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EINet Alert ~ Jan 20, 2006


*****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:
- Global: $1.9 billion pledged for global avian flu battle
- Global: Bird flu virus could spill over to Africa and Europe in springtime
- Global: Roche to give another 20 million doses of Tamiflu to WHO
- Turkey: Additional case of human infection with H5N1 avian influenza virus
- Turkey: Avian influenza outbreaks began earlier; useful maps of Turkey situation
- Turkey: First wide-scale summit on avian influenza; Aid for poultry workers
- Turkey: Laboratory findings from the fatal Turkish cases
- Iran/Syria: Destruction of birds by Turkish border
- Ukraine (Crimea): New cases of avian influenza suspected among wild birds
- Eurasia: Cumulative number of human cases of avian influenza A/(H5N1)
- Pan Asia: Commit to an early response to the threat of an influenza pandemic
- Indonesia: Additional fatal human case of avian influenza; more suspected cases
- China (Sichuan): Ninth confirmed case of human infection with H5N1 virus
- Hong Kong: Dead oriental magpie robin found infected with H5N1 strain
- Russia: Return of avian influenza expected from migratory birds
- Japan (Ibaraki): Current situation and review of avian influenza H5N2
- USA: CDC Recommends against the use of Amantadine and Rimandatine
- USA: USDA statement on fraudulent, unapproved influenza-related products

1. Updates
- Influenza

2. Articles
- Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts

3. Notifications
- Singapore's SARS Experience to Contribute to Avian Influenza Seminar


Global
Global: $1.9 billion pledged for global avian flu battle
Governments and organizations at a conference in Beijing have pledged $1.9 billion for a global fund to fight avian influenza, well above the $1.2 billion to $1.5 billion that organizers had hoped for. The 2 day conference is the second such gathering of its kind following a Nov 2005 meeting, which agreed on a 3 year plan for tackling the disease. The conference yielded pledges for almost $1 billion in grants, mainly for poor countries in Southeast Asia, and about $900 million in loans. The US led the list of donors with a $334 million pledge, saying the money would be mainly in the form of grants and technical assistance. The European Union promised about $260 million, including $138 million directly from member states and the rest from the European Commission. Japan signed on for $159 million, and smaller sums were promised by Russia, Australia, and China. China, which hosted the conference along with the World Bank and the European Commission, pledged $10 million. "We've got a fantastic set of pledges from poor countries as well as rich countries," said David Nabarro, UN coordinator for avian and pandemic influenza. "Even countries that cannot put money into the funding are saying we are going to commit our people and our governments to get the results."

Jim Adams, vice president of the World Bank, said that between $100 million and $200 million of the pledged funds would go into a trust fund to be managed by the World Bank. Some of the remaining money will be managed bilaterally between donors and recipients, he said. WHO Director-General Lee Jong-wook said the critical needs include reducing people's exposure to the avian flu virus, strengthening early warning systems, enhancing "rapid containment operations," building capacity to cope with a pandemic, and coordinating research and development. Most of the pledged funds will be used to build public awareness, strengthen outbreak detection and response, slaughter and vaccinate poultry, and compensate farmers for poultry losses. The World Bank has estimated that a year-long pandemic could cost the global economy up to $800 billion.

For OIE’s Director general Dr Vallat's key note address at the Pledging Conference: http://www.oie.int/eng/en_index.htm. For WHO’s Director-General, Dr Lee Jong-wook’s address: http://www.who.int/dg/lee/speeches/2006/flumeeting_beijing/en/index.html. (Promed 1/18/06, 1/20/06; CIDRAP 1/18/06 http://www.cidrap.umn.edu/ )

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Global: Bird flu virus could spill over to Africa and Europe in springtime
The avian influenza virus could become entrenched in the Black Sea, Caucasus and Near East regions through trade and movement of people and animals and it could be further spread by migratory birds particularly coming from Africa in the spring, the UN Food and Agriculture Organization warned. “FAO is concerned that with trade, the movement of people and animals and migratory birds, new countries could become infected,” said FAO Deputy Director-General David Harcharik at the Pledging Conference in Bejing. “Countries in Africa deserve special attention. If it were to become rooted in the African countryside, the consequences for a continent already devastated by hunger and poverty could be truly catastrophic,” Harcharik said. In endemic areas, the movements of animals, products and people should be controlled. FAO also urged all countries along the routes of migratory birds to be vigilant and be prepared for a further spread of the disease in animals.

“Fighting the avian influenza virus in animals is the most effective and cost-effective way to reduce the likelihood of H5N1 mutating or reassorting to cause a human flu pandemic,” Harcharik said. “Containing bird flu in domestic animals. . .will significantly reduce the risk to humans. Avian influenza should not only be considered as a human health issue, but as a human and animal health issue. . .Countries that foster close collaboration between the human health and agricultural sectors are likely to be the most successful in battling the disease,” Harcharik said. Centrally organised veterinary services are essential for successful bird flu control campaigns. “Governments will fail in combating avian influenza if they don’t give their veterinary services the political support as well as the technical and financial means to fight the virus. . .” he said.

