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EINet Alert ~ Feb 03, 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: WHO issues rapid-response plan for influenza pandemic
- Turkey: Avian Influenza Situation & Assessment of the Outbreak
- Iraq: Confirmation of first case of human infection with H5N1; suspected cases
- Near East region: Implications from Iraq’s first human avian flu case and diagnostic tests
- North Cyprus: Confirmation of H5N1 in dead birds; Culling of 1200 poultry
- Saudi Arabia: Fatal case of avian influenza H5N1 infection in falcon
- Romania: Tests confirm no sign of avian influenza in 81-year-old woman
- Algeria: Death of poultry breeder not due to Avian Influenza; economic impact
- Eurasia: Cumulative number of confirmed human cases of avian influenza A/(H5N1)
- Hong Kong: Dead chicken found infected with H5N1; 3 human patients test negative
- Hong Kong: More dead wild birds found infected with H5N1
- Indonesia: Suspected fatal human case of avian influenza infection
- North Korea: Denial of avian influenza report
- USA: New laboratory assay for diagnostic testing of avian influenza A/H5 (Asian Lineage)
- USA: Roche receives HHS letter of intent to buy 46 million oseltamivir treatment courses

1. Updates
- Influenza (and avian/pandemic influenza)

2. Articles
- Large-Scale Sequence Analysis of Avian Influenza Isolates
- Medical Countermeasures for Pandemic Influenza: Ethics and the Law
- Adamantane resistance among influenza A viruses isolated early during the 2005-2006 Influenza season in the United States
- Community Studies for Vaccinating Schoolchildren Against Influenza
- Childhood Influenza Vaccination Coverage --- United States, 2003--04 Influenza Season

3. Notifications
- WHO trains its staff in emergency preparedness

4. APEC EINet activities
- APEC EINet pandemic influenza videoconference


Global
Global: WHO issues rapid-response plan for influenza pandemic
WHO has released a draft plan for nipping a potential influenza pandemic in the bud, saying that even if such an attempt fails, it may buy precious time to make more vaccine and improve other preparations. The 16-page plan calls for using quarantine, social distancing, and antiviral drugs to try to stop an emerging pandemic flu virus, if it can be detected early enough. "Containment of a potential pandemic has never been attempted; the world has never before received an advance warning that a pandemic may be imminent," the "WHO Pandemic Influenza Draft Protocol for Rapid Response and Containment" states. "The practical and logistics challenges are formidable and success is not assured." Indeed, many experts are skeptical that stopping an emerging pandemic is possible, given the weak public health and disease surveillance systems in many of the countries hardest hit by H5N1 avian flu, where a pandemic is considered most likely to start. Skeptics also cite the lack of a vaccine and scant supplies of antiviral drugs. But the WHO document says the attempt should be made: "Each day gained following the emergence of a pandemic virus—if rapidly detected—allows the production of around 5 million doses of a pandemic vaccine. Each added day gives countries more time to adapt routine health services to an emergency situation." In addition, efforts to develop a capability for rapid containment will help strengthen national, regional, and international health capacities, the plan says. WHO cites Hong Kong's experience with the H5N1 virus in 1997, when the destruction of all poultry prevented further avian outbreaks and human cases. The plan also mentions 2 mathematical modeling studies that suggested that containment may be possible under certain conditions.

The purpose of the plan is to facilitate rapid detection of potential signs that the H5N1 virus (or other potential pandemic flu strains) is becoming more transmissible among humans and to guide effective responses before the virus can escape an initial outbreak zone. Under the plan, countries are responsible for surveillance—looking for signals indicating that a novel flu virus has begun to spread from person to person. One possible signal would be the discovery of a virus that has a hemagglutinin gene derived from a nonhuman flu virus and internal genes derived from a human flu virus. Another likely signal would be a finding that a novel flu virus has spread from 1 person to at least 5 others. Countries are expected to report such signals to WHO within 24 hours. The agency then will consider whether a containment effort is warranted and feasible. Containment will not be attempted if there is no lab confirmation of a novel flu virus or if the virus has already spread so far as to make quarantine impractical.

If containment is attempted, the country involved will be expected to coordinate with WHO in implementing quarantine measures, distributing and administering antiviral drugs, conducting surveillance, and implementing other public health measures. In the quarantine zone, antivirals will be used to treat sick people and to prevent illness in those with no symptoms. "The concept of rapid containment depends upon the rapid availability of antiviral drugs and additional supplies and equipment," the plan notes. It says WHO's stockpile of oseltamivir now amounts to 1.5 million treatment courses and will grow to 3 million courses by May, with another 2 million courses pledged by Roche. A number of countries are building their own stockpiles, and some regional stockpiles are planned as well. There is no coordination among the various stockpiles, but WHO hopes to "define the operational relationships" among them so that they can be used in a coordinated way to support rapid response.

WHO will mobilize and coordinate all international and regional support for an affected country, the plan promises. The agency plans to assign 3 to 5 staff to a working group, augmented by recruits from other organizations, to further develop the plan. WHO timeline calls for drafting a more detailed plan by Mar 6 and then holding a global meeting in Geneva from Mar 6 to 10 to reach agreement on "fundamental concepts and standard operating procedures." Next the agency will develop teaching materials and recruit faculty so that training of rapid-response teams can begin in May. Teams will include people with skills in laboratory diagnostics, epidemiology, clinical management, infection control, veterinary medicine, ethics, and other areas. They will receive about 2 weeks of training. The rapid-response plan is 1 of 3 major strategies for addressing the pandemic threat, WHO says. The other 2 consist of the efforts to contain H5N1 avian flu in poultry and the efforts to improve the world's general preparedness for a pandemic. (CIDRAP 1/27/06 http://www.cidrap.umn.edu/ )

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Turkey: Avian Influenza Situation & Assessment of the Outbreak
A WHO collaborating laboratory in the UK has now confirmed 12 of the 21 cases of H5N1 avian influenza previously announced by the Turkish Ministry of Health. All 4 fatalities are among the 12 confirmed cases. Samples from the remaining 9 patients are undergoing further investigation. Testing for H5N1 infection is technically challenging, particularly under the conditions of an outbreak in which large numbers of samples are submitted for testing and rapid results are needed to guide clinical decisions. Additional testing in a WHO collaborating lab may produce inconclusive or only weakly positive results. In such cases, clinical data about the patient are used to make a final assessment. Meanwhile, the Ministry said 14 H5N1 carriers had been discharged from hospital after recovering, and 3 others remained under treatment. "It is encouraging that there have been no new cases (since 17 Jan 2006), but precautions should continue," it added.

