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EINet Alert ~ Oct 28, 2005


*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
- EU: Bans imports of captive live birds from third countries
- Global: WHO recommended H5N1 prototype strains for influenza pandemic vaccine development remain the same
- Global: Roche limits Tamfilu shipments to prevent hoarding
- Europe: Very low risk to human health from A/H5N1 avian influenza
- Romania: New suspected bird case of avian influenza
- Romania: OIE report on avian influenza
- Russia (Tambov, Chelyabinsk, Altai, Tula): Avian influenza spreading
- Croatia: H5N1 virus confirmed in bird flu case
- UK: Probably had 2 birds with avian flu H5N1
- Greece: Avian influenza confusion
- Sweden (Eskilstuna): mallard, H5N3 strain confirmed
- South East Asia: Cumulative number of human cases of avian influenza A/(H5N1)
- Indonesia: Suspected avian flu cases test negative, but 2 additional confirmed cases
- Indonesia: Possible bird flu deaths on Bali Island
- Indonesia: FAO to help Indonesia fight avian flu
- Thailand: Avian influenza spreading; additional human case
- Taipei/China: Follow up on smuggled birds, H5N1 confirmed; Taipei preparedness
- China (Hunan): Avian influenza outbreak
- USA: CDC sets rules for handling 1918 flu virus
- USA: Flu shots now open to all; officials fear fake Tamiflu
- USA: USDA Efforts and Response to Avian influenza

1. Updates
- Influenza

2. Articles
- Avian influenza outbreaks in the WHO European region and public health actions
- Susceptibilities of Antiviral-Resistant Influenza Viruses to Novel Neuraminidase Inhibitors

3. Notifications
- WHO Comprehensive Avian Influenza website
- Controlling avian influenza does not authorize inappropriate animal depopulation methods
- Banning poultry imports should be based on established rules


Global
EU: Bans imports of captive live birds from third countries
Member States endorsed a draft Commission decision to ban imports from third countries of captive live birds other than poultry for commercial purposes, at a meeting of the Standing Committee on the Food Chain and Animal Health. These measures aim to strengthen further the EU's defenses against avian influenza. The ban covers captive live birds other than poultry imported for commercial purposes. A separate decision regulates the movement of birds accompanying their owners which will be subject to certain conditions. The ban on commercial imports of captive live birds and the regulation of movements from third countries of birds accompanying their owners (pet birds) will be effective immediately following adoption by the Commission. Birds will be allowed to be moved between approved zoos and similar institutions. Hatching eggs of non-poultry birds can be imported for use in authorised hatcheries if their shells are decontaminated upon arrival, or if they are being sent to zoos. Concerning the movement of birds accompanying their owners, Member States can allow no more than 5 birds accompanying their owners to enter from third countries on condition that they have undergone a 30-day quarantine in approved third countries, otherwise they must be subject to 30 days quarantine in the Member State of destination. As an alternative to quarantine, such birds may be admitted if they have been vaccinated against avian influenza, or have tested negative for avian influenza during a 10 day isolation period before movement. The movement of birds accompanying their owners is not restricted for Norway, Switzerland, Liechtenstein, Andorra, Iceland, Greenland, Faeroe Islands and San Marino.

Import bans have already been imposed on live birds from areas where H5N1 has been confirmed, including Turkey, Romania and the Greek island of Chios. Alan Jones, a leading avian vet, said there should be an urgent review of the UK quarantine conditions. "In my experience there should never have been a situation where birds from different continents shared the same air space," he said. Debby Reynolds, the government's chief veterinary officer, said that quarantine regulations would be examined, adding there were "quite a number of unanswered questions." Quarantine facilities are privately run and licensed by Defra, but Duncan McNiven, an RSPB investigative officer, said the system was badly regulated. Some vets fear the import ban could also fuel a thriving underground trade in bird imports.

In addition, Congo banned 21 Oct 2005 the import of live birds, pigs and livestock from countries affected by H5N1. Other African countries have also banned poultry imports, including Senegal, Uganda and neighboring Congo-Brazzaville. (Promed 10/23/05, 10/25/05, 10/26/05)

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Global: WHO recommended H5N1 prototype strains for influenza pandemic vaccine development remain the same
The WHO Global Influenza Programme has been closely monitoring the antigenic and genetic evolution of circulating H5N1 viruses, especially human isolates. Recent investigations have indicated that H5 haemagglutinins (HA) genes of viruses from birds in China, Indonesia, Japan, Mongolia, Russia, South Korea and Turkey, and 3 viruses from humans in Indonesia are genetically distinguishable from the prototype strains selected last year for influenza pandemic vaccine development. There is also evidence of antigenic variation among the HA of recent viruses. However, their geographical spread and pathogenicity in human populations remain unclear. At present WHO does not recommend changing the previously selected H5N1 prototype strains for ongoing pandemic vaccine development. But, for vaccine research purposes, the WHO H5 Reference Laboratory Network has initiated the development of experimental H5N1 vaccine prototype strains from the recent viruses. Analyses of more recent viruses, from both animals and humans, are urgently needed in order to obtain a better understanding of the evolution of the viruses and their antigenic relationships. WHO calls for rapid sharing of avian influenza virus isolates/specimens from affected Member States. (WHO 10/28/05 http://www.who.int/csr/disease/avian_influenza/statement_2005_10_28/en/index.html)

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Global: Roche limits Tamfilu shipments to prevent hoarding
Drug maker Roche announced it was suspending shipments of oseltamivir (Tamiflu) to US pharmacies to prevent hoarding that could lead to a shortage of the drug during the flu season. The company said it was concerned that hoarding by people worried about a flu pandemic could lead to a shortage of the drug for those who will need it for treatment of ordinary seasonal flu. Roche said the decision was based on the concern that news coverage of avian flu has caused companies and other organizations that don't need oseltamivir yet for this year's flu virus to hoard it. "We've seen recently some very large purchases at the wholesale level, companies or large entities who are possibly hoarding Tamiflu right now," said Hoffman-La Roche spokeswoman Darien Wilson. The suspension will not affect the federal government's current stockpiling of oseltamivir for use in a potential flu pandemic. Roche officials in Switzerland, Germany, and Canada already had revealed that they were limiting shipments to pharmacies in those countries in an effort to prevent hoarding. Verispan, a firm that monitors prescription drug sales, said US sales of oseltamivir last week were 4 times the level during the same week a year ago. Prescriptions totaled 67,443, versus 17,172 last year. Meanwhile, GlaxoSmithKline said it plans to increase production of zanamivir (Relenza), the other antiviral drug that could be of some use against a pandemic flu strain. The company also is offering free licenses to partners to produce the drug. (CIDRAP 10/27/05 http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/oct2705tamiflu.html)

