EINet Alert ~ May 12, 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: Cumulative number of human cases of avian influenza A/(H5N1)
- Pan-Europe: Migratory birds return to Europe without avian influenza virus
- Denmark: Excerpts from the OIE report on avian influenza H5N1; restrictions removed
- France: Excerpts from the OIE report on avian influenza H5N1
- Germany: Avian influenza H5N1 update in animals
- Switzerland: Excerpts from the OIE report on avian influenza H5N1
- UK: Avian Influenza H7N3 in poultry (excerpts from the OIE report)
- China (Qinghai): 17 wild birds reportedly infected with avian influenza H5N1
- Indonesia : 33rd case of human infection with avian influenza H5N1
- Pakistan: 2 more poultry farms hit by avian influenza H5N1
- Russia (Novosibirsk): Poultry reportedly killed by avian influenza H5N1
- Cote d'Ivoire: Suspected human case of avian influenza H5N1 infection
- Djibouti: Confirmation of human infection with avian influenza H5N1
- Nigeria: Spread of avian influenza H5N1 appears to be declining

1. Updates
- Influenza

2. Articles
- Viet Nam: Possible avian influenza transmission via the gastrointestinal tract
- H5N1 Influenza A Virus and Infected Human Plasma
- Study suggests older antivirals could help fight H5N1
- Sanofi reports results for H5N1 vaccine with adjuvant
- Delaying the International Spread of Pandemic Influenza

3. Notifications
- FAO/OIE International Conference on Avian Influenza & Wild Birds

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

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

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

Cambodia / 4 (4)
China / 8 (5)
Indonesia / 17 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 95 (41)

Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 10 (7)
Djibouti / 1 (0)
Egypt / 13 (5)
Indonesia / 16 (14)
Iraq / 2 (2)
Turkey / 12 (4)
Total / 64 (39)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 208 (115)
(WHO 5/12/06 http://www.who.int/csr/disease/avian_influenza/en/ )


Europe/Near East
Pan-Europe: Migratory birds return to Europe without avian influenza virus
Migratory birds that flew south to Africa last autumn and then back over Europe in recent weeks did not carry the H5N1 flu virus or spread it during their annual journey, scientists concluded. Health officials had feared that the disease was likely to spread to Africa during the winter migration and return to Europe with a vengeance during the reverse migration this spring. That has not happened - a significant finding for Europe. In Europe, there have been only a handful of cases detected in wild birds since Apr 1, 2006, at the height of the northward migration. The number of cases in Europe has decreased so dramatically compared to Feb 2006, when dozens of new cases were found daily, that experts believe the northward spring migration played no role. Agriculture officials in many European countries have this month lifted restrictions designed to protect valuable domestic poultry from infected wild birds. In early May 2006, both the Netherlands and Switzerland rescinded mandates that poultry be kept indoors. Austria has loosened similar regulation and France is considering doing so. [However, the EU has also decided to extend strict safety measures to guard against the spread of the bird flu virus, acknowledging that the danger has not yet passed. EU experts endorsed a plan to prolong surveillance of poultry farms and restriction on the movement and sale of poultry in high-risk areas until late Jul 2006. France received permission to continue vaccinating birds.] The February cases in Europe were attributed to infected wild birds that traveled west to avoid severe cold in Russia and Central Asia but apparently never carried the virus on to Africa.

Juan Lubroth, a senior veterinary official at the UN Food and Agriculture Organization, said, "Perhaps it is because it was not as bad as we feared, or perhaps it is because people took the right measures.” Specialists from Wetlands International, who were deputized by the UN FAO, sampled 7,500 African wild birds last winter. They found no H5N1, Ward Hagemeijer, an avian influenza specialist with Wetlands International, said, so it is not surprising that H5N1 did not return to Europe with the spring migration. Mr. Hagemeijer thinks that the virus's strength among wild birds may have weakened as the southward migration season progressed. That probably limited its spread to Africa, he said. Many avian influenza viruses are picked up by migratory birds in their nesting places in northern lakes during the summer and autumn breeding season. As the months pass, the viruses show a decreasing pattern of spread and contamination. "So it tends to be mostly a north-to-south spread, and then it wanes," he said. Still, this means that the cycle could well start again this summer, if the H5N1 virus has persisted in those breeding areas. (Promed 5/6/06, 5/10/06)