The outbreak was investigated by international teams coordinated by WHO. Teams in Ankara and Van province have now completed their work, which has included an overall assessment of the epidemiological situation, the effectiveness of control measures, and the risk of further human cases. Mechanisms of close collaboration with the Ministry of Health will remain in place. Epidemiologists in Van investigated several clusters of childhood cases in families from the Dogubayazit district, where the majority of patients, and all fatal cases, resided. Field investigations, including interviews with family members, have found that almost all cases had a documented history of direct exposure to diseased or dead poultry. The investigation found no clear evidence of human-to-human transmission and no evidence that the virus is now spreading more easily from birds to humans. The vast majority of cases have occurred in children aged 15 years or younger. This age pattern remains puzzling, as adult members in some families were engaged in high-risk behaviors did not develop infection. This observation further supports the possibility, raised previously during field investigations in Asia, that some as yet unidentified genetic or immunological factor may influence the likelihood of human infection.

Monitoring of patient contacts and of staff at hospitals treating patients found no evidence of infection in these groups, further supporting the conclusion that the virus is not spreading easily from person to person. The WHO team found that patients received a high quality of clinical care. The rapid detection of cases, facilitated by high public awareness of the disease, may have contributed to the lower fatality seen in Turkey. On 16 Jan 2006, WHO established a virtual network of clinicians experienced in the management of H5N1 infection and other severe respiratory diseases, allowing Turkish doctors to confer, in real time, with experts elsewhere. At present, all evidence, including laboratory and radiological findings, suggests that the disease seen in Turkey is similar to that seen in the Asian outbreaks. In all outbreaks, severe pneumonia and a rapid progression to respiratory failure have been characteristic features in severe cases of infection. Data on cases in the Turkish outbreak show that patients were hospitalized between 31 Dec 2005 and 13 Jan 2006. Dates of symptom onset indicate that all infections were acquired prior to the implementation of control measures. These have included heightened surveillance for poultry outbreaks, culling operations, intensive public information campaigns, contact tracing and prophylactic or post-exposure administration of oseltamivir, and good infection control practices in hospitals managing patients or investigating possible cases.

Meanwhile, the Bird Flu National Coordination Center stated 30 Jan 2006 that the number of bird flu positive cities rose from 28 to 31. The number of bird flu detected localities is 67. The number of bird flu suspected cities dropped from 27 to 26, and localities from 73 to 66. A total of 1,596,000 poultry have been culled across the country due to bird flu so far. Reportedly, (southwestern) Burdur, (central Anatolian) Eskisehir and (eastern) Malatya are the new cities where avian influenza was detected. To see Turkey's territory that have already become infected, see interactive map (updated 22 Jan 2006) at http://poultrymed.com/files/index.html (go to Maps). For an interactive map reflecting the AI situation in Turkey and its neighbours (updated 31 Jan 2006): http://disasters.jrc.it/AvianFlu/Turkey/. H5N1 has, so far, been confirmed in the following Near-Eastern countries: Turkey, Cyprus (north), Iraq, Saudi Arabia and Kuwait. In the latter 2, the virus was identified in captive birds.

As in many parts of Asia, the poultry outbreaks in Turkey have involved mostly free-ranging backyard flocks. Control measures under this type of poultry production system are more difficult and time-consuming to implement than those involving outbreaks in large commercial farms. Full control of the disease in birds is likely to remain a goal for some time to come. Experience with this disease over the past 2 years in Asia has shown that the risk of sporadic human cases persists as long as the virus continues to circulate in birds. For this reason, some additional human cases may occur, but the numbers are expected to be small. This risk will diminish as culling operations further reduce the presence of the virus in its animal reservoir and thus limit opportunities for human infections to occur. High public awareness of risks to avoid reduces these opportunities even further. (Promed 1/27/06, 1/29/06, 1/30/06, 1/31/06, 2/1/06)

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Iraq: Confirmation of first case of human infection with H5N1; suspected cases
Specimens from Iraq's first reported case of human infection with the H5N1 avian influenza virus have now been tested at a WHO collaborating laboratory in the UK. The case was a 15-year-old girl from the northern part of the country who died of severe respiratory disease 17 Jan 2006. The girl died 3 days after touching a dead bird infected with the virus, the Iraqi health minister said. Test results have now confirmed her infection (WHO said 19 Jan 2006 the girl did not have avian influenza, based on tests carried out only in Iraq). Specimens from the girl's 39-year-old uncle, who died 27 Jan 2006, and a 54-year-old woman under treatment for respiratory illness are being sent to the UK laboratory but have not yet arrived. A joint WHO/FAO/OIE team of international experts has been despatched to Iraq at the request of the Ministry of Health. The initial team of epidemiologists and experts on animal disease will conduct a rapid assessment of the situation in the Sulaimaniyah area of northern Iraq (close to the border with Turkey). At present, an additional 2 people, showing symptoms suggestive of H5N1 infection, have been hospitalized for treatment in the Sulaimaniyah area. Health officials, with support from WHO staff, have set up an emergency operations room to respond to the outbreak, investigate rumours, and address public concerns. Rumours of possible human cases in other parts of the country have been systematically followed up. To date, no such rumours have been substantiated.