Improved surveillance and detection will allow farmers and veterinary services to intervene quickly and apply the internationally recommended set of actions, such as culling, biosecurity measures and vaccination. Risky farming practices such as mixing poultry species in farms or in live markets, should be changed as quickly as possible. The impact of these changes on the livelihoods of small farmers should be mitigated. The movements of animals, products and people from endemic areas to other regions should be strictly controlled. “Funding will be needed for compensation schemes for farmers to encourage their participation in control campaigns,” Harcharik added. To date, FAO has received about $28 million from donors, and since the onset of the bird flu crisis in 2003 the agency has spent more than $7 million from its own resources to help affected countries to design bird flu control programmes, supporting surveillance and laboratory diagnostics. Socio-economic studies on the impact of the disease and the cost of control programmes, as well as on options for restructuring, have been carried out. Over the next 3 years, FAO will require at least $50 million more to continue its support for essential regional and global coordination and cooperation and some $80 million to assist countries to implement their national bird flu control programmes. (FAO 1/18/06 http://www.fao.org/newsroom/en/news/2006/1000215/index.html )

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Global: Roche to give another 20 million doses of Tamiflu to WHO
The Swiss drug company Roche said it would give another 2 million treatment courses of its anitivral drug oseltamivir (Tamiflu) to the WHO for developing countries to use to fight avian influenza in humans. Roche announced it would give 20 million doses of oseltamivir, enough to treat 2 million people with the recommended regimen of 2 doses a day for 5 days. This is in addition to 3 million treatment courses the company pledged Aug 2005 for a WHO stockpile to be used to try to snuff out any emerging pandemic. "While the donation made last year is stored centrally, these additional 2 million treatment courses will be stored as regional stockpiles in locations to be determined by WHO to serve the needs of developing countries," Roche said. The 2 donations, plus a smaller one made in 2004, add up to 5.125 million treatment courses of oseltamivir available to the WHO. The donations apparently are based on the standard Tamiflu regimen of 75 mg twice a day for 5 days. However, a report published Dec 2005 suggested that a higher dosage or longer treatment course may be needed in some cases of H5N1 infection. (CIDRAP 1/17/06 http://www.cidrap.umn.edu/ )

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Turkey: Additional case of human infection with H5N1 avian influenza virus
As of 18 Jan 2006, tests conducted at Turkey's National Influenza Centre have confirmed an additional case of human infection with the H5N1 avian influenza virus. The case is a 4 year old boy from the district of Dogubayazit in Agri Province in the eastern part of the country. An outbreak in poultry began in the district in Dec 2005. The child developed symptoms 5 Jan 2006 and was admitted to hospital 13 Jan 2006. He is being treated at a hospital. Like the 2 cases confirmed 16 Jan 2006, also from Dogubayazit, exposure in this case occurred before the government's launch of an intensive public education campaign. Rapid surveys conducted in the most severely affected eastern part of the country have found an almost universal awareness of the disease and of the risk factors for infection. This awareness has been accompanied by behavioral changes that are expected to reduce opportunities for human infections to occur.

As the virus is now known to be present in poultry in many parts of the country, some additional human cases should be anticipated in the immediate future. The number of these cases is, however, expected to decline as high-risk behaviours become less common and culling operations, which are presently under way, reduce the number of infected birds. The newly confirmed case brings the total in Turkey to 21. Of these cases, 4 were fatal. All 4 were residents of Dogubayazit. A second shipment of laboratory specimens arrived at a WHO collaborating laboratory in the UK. Apart from providing diagnostic confirmation, the lab will undertake viral characterization and genetic and antigenic analyses of viruses. These studies help determine whether the virus is evolving.

Prime Minister Tayyip Erdogan said 17 Jan 2006 that 5 patients with H5N1 had recovered and had been discharged from hospital. Many of the remaining 12 people are reported to be stable, but doctors said the condition of the 5 year old brother of a girl who died 15 Jan 2006 was serious. Reportedly, 3 people have been urgently admitted into the Mugla town hospital after they had been in contact with dead hens that had tested positive for the bird flu virus. There are still confirmed H5 outbreaks in poultry in 13 provinces, and suspected outbreaks are being investigated in a further 19 of the 81 provinces of Turkey (note: a single bird with confirmed H5N1 is counted as an outbreak). Said the Prime Minister, 17 Jan 2006, "Nearly 1 million poultry have been culled so far (due to bird flu) in Turkey, and breeders were paid compensation". (Promed 1/18/06, 1/19/06)

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Turkey: Avian influenza outbreaks began earlier; useful maps of Turkey situation
The current wave of lethal bird flu in Turkey began in mid Nov 2005, more than 3 weeks before an initial report, the World Organization for Animal Health (OIE) said. Outbreaks of the H5N1 avian influenza virus affected birds as early as 21 Nov 2005, Huseyin Sungur, a government official, said in a 12 Jan 2006 report to the OIE. Turkey, in a statement 27 Dec 2005, said outbreaks began 15 Dec 2005 in Igdir province. The delay in reporting the outbreak highlights the need to improve early detection and reporting systems to help contain infections. The H5N1 virus was later reported to have caused outbreaks in the provinces of Agri, Sanli Urfa, Bitlis, Igdir, Erzum, Yozgat, Bursa, Van, Ankara and Istanbul. Turkey reported an initial H5N1 outbreak in its western region in Oct 2005. Top government officials have warned Turkey is at permanent risk of outbreaks because it is on the path of migratory birds.