Denmark: Excerpts from the OIE report on avian influenza H5N1; restrictions removed
Information received on (and up to) 4 May 2006 from Dr Preben Willeberg, chief veterinary officer, Danish Veterinary and Food Administration: Identification of agent: highly pathogenic avian influenza virus subtype H5N1. Date of start of event: 12 Mar 2006. New outbreaks: There has been 1 reported case and death of a great crested grebe in the town of Grasten located in the county of Southern Jutland 28 Apr 2006. The protection and surveillance zones have been established in accordance with European Union legislation. Grasten is located within the surveillance zone established 29 Mar 2006 in Southern Jutland. All poultry within the zones must be kept inside and all poultry holdings -- including hobby holdings -- must be registered. The Danish Veterinary and Food Administration will inspect all poultry holdings in the protection zones in order to look for possible further spread of avian influenza. Restrictions on movement of eggs and poultry have been imposed within the zones. All hunting within the zones is also prohibited.

On 8 May 2006, the protection and surveillance zones in Funen County were removed. There are no more protection and surveillance zones in Funen County. On 5 May 2006, the protection and surveillance zones in Storstrom County were removed. There are no more zones in Storstrom County. On 4 May 2006, the following zones were removed: Protection and surveillance zones in Frederiksborg County. There are no more zones in Frederiksborg County; Protection and surveillance zones surrounding Sonderborg and Kegnaes in South Jutland County were also removed. On 2 May 2006, the Danish Veterinary and Food Research Institute detected high pathogenic avian influenza (H5) in a great crested grebe (Podiceps cristatus), which was found in South Jutland County. Between 14 Mar 2006 -- when the first HPAI H5-infected wild bird (a Common buzzard) was confirmed in Denmark -- and 2 May 2006 -- when the (so far) last case was confirmed (a great crested goose) – the Danes identified a total of 43 infected wild birds. 716 dead wild birds were tested for the presence of avian influenza at the Danish Veterinary and Food Research Institute during the first 3 months of 2006. The latest news about avian influenza detected in wild birds in Denmark can be accessed on the Danish Veterinary and Food Administration's website: <http://www.uk.foedevarestyrelsen.dk/AnimalHealth/Avian_influenza/Latest_news/forside.htm> (Promed 5/6/06, 5/10/06)


France: Excerpts from the OIE report on avian influenza H5N1
Translation of information received 27 Apr 2006 (up to 26 Apr) from Dr Monique Eloit, deputy director general, General Directorate for Food (DGAL), Ministry of Agriculture, Food, Fisheries and Rural Affairs: Identification of agent: highly pathogenic avian influenza virus subtype H5N1. Date of start of event: 13 Feb 2006. New outbreaks: 2 villages in the Ain department (4 cases and deaths) reported outbreaks in mute swans. Source of new outbreak: unknown or inconclusive. Diagnosis: amino acid sequence at cleavage site reveals HPAI profile. Typing of the virus indicates that it is very similar to virus A/Chicken/Tula/10/2005 (H5N1), A/Bar Headed Goose/Qinghai/65/05 (H5N1), and also to A/common pochard/France/0667/2006 (H5N1), the virus typed in the first case in wildlife (wild duck) in France, detected at Joyeux, Ain. (Promed 5/6/06)


Germany: Avian influenza H5N1 update in animals
339 cases of avian influenza in wild birds from Germany have been confirmed by the Friedrich Loeffler Institute as of 3 May 2006. During 26 Apr 2006 - 3 May 2006, the following 9 new cases were confirmed:

Municipality / Administrative or City District / State / Species
Letschin / Maerkisch-Oderland / Brandenburg / White Stork
Harburg / Danube-Ries / Bavaria / Swan
Molfsee / Rendsburg-Eckernfoerde / Schleswig-Holstein / Crested Grebe
Denklingen / Landsberg on the Lech / Bavaria / Merganser
Parkstetten / Straubing (town) / Bavaria / Mute Swan
Kirchroth-Nierachdorf / Straubing (town) / Bavaria / Mute Swan
Kirchroth-Muenster / Town of Straubing / Bavaria / Mute Swan
Letschin / Maerkisch-Oderland / Brandenburg / White Stork
Bautzen (Neumalsitz) / Bautzen / Saxony / Wild Duck
(Promed 5/10/06)