The detection of the country's first human case occurred despite the absence of confirmed outbreaks of the disease in poultry. Detection of the case indicates a high level of awareness of the clinical features of this disease and good vigilance on the part of clinicians. It also points to an urgent need to investigate the extent of bird outbreaks in northern Iraq and possibly elsewhere. Team members will assess animal health issues and support the government in its efforts to control the spread of the disease in poultry. Experiences with poultry outbreaks of highly pathogenic H5N1 avian influenza in other countries have shown how quickly this virus can establish itself in poultry populations and spread widely when detection and control measures are delayed. Poultry culling is under way in northern Iraq and large numbers of birds have already been destroyed. WHO-led teams are currently conducting or completing field assessments in Armenia, Azerbaijan, Egypt, Georgia, Iran, Lebanon, Moldova, Syria, and Ukraine.

The confirmation of Iraq’s first human case suggests, officials said, that the disease may be spreading widely--and undetected--among birds in central Asia. As happened in Turkey earlier, the spread of the H5N1 strain to a new area became evident only through a human death. That is alarming to officials, because bird flu rarely infects humans, and usually does so late in the course of an animal outbreak, after close contact with sick birds. "We shouldn't be seeing human cases first, and this points to serious gaps in surveillance," a spokeswoman for WHO, Maria Cheng, said. A senior veterinarian at the UN FAO, Juan Lubroth, said that monitoring to detect the disease in animals was weak in much of the region and that governments needed to be more transparent. For example, Dr. Rod Kennard, who is managing a year-old UN project to rebuild veterinary services in Iraq, said that the local government in Sulaimaniyah was monitoring commercial poultry flocks, "but they don't really have the ability to monitor what's going on in village flocks." He said that "it is a really big question" whether a country in the throes of armed conflict could coordinate a response to a complicated problem like bird flu. Over the past few months, there have been occasional reports of large-scale bird deaths in both Iran and northern Iraq. But H5N1 was never implicated. In Oct 2005, there were large-scale deaths on commercial farms in northern Iraq, Dr. Kennard said. Birds were tested and "we were told it was negative," he said, "but we're not entirely sure how reliable that is." In most countries with serious bird flu outbreaks the military has provided the manpower required to contain them. That is not an option in Iraq.

Health officials in Iraq's 3 Kurdish provinces, which border Turkey, say a number of measures are being taken to stop the spread of the virus. These include decontaminating trucks crossing the border, banning the import of Turkish poultry and prohibiting the sale of live chickens inside Kurdistan. There is also a major public awareness campaign urging people to take precautions, including cooking instructions to minimize the risk of infection. Iraq's Kurdish provinces are a major poultry-producing region supplying chickens and eggs for much of the rest of the country. Reportedly, local authorities in northern Iraq have culled half a million birds in the border areas with Turkey and Iran. Iraqi Kurdistan has reportedly quarantined 14 people suspected of suffering from bird flu. (Promed 1/28/06, 1/30/06, 1/31/06, 2/1/06, 2/2/06)

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Near East region: Implications from Iraq’s first human avian flu case and diagnostic tests
The delays that have dogged H5N1 diagnosis wherever the virus has spread could prove critical to any efforts to contain a pandemic. The Iraqi girl died 17 Jan 2006 and 2 days later the WHO declared Iraqi tests had shown she had not died of bird flu. Fortunately, her doctors asked for a second opinion. On 30 Jan 2006, the US Navy Medical Research Unit in Egypt confirmed H5N1 in samples from the girl. Then, the National Institute for Medical Research (NIMR) in London, one of the WHO's official collaborating centres for flu, also confirmed the virus. "When we get a positive, we are sure," Alan Hay at the NIMR said. "But when we get a negative, we are not. One problem is getting a sample with virus in it. The amount of virus present during the course of bird flu in humans varies more than with human flu. And test samples are usually mucus from the nose or throat. But because H5N1 is a bird virus, it prefers the higher temperatures and the more bird-like cell-surface molecules of the lower lungs. But sometimes positive diagnoses can be also false."

"The now-negative samples might have degraded between tests. We have to look carefully at the victims' symptoms and circumstances before we decide," said Hay. "A problem is that 1 common test for the virus, amplifying any viral genes using a process called RT-PCR (reverse transcriptase polymerase chain reaction) is tricky and notoriously subject to contamination. Another, looking for antibodies to H5N1 in the blood, does not work until well into an infection, and the standard test kits which are designed for human flu, sometimes miss bird flu." But leaving the diagnostic tests to the world's scattered experts takes time, for local approval, transportation and then testing. "In the early days of an epidemic, when it is not clear whether the virus is in a country or not, it is important that tests be completely reliable," said Albert Osterhaus of Erasmus University in Rotterdam. "Better a little delay than a result you are not sure of." (Promed 2/2/06)

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North Cyprus: Confirmation of H5N1 in dead birds; Culling of 1200 poultry
Turkish Cypriot authorities said 1 Feb 2006 they had culled about 1200 poultry in a district struck by avian flu in an attempt to stop the disease from spreading. The European Commission confirmed 29 Jan 2006 the presence of the H5N1 strain of avian flu in a sample taken from dead poultry in northern Cyprus. "We have killed around 1200 poultry within a 10 km radius of the village where the dead birds were found," Kamil Aktulgali, head of the Turkish Cypriot government's veterinary service, said. He said authorities had stepped up monitoring of poultry around the enclave and were rounding up and culling stray birds. Health services have been disinfecting vehicles passing across the U.N.-patrolled Green Line which divides Cyprus into Greek Cypriot and Turkish Cypriot zones. The Greek Cypriot government has said it has no plans to close any crossing points to the north. Cyprus is represented in the European Union and other international bodies by the larger, internationally recognized Greek Cypriot south. Only Turkey recognizes the breakaway Turkish Cypriot enclave in the north of the island. Erhan Ercin, the Turkish Cypriot government's EU coordinator, said EU experts visiting the island were satisfied with the enclave's efforts to contain the virus. Tourism is a mainstay of the economy on both sides of the Green Line. Economy and Tourism Minister Dervis Deniz said it was too early to say if the bird flu would harm economic growth. "So far we have not seen an effect... on the economy as a whole. It is only the 4 or 5 big commercial chicken farms that are losing out, and that is purely because Turkish Cypriots are not buying chicken or eggs as much as before," he said. "North Cyprus does not export chicken, so a newly imposed ban on imports of poultry into the EU from north Cyprus will not have an impact." (Promed 1/31/06, 2/1/06)