European Commission map showing human and animal cases in Turkey: http://disasters.jrc.it/AvianFlu/Turkey. A map demonstrating Turkey's confirmed and suspected HPAI outbreaks in poultry, as of 17 Jan 2006: http://www.ecdc.eu.int/images/maps/turkey_poultry_17jan06.BMP. Maps of numbers and locations of confirmed human cases and the locations of suspected and confirmed outbreaks of disease in poultry in Turkey: http://www.eurosurveillance.org/ew/2006/060112.asp#1. (Promed 1/13/06, 1/14/06, 1/18/06, 1/20/06)

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Turkey: First wide-scale summit on avian influenza; Aid for poultry workers
Turkey's first wide-scale summit on measures to combat avian influenza is to be held 20 Jan 2006. Health minister Akdag stressed that the necessary short term measures were being taken but that the summit would look at medium and long term plans. Apart from having the governors of all of Turkey's 81 provinces, the summit will also be attended by the health minister, the agriculture minister, the forestry and environment minister, and the interior minister. The governors from the provinces of Van and Igdir, where most of the human cases of avian flu have occurred, will give briefings on the latest measures being conducted and Edmond McLoughney of the UN will also address the meeting. To date, at least 5 people have died after contracting H5N1 strain of the virus, with another 16 people having been infected. 13 of Turkey's 81 provinces have confirmed outbreaks of avian flu, with a further 28 reporting suspected outbreaks.

The Turkish government unveiled a USD 40 million aid package 20 Jan 2006 for poultry firms hit by bird flu, including compensation for culled chickens and postponement of tax and debt payments. Bird flu has hit the USD 3 billion sector hard. Sales have fallen dramatically in the domestic market and a number of countries have imposed import bans on Turkish poultry products. Deputy prime minister Abdullatif Sener said the industry had annual poultry meat output at 914 000 tonnes in 2004. Exports stood at USD 35 million and imports at USD 21 million. Turkey has slaughtered more than 1.1 million poultry since the outbreak emerged. Up to a third of the country is suspected of having bird flu among poultry and Turks have reported 21 human cases, including 4 deaths. The government is allocating 15.4 million lira from the budget in compensation for 14 million egg-producing chickens that are going to be culled, said Sener. Due dates of loans provided by the state bank Ziraat and agriculture cooperatives to poultry firms will be postponed for 1 year, he added. However, industry representatives said the measures did not go far enough. (Promed 1/14/06, 1/20/06)

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Turkey: Laboratory findings from the fatal Turkish cases
Scientists studying virus samples from the human outbreak of avian influenza in Turkey have identified 3 mutations in the virus's sequence. They say that at least 2 of these look likely to make the virus better adapted to humans. The Turkey outbreak is unusual, because of the large family clusters of cases; the fact that many of those infected have only mild symptoms; and the speed with which infections have arisen -- 20 cases, including 4 deaths, in less than 2 weeks. "With such a large number of cases within such a short period of time, human-to-human transmission is something that we've had to consider," says Maria Cheng, a spokeswoman at WHO. "Turkey is seeing a fatality rate of 20 per cent, which is lower than the fatality rate observed in Asia, which was around 58 per cent," Cristiana Salvi, a spokeswoman for WHO's mission in Turkey, said, citing early detection and treatment as the primary cause. "There could be other factors which we are investigating as a lot of cases are still in hospital," she cautioned, however.

Samples from the first 2 teenagers in the country to die had been sequenced by the National Institute of Medical Research (NIMR) in London. The first mutation found, involves a substitution in 1 sample of an amino acid at position 223 of the haemoagglutinin protein. This protein allows the flu virus to bind to the receptors on the surface of its host's cells. This mutation has been observed twice before -- in a father and son in Hong Kong in 2003, and in 1 fatal case in Viet Nam during 2005. It increases the virus's ability to bind to human receptors, and decreases its affinity for poultry receptors, making strains with this mutation better adapted to infecting humans. The same sample also contained a mutation at position 153 of the haemagglutinin protein. Cheng says "it is not clear what role this particular change plays". Finally, both samples from the Turkish teenagers show a substitution of glutamic acid with lycine, at position 627 of the polymerase protein, which the virus uses to replicate its genetic material. This mutation has been seen in other flu sequences from Eurasian poultry over the past year. It was also present in the 1 person who died during an outbreak of H7N7 in the Netherlands in 2003, and in a few people in Viet Nam and Thailand. The polymerase mutation is 1 of the 10 genetic changes that gave rise to the 1918 pandemic flu virus. Like the 223-haemagglutinin mutation, it signals adaptation to humans, says Alan Hay, Director of a WHO influenza laboratory at the NIMR. The gene sequences of these samples also indicated that they were sensitive to Tamiflu and amantadine.