Switzerland: Excerpts from the OIE report on avian influenza H5N1
Information received 2 May 2006 (and up to 1 May) from Dr Hans Wyss, director of the Federal Veterinary Office: Identification of agent: highly pathogenic avian influenza virus subtype H5N1. Date of start of event: 26 Feb 2006. There have been no confirmed cases for the high pathogenic avian influenza virus subtype H5N1 reported since 24 Apr 2006. Since the beginning of the event, a total of 9 wild birds (2 tufted ducks [Aythya fuligula], 1 common coot [Fulica atra], 1 goosander [Mergus merganser], 2 common pochards [Aythya ferina], 1 little grebe [Tachybaptus ruficollis] and 2 ducks [Anatidae]) have tested positive for highly pathogenic avian influenza H5N1. The above 9 birds have been tested positive for H5N1; 23 additional birds, which were H5 positive but not tested for H5N1, are included in the full list of 32 wild birds, found positive for H5/H5N1 out of 1050 dead wild birds which have been tested in Switzerland since the beginning Feb 2006. The zoning measures were lifted 1 May 2006, but the national monitoring programme for avian influenza is still in place. (Promed 5/6/06)


UK: Avian Influenza H7N3 in poultry (excerpts from the OIE report)
Information received on 29 Apr 2006 from Dr Debby Reynolds, Director General for Animal Health and Welfare, Department for Environment, Food and Rural Affairs (DEFRA): Report date: 28 Apr 2006. Identification of agent: low pathogenic avian influenza virus subtype H7N3. Date of start of event: 20 Apr 2006. New outbreaks: There has been reported at Mattishall in the Norfolk Distrist an outbreak of low pathogenic avian influenza subtype H7N3. The Animal health regulation authority has destroyed 34 358 susceptible birds along with the 87 birds that died during the outbreak. Description of affected population: Commercial poultry (broiler and breeder chickens). Diagnosis: The avian influenza outbreak diagnosis was established by the OIE/FAO Reference Laboratory 28 Apr 2006. RT-PCR, serology and virus isolation were positive for H7 Avian Influenza.

Also, information received (and up to) 2 May 2006 from Dr Debby Reynolds: Date of start of event: 30 Mar 2006. Following the completion of a programme of veterinary inspections on all premises with poultry in the "wild bird surveillance zone" and taking account of epidemiological advice, restrictions were lifted 1 May 2006. The restrictions in the associated "wild bird risk area" were lifted simultaneously. All restrictions have therefore been lifted and the incident is now considered closed. (Promed 5/5/06, 5/6/06)


China (Qinghai): 17 wild birds reportedly infected with avian influenza H5N1
The Ministrty of Agriculture confirmed 5 May 2006 another case of bird flu outbreak among wild birds in a remote area of Qinghai Province. 17 bar-headed geese were found dead on a wetland in Yushu County 23 Apr 2006 (the area is reportedly said to be uninhabited with no domestic birds). The number of dead wild birds had risen to 125 by 4 May 2006, of which 123 were bar-headed geese, the ministry said. The national bird flu laboratory confirmed that the dead birds had tested positive for the H5N1 strain. The province's veterinary departments has sterilized the area and is keeping a close eye on any new cases. Nearby livestock have been transferred to summer pastures far from the outbreak location. Local authorities have demanded local herdsmen keep a distance from the dead birds to prevent the virus from infecting human beings. The outbreak is the second case found in the province in a month after a dead bar-headed goose in Gangcha County was found carrying the virus 29 Apr 2006. Reportedly, the mainland and Hong Kong will host a joint exercise to test their ability to cope with the flu pandemic.

Qinghai has become a major focus for studying the H5N1 virus. A year ago, scientists believe a mutated form of the virus killed thousands of wild birds at Qinghai Lake, a major stop-off point for migratory birds. Soon after the mass die-off of birds in Apr and May 2005, the virus spread West to Europe and then to the Middle East and Africa, underscoring the importance of monitoring what's happening at the lake, and elsewhere in China. WHO says the Qinghai Lake form of the H5N1 virus is almost identical to the strain found in recent outbreaks in Nigeria, Iraq and Turkey. Prior to the Qinghai Lake event, H5N1 was known to cause occasional sporadic deaths in migratory waterfowl, but not to kill them in large numbers or be carried by them over long a distance, WHO has said. China has reported almost 40 outbreaks of bird flu in poultry across a dozen provinces over the past year. Health experts see the country as being particularly at risk because of its huge human population and many poor, remote areas. As in many other parts of Asia, poultry often live near humans in China, increasing the risk of transmission from poultry to people.