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Saudi Arabia: Fatal case of avian influenza H5N1 infection in falcon
Saudi authorities have culled 37 falcons after discovering 5 cases that have tested positive to the H5 [strain] of the avian flu [virus], the agriculture ministry said. A ministry team inspecting falcons kept in a veterinary centre in Riyadh, which takes care of the birds that are usually used for hunting, discovered the cases, said a ministry statement. Laboratory tests were being conducted to establish if the cases test also positive for the N1 component. Reportedly, the first confirmed case of avian influenza subtype H5N1 in Saudi Arabia [earlier than Jan 2006, probably in Dec 2005] involved a saker falcon (Falco cherrug) that had been in the country for the past 2 years. It had a history of anorexia, for 2 days, and passing green feces. The falcon died overnight. A few days later, it was confirmed that the falcon had died of avian influenza and had tested positive for H5N1.

The virus might have been introduced from illegally imported falcons from China and Mongolia early in the season. These reports show a demonstrated potential for H5N1 being moved globally through illicit falconry trade networks. Earlier H5N1 incidents related to bird trade have been recorded in Taiwan, Belgium, and the UK. Saudi Arabia had said in Nov 2005 that it was banning all bird imports from neighbouring countries amid heightened regional concerns about bird flu. That decision came a day after Kuwait announced a bird stricken with avian flu in the country carried the H5N1 strain, in the first case of its kind in the Gulf region. Another bird was found to have the milder H5N2 strain. US Fish & Wildlife Service investigations have shown that there is a long standing and well established illegal global trade in raptors and that as long ago as 1984, individual falcons caught from the wild could command prices of USD 10 000 - 50 000 from buyers in Europe and the Middle East. NGOs have estimated that the illicit trade in falcons may involve as many as 14 000 or more birds annually and say that individual falcons of the most sought-after species can bring prices of USD 500 000 or higher.

The control upon international trade in animals is the responsibility of national Veterinary Services. The need for capacity building of such services -- especially at disease sources -- was highlighted during the 17-18 Jan 2006 International Pledging Conference on Avian and Human Pandemic Influenza. It was suggested that the evaluation of National Veterinary Services will be prioritized. The evaluation is crucial for the preparation and the design of national investments to be made in order to address the prevention and control of emerging and reemerging diseases linked to globalization and to enable the determination of national needs on capacity building. (Promed 1/28/06, 1/30/06, 2/1/06)

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Romania: Tests confirm no sign of avian influenza in 81-year-old woman
Final laboratory tests 29 Jan 2006 failed to confirm that a Romanian woman admitted to hospital 28 Jan 2006 with symptoms similar to those caused by the H5N1 virus had contracted avian influenza, an official said. Earlier in Jan 2006, Romania tightened safeguards against avian influenza, stepping up disinfection measures on major roads and introducing luggage checks at airports, train stations and seaports. Romania has found avian flu in poultry in 26 villages since Oct 2005 but has recorded no human cases.

***Suspected human cases, subsequently discounted, have been reported among travellers returning to several European countries. The 28 countries participating in the European Influenza Surveillance Scheme (http://www.eiss.org ) have been invited to report any lab tests for H5N1, and by 25 Jan 2006, 6 countries had reported a total of 19 tests (http://www.eurosurveillance.org/ew/2006/060126.asp#2is ). All tests have been negative. (Promed 1/28/06, 1/30/06)

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Algeria: Death of poultry breeder not due to Avian Influenza; economic impact
Algeria announced 30 Jan 2006 that tests for H5N1 avian influenza on a deceased poultry breeder had proved negative, easing fears that had depressed the price of poultry by more than 50 percent. Authorities said last week they were carrying out blood tests after a poultry breeder died and 3 of his relatives fell ill and were taken to hospital. "There is no sign of bird flu. The tests were negative," a health ministry official said. Algerian media had reported that the 4 people had shown flu-like symptoms in the western city of Oran. The reports pushed poultry prices down more than 50 percent, and breeders, seeing sales dropping, urged the government to reassure consumers. Algeria plans to spend 8 billion dinars (USD 111 million) to counter any outbreak of bird flu. It plans to import more than 7 million doses of anti-viral drugs and buy 7 million masks for health staff in case of any outbreak. Health Minister Amar Tou said that no case of the disease had been reported in people or poultry in Algeria. The authorities have said they plan to step up health checks at airports and ports to ensure passengers and goods from countries hit by the virus do not bring it into the North African country of 33 million. (Promed 1/30/06)

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Asia
Eurasia: Cumulative number of confirmed human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)

2003
Viet Nam / 3 (3)
Total / 3 (3)

2004
Thailand / 17 (12)
Viet Nam / 29 (20)
Total / 46 (32)

2005
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 16 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 94 (41)

2006
China / 2 (2)
Indonesia / 3 (3)
Iraq / 1 (1)
Turkey / 12 (4)
Total / 18 (10)

Total number of confirmed human cases of avian influenza A/(H5N1), 26 Dec 2003 to present: 161 (86)
(WHO 2/2/06 http://www.who.int/csr/disease/avian_influenza/country/en/index.html )