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Europe: Very low risk to human health from A/H5N1 avian influenza
The direct risk to the health of people in Europe from the avian influenza detected in Romania and Turkey is very low, according to the European Centre for Disease Prevention and Control (ECDC). The risk is almost entirely confined to people living on farms with infected poultry or workers involved with culling and disposal of infected birds. There has been considerable confusion in the media about the arrival of avian influenza A/H5N1 into Europe and the arrival of pandemic influenza. Not only could this confusion cause unnecessary anxiety and fear of harmless wild birds, it could undermine efforts to prepare for a pandemic, as a pandemic may not occur for several years and may not be caused by H5N1 avian influenza at all. There are many other candidate influenza strains. ECDC has published interim guidance for workers directly involved in controlling avian influenza.

(1) Controlling infection in birds
(2) Minimising the number of people possibly exposed to the virus
(3) Proper use of personal protective equipment for those working with potentially infected animals
(4) Vaccinating the above described workers with seasonal influenza vaccine, especially if seasonal influenza is circulating, to aid in correct diagnosis of influenza-like illness and to minimise the chance of viral reassortment should a person become dually infected.
(5) Surveillance for infection among those potentially exposed, and instant treatment if cases identified.

The precautions for the public is good personal hygiene (hand washing, especially after contact with birds) and in particular, not touching birds found sick or dead. It is also recommended that people follow pre-existing advice to cook eggs and poultry thoroughly. The advice to travellers to regions and countries where A/H5N1 is present remains the same: avoiding markets where live poultry is sold, avoiding contact with live poultry, and good personal hygiene. For more information: http://www.ecdc.eu.int. (Promed 10/21/05)

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Romania: New suspected bird case of avian influenza
Romania detected a new suspected case of bird flu close to the border with Moldova, some 100 km north of the Danube delta. Romania became the first European mainland country to detect the H5N1 strain. The Danube delta on the Black Sea, Europe's largest wetlands, is a major way station for migratory wild birds heading from Asia towards winter habitats in North Africa. "A sample coming from a heron found on the shore of the river Prut, in Vaslui county, tested positive for bird flu antibodies," Agriculture Ministry spokesman Adrian Tibu said. The presence of antibodies does not necessarily mean the birds have the strain of the virus, and further tests must be carried out. "First of all we will tell people to keep chickens shut in their pens. We have closed the bird and animal markets," Ioan Zaharia, the government's representative in Vaslui county, said. The farm ministry said that hundreds of samples tested over the past few days across the country had proved negative, and that he hoped the measures taken would help contain the disease. So far H5N1 was found in samples taken from 2 villages in the Danube delta. (Promed 10/21/05)

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Romania: OIE report on avian influenza
Information received 14, 19 and 20 Oct 2005. Precise identification of agent: highly pathogenic avian influenza virus subtype H5N1. Description of affected population in the new outbreaks:
- Outbreak in Maliuc village: 537 swans;
- Outbreak in Vulturu village: 46 hens and 2 turkey hens (backyard flock).
Source of outbreaks: contact with migratory birds. Control measures undertaken: stamping out applied to poultry; quarantine; movement control inside the country; screening; zoning; disinfection of infected premises/establishment. Control of wildlife reservoirs to be undertaken. Surveillance studies on wild migratory water birds have been started. All notifications and suspect samples have been investigated.

The haemagglutinin (HA) and neuraminidase (NA) genes of the influenza A virus subtype H5N1 isolated from the duck are 100 percent identical to those of the virus from the chicken. Molecular phylogeny indicates that the NA gene of both viruses is identical to that of the H5N1 highly pathogenic avian influenza virus strain A/turkey/Turkey/1/05 and therefore, as for the HA gene, is closely related to viruses detected recently in Central Asia. The haemagglutinating agents received (both samples 1 and 2) have been confirmed as influenza A subtype H5N1. The results indicate a direct relationship with viruses detected elsewhere in Romania, Turkey and Central Asia.

In the Maliuc and Vulturu outbreaks, stamping-out activities have been completed; a total of 3562 domestic poultry were killed and their carcasses destroyed. The outbreak in Ceamurlia-de-Jos was eradicated. A total of 18 626 domestic poultry were killed and their carcasses incinerated, and disinfection was carried out. Measures have been taken to protect the human population. (Promed 10/22/05)

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Russia (Tambov, Chelyabinsk, Altai, Tula): Avian influenza spreading
Another region in European Russia, Tambov, located 400 km south east of Moscow, has confirmed an outbreak of bird flu, a senior regional animal health official said on 24 Oct 2005. "Laboratory tests have confirmed the presence of the H5N1 strain (of bird flu)... in some dead fowl tissue samples," the official said. He said the disease killed 12 hens at a private dacha in Morshansk district, after which authorities destroyed 53 ducks and hens remaining in the locality, and imposed a quarantine on it.

Russian vets have also found bird flu in a village in the southern Urals, the emergency ministry said 22 Oct 2005. In the village of Sunaly in the Chelyabinsk region in the southern Urals, 31 chickens died, and authorities found bird flu in 6 samples out of 12. A Chelyabinsk emergency ministry official said vets had found the H5N1 strain and suspected that the infection came with migrating birds. "There are 1060 birds in the village," the official said. "They will all be killed. A quarantine was imposed from today. Vaccination of all 89 people in the village will start on Monday [24 Oct 2005]." Authorities are also investigating another suspected outbreak in the Altai region. The Moscow emergency ministry official said bird flu was suspected in a village in Altai, where 59 birds died in the village of Pokrovka 21 Oct 2005. "A quarantine zone has been imposed, although we have only found antibodies for bird flu in the preliminary tests. The final decision on whether it is bird flu and what will be done will only be taken on Monday [24 Oct 2005]," the official said. Russia has been fighting bird flu since mid-July 2005 and has killed more than 600 000 domestic fowl.

