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EINet Alert ~ Oct 14, 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:

1. Updates
- Turkey and Romania: OIE Update on avian influenza and recommendations
- Turkey and Romania: Avian influenza outbreaks and implications
- Global: Experts cite differences between H5N1 and ordinary flu
- South East Asia: Cumulative number of human cases of avian influenza A/(H5N1)
- Russia: OIE Mission report on avian influenza
- Indonesia: Fifth laboratory confirmed human case of avian influenza
- Indonesia: More suspected avian influenza cases
- Indonesia: Corruption sparks bird flu vaccine test
- **South Asia: Earthquake in Pakistan**
- USA: Avian and pandemic flu in political spotlight
- USA: Plan paints grim picture of flu pandemic
- USA: Chiron gets FDA nod to ship flu vaccine
- Columbia: Avian influenza (H9) in poultry

2. Notifications
- CDC: Latest updates of avian influenza


1. Updates

Global
Turkey and Romania: OIE Update on avian influenza and recommendations
Samples collected from sick turkeys in Kiziksa, Balikesi in Turkey and sent to the OIE Reference Laboratory for Avian Influenza, Weybridge, UK have been confirmed to contain avian influenza virus H5N1. The virus isolated seems to be very close to one of the viruses isolated in Siberia. In Romania, laboratory tests conducted at the Institute for Diagnostics and Animal Health (Bucharest) have now identified the virus isolated from sick poultry in the locality of Ceamurlia-de-Jos to be of subtype H5. Further tests being necessary, confirmatory diagnoses are being carried out. The probability of finding the same virus is high. Viruses are also being sent to WHO reference laboratories for comparison with human H5N1 isolates from Asia.

OIE emphasizes the importance for both affected and at-risk countries of implementing all the necessary measures to ensure the early detection of sick poultry and a rapid response to the immediate control of the disease. The rapid response consists of eliminating the sick and in-contact animals in case of suspicion based on clinical signs seen by veterinarians on the farm. Of particular importance is the involvement of farmers in reporting the first occurrence of unexplained mortalities in their flocks and the creation of rapid and equitable compensation schemes. Supporting national veterinary services so that they can implement a rapid response in case of suspicion and outbreak is also crucial in the control of avian influenza in animals worldwide. OIE recalls that the transmission of the AI virus to humans by food consumption has not been reported. The virus in meat is killed by cooking at 70C for several seconds.

Authorities in the 2 countries have undertaken control measures as recommended by OIE and FAO. WHO is sending diagnostic reagents and other supplies to support testing in national labs. The spread of H5N1 to poultry in new areas is of concern, as it increases opportunities for further human cases to occur. However, all evidence to date indicates that the H5N1 virus does not spread easily from birds to infect humans. WHO advises countries experiencing outbreaks in poultry to follow certain precautions, particularly during culling operations, and to monitor persons with a possible exposure history for fever or respiratory symptoms. The early symptoms of H5N1 infection mimic those of many other respiratory illnesses, meaning that false alarms are likely. Also, countries located along migratory routes of wild birds need to be vigilant for signs of disease in wild and domestic birds. Recent events make it likely that some migratory birds are now implicated in the direct spread of H5N1 in its highly pathogenic form.

The WHO level of pandemic alert remains unchanged at phase 3: a virus new to humans is causing infections, but does not spread easily from one person to another. WHO continues to recommend that travelers to areas experiencing outbreaks of highly pathogenic H5N1 in poultry should avoid contact with live animal markets and poultry farms. Large amounts of the virus are known to be excreted in the droppings from infected birds. Populations in affected countries are advised to avoid contact with dead migratory birds or wild birds showing signs of disease. Direct contact with infected poultry, or surfaces and objects contaminated by their droppings, is considered the main route of human infection. Exposure risk is considered highest during slaughter, defeathering, butchering, and preparation of poultry for cooking.
(Promed 10/14/05; WHO 10/13/05 http://www.who.int/csr/don/2005_10_13/en/index.html; OIE 10/13/05 http://www.oie.int/eng/press/en_051013.htm)