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Hong Kong: Dead chicken found infected with H5N1; 3 human patients test negative
Preliminary laboratory tests for H5N1 avian influenza virus came up negative for 3 people in Hong Kong who were isolated after a chicken they had kept was found to have been infected with the H5N1 virus. The chicken was smuggled into Hong Kong 26 Jan 2006 without symptoms and became ill 31 Jan 2006 (typical incubation period for the disease in birds is 2 to 10 days). Health experts do not know if it contracted the virus in China or Hong Kong, raising the worrying prospect of a possible bird flu outbreak in Guangdong province. The 3 people--a 78-year-old woman, a 39-year-old woman and a man aged 42--not only came into contact with the infected chicken but also ate another that had been in contact with the infected bird in their village. The government has said none of the 3 had a fever, but all of them had been given the anti-viral drug Tamiflu as a precaution. All 3 remain isolated in hospital under close observation. As a precaution, the government will cull all poultry within 5 km of the small holding where the chicken died and also close the city's walk-in aviaries and a large nature reserve, said Thomas Sit, Acting Assistant Director of Agriculture, Fisheries and Conservation (AFCD). Despite bird flu worries, the government increased the number of chickens shipped into Hong Kong from mainland China around the 29 Jan 2006 Lunar New Year. People across the region celebrate the lunar New Year--families get together for special meals, often involving chicken.

The chicken fell ill and died about half a km from the border with China in an area where the government said 29 Jan 2006 that an Oriental Magpie Robin also died of H5N1. Hong Kong has found bird flu in dead wild birds in recent weeks, but it's the first time the disease has been detected in chicken. Hong Kong farms have strict biosecurity measures in place that keep poultry from coming into contact with wild birds, but there are many small, unprotected backyard farms raising small flocks. The Hong Kong government pledged to cull all the chickens in the territory in the event of 2 confirmed H5N1 cases in local poultry farms and suspend the local live poultry trade. AFCD deputy director Lau Sin-pang advised backyard poultry owners to contact his department through the government's 1823 hotline if they decide to surrender or vaccinate their chickens. 2 bird flu drills were conducted during 2005 and a hefty fine was imposed on people feeding pigeons or ducks to reduce human contact with wild birds. (Promed 1/27/06, 2/1/06, 2/2/06)

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Hong Kong: More dead wild birds found infected with H5N1
Hong Kong confirmed 29 Jan 2006 that an Oriental Magpie Robin, the second this month, died of H5N1 avian influenza and warned people to avoid contact with wild birds. The bird was found dead in a privately owned hut in an area called Sha Tau Kok, not far from the border with China. Oriental Magpie Robins are common in Hong Kong and often kept as pets. Also, a dead wild crested myna was found in an urban playground and had the H5N1 bird flu virus, according to preliminary tests. There are now 4 H5N1 infected birds found in Hong Kong: 2 oriental magpie robins, 1 crested myna, and a chicken.

From official OIE report (regarding first oriental magpie robin found positive for H5N1):
Information received 20 Jan 2006 from the Director of the Agriculture, Fisheries and Conservation Department (AFCD), Hong Kong: Identification of agent: avian influenza virus subtype H5N1. Date of start of the event: 10 Jan 2006. Estimated date of first infection: 4-8 Jan 2006. First administrative division: New Territories. Name of the location: Tai Po. Affected population: a single male adult Oriental magpie robin (Copsychus saularis). Diagnosis: the bird was found dead 10 Jan 2006 and was submitted for virological examination. Source of agent / origin of infection: unknown or inconclusive.

Copsychus saularis is distributed in the Indian subcontinent, Southeast Asia, Indochina, the Philippines, the Andamans, Greater Sundas and southern China south of the Yangtze River. All poultry farms within 5 km of where the oriental magpie robin was found have been checked, and no unusual mortality or illness was detected. An intensive surveillance system is in place on all poultry farms. Local poultry farms are routinely under a constant monitoring and surveillance program involving serological and virological testing and have individual farm biosecurity plans, which include bird-proofing of all sheds. All chicken farms are routinely vaccinated with inactivated H5N2 vaccine, and each batch of chickens has 60 unvaccinated individually identified sentinels, which are monitored over the production life of the batch.

Extensive virus culture and surveillance is conducted in wholesale and retail poultry markets and in bird parks and wild bird populations throughout Hong Kong. In 2005, over 9800 fecal or cloacal/tracheal swabs from local poultry farms, 14 100 from wholesale or retail live poultry markets, 2900 from waterfowl and aviaries in recreational parks, 3000 from pet bird shops and markets and 9000 from wild birds were tested in Hong Kong. The only case of H5N1 infection detected was the Chinese pond heron reported 14 Jan 2005. In the past 3 months, over 1600 wild bird carcasses collected from various locations were tested, and the only positive case was this one. There were no reports of unusual mortality in wild birds. Ongoing territory-wide surveillance is continuing. (Promed 1/29/06, 1/30/06, 2/1/06)

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Indonesia: Suspected fatal human case of avian influenza infection
A 15-year-old boy [whom local tests showed to be affected by] bird flu, has died at Hasan Sadikin Hospital in the town of Bandung, local media reported 2 Feb 2006. If the tests are confirmed by the WHO’s accredited lab in Hong Kong, the case would be Indonesia's 15th human fatality from bird flu, said The Jakarta Post. The teenager, a resident of Padalarang in Bandung regency, some 150 km south of Jakarta, was admitted to the hospital 30 Jan 2006 with high fever and in severe respiratory distress. He died 1 Feb 2006. According to Bandung regency's health office, some chickens reportedly died near the boy's house shortly before he became ill. Indonesian health officials are also awaiting WHO confirmation for a market vendor who died last week after coming into contact with sick poultry. (Promed 2/2/06)

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North Korea: Denial of avian influenza report
North Korea has denied a report that a woman in its capital Pyongyang became infected with avian influenza and said it had had no outbreaks of the disease, the U.N. Food and Agriculture Organization (FAO) said 27 Jan 2006. The group "Rescue the North Korean People Urgent Action Network" said earlier this week that a woman was infected after chickens carrying the disease were found in Pyongyang. "The Ministry of Agriculture ruled out all these kinds of rumors, and there is no outbreak and no human cases," said Noureddin Mona, who heads the FAO office in China and also oversees North Korea. North Korea's state media said in Nov 2005 that it was stepping up efforts to keep avian influenza out. (Promed 1/27/06)

