Bird flu has wreaked havoc on much of Asia in recent years. Millions of birds have been culled to prevent the spread of the disease, but by the middle of 2005, some 50 people had died from bird flu. Given fears that the virus will mutate to a more contagious form, experts continue to warn of the potential for a full-blown pandemic, much like the 1918 flu epidemic. Here keeps tabs on the situation from day to day.

For a full timeline reaching back to 1890, and monthly summaries of events, click here.

23 December 2005 The Indonesian government may grant a stay of execution to a US military research unit in Jakarta that is a key player in the fight against avian flu. Earlier this month it was revealed that the government had ordered the US Naval Medical Research Unit No. 2 (NAMRU-2) to cease all research activities by 31 December on the grounds that the 1970 agreement creating the centre had expired (see 'Avian flu centre put under threat of closure')

Following talks between Namru-2 and the health ministry, however, the government is to assess the centre's research projects on a case-by-case basis, and may grant them extensions to continue beyond the 31 December deadline, pending negotiation by the US and Indonesian governments of a new agreement on the centre's future.

21 December 2005 Two patients in Vietnam have died after failing to respond to the drug Tamiflu. An additional two patients who did respond to the treatment nevertheless succumbed to the disease. The cases, reported in the New England Journal of Medicine today, suggest that the H5N1 virus is mutating and becoming resistant to the drug. The lead researcher described the findings as "very worrying" but not surprising. Researchers again note that it would be a good idea to stockpile more than one type of drug against the flu.

5 December 2005 Ukraine is fighting a large outbreak of bird flu, with around 2,000 domestic birds dead in six villages on the Crimean peninsula, in the Black Sea. The army are enforcing a cull of all poultry in the area, and providing villagers with vaccinations against human flu to increase their resistance to bird varieties.

Tests by the agriculture ministry showed the virus was of the H5 subtype, and samples of the strain have been sent to the UK and Italy to determine whether it is the deadly H5N1 strain already detected in two of Ukraine's neighbours, Russia and Romania. The villages are all near Lake Sivash, a large lagoon by the Azov Sea visited by birds migrating between Russia and Africa or the Middle East.

President Victor Yushchenko declared a state of emergency in the area and dismissed his chief veterinary officer, blaming him for an initially slow response to the outbreak. Officials report the cull began just a day after the first dead birds were reported, but locals have told reporters the disease has been killing their birds since September.

25 November 2005 On 23 November, a report appeared on ProMED, a medical alert website, that Masato Tashiro, head of virology at the National Institute of Infectious Disease in Tokyo, "believes that China has had 300 human deaths from avian influenza and [China] is hiding the true extent of the disease from the rest of the world". The story appeared originally in the Frankfurter Allgemeine Zeitung and was based on a talk given by Tashiro at the University of Marburg.

The report was rapidly denied by Tashiro, who posted to ProMED a note saying that the first story "is not correct".

Tashiro wrote that in his talk he merely pointed out that the World Heath Organization's official numbers of H5N1 human cases in China include only those that have been confirmed in a laboratory - and they may be an underestimate, since the surveillance system in China is poor. Tashiro notes that he discussed some of the rumoured cases but adds he does "not think that the Chinese Authority will conceal the facts from the world". was not able to contact anyone who attended the talk for comment.

21 November 2005 Officials in Canada say that two wild ducks found dead in Manitoba last week were infected with an H5N1 avian influenza virus.

But they point out that the virus is not the same as the virulent H5N1 variety currently rampaging through domestic poultry in Asia and causing human deaths.

The H5N1 virus identified in the Canadian ducks is not an immediate threat, say officials. It does not spread quickly between birds, and there are no reports that it has ever jumped into humans.

The difference lies in the molecular make-up of the two viruses. Although the proteins on the surface of the Canadian and Asian viruses — H (haemaglutanin) and N (neuraminidase) — are of the same type, the genes inside the viruses are not the same.

16 November 2005 China's Ministry of Health today confirmed three human cases of bird flu, after much speculation about some patients with avian-influenza-like symptoms.

The announcement, which provided no further details, was posted on the web site of Xinhua, China's official news agency.

15 November 2005 China announced today that it will carry out a massive poultry vaccination campaign — potentially the biggest ever seen - to combat the spread of bird flu.