An outbreak of H5N1 in Tula region, 200 km south of Moscow, has also been confirmed. OIE report:
Information received 18 and 19 Oct 2005. Precise identification of agent: influenza A virus subtype H5N1. First administrative division (region): Tula. Approximately 3,000 birds were destroyed. The reasons for suspicion were the clinical signs, the presence of a lake on the territory of the affected village, and the presence of migratory birds (unidentified ducks, probably mallard) during the week before the outbreak. Control measures applied: stamping out applied to all birds within the affected village; quarantine (all transport of poultry, poultry products, feed, etc. is prohibited; restriction measures are being applied to the affected village); disinfection of backyards and roads in the village. (Promed 10/22/05, 10/24/05)

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Croatia: H5N1 virus confirmed in bird flu case
Croatia said 26 Oct 2005 tests had confirmed H5N1 strain in wild swans found dead at a pond in eastern Croatia in the third week of October 2005. "Results from the laboratory in Weybridge confirmed the H5N1 virus, which shows that our measures were justified. I once again urge poultry producers to take this seriously and keep poultry indoors," said veterinary expert Vladimir Savic. "The situation is serious for the whole of Europe until a strategy is found, so I cannot say for how long the poultry will have to be kept indoors," Savic added. Croatian authorities culled 17 000 poultry around the pond. Another 10 000 poultry were killed around another pond nearby, where 2 more wild swans died of bird flu. Agriculture Minister Petar Cobankovic said the government would pay some 0.8 million kuna (USD 130 800) in compensation for the culled poultry starting 27 Oct 2005. Mate Brstilo, who heads the national committee for bird flu prevention, said the authorities remained on alert. "Every reported case of dead birds is being thoroughly tested. That is why we managed to detect bird flu in wild birds as soon as it appeared, and this prompted some other European countries to do the same," he said. Some 800 veterinary experts and inspectors are monitoring poultry farms and areas which host migratory birds, he added. Ornithologist Dragan Radovic said the situation could become more dangerous when a larger number of wild swans leave northeastern Europe and land in Croatia in the next few weeks. Croatia has banned hunting and transport of wild fowl and poultry. The European Commission banned exports of wild fowl, live poultry and certain poultry products from Croatia.

Avian influenza in Croatia, OIE report
Information received 21 Oct 2005. An outbreak of avian influenza was reported in wild migratory swans in Zdenci municipality, Viroviticko-Podravska county. Out of approximately 1500 wild migratory swans, 15 birds died. Source of outbreak or origin of infection: seasonal migration of wild birds: swans. Control measures undertaken: quarantine; movement control inside the country; screening; zoning; disinfection of infected premises. Control measures to be undertaken: control of wildlife reservoirs; stamping out. Highly pathogenic avian influenza has previously never been reported in Croatia. (Promed 10/21/05, 10/24/05, 10/26/05)

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UK: Probably had 2 birds with avian flu H5N1
Britain said 26 Oct 2005 it probably had 2 birds, not just one, with the H5N1 bird flu virus in quarantine. Britain confirmed 23 Oct 2005 its first case of bird flu since 1992, a parrot that died of the disease in quarantine. The bird originated from Surinam, South America, and entered the country in a consignment of 148 birds 16 Sep 2005. 11 days later a batch of 218 birds from Taiwan were also moved into the quarantine premises, and 2 parrots were found dead 20 Oct 2005. Only one was found to contain the suspect H5 strain, though further tests on tissue samples from both birds confirmed the H5N1 strain. The closest match is a strain identified in ducks in China earlier this year. It is not so similar to the strains from Romania and Turkey. It is not a strain that the Veterinary Laboratory Agency has seen before. "We now consider the virus was found in samples taken from 2 birds . . . which had died on 16 Oct 2005," Environment, Food and Rural Affairs Secretary Margaret Beckett said.

The birds were among 2 batches of exotic birds from Suriname and Taiwan kept together and experts are working on the hypothesis that the virus came from Taiwan and was transferred during quarantine. But authorities in Taiwan said there had been no reports of cases of H5N1 on the island and the British Government's theory had no "solid evidence" to back it up. An alternative possibility is that birds in an earlier batch delivered to the facility could have had a "subclinical" infection and began secreting virus only after the stresses of quarantine. Contaminated droppings could have released the airborne virus that may have infected subsequent batches of birds from Taiwan and South America. Other birds had died in the quarantine area before 16 Oct 2005, and 32 of those were kept for analysis in a freezer. "Initial tests, which have not yet been validated, identified that H5 is present in some of these birds," Beckett said. "The quarantine system succeeded in providing the protection that it is in place to deliver," she said. Chief veterinarian Debby Reynolds said the country's disease-free status was not affected by the case of bird flu, because the birds died while in quarantine. The necessary actions to protect human health have been taken: culling of the bird consignment and giving antiviral treatment as a precautionary measure to the small number of people who have been in contact with the birds.

Birds caught in the wild end up for sale in the pet shops and markets of Europe, part of an often illicit global trade that is raising concern as avian flu spreads globally. EU legislation requires that birds imported into member states from outside the EU must remain in quarantine for at least 30 days post-import. Once birds enter the EU and are released from quarantine, they can move freely within the 25-nation bloc. Animal protection groups warn the conditions in which exotic birds are held and transported make them highly vulnerable to infection and ripe for carrying viruses across borders. Elaine Toland, director of the Animal Protection Agency, an advocacy group, said between 2 million and 5 million birds are captured and sold legally each year. It's harder to estimate the number traded illicitly, but it may be nearly as high, she said. About 65 percent of the legal trade ends up in Europe, Toland said. As many as 75 percent of the birds die between capture and sale. US sharply restricted imports of exotic birds with the Wild Bird Conservation Act of 1992, and most pet birds sold in the US are now raised in captivity. (Promed 10/21/05, 10/23/05, 10/25/05, 10/26/05)

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Greece: Avian influenza confusion
The EU has said initial tests for bird flu in Greece were negative, but stressed it cannot yet exclude the presence of the virus in the EU state. The provisional good news was also tempered by wrangling in Greece over exactly which sample was sent for testing by EU experts following a suspected case on an Aegean island (a lone turkey that originally sparked the scare). Confirmation of the H5N1 strain in Greece would mark its first-ever arrival in the 25-nation bloc. While announcing the negative result, the EU's executive arm underlined that precautionary measures slapped on the islet of Oinousses [5 km from the region's main island, Chios] will therefore remain in place. A "preliminary test was carried out ... which proved negative but it is not possible at this point definitively to conclude from this that the suspicion of avian influenza" can be entirely excluded, said spokeswoman Pia Ahrenkilde. "Therefore, precautionary measures remain in place," she added. "At this point we cannot exclude the possibility of avian flu in Greece and in the area." EU-certified laboratories in Britain and Greece have been testing samples from birds in the same flock where a suspect case was found to determine if it was the H5N1 strain. An EU spokesman said that the test, carried out at in Britain had proved negative for the H5 strain.