The Turkey strains are the first in which the polymerase and receptor-binding mutations have been found together. They could make it easier for humans to catch the virus from poultry. But they might also favour human-to-human transmission. This is because the polymerase change helps the virus to survive in the cooler nasal regions of the respiratory tract, and the haemagglutinin mutation encourages the virus to target receptors in the nose and throat, rather than lower down in the lungs. The virus is thought to be more likely to spread through droplets coughed from the nose and throat than from infections lower down. Establishing what effects these changes are having on the epidemiology of the current outbreak is a priority for researchers. "We must learn more about the mild cases and be absolutely sure of whether these viruses are behaving differently from those we have seen elsewhere," says Hay. Recently, researchers at the Scripps Research Institute in USA said they had developed a quick test, called a glycan array, that could alert scientists to when the virus changes. (Promed 1/14/06, 1/18/06, 1/20/06)

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Iran/Syria: Destruction of birds by Turkish border
Iran has destroyed thousands of birds in an area along its border with Turkey in an effort to create a buffer against the spread of bird flu. Homayoon Hamidi, head of the Veterinary Organization of Maku, West Azarbaijan province, said 2600 birds in 9 villages were destroyed, with all birds in the remaining 23 villages facing the same fate in the next 6 days. The health and veterinary officials are on alert in the area "to take controlling measures and prevent the disease from entering Iran," health ministry official Seyed Moayed Alavian said. "Only free range birds are to be destroyed, as factory reared chickens are under control," another press report quoted Kamyar Dahim, the head of West Azarbaijan province's Veterinary Organization, as saying. Iran's Health Minister, Kamran Lankarani, said no bird flu cases have yet been found in Iran. The Islamic republic has already banned poultry imports from Turkey and urged its citizens not to travel there. It has also closed its land frontier to single day cross border traders. State television showed pictures of officials disinfecting vehicles crossing into Iran from Turkey. Fearing the transmission of the disease by migrating birds, Iran's Environmental Organization has put 10 inland water areas on red alert and has strictly banned hunting and the sale of hunted wildfowl. 2 Turkish children from the town of Dogubeyazit, just 45 km from the country's eastern border with Iran, died recently after playing with a sick chicken.

Also, Syria culled birds at a market near the Turkish border 15 Jan 2006 to prevent the spread of bird flu across the border, though the birds showed no sign of illness. "Any poultry on sale in an unregulated market and any pigeons or game are now culled," said George Khoury, head of the animal health department at the Agriculture Ministry. The birds were being traded at an unregulated market where live birds are sold every Sunday in Kameshli on the Turkish border, he said. Health officials also shut down the town's regular bird market and inspected poultry shops for hygiene. Syria shares a 490 km border with Turkey. More than 18 000 birds have been tested in Syria, and no human cases of bird flu have been reported, Khoury said. (Promed 1/13/06, 1/15/06)

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Ukraine (Crimea): New cases of avian influenza suspected among wild birds
Officials in Ukraine's Crimea peninsula said 18 Jan 2006 that new cases of bird flu had been detected among wild birds and urged residents to exercise caution to prevent a spread to domestic livestock. Officials said that tests showed 5 birds found dead in the port of Sevastopol had been infected with bird flu. A municipal spokesman said the city had been declared a "potentially dangerous zone" after the discovery. Residents in and around Sevastopol were told to keep domestic birds in enclosures and to destroy any with suspicious symptoms. Testing in Ukraine is insufficiently sophisticated to detect H5N1 bird flu strain -- which has already been found in other regions of Crimea, a key centre for migratory birds. No human cases of bird flu have been recorded. Specialized teams of sanitary workers have already destroyed over 200 000 birds in Ukraine -- both privately held and at industrial plants -- since the discovery of the H5N1 virus in villages in Crimea late 2005. Ukrainian authorities have repeatedly said that the outbreak is under control but expect further difficulties when migratory birds pass through Ukraine in the spring. (Promed 1/19/06)

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Asia
Eurasia: Cumulative number of human cases of avian influenza A/(H5N1)
Cumulative number of confirmed human cases of avian influenza A/(H5N1), 2005: Economy / Cases (Deaths)
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 16 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 94 (41)

Cumulative number of confirmed human cases of avian influenza A/(H5N1), 2006: Economy / Cases (Deaths)
China / 1 (1)
Indonesia / 1 (1)
Turkey / 4* (2)
Total / 6 (4)

*A large number of patient samples from Turkey have been sent to a WHO collaborating laboratory in the UK for verification. WHO will adjust the number of cases and deaths in Turkey in its cumulative table of lab-confirmed cases upon receipt of results from the UK laboratory.

Total number of confirmed human cases of avian influenza A/(H5N1), 26 Dec 2003 to present: 149 (80)
(Promed 1/16/06; WHO 1/19/06 http://www.who.int/csr/disease/avian_influenza/country/en/index.html )

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Pan Asia: Commit to an early response to the threat of an influenza pandemic
Asian countries threatened by avian influenza have outlined an action plan that could, under the right circumstances, contain the initial eruption of an influenza pandemic in the region. The action plan and commitments came at the end of the Japan-WHO Joint Meeting on Early Response to Potential Influenza Pandemic in Asia in Tokyo, Japan, 12 - 13 Jan 2006. Containment of an emerging influenza pandemic has never been attempted but modelling studies demonstrate that success is dependent upon the early detection and rapid reporting of signals that an influenza pandemic may have begun. For this reason, many of the actions outlined at the meeting focused on strengthening public health infrastructure. To do this, delegates agreed that the top priorities for rapid response and containment capability are to enhance country, regional and global capacities in surveillance, epidemiology, laboratory capacity, risk assessment and public communications. Japan and ASEAN countries in collaboration with WHO were asked to develop a detailed operational plan on stockpiles, including antivirals. Specific actions finalized in the meeting called on WHO, countries, agencies and donors to:

• Strengthen national capacities to detect and respond to the earliest signals of a potential pandemic and any other public health emergency.
• Assist countries to develop or strengthen their local and national laboratory facilities so that early signals of a potential pandemic can be rapidly confirmed.
• Establish a global influenza task force to act in an advisory role when assessing potential early signals of pandemic influenza.
• Identify and address all practical issues including legal, logistical and operational issues to allow implementation of rapid containment.
• Strengthen regional and global laboratory networks.
• Draft a comprehensive strategy, supported by protocols and standard operating procedures for a rapid, coordinated and effective response.
• Coordinate the development of an appropriate communication strategy, including outbreak communications and communications for behavioural change.
• Train identified local and international experts in the concepts of rapid response and containment.
(WHO/WPRO 1/16/06 http://www.wpro.who.int/ )

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Indonesia: Additional fatal human case of avian influenza; more suspected cases
A 13 year old Indonesian girl died of avian influenza and 2 of her siblings have tested positive for the H5N1 virus, a health ministry official said 16 Jan 2006, citing the results of local tests. "We found 3 positive bird flu cases in 1 family coming from Indramayu, West Java," said Hariadi Wibisono, the Ministry's director of control of animalborne diseases. He said this was Indonesia's fifth cluster of bird flu cases, where people living in close proximity had fallen ill. There was no evidence of human-to-human transmission and dead chickens had been found in the neighborhood, he added. Wibisono said the girl died in an Indramayu hospital while her 15 year old sister and 3 year old brother had been sent to a hospital in Jakarta designated to care for avian influenza patients. "A lot of poultry died around the neighbourhood where they lived. But we don't know yet whether these birds were carrying the virus. We sent a team there to investigate this morning," he said, adding that anyone who has had close contact with the children will be tested. Trying to build awareness among Indonesian owners of backyard chickens, Red Cross volunteers wearing protective suits went to a village on the outskirts of Jakarta and showed residents how to keep poultry cages properly cleaned. If confirmed by WHO-accredited laboratories, the latest cases would take total known deaths in Indonesia from avian influenza to 13 and the number who have had avian influenza to 20.

Additionally, WHO confirmed that a 29 year old Indonesian woman was the country's 12th death from bird flu. The woman worked as a midwife at the maternity ward in a Jakarta hospital. She developed symptoms 31 Dec 2005, was hospitalized 2 Jan 2006, and died 11 Jan 2006. Investigations conducted by the Ministry of Health and WHO found evidence of poultry deaths in her neighborhood in the 2 weeks prior to onset of illness. Other findings indicate that the patient visited a live-bird market to select and purchase freshly slaughtered chicken in the days immediately prior to symptom onset. Investigations at these sites are continuing. The possibility that the patient acquired her infection from an occupational exposure is considered unlikely. Investigations conducted reveal that none of her co-workers was ill prior to the start of her illness. According to hospital records, no patients in the ward where she worked showed signs of influenza-like illness while hospitalized. At this stage, there is no evidence that she transmitted the infection to any patients under her care or to colleagues at the hospital. Similarly, there are no signs of illness in family members or neighbors. Health monitoring of contacts will continue until the maximum incubation period has ended. Indonesia is also awaiting results from tests in Hong Kong on a 39 year old man who died earlier this month. Local tests, which are usually reliable, confirmed that he also had bird flu. (Promed 1/14/06, 1/16/06)

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China (Sichuan): Ninth confirmed case of human infection with H5N1 virus
As of 19 Jan 2006, the Ministry of Health in China has confirmed an additional case of human infection with the H5N1 avian influenza virus. The case occurred in a 35 year old woman, from Jianyang city in the south-central province of Sichuan, who had been employed as a poultry culler. No outbreak of the disease among poultry had been reported in Jianyang, with the closest H5N1 outbreak recorded in Sichuan's Dazhu county 245 km away. She developed symptoms 3 Jan 2006, was hospitalized 10 Jan 2006 with symptoms of fever and pneumonia, and died 11 Jan 2006. Further investigation is under way to determine whether the woman may have acquired her infection during culling operations or as a result of direct exposure to infected birds in her village. She lived in a compound where 8 families were housed in close quarters. Members of these families and other close contacts have been placed under medical observation. No signs of influenza-like illness have been reported to date. The newly confirmed case is the ninth in China. Of these cases, 6 have been fatal. The cases have occurred in 7 provinces and regions: Anhui, Guangxi, Liaoning, Jiangxi, Fujian, Hunan, and Sichuan. (Promed 1/20/06)

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Hong Kong: Dead oriental magpie robin found infected with H5N1 strain
A dead bird found in Hong Kong has tested positive for the H5N1 strain of bird flu, the government said 19 Jan 2006. It is the first confirmed case of bird flu in a year in the territory. Thomas Sit, assistant director of agriculture, fisheries and conservation, said it remains unknown how the oriental magpie robin was infected. "The bird is a resident species in Hong Kong and can be found in the city area," Sit said (also kept often as pets). "How it got infected or where it got the virus is still unknown at this stage. Similar to cases in other parts of the world, it is difficult to trace the source of infection." The robin was found 10 Jan 2006 by a villager in a rural bush area of the New Territories, and it is one of the 1500 bird samples taken since Oct 2005. Chicken farms within a 5 km radius were all clear of the virus, Sit said. He said there is no cause for alarm but still warned the public not to come into contact with wild birds. Hong Kong can still be considered a bird flu-free area because according to the definition of the World Organization for Animal Health [OIE], bird flu is present in an area only if poultry is infected, he said. Since 1997, wild birds of the following species have been found infected with HPAI H5N7 in Hong Kong: peregrine falcon, grey heron, Chinese pond heron, black-headed gull, little egret, greater flamingo, pigeon, tree sparrow, and "various waterfowl". (Promed 1/20/06)