"Animal surveillance remains extremely important and there is probably even greater need for enhanced surveillance now because although reports of animal outbreaks are on the decrease, we are still seeing human cases," Julie Hall, WHO's China bird flu coordinator, said. China was being a lot more open with sharing information and samples, she added, even if there remained areas of concern. In Mar 2006, WHO said that China had agreed to share virus samples from outbreaks in poultry to meet a request the country go beyond sending samples collected from people and help global efforts to limit the spread of the disease. "The Ministry of Agriculture is in the process of catching up in terms of what has not been shared for a year to 18 months. We hope that this is a sign that in the future there will be more timely and easier sharing of information and viruses," Hall said.
(Promed 5/6/06, 5/11/06; CIDRAP 5/8/06 http://www.cidrap.umn.edu/ )


Indonesia : 33rd case of human infection with avian influenza H5N1
As of 8 May 2006, the Ministry of Health has confirmed the country's 33rd case of human infection with the H5N1 avian influenza virus. The fatal case occurred in a 30-year-old man from greater Jakarta. He developed symptoms 17 Apr 2006, was hospitalized 21 Apr 2006, and died 26 Apr 2006. An investigation to determine the source of his infection is continuing. He lived in close proximity to pens where animals, including poultry, were kept. Of the 33 laboratory-confirmed cases, 25 have been fatal. Indonesia has reported the greatest number of human cases (16) of H5N1 avian influenza of any country during 2006. It has also reported the highest number of deaths (14) and thus the greatest percentage mortality (88 percent). The reason for the higher mortality in Indonesia than elsewhere has not yet been established.

Elsewhere, in Myanmar, British and Australian avian flu experts plan to spend 2 months increasing public awareness and combating the spread of the disease, according to another AFP report. Their visit to the central Myanmar farmlands comes after the region experienced more than 100 outbreaks in March.
(CIDRAP 5/8/06 http://www.cidrap.umn.edu/ ; Promed 5/8/06)


Pakistan: 2 more poultry farms hit by avian influenza H5N1
Authorities culled over 6000 chicks and chicken birds following outbreak of avian influenza strains at 2 more poultry farms in north eastern and south eastern cities of Pakistan on 4 May 2006. The new outbreak was confirmed at 2 poultry farms in the Teratt area of Murree, about 35 km north east of Islamabad, and Sialkot, 400 km south east of Islamabad, sources at Federal Food and agriculture Ministry said. They said following suspicions of bird flu virus, blood samples of chickens were sent to the National Laboratory in Islamabad. "The Laboratory results Thursday confirmed outbreak of H5N1 deadly virus", they added. Reportedly more than 6000 chicks and chicken birds have been culled so far, adding that the process was still continuing. Earlier, following H5N1 outbreak at 13 farms in the outskirt of Islamabad, 2 in North West Frontier Province (NWFP), and 1 in eastern Hafizabad district, over 60 000 chickens had been culled. (Promed 5/6/06)


Russia (Novosibirsk): Poultry reportedly killed by avian influenza H5N1
Bird flu has been registered in the Kochkovo district, the Novosibirsk region, Siberia, the head of the Russian agriculture agency, Sergei Dankvert, said. "H5N1 virus has been found in non-vaccinated poultry in private households of the Reshety village," he said. So far the flu has killed 64 birds. The village has 35 000 poultry, Dankvert said. Bird flu has been recently registered in 6 villages, 4 of them in Dagestan, 1 in the Krasnodar Territory and another one in the Novosibirsk region. As of 5 May 2006, 65.3 million doses of anti-bird flu vaccine was delivered to Russia's regions. Almost 33 million birds were vaccinated all over Russia. The first H5N1 outbreak in Siberia was reported in Novosibirsk Jul 2005. The epizootic spread to 9 other regions (Altai, Astrakhan, Chelyabinsk, Kalmykia, Kurgan, Omsk, Tambov, Tiumen and Tula), causing 62 outbreaks. The involvement of domestic poultry was terminated Oct 2005, but in Feb 2006, outbreaks in commercial poultry returned. In Mar 2006, Russia decided to apply mass vaccination. (Promed 5/11/06)