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Turkey and Romania: Avian influenza outbreaks and implications
The European Commission met in an emergency meeting 13 Oct 2005, whose first measure was to ban imports of live birds and poultry from Romania. The EU has also banned the import of live birds and feathers from Turkey until April 2006. EU foreign ministers are also to hold emergency talks on the bird flu threat 18 Oct 2005 when they meet for WTO negotiations. Meanwhile, the slaughtering of the birds from certain areas in Tulcea County, Romania carried on, and quarantine measures taken by authorities have been stepped up. Agriculture Minister Gheorghe Flutur said that measures had been taken to completely isolate the village in Tulcea. Authorities urged population to stay calm, but also asked people to comply with the minimum of hygienic measures, to avoid purchasing poultry from unauthorised sources and to take antiviral medicines. The National Audiovisual Council (CAN) also called on radio and television stations to broadcast information from authorized sources to avoid creating panic among the population.

The risks of the bird flu spreading in Romania are small, say experts of the European Commission. "Given that the virus emerged in a small locality, where locals do not buy birds from outside their community, chances of the disease spreading are smaller compared with what would be in a similar case in western Europe," says Danish expert Jorgen Westergaard. The European Commission has announced it will provide assistance to Romania in eliminating the bird flu. Answering a request for medicines by Romania's Health Minister, WHO agreed to supply, at no charge, 1000 of the 5000 doses of antivirals the government needs for the preventive treatment of the population that came into contact with the identified focus of avian flu. During the next few days, the Health Ministry will be made available 25 000 doses of antiviral medicine. In about 10 days, the ministry emergency stock will be supplemented by another 20 000 doses.

Health minister Eugen Nicolaescu said that aside from the protection offered by the ministry, "citizens need to know 3 basic things: firstly, to wash their hands with water and soap, secondly, to only purchase poultry and egg from authorised sources, namely veterinary-certified stores, and thirdly, to keep away from dead birds or birds that had come in contact with dead birds". Fowl farmers are claiming that the contradictory information regarding the existence of the bird flu in Romania has triggered a fall of 40 per cent in the sales of fowl and products, although the risks of an epidemic are minimal as long as the population eats only tested meat.

Meanwhile, neighbouring counties of Tulcea County stepped up safety measures. Teams made up of border police and representatives of the Braila Veterinary Department beefed up the road blocks at the Bac Smardan crossing point that connects the county to the neighbouring county of Tulcea. All the vehicles crossing the Danube and entering the municipality through that point are inspected and disinfected with a special pump. All ship captains received written advisories against transporting birds and animals from Tulcea. Similar safety measures have also been taken at the Small Island of Braila County, which is considered high risk of avian flu, given its opening to the Danube and the large number of migratory birds that take shelter here each year.

9 people are under medical observation in Turkey after reports of 40 pigeons in their neighborhood died mysteriously. Samples from the dead pigeons have been sent for testing in Izmir. All 9 are from Manisa, which is close to the village where the H5N1 strain of bird flu was identified. Osman Ozturk, deputy head of the Manisa health department, said: "There is no sign of illness in the 9 people." He said they were put under medical observation simply as a precaution while their house was being disinfected. In Turkey, around 8600 birds were culled this week in and around the village of Kiziksa, in the neighbouring province to Manisa. (Promed 10/14/05)

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Global: Experts cite differences between H5N1 and ordinary flu
A recent and extensive review of research on H5N1 avian influenza in humans shows the illness differs from ordinary flu in several ways. The report by a WHO committee says avian flu may have a longer incubation period and is more likely to cause diarrhea than typical flu viruses are, among other differences. Published in the Sep 29, 2005 New England Journal of Medicine, the review was written by experts from several countries who reviewed 71 published studies and reports, including details on 41 confirmed human cases from Vietnam, Thailand, Cambodia, and Hong Kong. The H5N1 virus first jumped from birds to humans in Hong Kong in 1997, infecting 18 people and causing 6 deaths. In late 2003 the virus began sweeping through poultry flocks in East Asia, and since then it has struck at least 116 people and killed at least 60.