Jia Youling, chief veterinary officer in the Agriculture Ministry, told the official New China News Agency that China's entire stock of poultry, including 14 billion chickens, ducks and geese, could be subject to the vaccination.

It isn't clear how China would be able to accomplish such a massive vaccination programme, or whether they are capable of producing that much vaccine. Officials later clarified that some large-scale industrial poultry farms could be exempted if they could isolate their stocks and prove they are free of disease. But China is packed with many smaller, back-yard farms.

There have been no officially confirmed cases of human H5N1 infection in China, although several people have fallen ill with symptoms that match the disease. The WHO has dispatched six people to China to help determine the cause of these illnesses.

11 November 2005 Everyone knows that the bird flu virus is more deadly than the usual winter flu. But researchers are just starting to get the full picture of how and why the H5N1 virus proves so lethal.

A study published today details the inflammatory response induced by H5N1 in human lung cells. Michael Chan of the University of Hong Kong and his colleagues looked at levels of pro-inflammatory proteins called 'cytokines' and 'chemokines' in cells cultured in the lab.

When the lung cells were infected with a seasonal flu virus, levels of a particular chemokine (IP-10) reached 200 picograms per millilitre. But the levels of chemokine reached ten times that — roughly 2,000 picograms — when infected with H5N1. The findings appear in the journal Respiratory Research.

Previous research has also shown that the avian flu virus increases production of pro-inflammatory proteins in other cells.

9 November 2005 A man has died in Vietnam of the H5N1 virus. Since mid-December 2004, Vietnam has reported 65 cases, of which 22 were fatal.

The newly confirmed case coincides with a recurrence of outbreaks in poultry.

7 November 2005 From 7-9 November, more than 400 animal and human health experts, senior policy-makers, economists and industry representatives are gathering in Geneva to work towards a strategy to control the H5N1 virus in domestic animals and prepare for a potential human influenza pandemic.

The meeting is co-organized by the World Health Organization (WHO), the Food and Agriculture Organisation (FAO), the World Organisation for Animal Health (OIE) and the World Bank.

It will focus initially on controlling the virus in birds. But experts will also discuss how to strengthen disease surveillance, detection and response.

7 November 2005 The Ministry of Health in Indonesia has confirmed two additional cases of human infection with H5N1 avian influenza: a 19-year-old woman from Tangerang, near Jakarta, and her 8-year-old brother.

The woman developed symptoms on 19 October, and died in hospital on 28 October. Her brother was admitted to hospital on 25 October but remains in good condition. The boy lives in an area with sick chickens, and the woman is known to have visited him there.

Indonesia has confirmed 9 cases of human H5N1 infection to date, of which 5 have been fatal.

4 November 2005 Nature Medicine 's news editor, Apoorva Mandavilli, was in China in late October. She sends us this report on bird flu.

To test whether a chicken is healthy, the vendors hold it upside down and check its rear for pinkness. Credit: Credit: Marc Lipsitch

It all begins in Asia. That's the recurring theme in the countless stories that, probably like you, I've been reading the past few months. But none of it really hit home till last week when I was in China, where I got to see people and poultry mingling uncomfortably close.

At one street market in Shanghai, a few blocks west of the city's famed Yuyuan Gardens, vendors piled plucked chickens next to stalls of vegetables, fruit and fried insects. The sheer volume of unidentifiable creatures and creature-parts was bizarre enough. But truly frightening was how the vendors handled the birds.

To test whether a chicken is healthy, the vendors hold it upside down and check its rear for pinkness. And to do that, they have to remove any debris out of the way. Most of the time, that just means blowing on the area - and that, of course, sends whatever is on the chicken's rear end flying in all directions. "It's basically a great way to aerosolize a fecally transmitted virus," says Marc Lipsitch, with the departments of epidemiology and immunology & infectious diseases, at the Harvard School of Public Health in Boston.

Lipsitch, who had gone to a similar (perhaps the same) market a couple of days earlier, was a bit braver than I was and got close enough to take pictures. On the plus side, he says, the vendors seemed to be wetting the birds before plucking them, and killing them before slitting their necks - actions that prevent the feathers and blood from scattering everywhere and hopefully limit virus transmission.