Cote d'Ivoire: Suspected human case of avian influenza H5N1 infection
Health and government officials in Cote d'Ivoire have announced a range of measures to stamp out bird flu after the discovery of at least 3 outbreaks in Abidjan. Minister of animal production and fish resources, Alphonse Douaty, said veterinarians are to cull all poultry in markets through the city as the government prepares a system for reimbursement. The ministry was also planning to inspect industrial poultry farms and issue a stamp of approval to reassure costumers. The city's 4 million people will be able to call a free hotline. Douaty said the government needed at least 6 billion CFA, or 11 million US dollars, to compensate poultry farmers. The first cases of bird flu were reported 26 Apr 2006 by the World Organization for Animal Health (OIE), but the Ivorian government only this week issued official confirmation. The latest of the 3 outbreaks was found in domestically kept chickens in the populous suburb of Yopougon. Reportedly, several people in the area were being monitored for potential human infections of the H5N1 avian virus. (Promed 5/7/06)


Djibouti: Confirmation of human infection with avian influenza H5N1
The Ministry of Health in Djibouti has confirmed the country’s first case of human infection with the H5N1 avian influenza virus. The patient is a 2-year-old girl from a small village in Arta district. She developed symptoms 23 Apr 2006. She is presently in stable condition with persistent symptoms. 3 tests conducted 10 May 2006 by the US Naval Medical Research Unit 3 (NAMRU-3) confirmed the child’s infection with the H5N1 virus. She is the first case of human infection reported in the Horn of Africa. 3 of the child’s siblings are under investigation for possible infection and are also receiving care. Samples have been taken and are being sent to NAMRU-3 for testing. Health authorities in Djibouti initiated surveillance for human cases following reports of a small number of chicken deaths in early Apr 2006. NAMRU-3 has also confirmed the presence of H5N1 virus in samples from 3 chickens. Surveillance for additional human and animal cases is presently under way, but is hindered by the country’s lack of resources and of epidemiological and laboratory capacities. The search for human cases has been further complicated by a concurrent outbreak of dengue fever, which can mask the occurrence of other febrile illnesses with abrupt onset of symptoms, including H5N1 infection. The situation in animals is poorly understood. Most of the country’s population is concentrated in the Djibouti district, where many households keep small numbers of poultry. Poultry production in other parts of the country is limited. High mortality in poultry flocks has not been detected to date. At the request of the Ministry of Health, WHO is arranging urgent support for the country’s investigation and response to the outbreak.

Also, Sudan reported to the OIE 8 May 2006 as follows: "A new outbreak has been identified at Atbara, in River Nile State, 250 km to the north of Khartoum. New outbreaks have also been reported in Gezira State in 4 poultry farms located 40-50 km to the south of Khartoum town.
(WHO 5/11/06, 5/12/06 http://www.who.int/csr/don/2006_05_12/en/index.html )


Nigeria: Spread of avian influenza H5N1 appears to be declining
The spread of H5N1 bird flu in Nigeria is slowing 3 months after the disease was first detected in Africa's most populous country, officials said 10 May 2006. The first African state to be hit by bird flu, Nigeria has not reported any human cases of the disease, although experts warn surveillance may not be completely effective and cases may have gone undetected. In the first few weeks, bird flu spread rapidly in poultry across the country despite measures to contain it such as culling and quarantine, and outbreaks were reported in 13 of Nigeria's 36 states and in the Federal Capital Territory. But there have been no outbreaks in new states since the disease reached the largest city, Lagos, Mar 2006. "No new states have been affected since Lagos, but that doesn't mean the outbreaks have completely stopped," said Tony Joannis, head of the viral research department at the National Veterinary Research Institute. In the past 2 or 3 weeks there have been 2 new outbreaks in states that were already affected, Bauchi and Plateau, he said, adding the rate of new outbreaks had slowed dramatically. Joannis said it would not be safe to consider the disease contained, but recent evidence suggested measures to prevent its spread were working better than at the start. Many Nigerians stopped eating chicken after bird flu was confirmed, and a month later a poultry farmers' association reported sales had dropped by 85 percent. Sales are still slower than before bird flu hit. Many Nigerians are too poor to afford the luxury of rejecting chicken if they are able to get hold of it, however. (Promed 5/11/06)