3 EU experts arrived in Greece. Government spokesman Theodoros Roussopoulos said tests conducted on 56 bird samples collected from across the country had turned up negative for bird flu. But ordinary Greeks have been alarmed by the outbreak: sales of poultry in Greece have plummeted by up to 70 percent since the suspected case was reported, a union of Greek meat vendors said. The Greek poultry industry is having difficulty adapting, said Spyros Nonikas, general director of the association of Greek poultry companies. In Albania, meanwhile, local television reported that thousands of Greek chickens were buried alive on the border after authorities refused to let them enter the country. (Promed 10/21/05)

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Sweden (Eskilstuna): mallard, H5N3 strain confirmed
The antigenic characterization of the AIV found in a dead mallard in Eskilstuna 21 Oct 2005 has been completed at the National Veterinary Institute. 7 dead ducks were found, 4 were tested and one came up positive for bird flu. The virus was identified as H5, the neuraminidase subtype was found to be N3. ***Note: According to the revised International Terrestrial Animal Health Code, all H5 and H7 avian influenza viruses are regarded as "notifiable avian influenza" (NAI). If found highly pathogenic in poultry, they become HPNAI. The results of tests being conducted on dead wild birds (reportedly wild geese) found in Germany on 25 Oct 2005 and from poultry (reportedly turkey) said to be suspected of avian influenza in Greece on 17 Oct 2005 are pending.

Also, signs of the virus were found 25 Oct 2005 in 2 dead migratory birds at a lake in Neuwied, Germany, although the bodies of another 23 birds found at the same location did not contain any traces. Further tests are needed to confirm the strain. Many EU states were poised to follow the action of the French 25 Oct 2005 and order all poultry and game birds to be locked indoors. The order applies to farms in 21 French departments to protect them from the threat of migratory birds. Hunters were also banned from using live birds as bait amid fears of contact with migratory birds. (Promed 10/23/05, 10/26/05, 10/27/05)

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Asia
South East Asia: Cumulative number of human cases of avian influenza A/(H5N1)
Cumulative number of confirmed human cases of avian influenza A/(H5N1), 16 Dec 2004 to present:
Economy / Unofficial (Official) Cases / Unofficial (Official) Deaths
Indonesia / 10 (7) / 6 (4)
Cambodia / 4 (4) / 4 (4)
Thailand / 2 (2) / 1 (1)
Viet Nam / 68 (64) / 23 (21)
Total / 84 (77) / 34 (30)

Cumulative number of confirmed human cases of avian influenza A/(H5N1), 3 Dec 2003 to present:
128 (121) / 66 (62)
(CIDRAP 10/24/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/case-count/avflucount.html)

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Indonesia: Suspected avian flu cases test negative, but 2 additional confirmed cases
The results of local tests on an Indonesian father and son hospitalised in Jakarta with bird flu symptoms show that they have not contracted avian H5N1 influenza virus infection, a senior Health Ministry official said 21 Oct 2005. Hariadi Wibisono, a Director at the Ministry, said samples would still be sent to the WHO laboratory for confirmation of the negative result. However, the Ministry of Health has confirmed 2 additional cases of human infection with H5N1. The first newly confirmed case is a 4-year-old boy from Sumatra Island in Lampung Province. He developed symptoms 4 Oct 2005, was hospitalized, recovered fully, and has returned home. This case is the nephew of the 21-year-old man from Lampung, who was reported 10 Oct 2005. Although the 2 cases are related and lived in the same neighborhood, human-to-human transmission is considered unlikely. The second newly confirmed case was a 23-year-old man from Bogor, West Java. He was hospitalized 28 Sep 2005 and died 30 Sep 2005. Epidemiological investigations uncovered exposure to infected poultry as the likely source of infection in both cases. To date, Indonesia has reported 7 human cases of H5N1 avian influenza. 4 of these cases were fatal. (Promed 10/21/05, 10/24/05)

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Indonesia: Possible bird flu deaths on Bali Island
Indonesia was investigating the deaths of dozens of backyard chickens on Bali 26 Oct 2005 amid fears they may have had bird flu. Though villagers say more than 25 previously healthy birds have dropped dead in the last 5 days, Ida Bagus Raka, the chief of Bali provincial animal husbandry agency, said it is possible they had Newcastle Disease, which is not dangerous to humans. Samples have been sent to a lab for testing. Residents in Padang Sambian said their backyard chickens suddenly started falling sick. The H5N1 strain of the bird flu killed or forced the slaughter of 600 000 chickens on Bali last year. According to Indonesia's official reports to the OIE, the last outbreak of clinical HPAI in avians occurred in Indonesia 4 May 2005. Though human cases have been reported later, only serological findings from asymptomatic avians have been reported in the last available OIE follow-up report. (Protein 10/26/05)

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Indonesia: FAO to help Indonesia fight avian flu
The UN Food and Agriculture Organization said it would set up a team to "kick start" avian influenza control efforts in Indonesia, which has been criticized for its response to the disease. "The bird flu virus is threatening to become endemic in several parts of the country," and a "strong, coordinated response" is needed, said Joseph Domenech, the FAO's chief veterinary officer. The government has promised several times to respond with mass poultry culls and quarantines, but has actually done little. Domenech said the FAO is concerned that the virus is present in millions of backyard poultry flocks. "There still seems to be a lack of awareness in the rural and suburban communities about the threat the virus poses to humans and animals," he added. FAO said it would set up a task force of experts from Indonesian veterinary and health agencies, WHO, and the World Food Programme. "Our basic objective is to kick-start virus control activities in the field," said Peter Roeder, an FAO animal health officer who will head the team. "FAO will therefore establish local disease control centres in hot-spot areas. These centres will offer up-dated information and will train animal health technicians and veterinarians in how to carry out rapid disease search and control." Based on an approach used in Thailand, plans call for workers to go from house to house to identify areas affected by avian flu and to decide, with Indonesian officials, on control measures such as slaughtering, vaccination, and biosecurity. "FAO will bring in a team of experienced Thai veterinarians to share their experience with Indonesian animal health experts and to train hundreds of animal health technicians. We believe that Indonesia can learn a lot from the Thai experience." The project will be funded by $1.5 million from the US Agency for International Development. FAO promised to explore the possibility of compensating farmers for their loss when chickens are culled.