Washing birds might help to limit the transmission of any viruses. Credit: Credit: Marc Lipsitch

There have been recent reports that the Chinese government is regulating the sale of chickens. And at one market I went to, there were no chickens in sight. But when the Chinese person I was with began inquiring about chickens, one vendor quickly pulled one out from underneath the table-and just as quickly put it back, yelling at us, when she spotted the camera in my hand.

Educating not just these vendors, but everyone who handles chickens, is a monumental task. Just the number of non-commercial backyard chickens in china has been estimated by some to be a staggering 10 billion. And that provides far too many chances to do things the wrong way.

Apoorva Mandavilli

3 November 2005 It seems that researchers are taking steps to help the current stocks of Tamiflu go further. Plans are now being made for a clinical trial of probenecid as a drug-sparing strategy with Tamiflu, Nature has learnt (see 'Wartime tactic doubles power of scarce bird-flu drug').

Mark Holodniy, director of the Public Health Research and Consultation Program at the US Department of Veterans Affairs and a medical professor at Stanford University, has submitted a protocol proposal to the US Department of Veterans Affairs and the US Food and Drug Administration. The FDA, as a matter of policy, would not comment on the issue or how long it generally takes submissions to be processed.

Declan Butler

1 November 2005

Experts warn that a human bird flu pandemic is still a threat. Credit: © Punchstock

Research in the Proceedings of the National Academy of Sciences reveals a potentially faster way to make vaccines against bird flu.

The idea could save about a week's worth of work, the BBC reports, in a process expected to take about six months. While that might not sound like a lot, every little bit of help could make a difference in the event of a pandemic.

Scientists currently use a process called 'reverse genetics' to make an altered version of an offending virus - disabling it enough so that it does not cause disease, while leaving enough of the virus in tact to prompt an immune system response. The altered viral DNA is then seeded into cells, such as monkey kidney cells or human cells, and this is then grown up in chicken eggs to produce large enough numbers for a vaccine dose.

Scientists at the University of Wisconsin-Madison, working with colleagues from the University of Tokyo, now say the process of seeding can be made more efficient. By bundling different bits of viral RNA together into a single plasmid - a chunk of DNA that can help transfer genes between cells - they made the process of introducing viral RNA into incubating cells (in this case monkey cells) much simpler (G. Neumann, K. Fujii, Y. Kino and Y. Kawaoka Proc. Natl Acad. Sci. USA, doi:10.1073/pnas.0505587102 ).

But experts caution that the next steps often take the most amount of time: growing the altered viruses up in bulk in chicken eggs and getting them trialled are often the biggest barriers to production, they say.

26 October 2005 Croatia has fallen victim to the H5N1 strain of bird flu, with the virus killing swans in a park.

Meanwhile, the death of 500 additional chickens and ducks in China has spurred another cull of birds in that country.

26 October 2005 Experts caution that a widely published map of the flyways of migratory birds, published in a recent FAO report 'Wild birds and Avian Influenza' and elsewhere, has limited relevance to avian flu. The map shows flyways of a particular type of bird called waders, says Jan Veen, a biologist at Wetlands International. But the birds that are of greatest concern belong to the Anatidae family of ducks, geese and swans, he says. Waders don't tend to carry flu as often as Anatidae birds, nor do they tend to come into contact with humans.

For a map of the migration route of a more relevant bird, the Garganey duck, see 'Migration threatens to send flu south '.

Researchers add that the best way to assess the risk of migratory birds spreading the virus is to look at the flyways of individual species, and even populations, to get a handle on which birds, and how many, are flying where. Experts also need to factor in aspects of bird virology, bird behaviour, and whether individual flyways coincide with concentrations of poultry farms.

The European Commission has made a start on this. Last month it published a hit list of 15 species that it reckons pose the greatest threat to Europe.

Veen, who made this list, says he took many factors into account. Species with larger migratory populations, such as the 3.4 million Northern Lapwings, got a higher risk rating. And species whose behaviour patterns bring them into contact with human activities, such as mallard ducks, also got a risk boost.

This is only an initial assessment, which will need continual refinement, emphasizes Veen. "The danger is that when you make something very preliminary and you show it to politicians, it goes all over the world."

Declan Butler

24 October 2005 British officials have confirmed that a South American parrot that died in a quarantine unit in southern England on 16 October was infected with the H5N1 strain. This is the first confirmed appearance of the virus in Western Europe, and has prompted calls for the transporting of exotic birds to cease until the current pandemic fears die down.