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Russia: Return of avian influenza expected from migratory birds
Scientists warned 19 Jan 2006 that bird flu would return and that southern regions would be the first to suffer. The first regions that will be hit when migrating birds come back after the winter will be Stavropol, Rostov and Krasnodar, as well as the republics of Dagestan and Kalmykia, said Konstantin Litvin, head of the bird-tagging center at the Academy of Sciences' Institute of Ecology and Evolution. "Wild birds are the main source of transmitting avian flu," he said. The birds will return from Turkey, Central Asia, and other warmer regions when it begins to warm up in Russia. Viktor Zubakin, president of Russia's Bird Preservation Union, and other scientists warned against shooting wild birds, saying that doing so would hasten the spread of the virus. "Those birds would be left for predators, crows, which frequent residential areas, so we would bring infected birds closer to us," said Alexei Zimenko, head of the Wildlife Preservation Center. Scientists also cautioned that vaccinating domestic fowl was not the best answer. Vaccinations dull the symptoms but do not eradicate the virus, making the culling of birds in affected areas the most effective way to combat bird flu, they said. Bird flu hit several Russian regions during the summer of 2005, but no cases of people catching the disease have been recorded. (Promed 1/20/06)

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Japan (Ibaraki): Current situation and review of avian influenza H5N2
Japan will cull another 770 000 birds after authorities detected what is probably a mild form of avian flu virus at a farm, an official said 16 Jan 2006. A virus of the H5 strain was detected among chickens at Moriya farm in Ibaraki prefecture. 6 months have passed since bird flu was confirmed to have infected chickens at a poultry farm in Ibaraki. The source of the Ibaraki outbreak has not been found, but the use of what has been called an "underground vaccine" to contain the disease is suspected to have aided its spread. The first case of bird flu was confirmed on a poultry farm in Mitsukaido, Ibaraki, 26 Jun 2005. The H5N2 strain of the virus found on the farm was relatively weak. As the Ibaraki strain did not kill many chickens, officials concluded there was little chance of the outbreak spreading. But infections were later confirmed at poultry farms around the Mitsukaido farm. In early July 2005 the ministry decided to conduct nationwide tests for the disease. 31 bird flu cases were confirmed, including 1 in Saitama Prefecture. As of Dec 2005, an additional 10 cases had been found.

The cases showed that the basic method of controlling the breakout by containing the virus through accurate tracking of the areas of infection had been inadequate. Officials of the Ibaraki prefectural government who were in charge of animal infection control were not present when tests were conducted at 14 poultry farms. The prefectural police launched investigations by searching 2 poultry breeders that allegedly switched chickens to be examined. The Ibaraki prefectural government began re-inspections Dec 2005. The type of virus in the 40 poultry farms in Ibaraki is almost identical to that of a strain that originated in Central America. The possibility of a strain of bird flu so similar to the Central American strain developing independently in Japan is extremely slim. Therefore, a ministry subcommittee for poultry disease pointed out in Sep 2005 the possibility that an illegal bird flu vaccine was used. If a vaccine is chemically processed incompletely, infectious virus remains in the vaccine and can spread when administered to poultry. The government prohibits the use of unapproved vaccines because their use makes it difficult to trace infections.

As of 29 Dec 2005, about 2.39 million chickens had been destroyed, with about 100 000 more slated to be killed. The remaining 3.29 million will be raised in isolated poultry farms. The ministry said the possibility of those raised on isolated farms becoming infected with bird flu is low. The ministry is monitoring those flocks. Those farms are still approved to ship eggs and chickens for human and animal consumption. Recently, 77 poultry workers from the affected farms have been found sero-positive to the H5N2 virus. (Promed 1/16/06)

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Americas
USA: CDC Recommends against the use of Amantadine and Rimandatine
CDC alerts against the use of Amantadine and Rimandatine for the treatment or prophylaxis of influenza in the US during the 2005-06 influenza season. Recent evidence indicates that a high proportion of currently circulating Influenza A viruses in the US are resistant to these medications. While the primary strategy for preventing complications of influenza infections is annual vaccination, antiviral medications with activity against influenza viruses can be effective for the prophylaxis and treatment of influenza. 2 classes of antivirals are currently available: the M2 ion channel inhibitors (the 2 adamantanes amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir and zanamivir). The adamantane drugs are older, less-expensive and less commonly prescribed drugs--they are commonly prescribed to prevent infection in elderly or chronically ill people at high risk for complications from the infection. The neuraminidase inhibitors are effective for the treatment and prophylaxis of influenza A and B, while the adamantanes are only active against influenza A viruses.

