
In addition to paying attention to the role of wild birds in avian influenza, limiting the contact between poultry and wild birds should be a key part of avian influenza prevention strategy. We should reduce the contact between people, poultry and wild birds as much as possible, improve the level of poultry raising and avoid free-range; Strictly manage the poultry and wildlife trading market; Strengthen quarantine and immunization work; Put an end to illegal unlicensed poultry and wildlife trade.
In order to prevent the spread of HPAI, it is urgent to carry out scientific research on wildlife diseases. Establish a monitoring network for avian influenza in poultry and wild birds. Monitoring, sampling and analyzing the evolution and variation of avian influenza subtype virus in wild birds. Establish and improve the laboratory research ability to quickly detect and analyze the characteristics and types of viruses. Establish a perfect monitoring network of wild bird epidemic focus in order to quickly respond to virus emergencies and provide timely reference for national decision-making. Long-term monitoring and detection of avian influenza epidemic situation. Investigate the wild host distribution of avian influenza virus, study the variation law of the virus, determine the distribution, types and natural history of avian influenza virus in wild birds, and explore the relationship between wild migratory birds and agriculture and aquaculture structure and its role in the transmission of avian influenza virus to poultry and people. Develop and reserve safe vaccines and antiviral drugs against avian influenza virus. Organize veterinarians, wildlife experts, ornithologists, virologists, molecular biologists and other multidisciplinary experts to jointly study the changing law of avian influenza, fully understand the role of wild birds in the spread and spread of avian influenza virus, and prevent the outbreak of avian influenza and human influenza.
Acknowledgement This research plan has received strong support from the Ministry of Science and Technology, the Chinese Academy of Sciences, the State Forestry Administration, the Ministry of Agriculture, the Science and Technology Research Group of the National Highly Pathogenic Avian Influenza Prevention and Control Command, and the Institute of Zoology of the Chinese Academy of Sciences. It is supported by the key project of the Ministry of Science and Technology (2004BA519A11), the President’s Fund of Chinese Academy of Sciences and the frontier project of the Institute of Zoology. Thank you very much!
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