The report says the virus may incubate longer than other human flu viruses before causing symptoms. Incubation periods in ordinary flu range from 1 to 4 days, with an average of 2 days. In H5N1 cases, the incubation time has mostly been from 2 to 4 days but has stretched to 8 days. In household clusters of cases, the time between cases has generally ranged from 2 to 5 days but sometimes has been as long as 17 days. Initial symptoms are more likely to include diarrhea in avian flu than in ordinary flu. The problem can appear up to a week before any respiratory symptoms. That feature, combined with the detection of viral RNA in stool samples, suggests that the virus grows in the gastrointestinal tract.

Lower respiratory tract symptoms such as shortness of breath appear early in the course of the illness, whereas upper respiratory symptoms such as runny nose are less common. Also, unlike in ordinary flu cases, the virus may be found in larger amounts in the throat than in the nose. Most cases so far have been linked with exposure to poultry. Specific activities that have been implicated include plucking and preparation of diseased birds; handling fighting cocks; playing with poultry, especially asymptomatic infected ducks; and consumption of duck's blood or possibly undercooked poultry. Blood tests of people in contact with H5N1 patients in Vietnam and Thailand have shown no evidence of asymptomatic infections. However, surveillance involving polymerase chain reaction (PCR) tests has revealed mild cases, more infections in older adults, and an increase in family clusters of cases in northern Vietnam—"findings suggesting that the local virus strains may be adapting to humans," the article says. But it adds that more work is needed to confirm these findings, and so far the disease has rarely spread to healthcare workers, even when appropriate isolation measures were not used.

The relatively low number of human cases amid widespread infection in birds suggests that the species barrier to human cases of H5N1 is substantial. The authors add that family clusters of cases may be caused by common exposures rather than by person-to-person transmission. The report also discusses the "severe" lung injury found in autopsies of H5N1 victims, whose lungs become choked with debris resulting from the body's intense response to the infection. The body's innate immune response to the virus, involving heavy release of proteins that trigger inflammation, may contribute to the severity of the disease. Most patients hospitalized for H5N1 infection have received antiviral drugs, usually oseltamivir. This treatment appears to be helpful only when started early in the illness. Recent experiments on mice suggest that the virus has become less susceptible to oseltamivir since 1997. To reap a similar benefit, mice infected with a 2004 strain of the virus needed a higher dosage and longer course of oseltamivir than mice infected with a 1997 strain did. Hence, the report suggests that physicians treating severe infections should consider doubling the approved dose. Oseltamivir is one of the 2 neuraminidase inhibitors used for flu. The other one, zanamivir, has not been studied in H5N1 cases.

This report was described on 9/29/05 EINet Alert. The link to the article is: http://content.nejm.org/cgi/content/full/353/13/1374. (CIDRAP 10/11/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/oct1105flureview.html )

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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 / 9 (5) / 6 (3)
Cambodia / 4 (4) / 4 (4)
Thailand / 0 (0) / 0 (0)
Viet Nam / 68 (64) / 23 (21)
Total / 81 (73) / 33 (28)

Cumulative number of confirmed human cases of avian influenza A/(H5N1), 3 Dec 2003 to present:
125 (117) / 65 (60)
(CIDRAP 10/10/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/case-count/avflucount.html)

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Russia: OIE Mission report on avian influenza
At the request of the Russian authorities the World Organisation for Animal Health sent a team of worldwide renowned experts in avian influenza and ornithology to Siberia in order to assess the avian influenza situation in the region. The complete Mission Report of this scientific mission is now available online. One of the main conclusions of the report is that in certain conditions migratory birds could carry the Asian H5N1 influenza virus to other parts of the world. The migratory routes of these potentially infected wild birds are mainly directed to the Caspian Sea , the Middle East and Africa. A few number of these birds could rest during the migration or migrate to western Europe. Facing the current and potential evolution of the Avian influenza spread, the OIE confirms its position about the priority of eliminating the virus at the animal source, emphasizing the importance of the early detection and rapid response mechanisms carried out by Veterinary Services in countries at risk. (OIE 10/14/05 http://www.oie.int/eng/press/en_051014.htm)