The parrot, which came from Surinam in South America, is thought to have contracted flu after being caged with some 216 birds from Taiwan, where the strain is believed to be endemic. There is no suspicion that the virus has spread as far as South America.

The fact that the incident occurred in a quarantine unit, where all birds that came into contact with the parrot are now being tested and destroyed, will reassure those fearful that the virus could escape into wild or domestic populations in Western Europe. But others argue that quarantine measured should be tightened further to avoid birds from Southeast Asia having any contact with those from elsewhere. And epidemiologists point out that a blanket ban on bird imports will fuel the illegal trafficking of exotic birds - already the third-largest black market in the European Union after guns and drugs.

There is also, as yet, no sign that the H5N1 strain is swapping genes with other influenza viruses to make it easily transmissible between humans. Continuing strict quarantine measures will stop the virus spreading into other species where this process might be hastened.

18 October 2005 Panic demand for drugs against bird flu has driven up prices and put drugs on public auction sites such as eBay.

EBay reportedly pulled the sale of the flu drug Tamiflu from its web site on Tuesday, after prices hit more than $174 for a packet of the drug. "The Tamiflu listings on were removed from the site as soon as we became aware of them," said a company spokeswoman in a statement. "We do not permit the listing of any controlled drug or item that requires a prescription."

Private prescriptions for Tamiflu can cost about $50 in Europe but national governments have purchased stockpiles of the medicine for less.

Swiss drug maker Roche Holding has urged consumers not to buy Tamiflu over the Internet, to avoid the risk of purchasing counterfeit pills. And recent research has highlighted that the drug should be taken under controlled conditions to avoid nurturing resistant versions of the virus (see 'Researchers call for more bird flu drugs' ).

In the meantime, the Indian pharmaceutical company Cipla Ltd has started laboratory tests on a generic version of Tamiflu. Pressure is mounting on Roche to allow such companies to market generic versions of the drug, though Roche has said it would probably take two to three years for another company to ramp up production of such a drug.

17 October 2005 The bird virus in Romania was finally confirmed as H5N1 over the weekend. A second outbreak has also been reported in the country, 60 km from the first one.

In Turkey, more information is currently being requested of the Turkish authorities concerning a second possible outbreak located at the borderline with Iran.

14 October 2005 Virus samples from dead birds in Romania have still yet to be confirmed as H5N1 thanks to delays at customs. The European Commission released a statement today saying the dispatch of the samples to the Community Reference Laboratory has been held up thanks to customs procedures that come into play for the transport of 'dangerous material'.

Results are not expected until Saturday afternoon.

14 October 2005 A committee investigating the risk of a bird flu pandemic met at the UK House of Lords yesterday. Jan Slingenberg of the UN's Food and Agriculture Organization (FAO) said there is "near certainty" that the Romanian cases are the feared virus. "The avian H5N1 virus has now entered Europe," he said.

The new cases seem to confirm that the virus is being spread by migrating birds, Slingenberg said. The confirmed H5N1 cases in Turkey were on a turkey farm where birds lived outside and could potentially have come into contact with migrating waterfowl. Birds including ducks, geese and swans are known to be effective carriers of the virus and often migrate or routinely travel large distances.

Such birds are expected to migrate past Turkey to northern Africa this winter, which could potentially spread the virus. But while bird migration patterns from that part of the world steer clear of Western Europe, the appearance of H5N1 on their doorstep has caused officials to increase their preparedness for possible further spread of the virus.

In the UK from Monday, researchers will start testing wild birds for the virus, including birds being tagged for research and those shot for recreation. EU experts are expected to issue advice on how to keep farmed animals out of contact with wild birds, and on the risks for people that come into contact with migratory birds.

13 October 2005 The H5N1 virus has hit Europe.

The European Commission will hold emergency meetings this afternoon and tomorrow, following confirmation of H5N1 in birds in Turkey and a virus of type H5 in Romania. In a statement the commission said that analysis of samples from Turkey suggested that the virus was "closely related" to the virus from this summer's outbreak in central Asia.

Experts on avian influenza and migratory birds will meet tomorrow to assess the risk posed by migratory birds in spreading H5N1 in Europe, and measures to avoid risk for humans.