1. Updates
USA. Influenza activity in the US peaked in early March and continued at low levels during week 18 (April 30 – May 6, 2006). 93 specimens (8.9%) 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) was below the national baseline. The proportion of deaths attributed to pneumonia and influenza was below the threshold level. 5 states reported local influenza activity; 38 states, the District of Columbia, New York City, and Puerto Rico reported sporadic influenza activity; and 7 states reported no activity.
(CDC 5/12/06 http://www.cdc.gov/flu/weekly/ )

Avian/Pandemic influenza updates
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html. Includes Global/country maps.
- UN FAO: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html. Information on donor funding for FAO’s avian influenza program is included.
- OIE: http://www.oie.int/eng/en_index.htm. Includes information on major upcoming Avian Influenza conferences 2006.
- US CDC: http://www.cdc.gov/flu/avian/index.htm. Includes page on “bird flu in the movies”.
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/. Latest updates on U.S. State Summits are available. A “Spotlight” on the recent ABC pandemic flu movie is available.
- CIDRAP: http://www.cidrap.umn.edu/. Frequently updated news and scholarly articles.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm. National Preparedness and Response Plan for an Influenza Pandemic (Mexico) is available.
- American Veterinary Medical Association: http://www.avma.org/public_health/influenza/default.asp.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information (with bulletins, maps, and news reports): http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp.


2. Articles
Viet Nam: Possible avian influenza transmission via the gastrointestinal tract
Avian influenza may be capable of invading people through the gut, not just the respiratory system, and diarrhea is sometimes the first symptom, said virologist Menno de Jong, whose team observed 18 cases in Viet Nam. Particles of the H5N1 virus contained in the meat and blood of infected poultry may have been ingested by some patients, possibly causing their infection, said De Jong, who is head of the Virology Department at the Oxford University Clinical Research Unit in Ho Chi Minh City. "In a number of patients the only exposure risk has been drinking raw duck blood," De Jong said. "That could imply that the gastrointestinal tract is also a route of transmission or a route of first infection, and there are experiments in animals" that suggest this. If live virus particles are carried outside the lungs and surrounding tissues to other parts of the body, some antiviral treatments such as inhaled zanamivir, marketed by GlaxoSmithKline Plc as Relenza, may not be effective treatments, De Jong said. GlaxoSmithKline, Europe's biggest drugmaker, is developing an intravenous form of Relenza, Nancy Pekarek, a U.S. spokeswoman for the company, said. Scientists are still formulating the compound, and testing in people hasn't started, she said.

In uncomplicated cases of seasonal influenza, disease is limited to infection in the nose, throat and lungs. In contrast, H5N1 was observed to have caused encephalitis, or swelling of the brain, in 1 patient in Viet Nam, De Jong said. Virus particles collected from numerous sites could be cultured, including from the throat, rectum, blood and cerebralspinal fluid, he said. De Jong said it is possible H5N1 may be replicating in the gastrointestinal tract after the virus was cultured from a rectal swab in a patient who had diarrhea. For some patients, the gastrointestinal tract may have been the initial site of infection, possibly after the consumption of raw chicken or raw duck products, he said. Some scientists said survival of flu particles in the gut would be difficult because of enzymes and bile that break down fats in the process of food digestion. Flu particles are enveloped by a layer of lipids or fats. (Promed 5/9/06)


H5N1 Influenza A Virus and Infected Human Plasma
Live H5N1 avian influenza virus can be isolated from the blood of its human victims, Thai researchers reported. Evidence that H5N1 can spread via the bloodstream to parts of the body not normally attacked by influenza viruses confirms this particular flu strain poses special challenges. "This is the first report of a large amount of (H5N1) virus in blood in humans," University of Ottawa virologist Earl Brown said of the findings, outlined in a letter slated for publication in the Jun issue of Emerging Infectious Diseases. While some types of viruses spread well in blood, cases of viremia--viral infection in the bloodstream--have only rarely been reported with influenza. The Thai researchers reported on the case of a 5-year-old Thai boy who died of H5N1 infection 7 Dec 2005. A blood sample drawn on the day he died contained high levels of live virus. The finding helps to explain reports that some humans with H5N1 experience systemic infection, with the flu virus spreading beyond the respiratory track to organs that would typically go untouched by human flu viruses. Other researchers have reported finding traces of H5N1's RNA in blood. Those findings were highly suggestive that the virus was using the bloodstream to disseminate, but were not strong enough evidence to rule out that spread was actually occurring via other routes such as the lymphatic system.