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Americas
USA: New laboratory assay for diagnostic testing of avian influenza A/H5 (Asian Lineage)
On Feb 3, 2006, the Food and Drug Administration (FDA) announced clearance of the Influenza A/H5 (Asian Lineage) Virus Real-Time Reverse Transcription--Polymerase Chain Reaction (RT-PCR) Primer and Probe Set and inactivated virus as a source of positive RNA control for the in vitro qualitative detection of highly pathogenic influenza A/H5 virus (Asian lineage). 2 genetic lineages of influenza A/H5 viruses exist: Eurasian (Asian) and North American. The primer and probe set, developed at CDC, is designed to detect highly pathogenic influenza A/H5 viruses from the Asian lineage associated with recent laboratory-confirmed infections of avian influenza in humans in east Asia, Turkey and Iraq.

No infections with avian influenza A/H5 (Asian lineage) have been reported in animals or humans in North America. Since Feb 2004, CDC has recommended enhanced surveillance in the US for possible cases of human infection with avian influenza A (H5N1) virus. Consistent with these interim recommendations, testing for this virus is indicated when a patient has symptoms of severe respiratory illness and a risk for exposure (e.g., direct contact with ill, dead, or infected poultry in a country with outbreaks of influenza H5N1 among poultry). Testing for influenza A/H5 (Asian lineage) should be considered on a case-by-case basis in consultation with local or state health departments. Testing with the FDA-cleared laboratory RT-PCR assay should be conducted in conjunction with other laboratory testing and clinical observations to help diagnose influenza in patients who might be infected with influenza A/H5 (Asian lineage) viruses and to provide epidemiologic information for surveillance purposes. The test also will help to identify influenza A/H5 (Asian lineage) viruses in laboratory viral cultures. Definitive diagnosis of influenza A/H5 (Asian lineage), either directly from patient specimens or from viral culture, might require additional laboratory testing and clinical and epidemiologic assessment in consultation with national influenza surveillance experts. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.

Testing with the new assay will be limited to laboratories designated by the Laboratory Response Network (LRN), which consists of approximately 140 U.S. laboratories in 50 states. LRN-designated laboratories ensure that the laboratory employs experienced personnel who 1) are trained in standardized rapid molecular procedures, 2) perform analyses in facilities with appropriate biosafety equipment and containment procedures, and 3) use established means for communication with public health programs. Influenza A/H5 (Asian lineage) assay protocols and reagents will be distributed by CDC to designated LRN laboratories nationwide during the week of February 6--10, 2006. The real-time RT-PCR primer and probe set is the only laboratory method that has been cleared by FDA for avian influenza A/H5 (Asian lineage) testing and in vitro diagnostic medical device use in the US. See: http://www.fda.gov. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55e203a1.htm

***This new test offers preliminary detection of H5 avian influenza in human patients in about 4 hours, compared with 2 to 3 days for other methods. "This laboratory test is a major step forward in our ability to more quickly detect cases of H5 avian influenza and provides additional safeguards to protect public health," Health and Human Services Secretary Mike Leavitt said. The FDA announced its approval of the test, following an unusually quick 2-week review. Acting FDA Commissioner Andrew von Eschenbach said the rapid review did not compromise the quality of the review process.

Steve Gutman of FDA's Center for Devices and Radiological Health said the test yields "a presumptive not a definitive positive." The test determines only the hemagglutinin (H) type of the virus; further testing is needed to confirm the result and identify the neuraminidase (N) type. When LRN labs using the test get positive or equivocal results, they will send the sample to the CDC for confirmatory testing, which will take about 2 to 4 hours once the sample arrives, said Stephan Monroe, acting director of the CDC's Viral and Rickettsial Diseases Division. CDC is sharing the test with WHO and its collaborating labs, which so far have included labs in the UK, Japan, and Australia. Concerning use of the test by other labs outside the US, Monroe said CDC would distribute the technology only to labs that the CDC judges to have the technical capacity and biosafety measures to use the test properly. CDC is not charging other labs for the test and is not making money on it, Monroe said.
(MMWR February 3, 2006 / 55(Early Release); CIDRAP 2/3/06 http://www.cidrap.umn.edu/ )

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USA: Roche receives HHS letter of intent to buy 46 million oseltamivir treatment courses
Reportedly, a Roche official said the Department of Health and Human Services (HHS) signaled an intention to buy 46 million treatment courses of oseltamivir, triple the amount previously ordered. George Abercrombie, president and CEO of Hoffmann-La Roche, Roche's US unit, told a Senate hearing the company had received an HHS letter of intent to buy 46 million treatment courses. Roche spokesman Darien Wilson said the company could deliver 26 million treatment courses this year if a contract were signed. A treatment course under current recommendations is 10 capsules. When HHS officials released their pandemic preparedness plan last Nov 2006, they announced a goal of acquiring 81 million treatment courses of oseltamivir by summer 2007. (CIDRAP 2/3/06 http://www.cidrap.umn.edu/ )

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1. Updates
Influenza (and avian/pandemic influenza)
Seasonal influenza activity for the Asia Pacific and APEC Economies
WHO’s surveillance information has not been updated since the 18 Jan 2006 report. Please see EINet’s 20 Jan 2006 Alert for further details.