A recent report on the global prevalence of adamantane-resistant influenza viruses showed a significant increase (from 1.9 percent to 12.3 percent) in drug resistance over the past 3 years. In the US, the frequency of drug resistance increased from 1.9 percent in 2004 to 14.5 percent during the first 6 months of the 2004-05 influenza season. For the 2005-06 season, 120 influenza A (H3N2) viruses isolated from patients in 23 states have been tested at CDC through 12 Jan 2006; 109 of the isolates (91 percent) contain an amino acid change which confers resistance to amantadine and rimantadine. 3 influenza A(H1N1) viruses have been tested and have demonstrated susceptibility to these drugs. All influenza viruses from the US that have been screened for antiviral resistance at CDC have demonstrated susceptibility to the neuraminidase inhibitors. In Asia, resistance to the adamantanes increased from 2 percent in 2001 to 27 percent in 2004, with some countries reporting much higher rates. In China's last flu season [2004-2005], 74 percent of virus samples were resistant to the adamantanes.

On the basis of available results, CDC is providing an interim recommendation that neither amantadine nor rimandatine be used for the treatment or prophylaxis of influenza A in the US for the remainder of the 2005-06 influenza season. During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza. Testing of influenza isolates for resistance to antivirals will continue. Annual influenza vaccination remains the primary means of preventing morbidity and mortality associated with influenza. For more information: http://www.cdc.gov/flu/protect/antiviral.

There are 2 ways drug resistance can increase. Flu virus can undergo a spontaneous mutation that makes it resistant to a drug. Alternatively, using an antiviral drug during an infection -- particularly if the dose is inadequate -- can put evolutionary "pressure" on a virus to develop resistance. Which of these mechanisms was responsible for the jump in adamantane resistance is uncertain. In recent years, however, drug-resistant strains have been found widely throughout China, even where antivirals are rarely used, suggesting that chance may be an important factor. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d117a1.htm (Promed 1/15/06; MMWR January 17, 2006 / 55(Dispatch);1-2)

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USA: USDA statement on fraudulent, unapproved influenza-related products
The U.S. Food and Drug Administration considers the sale of unlicensed or unapproved influenza -related products as a potentially significant threat to the public health and is taking measures to protect consumers from fraudulent products that claim to prevent or treat seasonal or avian influenza in people. Consumers should be aware that currently there are no approved vaccines for preventing avian influenza in people nor are there any drugs approved for treating the specific symptoms of avian influenza. For the most part, the seasonal and avian influenza-related products promoted to consumers without a specific endorsement by a registered pharmacy or health care professional and/or without a valid prescription written by a healthcare professional are not approved by the FDA and have not been determined to be safe and effective by the FDA.

FDA, in cooperation with the U.S. Customs and Border Protection Agency, recently intercepted products at the border that purported (to be "generic" Tamiflu,) but which, in fact, contained Vitamin C and other ineffective substances. In another recent case, Special Agents from the FDA Office of Criminal Investigations (OCI) worked in coordination with the FBI to arrest an individual in Texas who administered counterfeit influenza vaccine to employees attending a corporate-sponsored health fair. And in July 2005, another investigation resulted in the indictment of an individual by a federal grand jury for his role in smuggling foreign, unlicensed influenza vaccines into the US, and attempting to sell the illegal vaccines to hospitals. Most recently, a Licensed Practical Nurse was sentenced to 9 months in prison for operating a series of unauthorized influenza vaccine clinics, after pleading guilty to dispensing drugs without a doctor's prescription. The nurse admitted to diluting some of the vaccine with saline to increase the quantity of her supply. These illustrate the dangers of buying drugs from unknown sources. (US FDA 1/20/06 http://www.fda.gov/bbs/topics/news/2006/NEW01301.html )

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1. Updates
Influenza
Seasonal influenza activity for the Asia Pacific and APEC Economies
From week 50 in 2005 to week 1 in 2006, influenza activity continued to increase in several countries of North America and South-East Asia. Overall activity remained low.

Canada. Widespread influenza activity was reported in southern Alberta during weeks 50–51 but quickly declined in week 52. Current activity remained low. Hong Kong. A slight increase of influenza A(H1) and B activity was observed in week 1 of 2006. Overall activity remained low.

Japan. Influenza A(H3N2) activity continued to be reported as regional until week 1, when a decline was observed.

Other reports. Low influenza activity was detected in Mexico (H3, A and B) and Russia (H1, H3 and B). Chile, Peru, and Philippines reported no influenza activity.
(WHO 1/18/05 http://www.who.int/csr/disease/influenza/update/en/ )

USA. During week 2 (Jan 8 – Jan 14, 2006), influenza activity continued approximately at the same level as recent weeks in the US. 238 (11.8%) specimens tested by U.S. WHO and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories were positive for influenza. 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. 8 states reported widespread influenza activity; 14 states and New York City reported regional influenza activity; 11 states reported local influenza activity; 16 states, the District of Columbia, and Puerto Rico reported sporadic influenza activity; and 1 state reported no influenza activity. (CDC 1/20/06 http://www.cdc.gov/flu/weekly/ )

A comprehensive update on recent influenza activity in the USA (“Update: Influenza Activity--United States, January 1--7, 2006”) is available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5502a8.htm. (MMWR January 6, 2006 / 54(51&52);1305-1307)