Virologist Menno de Jong and colleagues, at Oxford University's Clinical Research Unit at the Hospital for Tropical Medicine in Ho Chi Minh City, said his group has found viral RNA in the blood of about half of the H5N1 patients in which they've looked for it. "It was really surprising for influenza, because the case reports of human influenza and viremia are so rare," he said. "It's probably quite common in H5N1 infected patients." That poses challenges for treating patients infected with H5N1, because if the virus is spreading through the blood, so too must drugs that aim to combat the infection. Currently there are only 4 flu antivirals on the market and one, zanamivir (sold as Relenza) is administered to the respiratory tract by inhalation. The drug would need to be formulated in an injectable form to be useful for systemic infection, Dr. de Jong said. It also raises concerns about infection control for health-care workers and laboratory scientists coming in contact with the blood of H5N1 patients.

The findings also raise questions about whether blood transfusions could be a source of infection if H5N1 became a pandemic strain. Canadian Blood Services and the American Red Cross have been studying the issue, but currently it is believed that the risk is low, because flu’s incubation period is so short. Once people develop symptoms they would be unlikely to want to give blood and would probably be turned away if they showed up to a blood-donor clinic. "From the blood-donor and blood-supply point of view, the issue would be whether there's virus in the blood before the patient becomes ill," said Dr. Jeffrey McCullough. (Promed 5/5/06)


Study suggests older antivirals could help fight H5N1
(Cheung C-L, Rayner JM, Smith GJD, et al. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis 2006 Jun 15;193)
An analysis of more than 600 H5N1 avian influenza viruses collected from several Asian countries suggests that 2 older antiviral drugs could be more useful in fighting a flu pandemic triggered by H5N1 than previously believed. Most H5N1 viruses collected from humans and poultry in Vietnam and Thailand have been resistant to the 2 older drugs, amantadine and rimantadine (the adamantanes). As a result, hopes for an effective drug have focused on the newer antivirals, oseltamivir and zanamavir. Many countries have been stockpiling oseltamivir. But a team of scientists is reporting that resistance to amantadine seems less common than has been believed, at least in some countries. "Amantadine appears to retain the potential to be useful in an H5N1 pandemic in the absence of a vaccine, as a prophylactic agent and as a component of combination antiviral therapy," says the report, published by the Journal of Infectious Diseases.

The study was done by scientists from the University of Hong Kong; Shantou University in China; St. Jude Children's Research Hospital in USA; and the Center for Indonesian Veterinary Studies in Jakarta. Chung Lam-Cheung and colleagues analyzed the genetic sequences of the M2 ion channel protein of 638 H5N1 viruses, including 599 from birds and 39 from humans. Most of the isolates came from Hong Kong, China, Vietnam, Thailand, and Indonesia, with a few from Cambodia, Malaysia, Japan, and Korea. The sequences were screened for 4 mutations predicted to confer amantadine resistance. Data in the report show that 92.6% (162 of 175) of the Vietnam isolates had resistance mutations, as did all the isolates from Thailand (58 of 58), Cambodia (9 of 9), and Malaysia (2 of 2). In contrast, only 13% (16 of 123) of the isolates from China and 6.3% (2 of 32) of those from Indonesia had such mutations. None of the 8 isolates from Japan and Korea, collected from poultry in late 2003, showed resistance.

"Although amantadine-resistant H5N1 viruses are present in Asia, their distribution appears to be largely limited to Thailand, Vietnam, and Cambodia," the report states. "That most H5N1 isolates from China and Indonesia are sensitive to amantadine is striking and perhaps surprising, in view of the reportedly widespread administration of amantadine to farmed poultry in some countries." Amantadine and rimantadine have been used in treating human flu for more than a decade. However, flu viruses can quickly become resistant to the drugs, because just 1 point mutation is required. Last January, US CDC advised physicians to stop prescribing the drugs for the rest of the flu season because the predominant strain of influenza A had turned highly resistant to them.
(CIDRAP 5/12/06 http://www.cidrap.umn.edu/ )