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Indonesia: Fifth laboratory confirmed human case of avian influenza
The Ministry of Health in Indonesia has confirmed another human case of H5N1 avian influenza. The patient, a 21-year-old man from Lampung, Sumatra, developed symptoms 20 Sep 2005 and was hospitalized 24 Sep 2005. He remains hospitalized in a stable condition. Confirmatory testing was conducted at a WHO reference laboratory. Initial investigation has revealed that the man had direct exposure to diseased and dying chickens in his household shortly before the onset of illness. Contact tracing and field investigations are under way and samples have been taken to determine whether family members and other close contacts may have been infected. The man is the fifth lab-confirmed case of H5N1 infection in Indonesia. 3 out of 5 cases were fatal. (WHO http://www.who.int/csr/don/2005_10_10/en/index.html 10/10/05)

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Indonesia: More suspected avian influenza cases
Another suspected bird flu patient died in Indonesian hospital. "The man died yesterday after just a few hours at the hospital," said Dr Ilham Patu, spokesman for Jakarta's Sulianti Saroso hospital, where most suspected victims of the outbreak are being treated. The man showed symptoms of bird flu but the results of tests were not yet available. "For the moment, he is only suspected of having contracted the avian influenza virus," Patu said 11 Oct 2005. A 21-year-old man from Lampung, Sumatra has been confirmed by the WHO laboratory as infected with bird flu, while his nephew, a 4 year old boy has also tested positive according to tests carried out in a local laboratory. Director General of disease control and environmental health of the Indonesian Health Ministry I Nyoman Kandun said that the case brought the total number of people confirmed by WHO of having H5N1 infection to 5 in Indonesia. Now, officials are awaiting for the result of the 4 year old boy's blood sample from the WHO laboratory. Kandun said that so far over 98 suspected avian influenza cases with bird flu symptoms had been found across the country. The government has put in place emergency measures to stem the virus, including mandatory hospitalization of anyone with suspicious symptoms.

Jakarta's Ragunan zoo, which had been closed down since 19 Sep 2005 after some of its birds tested positive for bird flu, reopened 11 Oct 2005. "The zoo is now perfectly safe for visitors. The birds have been cleared of the virus, the entire zoo disinfected and birds still carrying the disease have been put in isolation and off limits to the public," said spokesperson Titisari Puntorini. (Promed 10/10/05; 10/12/05)

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Indonesia: Corruption sparks bird flu vaccine test
Indonesia would run tests on its stock of bird flu vaccine after a corruption scandal involving production of sub-standard doses. Government auditors suspect local companies assigned to make the vaccine produced doses of inferior quality to inflate profits, with the collusion of some ministry officials. The agriculture ministry's director for animal health, Syamsul Bahri, said his office would test vaccine now in stock or in circulation to determine whether it met minimum specifications. "Our laboratory capacity is limited, so we will gradually test samples and decide which vaccine can continue to be used and which (will) have to be withdrawn from circulation," Mr Bahri said. He could not immediately estimate the number of samples involved or the time needed for all of the necessary tests.

On 9 Oct 2005, agriculture minister April Aprijantono said there were 9 suspected corruption cases involving his ministry in 2004 totaling 733 billion rupiah (USD 96.2 million) in lost funds for the ministry, including the bird flu case, which cost 56.9 billion rupiah (USD 5.64 million). The minister said some testing conducted in Java in 2004 showed the vaccine's protection level was only about 11.8 to 28 per cent. Zainal Baharuddin, inspector general at the ministry, has said local producers intentionally lowered the vaccine quality to make more profits from the contract. He said farmers across the country had also complained they had not received compensation for culling flocks because officials had embezzled the money. (Promed 10/11/05)