Health officials said the need to control avian flu at the source is being neglected amid global worries that the disease will lead to a human flu pandemic. "Our first line of defense should be attacking the problem at the poultry level," said Alejandro Thiermann, advisor to the director-general of the World Organization for Animal Health (OIE). FAO Director-General Jacque Diouf said many people seem more concerned about a possible human pandemic than about containing the disease in poultry. FAO and the OIE had developed a $175 million strategy for controlling avian flu in birds, but so far donor countries have pledged only $30 million for the effort and have not actually paid a cent. (CIDRAP 10/25/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/oct2505fao.html and FAO 10/24/05 http://www.fao.org/newsroom/en/news/2005/108228/index.html)

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Thailand: Avian influenza spreading; additional human case
Cases of suspected human infections are on the rise as villagers resist efforts by livestock officials to cull fowl. Avian influenza has spread to more than half the country, with 39 provinces reporting confirmed or suspected cases of fresh bird-flu infections. Last week, authorities had just 21 provinces under close watch for bird flu, suggesting the virus is spreading rapidly. Meanwhile, Kanchanaburi, Nakhon Pathom, Nonthaburi, Suphan Buri and Kamphaeng Phet have been put on a list of provinces with severe bird-flu problems. Health volunteers were going to areas where bird-flu infections had been reported to check whether the disease had spread to any people. Samart Prasitphol, a senior livestock official in Kanchanaburi, said staff had set up checkpoints to enforce the ban on the movement of birds as a measure to curtail the spread of the deadly disease. Thailand's most current report to the OIE (25 Oct 2005) dealing with 5 new outbreaks in 4 provinces, is available at <http://oie.int/downld/AVIAN%20INFLUENZA/Thailand%20Follow-up%20Report%20No74.pdf>. The notification included the following comments: Thailand has been conducting the current nationwide surveillance since 1 Jul 2005; In total, there were 64 positive cases confirmed in 8 provinces. These 8 affected provinces are still in the Central Poultry Zoning of Thailand. The country has been divided into 5 poultry zones: Northern (9 provinces), Northeastern (19 provinces), Eastern (8 provinces), Central (25 provinces), and the Southern (15 provinces).

Thailand confirmed an additional case of human infection with H5N1 avian influenza. The patient, a 7-year-old boy from Kanchanaburi Province, developed symptoms 16 Oct 2005 and was hospitalized 19 Oct 2005. He is recovering. He is the son of a confirmed case who died 19 Oct 2005. The father fell ill after slaughtering sick chickens. The boy reportedly "had close contact with the virus" from being around the chickens. "The H5N1 viruses found in the boy and the father were the same strain that has been found for the last 2 years, with no signs of a mutation," Siriraj Hospital Director Prasit Watanapa said. The boy was treated with Tamiflu early in his illness. There is no evidence that the boy contracted the disease from his father. These are the first 2 confirmed cases in Thailand in a year. Since the start of the outbreaks in Asia, Thailand has confirmed 19 cases, of which 13 have been fatal. (Promed 10/24/05, 10/25/05)

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Taipei/China: Follow up on smuggled birds, H5N1 confirmed; Taipei preparedness
Tests of dead birds that were smuggled in from China found they were infected with the H5N1 virus. 8 of the 276 dead birds that were smuggled into Taiwan from China on a ship have tested positive for the H5N1 bird flu virus, but an outbreak is unlikely, as they have been seized and destroyed. The 1037 birds on board were smuggled from China, raising concerns over the risk of bird flu being brought to Taiwan. 19 types [species] of birds were found on board the ship, with 3 -- myna birds, black-naped orioles and Chinese nightingales -- found to be carrying the H5N1 virus.

Meanwhile, noting that the birds were smuggled from China, the Ministry of Foreign Affairs called on Beijing to adopt transparent measures in its actions against bird-flu to avoid becoming a "loophole" in other countries' efforts to combat outbreaks. A 40-person team that searched the ship and destroyed the birds was not quarantined, as team members had worn protective gear and did not come in direct contact with the infected birds. But they are being monitored as a precaution. Smugglers face up to 3 years imprisonment and a TWD 150 000 [USD 4400] fine. Officials are considering tightening the smuggling law. Meanwhile, as part of efforts to combat a possible avian flu outbreak, Taipei Municipal Hospital announced 20 Oct 2005 the establishment of a "vanguard team" of 108 hospital staff that will be stationed at Hoping Hospital (designated anti-avian flu center) should an outbreak occur. Officials hope to gain from the hospital's experience during the SARS outbreak of 2003.