Avian/Pandemic influenza updates
- WHO’s comprehensive information on the avian influenza: http://www.who.int/csr/disease/avian_influenza/en/index.html. WPRO website on avian influenza: http://www.wpro.who.int/health_topics/avian_influenza/overview.htm
- Latest FAO updates on avian influenza: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html.
- OIE updates and documents on avian influenza: http://www.oie.int/eng/en_index.htm.
- CDC website on pandemic influenza: http://www.cdc.gov/flu/pandemic.htm (“Highlights” have been updated Jan 2006). For avian influenza: http://www.cdc.gov/flu/avian/. “Key facts” have been updated 10 Jan 2006.
- The US government’s web site for pandemic flu: http://www.pandemicflu.gov/. New State Summit summaries have been uploaded; On 12 Jan 2006, HHS announced $100 million to accelerate State and Local Pandemic Influenza Preparedness Efforts.
- Influenza information from the US Food and Drug Administration: http://www.fda.gov/oc/opacom/hottopics/flu.html.
- Latest CIDRAP updates on avian/pandemic influenza: http://www.cidrap.umn.edu/index.html. The article, “H5N1 avian flu viruses: What's in a name?”, clarifies common questions and confusion arising from the nomenclature.
- PAHO’s updates on avian influenza: http://www.paho.org/English/AD/DPC/CD/influenza.htm.
- American Public Health Association (APHA) information on Influenza (http://www.apha.org/preparedness/influenza.htm) and Avian Influenza (http://www.apha.org/preparedness/avian.htm).
- The American Veterinary Medical Association information on avian influenza: http://www.avma.org/public_health/influenza/default.asp
(WHO; FAO, OIE; CDC; US FDA; CIDRAP; PAHO; APHA; AVMA)

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2. Articles
Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts
Am J Pathol. 2006 Jan;168(1):176-83
Researchers at the Erasmus Medical Center have demonstrated systemic spread of avian influenza virus in cats infected by respiratory, digestive, and cat-to-cat contact. The paper by Rimmelzwaan et al., appears in the Jan 2006 issue of The American Journal of Pathology. The paper is accompanied by a Commentary by C. Brown, “Avian influenza: Virchow's reminder”.

Avian influenza (H5N1) is highly contagious in birds and spreads easily due to the agricultural and migratory nature of the bird species infected. While spread of avian influenza from bird to man is known to occur, human-to-human spread is extremely rare. Thus, the disease events that take place during mammal-to-mammal spread are not well characterized. To assess the spread of H5N1 influenza virus in mammalian hosts, Rimmelzwaan et al. examined cats infected via the respiratory tract, via the digestive tract (by feeding on infected chicks), or by close contact with respiratory-infected cats. The researchers then examined mucous membranes (throat, nasal, and rectal swabs) and organ systems (respiratory, digestive, nervous, cardiovascular, urinary, lymphoid, and endocrine) for the presence of virus and viral protein. As expected, all cats were infected with H5N1 virus and exhibited clinical signs of disease, and virus was detected in throat, nasal, and rectal swabs, regardless of the original site of infection. Most interesting, virus spread throughout the organ systems with virus being found in respiratory and digestive tracts, liver, kidney, heart, brain, and lymph nodes. Furthermore, examination of infected tissues revealed cellular damage at sites containing viral proteins.

These data underscore the potential for influenza virus to spread not only from the respiratory tract but also from the digestive and urinary tracts, greatly increasing the possible routes of mammalian transmission. Systemic disease has long been known to occur in birds, with the fecal-oral route of transmission being most important. However, this is the first demonstration of systemic replication in cats, providing a cautionary tale for humans regarding how influenza is spread and how the disease presents itself. Rimmelzwaan and colleagues caution that because of the systemic nature of avian influenza, "H5N1 virus infection needs to be included in the differential diagnosis of a broader range of clinical presentations than is currently done." In addition better understanding of the mechanisms of spread, including possible fecal-oral route in humans, "may limit the risk of H5N1 virus developing into a pandemic influenza virus."

The susceptibility of carnivores to avian influenza A virus was first recorded in a paper published in the China Journal of Veterinary Science in 2003, demonstrating that tigers had died of influenza A virus infection in China in 2002. Subsequently in 2004 during the H5N1 avian influenza outbreak in Thailand considerable mortality occurred among zoo tigers and leopards probably as a result of ingestion of diseased poultry. More recently, deaths of chickens and dogs were reported in Turkey, although the cause was not determined. (Promed 1/14/06)

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3. Notifications
Singapore's SARS Experience to Contribute to Avian Influenza Seminar
Senior business executives that have been hand-picked by the Leaders of APEC Member Economies will meet in Singapore over the following week to address major economic issues of concern to regional business. The first APEC Business Advisory Council (ABAC) meeting of 2006 will cover issues including the business implications of a potential Avian Influenza Pandemic. The schedule will begin with a seminar on Avian Influenza before the formal ABAC meeting. This seminar will consider actions to help mitigate a possible pandemic and is expected to draw on the successful responses to epidemics in the past including Singapore's response to SARS. This is the first of 4 ABAC Meetings that will take place around the Asia-Pacific in 2006 with other meetings planned for Canada, the Philippines and Viet Nam. At the final meeting in Viet Nam in Nov 2006 ABAC will present a series of recommendations to APEC Leaders. (APEC 1/20/06 www.apec.org )

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 apecein@u.washington.edu