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**South Asia: Earthquake in Pakistan**
Unlike other natural disasters where people's basic needs are met within days, people affected by South Asia’s earthquake continue to face major threats. Facing cold nights and rainy days, many continue to struggle without clean water, shelter, food or basic medicines. Scores of badly injured people continue to stream into main centres for urgent medical attention to repair or amputate crushed limbs and treat horribly infected wounds. Along with the immediate injuries, people need to be protected against and treated for diseases including diarrhea and acute respiratory infections like pneumonia. Clean and safe water as well as appropriate sanitation continues to be a major problem. "The biggest problem is diarrhoea. We are seeing slightly more cases of dysentery than normal, which is a bad sign." said Dr Kumars Khoshashem, a WHO environmental health specialist assessing Balakot. "There is a spring, which is good. However the sanitation system is terrible. There are no latrines and garbage is strewn everywhere," he told said. The earthquake shifted plates so badly that many natural springs have been blocked. People need hundreds of thousands of litres of clean water to survive, and to reduce the risk of disease. WHO continues to appeal for chlorination kits, bottled water and portable water treatment facilities. (WHO 10/14/05 http://www.who.int/mediacentre/news/briefings/2005/mb5/en/index.html)

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Americas
USA: Avian and pandemic flu in political spotlight
Avian influenza and the threat of a flu pandemic were in the spotlight in Washington, DC, as officials from 80 nations met to discuss the situation. Paula Dobriansky, under secretary of state for democracy and global affairs, warned the conference delegates that a pandemic would be "catastrophic" and begged them not to conceal any outbreaks. She added, "Working through a global partnership offers we think the best chance, perhaps our only chance, of confronting this threat effectively on all fronts." The conference follows up on a 14 Sep 2005 speech by President Bush at the UN in which he announced an international partnership on avian and pandemic flu.

Health and Human services (HHS) Secretary Mike Leavitt told the delegates, "The world is clearly unprepared, or inadequately prepared, for a pandemic of H5N1 influenza". Everyone at the meeting has agreed in principle to share outbreak information quickly in the interest of containing a potential pandemic. The "core principles" supported by those attending the meeting also include donor support for countries that have been or might be affected by avian flu and a duty to work closely with WHO. Unnamed HHS officials "hinted strongly" that countries that conceal flu outbreaks should not expect other countries to give them flu vaccines and drugs.

Meanwhile, Bush was scheduled to meet with heads of vaccine companies to press for expansion of vaccine production capacity in the face of the pandemic threat. Bush and the company officials would discuss the problem of industry liability for harmful vaccine side effects, often cited as a reason many companies have quit making vaccines in recent years. The Senate voted last week to provide $3.9 billion to stockpile an antiviral drug, develop vaccines, and expand surveillance against the threat of a flu pandemic. The measure was an amendment to a 2006 defense-spending bill. The House has not adopted a similar measure. (CIDRAP 10/7/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/oct0705aimeetings.html )

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USA: Plan paints grim picture of flu pandemic
A not-yet-released version of the Bush administration's plan for dealing with an influenza pandemic predicts that such an event could exact an enormous toll in life and wealth. The New York Times, which obtained a recent draft of the plan, said it describes a worst-case scenario in which the flu would kill more than 1.9 million Americans, put 8.5 million in hospitals, and cost more than $450 billion. Those numbers suggest that the Department of Health and Human Services (HHS) is taking a more somber view of the risks than it did in the previous draft plan, released Aug 2004. That document cited earlier estimates that pandemic flu could cause between 89,000 and 207,000 deaths in the US.

The new draft predicts that an emerging pandemic in Asia would be likely to reach US shores in a few months or even weeks. Quarantines and travel restrictions, while recommended, probably would not postpone the disease's arrival "by more than a month or two." A pandemic could overwhelm hospitals, touch off riots at vaccination clinics, and lead to power and food shortages. However, infectious disease expert Michael T. Osterholm said the draft plan obtained by the Times is out of date. Until recently, the plan regarded a pandemic as "more like an earthquake or hurricane," he told the Washington Post. But a pandemic is an event that unfolds over 12 to 18 months, and the plan is now "in flux," he said. Osterholm confirmed that the plan predicts a death toll as high as 1.9 million, with as many as half of all Americans getting sick. Under the plan, he said, the military probably would be used to help move critical supplies and guard vaccination centers. But the document foresees only a small role for quarantines, and many decisions on how to manage disruptions and shortages would be made by local, not national, officials.