Genetic characterization of the H5N1 virus isolated from this incident showed that it shared 96 percent homology with the virus derived from yet another smuggled consignment of ducks in Kinmen (just offshore of the Fujian province of China, but governed by Taiwan) from China during the 2003 SARS period. The virus isolated shares 99 percent homology with the H5N1 virus currently circulating in Fujian. H5N1 virus was found in Japan in a shipment of frozen duck meat from Shandong province of China in 2003. Taiwan has destroyed 82 tons of animal products smuggled from abroad this year as well as 5146 animals, including 5070 birds. (Promed 10/22/05)

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China (Hunan): Avian influenza outbreak
China has reported bird flu in poultry in a village in the central province of Hunan, and declared it had been brought under control. China notified the UN of the latest outbreak in Xiangtan County, near the provincial capital, Changsha. The outbreak involved chickens and ducks; it started 22 Oct 2005 and was confirmed by the lab 25 Oct 2005. Out of 687 susceptible birds, 545 died; 2487 birds have subsequently been destroyed. In response to the outbreak, 43 750 avians have been vaccinated with an inactivated mono H5N2 vaccine. Full OIE report: <http://oie.int/downld/AVIAN%20INFLUENZA/China%20Follow-up%20report%20No5.pdf>. China has reported no human cases so far. The national bird flu laboratory said it had identified the strain as H5N1. On 25 Oct 2005, China reported another outbreak in Anhui and said that it too had been brought under control with no reported human infections. China notified OIE about an outbreak of highly pathogenic avian influenza, sub-type H5, in the village Liangying, in the province Anhui. The outbreak involved chicken and goose; it started 20 Oct 2005, confirmed by the laboratory 24 Oct 2005. Almost 45 000 birds have been destroyed. In response to the outbreak, 140 000 avians have been vaccinated with an inactivated mono H5N2 vaccine. The virus has apparently become endemic in China, the disease controlled mainly by vaccinations.

Hong Kong does not currently buy any poultry meat or live birds from Hunan but will bar any such imports from the province. There have been other recent outbreaks in Xinjiang, Qinghai and in Inner Mongolia. China's sheer size and its attempts to conceal the emergence of the SARS virus in 2003 have prompted fears among some experts that it has had more bird flu cases than officially recorded. But experts and UN officials said they believe China is better prepared and more open than in 2003. (Promed 10/24/05, 10/26/05)

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Americas
USA: CDC sets rules for handling 1918 flu virus
CDC, which reconstructed the 1918 pandemic influenza virus, has classified the virus as a "select agent". The designation means scientists and labs that want to work with the virus must register with CDC and are required to increase safeguards and security measures, including controlling access, screening personnel, and maintaining records to be included in a national database. "We've learned why this virus was so deadly and we know it's easily transmitted from person to person," CDC Director Julie Gerberding said. "But there is a lot we don't know so it's only logical that we take immediate steps to regulate this virus as a select agent as an added way to protect the public." In recent years scientists succeeded in recovering fragments of the 1918 virus from the frozen body of a victim in Alaska and from preserved tissue samples from a US soldier who died in the pandemic. Those materials were used to sequence the virus's genome. CDC scientists subsequently reconstructed the virus and reported that the reassembled virus was highly lethal to mice and that it grew explosively in lab cultures of human lung cells.

Experts fear that the current H5N1 avian flu virus may trigger a human flu pandemic that could echo the 1918 event. CDC said the 1918 virus was reconstructed to help public health officials prepare for the threat of a new pandemic, to learn what made the virus so harmful, and to help develop better flu drugs and vaccines. The virus now is one of 42 agents and toxins classified as select agents under the Bioterrorism Act of 2002. Other select agents include the pathogens that cause smallpox, Ebola fever, anthrax, plague, and tularemia, as well as botulinum toxin. Background checks on people working with the virus will be required. A CDC statement did not specify which of the four formal levels of biological security (biosafety, or BSL) will be required for labs handling the virus, but is reported to be "3-plus." (CIDRAP 10/21/05 http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct2105agent.html)

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USA: Flu shots now open to all; officials fear fake Tamiflu
Seasonal influenza shots are not just for high-risk groups anymore, and everyone interested in a shot should go ahead and seek one out. Officials also warned that the threat of a flu pandemic may spur the sale of fake versions of the antiviral drug oseltamivir (Tamiflu). To make sure they get the genuine article, people should seek the drug through their physician. "Starting today, October 24th, we're making influenza shots available to everyone," said Health and Human Services Secretary Mike Leavitt. He added that people seeking a flu shot should make an appointment, because some providers may not have received their vaccine yet. CDC had recommended that flu shots be reserved for people at risk for serious flu complications until 24 Oct 2005. (The recommendation did not apply to MedImmune's live-virus vaccine [FluMist], which is licensed only for healthy people between ages 5 and 49.)

CDC repeated their estimate that at least 71 million doses of flu vaccine will be available in the US this season, compared with about 60 million last year, when the loss of 48 million doses expected from Chiron triggered shortages. CDC still expects 60 million doses from Sanofi Pasteur, 3 million from MedImmune, and 8 million from GlaxoSmithKline. CDC also expects up to 18 million doses from Chiron, which until last week was projecting 18 million to 26 million. CDC Director Dr. Julie Gerberding recommended that clinicians who have an ample supply of vaccine inform local public health officers so the latter can help shift surplus doses to providers who need them. Gerberding said people who experience flu symptoms and have not been vaccinated, especially if they are in a high-risk group, should call their physician promptly to find out if treatment with an antiviral drug would be appropriate.

Leavitt observed that oseltamivir has been "much in the news". Because demand for the drug far exceeds the supply, said Leavitt, "We're concerned about the threat of counterfeiting of Tamiflu." Leavitt and Andrew von Eschenbach, acting commissioner of the FDA, said they had seen no evidence of counterfeiting to date. But Leavitt said, "It's a situation that's ripe for counterfeiting. The WHO [World Health Organization] now indicates that counterfeit drug making is a $34 billion–a-year industry. We're seeing it in many other instances." The best way to avoid fake oseltamivir is to get it from state-licensed pharmacies, said von Eschenbach. Also, Gerberding said that right now she does not expect a shortage of oseltamivir for use against seasonal flu. The FDA is forming a "rapid response team" of experts to help make sure antiviral drugs are available in the event of a flu pandemic (See http://www.fda.gov/bbs/topics/NEWS/2005/NEW01248.html). (FDA 10/24/05; CIDRAP 10/24/05 http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/oct2405flubriefing.html )

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USA: USDA Efforts and Response to Avian influenza
Agriculture Deputy Secretary Chuck Conner outlined USDA efforts to protect the US against highly transmissible forms of avian influenza. "Attacking the disease at its source overseas is a main focus for USDA. We also have strict importation restrictions to prevent the spread of the virus in our country and an elaborate surveillance system in place to monitor our bird populations." There are many strains of avian influenza (AI) virus, which can cause varying degrees of illness in poultry. Migratory waterfowl are also known to carry the less infectious strains of AI viruses. Each year there is a flu season for birds just as there is for humans and, as with people, some forms of the flu are worse than others.