USA. During Jan 15-21, 2006, the number of states reporting widespread influenza activity decreased to 5. 23 states reported regional activity, 9 reported local activity, and 13 reported sporadic activity. The percentage of specimens testing positive for influenza increased in the US overall. Since Oct 2, 2005, the largest numbers of specimens testing positive for influenza have been reported from the Mountain (919 positives) and Pacific (684 positives) regions, accounting for 30.6% and 22.8%, respectively, of positive tests reported during the 2005--06 influenza season. The percentage of outpatient visits for influenza-like illness (ILI) increased during the week ending Jan 21 and is above the national baseline. The percentage of deaths attributed to pneumonia and influenza (P&I) was below the epidemic threshold for the week ending Jan 21. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5504a4.htm. (MMWR February 3, 2006 / 55(04);103-105)

Avian/Pandemic influenza updates
- WHO’s comprehensive information on avian influenza: http://www.who.int/csr/disease/avian_influenza/en/index.html. WHO pandemic influenza draft protocol for rapid response and containment, updated 27 Jan 2006:
http://www.who.int/csr/disease/avian_influenza/guidelines/RapidResponse.pdf. WPRO website on avian influenza: http://www.wpro.who.int/health_topics/avian_influenza/overview.htm
- FAO updates on avian influenza: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html. Includes animation timeline of avian influenza outbreaks in Turkey and the latest official documents.
- OIE updates on avian influenza: http://www.oie.int/eng/en_index.htm. Includes the major veterinary proposals and official documents from OIE.
- CDC website on pandemic influenza: http://www.cdc.gov/flu/pandemic.htm. For avian influenza: http://www.cdc.gov/flu/avian/. “Key facts” and “Current Situation” have been updated.
- The US government’s web site for pandemic flu: http://www.pandemicflu.gov/. New State Summit summaries have been uploaded.
- 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/.
- PAHO’s updates on avian influenza: http://www.paho.org/English/AD/DPC/CD/influenza.htm.
- The American Veterinary Medical Association information on animal influenzas: http://www.avma.org/public_health/influenza/default.asp
- US Geological Survey, National Wildlife Health Center: http://www.nwhc.usgs.gov. NWHC Avian Influenza Information (with bulletins, maps, and news reports): http://www.nwhc.usgs.gov/research/avian_influenza/avian_influenza.html.
(WHO; FAO, OIE; CDC; US FDA; CIDRAP; PAHO; APHA; AVMA; USGS)

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2. Articles
Large-Scale Sequence Analysis of Avian Influenza Isolates
Scientists may have found out what makes the H5N1 influenza virus so deadly -- bird flu viruses have a gene that may make them especially destructive to cells, researchers reported 26 Jan 2006. All the avian influenza viruses studied by a team at St. Jude Children's Research Hospital had the gene and none of the human influenza viruses did, they said. People infected with the H5N1 bird flu virus in Viet Nam and Thailand had the "avian" version of the influenza virus, as did the victims of the 1918 influenza pandemic, which killed tens of millions of people globally, the researchers said. But the [human] influenza viruses that cause the normal seasonal misery, and those that caused the less deadly 1957 and 1968 human influenza pandemics, do not carry the avian genes.

These findings, published in Science, may provide a way to identify the more dangerous viruses and may also help companies trying to make better flu drugs, said Clayton Naeve, the St. Jude's team leader. "We documented a clear difference between avian viruses and human viruses. [But much more work will be required] to demonstrate this actually contributes to virulence in nature," Naeve said. Naeve and his colleagues have been working to sequence the genomes of all known influenza viruses. No one has done this, they said. "This is information we expect will be very important in understanding the attributes of this virus -- how it will cross from birds to humans. We are releasing these data so that other investigators worldwide can mine it for information," he said. The researchers used a collection of samples of 11 000 influenza viruses, including 7000 avian influenza viruses, assembled by St. Jude's Dr. Robert Webster over a period of 30 years. "We have sequenced a diverse sampling of 336 avian influenza viruses from this collection including isolates from ducks, gulls, shorebirds and poultry collected in North American, Eurasian, and Australasian countries, primarily during the years 1976 to 2004," the researchers said. Dr. Webster said, "This information is a true gold mine, and we are inviting all of the miners to help us unlock the secrets of influenza." The project produced 70 million bases of sequence information leading to DNA sequences for 2196 genes and 169 complete bird flu genomes from the St. Jude collection, including representatives of all known subtypes of the virus. "The major accomplishment of this project is that it gives the scientific community significantly more new data and analytical tools to use in the study of these potentially very dangerous viruses," said Dr. John C. Obenauer, a Bioinformatics associate research scientist at St. Jude's Hartwell Center.

Naeve's team may have identified 2 proteins to watch. They are called NS1 and NS2, for non-structural protein 1 and non-structural protein 2, and they are made only once the virus has infected a cell. The avian versions seem to allow the virus to do much more damage to a cell than the human versions of NS1 and NS2, Naeve said. "We were surprised to see a lot of variation in this NS protein[s]. That was the clue. We felt it must be playing an important biological role," he said. It is possible that a mutation that would allow a flu virus to more easily infect people will weaken the NS protein, Naeve said. But no one knows. "As time progresses one might expect that signature to change into a less virulent form," he said, or it may not, as was apparently the case in 1918.

26 Jan 2006 issue of Science (DOI: 10.1126/science.1121586): Large-Scale Sequence Analysis of Avian Influenza Isolates. Authors: John C. Obenauer and others. http://www.sciencemag.org/cgi/content/abstract/1121586v1 (Promed 1/27/06)

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Medical Countermeasures for Pandemic Influenza: Ethics and the Law
Lawrence O. Gostin. JAMA. 2006;295:554-556.
http://jama.ama-assn.org/cgi/content/extract/295/5/554
“Serious outbreaks of avian influenza A (H5N1) have occurred among birds in Asia, with cases now reported in Europe. Although H5N1 is highly contagious among birds, it is rare in humans due to a significant species barrier. As of January 7, 2006, 146 cases were reported with 76 deaths. Human-to-human transmission has occurred, but transmission to date has not continued beyond 1 person. The prevalence of H5N1 is currently very low and pales in comparison with pandemics of human immunodeficiency virus, malaria, and tuberculosis. However, recent evidence that the 1918 "Spanish" flu was caused by an avian influenza virus lends credence to the theory that current outbreaks could have pandemic potential. Extrapolating from the 1918 pandemic, which killed an estimated 20 million to 50 million people in a less-populated planet, modeling studies indicate that 500 000 to 1 million Americans. . .” (CIDRAP http://www.cidrap.umn.edu/ )