Sanofi reports results for H5N1 vaccine with adjuvant
(Bresson J-L, Perronne C, Launay O, et al. Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase 1 randomised trial. Lancet 2006).
In a human trial in France, an experimental H5N1 avian influenza vaccine with an adjuvant showed modestly better performance at a lower dose compared with a similar H5N1 vaccine that was tested earlier in the US. The new study, published in The Lancet, showed an immune response in 67% of patients receiving 2 doses of 30 micrograms (mcg) of the vaccine plus an adjuvant. An accompanying commentary, however, pointed out several obstacles that need to be addressed before an effective vaccine can be mass-produced. The vaccine is manufactured by Sanofi Pasteur. It is an inactivated, split-virion strain of H5N1 known as Vietnam/1194/2004. The company reported preliminary results of the trial Dec 2005. The study involved 300 adults (aged 18 to 40), divided into 3 groups receiving 7.5, 15, or 30 mcg of the vaccine, plus 3 groups receiving the same doses of vaccine combined with an aluminum hydroxide adjuvant. 4 of the groups comprised 50 people, one 49, and one 51. Study investigators included 2 from Sanofi Pasteur.

Each patient received the vaccine on the first day of the study and 21 days later. All patients were assessed on day 21 and day 42 for immune response. On day 42, of those receiving 30-mcg doses with adjuvant, 67% were seropositive (95% confidence interval, 52% to 79%), compared with 52% of the 30-mcg group without adjuvant. Percentages for both 15-mcg groups were 44%, and those for the 7.5-mcg groups were 43% and 28% without and with an adjuvant, respectively. In the US study published Mar 2006, 451 adults received 2 doses of 7.5, 15, 45, or 90 mcg of another H5N1 vaccine made by Sanofi, all without an adjuvant. Of the 99 volunteers who received two 90-mcg doses, 54% developed H5N1 antibodies. This compared with 43% in the 45-mcg group, 22% in the 15-mcg group, and 9% in the 7.5-mcg group. The vaccine was based on a different human isolate of H5N1 than the one used in the French study.

In the new study, some seroconversion was evident in each of the groups at day 21, after only 1 dose of the vaccine was administered. The patients had no serious adverse events, few severe reactions, and no oral temperatures higher than 38°C. In an accompanying commentary, however, Suryaparkash Sambhara from CDC and Gregory A. Poland of the Mayo Clinic write that the study results, though more promising than in the earlier US study, leave much to be desired. "The results of these two early clinical trials,” they write, “clearly indicate that we still do not have a highly immunogenic vaccine to use against H5N1 influenza.” They cite the following factors: It is unknown whether the antibodies induced by the vaccine would sufficiently protect people from a pandemic virus. No published reports indicate how this "clade 1" vaccine will cross-react with other H5N1 subtypes. The regimen of two 30-mcg doses is still high and would limit the number of doses available at current manufacturing capacity. No data exist on the vaccine’s effect on immunocompromised people. According to the study’s authors, “In a pandemic situation, the aim will be to immunize a maximum number of people to protect them against mortality and severe disease. The level of postvaccination antibodies needed to achieve this protection is not known. Limited manufacturing capacity implies the need to adapt dose-sparing strategies. The challenge, therefore, is to find the appropriate compromise between individual protection and protection from a population perspective.”
(CIDRAP 5/12/06 http://www.cidrap.umn.edu/ )


Delaying the International Spread of Pandemic Influenza
Ben S. Cooper, Richard J. Pitman, W. John Edmunds, Nigel J. Gay. PLoS Med. 2006 May 2;3(6):e212.
Abstract: “Background: The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. Methods and Findings: To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. Conclusions: Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.” (CIDRAP http://www.cidrap.umn.edu/ )


3. Notifications
FAO/OIE International Conference on Avian Influenza & Wild Birds
The Food and Agriculture Organization of the UN (FAO) and the World Organisation for Animal Health (OIE) are organizing the FAO/OIE International Scientific Conference on Avian Influenza (AI) and Wild Birds to be held in Rome, Italy 30-31 May 2006. The venue of the Conference is FAO Headquarters. For more information: http://www.fao.org/ag/AI-Conference. For practical reasons, FAO/OIE are unable to make open invitations, but if you are interested in participating, please contact us before 11 May 2006, 1200 hours local time at or . Please provide the following information ONLY: 1) Name and degrees/qualifications; 2) Organization you work for and your title; 3) Type of organization (government, NGO, University, etc.); 4) Your experience working with Avian Influenza, wild birds, disease ; diagnostics, ecology, or other (no more than 2 sentences).

For more information, contact: Willem Schoustra, Avian Influenza Consultant
Food and Agriculture Organization of the United Nations
Viale delle Terme di Caracalle
00100 Rome, Italy
(Promed 5/8/06)