AI strains are divided into 2 groups: low pathogenicity (LP) and high pathogenicity (HP). LPAI, or "low path" avian influenza, has existed in the US since the early 1900's. These strains of the disease pose no known serious threat to human health. HPAI, or "high path" avian influenza, is more fatal and transmissible. These strains of the disease in Asia have been transmitted from birds to humans, most of whom had extensive, direct contact with infected birds. HPAI has been detected 3 times in the US: in 1924, 1983, and 2004. The 2004 outbreak was quickly confined to one flock and eradicated. There were no human illnesses reported in connection with these outbreaks.

The USDA Animal and Plant Health Inspection Service (APHIS) works with states to monitor and respond to outbreaks of LPAI. APHIS has provided funding and support personnel to states when LPAI has been detected. When HPAI is detected, APHIS personnel are primary responders, due to its infectivity and high mortality rate among poultry. Close attention is also given to 2 subtypes of LPAI, the H5 and H7 strains, because of the potential for them to mutate into HPAI. To encourage producers to report sick birds, APHIS conducts an outreach campaign called "Biosecurity for the Birds." It provides poultry producers with the latest information on biosecurity, in several languages, to prevent the spread of this disease on the farm. Additional surveillance efforts specifically target live bird markets. USDA works closely with the industry to randomly test commercial flocks as well as testing birds that show signs of illness. USDA scientists have also been testing wild migratory birds since 1998 in the Alaska flyway.

In 2002, the USDA Agricultural Research Service (ARS) developed a rapid diagnostic test for avian influenza. ARS continually improves the sensitivity of the test. This test diagnoses avian influenza within 3 hours. The test has now been distributed to the National Animal Health Laboratory Network, which includes university and state veterinary diagnostic labs throughout the US, to better enable laboratories to monitor for and respond to avian influenza outbreaks. APHIS also maintains an AI vaccine supply for poultry that can be used to create a buffer around an identified area, in the event of a large outbreak among poultry. In addition, the agency has formed a national network to assist with surveillance and response in the event of an outbreak of HPAI or other foreign animal disease. That network includes more than 40,000 accredited private veterinarians who report any suspected disease outbreak.

For more information: http://www.usda.gov/birdflu and http://www.nwhc.usgs.gov/. (CIDRAP 10/26/05 http://www.cidrap.umn.edu/cidrap/ and USDA 10/26/05 http://www.usda.gov/wps/portal/usdahome)

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1. Updates
Influenza
Seasonal influenza activity for the Asia Pacific and APEC Economies
Influenza activity remained low during weeks 40–41

Canada.
Localized activity of influenza A was reported in Saskatchewan for weeks 40 and 41. Activity remained low in the rest of Canada.

Other reports.
During weeks 40-41, low influenza activity was detected in Chile (B), Hong Kong (H1, H3 and B), Mexico (A), and the USA (H3 and A). Russia reported no influenza activity. (WHO 10/27/05 http://www.who.int/csr/disease/influenza/update/en/)

USA
During week 42 (October 16 - October 22, 2005), influenza activity was low in the US. 9 (1.1%) specimens tested by U.S. WHO and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories were positive for influenza virus. The proportion of patient visits to sentinel providers for influenza-like illness (ILI) and the proportion of deaths attributed to pneumonia and influenza were below baseline levels. One state reported regional influenza activity; 12 states, New York City, and Puerto Rico reported sporadic influenza activity; and 37 states and the District of Columbia reported no influenza activity. (CDC http://www.cdc.gov/flu/weekly/)

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2. Articles
Avian influenza outbreaks in the WHO European region and public health actions
Caroline Brown, Olaf Horstick, Fanny Naville, Guenael Rodier, Bernardus Ganter.
“Outbreaks of highly pathogenic avian influenza H5N1 virus in poultry and wild birds in the World Health Organization (WHO) European region have caused widespread public concern due to fears that human cases may ensue, as has happened in South East Asia. Part of the concern is the mistaken assumption that the geographical spread of the H5N1 virus in bird populations signals the start of an influenza pandemic, even though it does increase the size of the human/animal interface and the chances of adaptation of an avian virus to a human host. However, efforts should continue to clarify that the spread of avian influenza in birds does not constitute an influenza pandemic in humans.

So far no human cases have been detected in the WHO European region, but we must be prepared for this event. Close collaboration between veterinarian and human surveillance is of utmost importance to ensure early detection of possible human cases. For these reasons, the WHO Regional Office for Europe (WHO EURO) is undertaking a number of actions to monitor the situation.

Outbreaks of avian influenza H5N1 have now been confirmed in 5 countries, either by the World Organisation for Animal Health (OIE) or national government agencies in the WHO European region: Croatia, Kazakhstan, Romania, the Russian Federation and Turkey. In addition to this, avian influenza H5N1 has been confirmed in an imported parrot in the United Kingdom. There are now numerous further outbreaks of disease in birds under investigation in several European countries.

Since the occurrence of outbreaks of highly pathogenic avian influenza H5N1 virus in migratory birds, the risk of transmission to domestic birds has increased. Surveillance in wild birds has thus become a priority and the European Union has made guidelines available. It is likely that migratory birds are responsible for the introduction of H5N1 in the European region, as the viruses from outbreaks in Kazakhstan, Romania and Turkey are phylogenetically almost identical to the virus that caused the wild bird die-off at Lake Qinghai in China in May 2005. Migratory bird flyways are complex, but indicate that additional introduction of the H5N1 virus by wild birds into domestic poultry in the European region may continue.

Between 17 and 20 Oct 2005, a joint WHO/ECDC mission performed a risk assessment and response evaluation in Romania at the request of the Romanian authorities. The situation was assessed to be under proper control following a timely and joint response by the national veterinarian and public health authorities. The H5N1 virus has been introduced in an area limited to the Danube delta, and the complete evaluation of this new animal reservoir requires additional investigations by veterinary and wildlife services. Measures to control the interface between wild bird and domestic poultry would have to be long-term and involve a regional approach, particularly with the countries sharing the Danube delta.