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Adamantane resistance among influenza A viruses isolated early during the 2005-2006 Influenza season in the United States
Rick A. Bright, et al. JAMA. 2006;295:(doi:10.1001/jama.295.8.joc60020). http://jama.ama-assn.org/cgi/content/abstract/295.8.joc60020v1 Abstract: “Context: The adamantanes, amantadine and rimantadine, have been used as first-choice antiviral drugs against community outbreaks of influenza A viruses for many years. Rates of viruses resistant to these drugs have been increasing globally. Rapid surveillance for the emergence and spread of resistant viruses has become critical for appropriate treatment of patients. Objective: To investigate the frequency of adamantane-resistant influenza A viruses circulating in the United States during the initial months of the 2005-2006 influenza season. Design and Setting: Influenza isolates collected from 26 states from October 1 through December 31, 2005, and submitted to the US Centers for Disease Control and Prevention were tested for drug resistance as part of ongoing surveillance. Isolates were submitted from World Health Organization collaborating laboratories and National Respiratory and Enteric Virus Surveillance System laboratories. Main Outcome Measures: Using pyrosequencing and confirmatory assays, we identified viruses containing mutations within the M2 gene that are known to confer resistance to both amantadine and rimantadine. Results: A total of 209 influenza A(H3N2) viruses isolated from patients in 26 states were screened, of which 193 (92.3%) contained a change at amino acid 31 (serine to asparagine [S31N]) in the M2 gene known to be correlated with adamantane resistance. Two of 8 influenza A(H1N1) viruses contained the same mutation. Drug-resistant viruses were distributed across the United States. Conclusions: The high proportion of influenza A viruses currently circulating in the United States demonstrating adamantane resistance highlights the clinical importance of rapid surveillance for antiviral resistance. Our results indicate that these drugs should not be used for the treatment or prophylaxis of influenza in the United States until susceptibility to adamantanes has been reestablished among circulating influenza A isolates.” (CIDRAP http://www.cidrap.umn.edu/ )

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Community Studies for Vaccinating Schoolchildren Against Influenza
M. Elizabeth Halloran and Ira M. Longini Jr. Science 3 February 2006: Vol. 311. no. 5761, pp. 615 - 616. DOI: 10.1126/science.1122143.
http://www.sciencemag.org/cgi/content/full/311/5761/615
“The Advisory Committee on Immunization Practices and several states are considering recommending annual influenza vaccination in groups beyond the currently recommended high-risk groups. This offers an opportunity that should not be missed: to conduct a nationwide study of the effectiveness of vaccinating schoolchildren against influenza as a means of reducing community transmission. Some public health officials speak of universal vaccination against influenza, meaning a recommendation for all age groups, but schoolchildren, aged 5 to 18 years, are a prime target as they are generally considered to be the most important source of community-wide transmission. Researchers also believe that the immune systems of children respond better to influenza vaccination than do those in the elderly at-risk population. To realize maximum benefit from a study of such effects, we must prospectively sort out the crucial features to be evaluated: effectiveness, benefits, risks, and costs. . .” http://www.sciencemag.org/cgi/content/full/311/5761/615

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Childhood Influenza Vaccination Coverage --- United States, 2003--04 Influenza Season
“Children aged <2 years are at increased risk for influenza-related hospitalizations. Beginning in 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged that, when feasible, children aged 6--23 months and household contacts and out-of-home caregivers for children aged <2 years receive influenza vaccinations each year. Beginning with the 2004--05 influenza season, ACIP strengthened the encouragement to a recommendation. Other children recommended to receive influenza vaccination include children aged 6 months--18 years who have certain high-risk medical conditions, are on chronic aspirin therapy, or who are household contacts of persons at high risk for influenza complications. This report provides an assessment of childhood influenza vaccination coverage for the 2003--04 influenza season, the second year of the ACIP encouragement for influenza vaccination of children aged 6--23 months. The findings demonstrate that vaccination coverage increased from the previous influenza season but remained low, with substantial variability among states and urban areas. . .” http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5504a3.htm
(MMWR February 3, 2006 / 55(04);100-103)

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3. Notifications
WHO trains its staff in emergency preparedness
In response to the increasing number of emergencies and disasters in the Western Pacific Region, staff from WHO country offices were trained on the principles and concepts of emergency preparedness and response at a staff induction briefing 24-27 Jan 2006. The Manila-based regional office trained the participants on the use of the WHO Emergency Response Manual, which seeks to enhance country offices’ emergency response capacity. An exercise on pandemic influenza was also conducted, involving not just the participants, but all representatives from technical and administrative offices of the Regional Office, including the experts fighting avian influenza. Discussions also focused on ways to streamline standard operating procedures and protocols to address the need for quick response in case of emergencies. WHO's Western Pacific Region has experienced a number of emergencies and disasters since the start of the 21st century, which have claimed many lives and caused economic setbacks.
(WHO/WPRO 1/30/06 http://www.wpro.who.int/media_centre/news/news_20060130.htm )

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4. APEC EINet activities
APEC EINet pandemic influenza videoconference
EINet celebrated its 10th anniversary of service to the Asia Pacific by hosting the APEC EINet Virtual Symposium on Pandemic Influenza Preparedness, Friday 20 Jan 2006, 02:00 – 07:00 UTC. Participants in the videoconference included the economies of: Australia, Canada, People’s Republic of China, Republic of Korea, Philippines, Singapore, Chinese Taipei, Thailand, USA, and Viet Nam. Each economy presented briefly their state of pandemic influenza preparedness, followed by moderated questions and answers. Overall, the collaborative event was very successful, and the economies were able to share a rich level of information and engage in productive discussions. For more information please visit: http://depts.washington.edu/einet/symposium.html.

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 apecein@u.washington.edu