According to the Times, the plan says the nation should have the capacity to produce 600 million doses of vaccine within 6 months, more than 10 times the current capacity. It also calls for a national stockpile of 133 million treatment courses of antiviral drugs. The administration has said it has 4.3 million treatment courses of oseltamivir (Tamiflu) and is aiming for 20 million. On the crucial question of who would get vaccine first in a pandemic, the plan's answer is workers who make the vaccines and flu drugs, along with medical personnel caring for flu patients. Following them would be the elderly and severely ill, pregnant women, transplant and AIDS patients, and parents of babies. Firefighters and government leaders would be next. One section of the plan describes a hypothetical scenario in which severe respiratory illness erupts in a village overseas in April, reaches the US in June, and triggers small outbreaks around the nation by July. When scientists isolate the virus, as the scenario goes, they determine that the avian flu vaccine developed in advance will provide only partial protection. (CIDRAP 10/10/05 http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct1005pandemic.html )

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USA: Chiron gets FDA nod to ship flu vaccine
Armed with full federal approval for the first time in more than a year, Chiron Corp. says it may start shipping influenza vaccine to US distributors next week. Chiron's first shipments since contamination problems blocked the company's vaccine shipments last year could help ease vaccine shortages caused by slow deliveries. The Food and Drug Administration (FDA) approved the first 3 lots of Chiron's Fluvirn vaccine for shipment. The lots amount to about 1.5 million doses. Chiron spokeswoman Alison Marquiss said the company needs to complete its own testing on the 3 lots before shipping them. "We'd expect to release them to distributors in the coming days for them to ship to their customers." In a survey of 120 local health departments last week, all but 6 reported that vaccine shipments were delayed or orders were not completely filled. The survey indicated that somewhere between zero and 40% of flu vaccine orders have been filled so far, Curtis Allen of the CDC's National Immunization Program said. "Many of those that have ordered from Sanofi [Sanofi Pasteur] have received at least 20% of their orders", he said. With Chiron having received FDA clearance, Allen added, "Hopefully those who have ordered vaccine from Chiron should be getting some soon."

Chiron expects to produce between 18 million and 26 million doses of flu vaccine this year, Marquiss said. She predicted it would take until early December to finish delivering vaccine for this season. Allen said the CDC has not changed its estimate of flu vaccine supplies for this year: 60 million doses from Sanofi Pasteur, 8 million from GlaxoSmithKline, 3 million from MedImmune, and 18 million to 26 million from Chiron. That comes to 89 million to 97 million doses in all, as compared with about 60 million doses made available last year. (CIDRAP 10/13/05 http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/oct1305chiron.html )

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Columbia: Avian influenza (H9) in poultry
Authorities have detected the first suspected cases of bird flu in the country, but insisted the strain was not harmful to humans. Avian influenza was discovered in chickens at 3 farms in Tolima state in western Colombia, and the affected flocks were immediately quarantined. There was no sign, however, of the H5N1 strain of bird flu. Tests will now be carried out on chickens across the country to check for the virus, the ministry also said. 2 cases of human H9N2 infection were reported in Hong Kong, Mar 1999. Infection was identified on nasopharyngeal aspirates from 2 children; H9N2 virus was confirmed. The illness in both children was mild and self-limited. A history of probable contact with poultry was reported for one of the children. In 1999, detection of antibody to H9N2 among persons in China and poultry workers in Hong Kong suggests additional unrecognized infection. To date, there was no evidence of human-to-human transmission of H9N2 virus. (Promed 10/12/05, 10/13/05)

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2. Notifications
CDC: Latest updates of avian influenza
CDC updated the following sections on avian influenza 14 Oct 2005: “Spread among birds”; “Avian flu vaccines”; “Avian flu A viruses”. “Outbreak information” on Asia was updated 11 Oct 2005, and “Notice to Travelers” section was updated 5 Oct 2005. (CDC http://www.cdc.gov/flu/avian/)

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 apecein@u.washington.edu