WHO EURO, in collaboration with the European Centre of Disease Prevention and Control (ECDC), can supply technical assistance to countries experiencing outbreaks of avian influenza. The avian influenza epidemiological situation is being closely monitored. On country request, WHO will give technical assistance to countries regarding influenza, particularly on surveillance, laboratory capacity and country preparedness planning. Further to this, in collaboration with the European Commission (EC) and the ECDC, the 2nd joint EC/ECDC/WHO EURO workshop on pandemic preparedness was held in Copenhagen this week. The results of this workshop will be available soon.”

This article also includes an updated map "Countries affected by avian influenza H5N1 in birds in the WHO European Region since July 2005": http://www.eurosurveillance.org/ew/2005/051027.asp#2. (Promed 10/27/05; Eurosurveillance 10/27/05)

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Susceptibilities of Antiviral-Resistant Influenza Viruses to Novel Neuraminidase Inhibitors
Vasiliy P. Mishin, Frederick G. Hayden, and Larisa V. Gubareva. Antimicrobial Agents and Chemotherapy, November 2005, p. 4515-4520, Vol. 49, No. 11
http://aac.asm.org/cgi/content/abstract/49/11/4515
Abstract: “The susceptibilities of five zanamivir-resistant and six oseltamivir-resistant influenza viruses were assessed against four neuraminidase (NA) inhibitors, including peramivir and A-315675, by a fluorometric NA activity inhibition assay. The enzyme activity of a majority of the variants was effectively inhibited by either A-315675 or both peramivir and A-315675 (50% inhibitory concentration, <10 nM). A novel oseltamivir-resistant influenza virus B variant carrying substitution at residue 198 (Asp Asn) (N2 numbering) retained susceptibility to peramivir and A-315675. In vivo, the Asn198 variant showed no apparent fitness impairment as judged by its recovery on day 5 from the nasal washes of ferrets coinfected with equal doses of the wild-type virus and the Asn198 variant. Based on the sequence analysis of the virus in the nasal washes, oseltamivir treatment (5 mg/kg twice daily for 5 days) did not provide growth advantage to the Asn198 variant. Nevertheless, treatment with A-315675 (prodrug A-322278) reduced the number of the animals (two of seven) shedding the Asn198 variant. These studies indicate that different patterns of susceptibility and cross-resistance between NA inhibitors may prove important if antiviral resistance to zanamivir and oseltamivir were to emerge.” (CIDRAP http://www.cidrap.umn.edu/cidrap/)

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3. Notifications
WHO Comprehensive Avian Influenza website
In addition to Frequently Asked Questions, WHO has now uploaded additional information on avian influenza:
http://www.who.int/csr/disease/avian_influenza/en/index.html. The latest documents include:
- Avian influenza and the pandemic threat in Africa: risk assessment for Africa
- H5N1 avian influenza: timeline (pdf file)
- WHO recommended H5N1 prototype strains for influenza pandemic vaccine development remain same
- WHO guidance on public health measures in countries experiencing their first outbreaks of H5N1 avian influenza
(WHO October 2005)

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Controlling avian influenza does not authorize inappropriate animal depopulation methods
OIE emphasized the need for veterinary services worldwide to address urgently outbreaks of avian influenza in poultry. However, as the international reference organisation for animal welfare, the OIE is committed to alerting about the necessity to use appropriate methods to kill infected and in contact birds. This action is carried out to protect other birds worldwide from the infection of the avian influenza virus. Concern is being expressed not only by animal welfare organizations worldwide, but also by the media and the public that in many cases killing methods are not being carried out appropriately.

OIE reminds that early detection and rapid response mechanisms are crucial to the successful control of the disease and help minimizing the number of animals to be killed to stop the spread of the virus. Specific guidelines have been adopted by all 167 OIE Member Countries with regard to appropriate methods for the killing of animals (including birds) for disease control purposes. The complete guidelines on the appropriate methods for the killing of animals for disease control purposes are available: http://www.oie.int/eng/normes/mcode/en_chapitre_3.7.6.htm. The respect of the OIE Terrestrial Animal Health Code on the surveillance of avian influenza in animals and the respect of the measures guaranteeing the safety of international trade in poultry and poultry products represent the cornerstone in the global fight against avian influenza and a crucial element for avoiding the spread of the disease in animals as well as a potential human pandemic. (OIE 10/28/05 http://www.oie.int/eng/press/en_051028.htm)

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Banning poultry imports should be based on established rules
FAO expressed concern about general and pre-emptive bans on poultry imports adopted in response to avian influenza. Import bans on poultry that do not distinguish between infected and non-infected countries are contrary to the spirit of the World Trade Organization (WTO), standards set by the World Organisation for Animal Health (OIE) and recommendations made by FAO, FAO said. As countries establish pre-emptive import bans on poultry to prevent possible bird flu outbreaks, FAO noted that in some cases, the bans include poultry from all countries, even those considered to be free of highly pathogenic avian influenza and those that have never experienced an outbreak of H5N1. Countries arbitrarily banning the import of poultry products from non-infected countries are increasing the vulnerability of international global markets to price shocks, FAO said.

The agency cautioned countries that "trade restrictions to safeguard human and animal health should be imposed only in proportion to the risk involved and that they should be removed promptly when no longer needed." However, countries exporting poultry products must also ensure that any incidence of the disease is immediately announced to all trading partners and necessary steps are taken to limit the spread. "Bans on poultry products from disease-free countries increase uncertainties in the global meat market, which is already threatened by potential supply shortages and rising meat prices because of continuing BSE-restrictions on North American beef shipments," according to FAO.

Recent outbreaks of transboundary diseases and the imposition of disease-related export restrictions had an immediate impact on global meat trade in the 2004/2005. International meat prices, as represented in the FAO meat price index, which is calculated using trade-weighted indicative international prices, have risen to 10-year highs. Consumer responses to potential bird flu outbreaks are having a disruptive impact on industries. In Europe the reaction has been mixed, for example in Germany there has been no change while consumption of poultry in Italy has declined by 40 percent. FAO reminded consumers that avian influenza is not a food-borne disease and that the bird flu virus is killed by the heat of normal cooking. Meat processors are urged to apply necessary safety measures to prevent virus transmission to humans. (FAO 10/27/05 http://www.fao.org/newsroom/en/news/2005/108286/index.html)

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 apecein@u.washington.edu