12 October 2005 A San Diego entrepreneur may ruffle feathers with a line of avian flu-themed clothing. Among the offerings: a 'Bird Flu Tour' T-shirt and baseball caps sporting the logo 'Pandemic Fever - Catch It!' The self-proclaimed non-profit website says that the business person in question is "not a freak", but "just fairly concerned with the looming spectre of pandemic. This is an attempt, in a slightly humorous (and slightly dark) way, to better get the word out." H5N1 wear

10 October 2005 Fears that H5N1 bird flu has reached Europe are intensifying with apparent outbreaks in Turkey and Romania.

More than 1,000 birds died in a farm in Turkey, leading officials to cull other birds near that village. And a Romanian village in the Danube delta, which is a stopover for migratory birds from Asia, was quarantined after 36 birds died.

But it has not yet been confirmed that these birds had avian influenza. And, if so, whether it is the same H5 strain that has hit Asia.

The European Commission has announced a ban on all imports of live birds and feathers from Turkey into the European Union.

7 October 2005 Delegates from 80 nations and international agencies began a meeting in Washington DC on Thursday to formulate the best way to fight bird flu.

"The world is clearly unprepared, or inadequately prepared, for a pandemic of H5N1 influenza," US Health and Human Services Secretary Mike Leavitt told the meeting.

The meeting was convened by US officials, who have become increasingly concerned about the epidemic, and are trying to wrest high-level political commitments for cooperation and transparency from other nations.

An HHS official speaking on condition of anonymity yesterday said that the United States is concerned that the world could see a repeat of the SARS epidemic, in which data about the emergence of the virus was tightly controlled by Chinese officials, hampering international response to the disease. US officials have already been criticized about their willingness to share information about avian flu samples kept by the US Centers for Disease Control and Prevention.

Everyone at the US meeting, sponsored by the State Department, agreed in principle to share information quickly to allow health experts study and contain the virus. Now, said officials, it is critical to make sure they actually do so.

President George Bush is also expected to meet today with flu vaccine makers. And Secretary Leavitt is expected to travel to Asia tomorrow to meet with leaders in Vietnam, Cambodia, Thailand, Laos and Indonesia.

30 September 2005 The 10-member Association of South East Asian Nations (ASEAN) has signed up for a three-year plan to curb bird flu. The regional framework doles out responsibilities for key tasks to different countries: it calls for Thailand to lead surveillance and diagnosis, Malaysia to take charge of containment and emergency measures, Indonesia to lead strategic vaccination initiatives, the Philippines to encourage public awareness, and Singapore to ensure proper information sharing.

The ASEAN ministers also agreed to create "disease-free" zones in bird flu-infected countries to hasten the resumption of chicken exports from the region to Japan and other countries.

Together they have pledged an initial US$2 million in seed money for their regional fund.

29 September 2005 In Indonesia, there are vast numbers of "suspected" cases of avian flu. On Thursday, Reuters reported ministry officials saying more than 50 cases were being investigated in hospitals, after a fourth confirmed case of H5N1 in September intensified surveillance efforts and heightened public concern.

Such symptoms are typical of many other diseases, however, in particular dengue fever, so many of these cases may turn out not to have bird flu.

The US National Institute of Allergy and Infectious Diseases (NIAID) and MedImmune have decided to jointly develop vaccines against bird flu.

The project aims to develop at least one vaccine for each of 16 known variations of a key influenza surface protein called haemagglutinin. This is the protein represented by the letter 'H' in bird flu virus names, as in H5N1.

Human influenza viruses are usually of the H1, H2 and H3 varieties. Potential pandemic viruses would likely contain one of the others, to which humans have never been exposed. Recent bird flu viruses of note have been H5 and H7, and H5 will be a high priority for the research team.

The scientists will add selected genes from avian flu viruses with pandemic potential into a weakened human flu virus to create weakened, live virus vaccine candidates.

It will probably take years to succeed. No bird flu vaccines have yet proven successful in low doses.

26 September 2005 The international community has so far come up with just $20 million of the $100 million needed for a 3-year plan to control avian flu in animals, the UN Food and Agriculture Organization warned today.

The estimate for the amount needed comes from the Global Strategy for the Progressive Control of Highly Pathogenic Avian Influenza, which was agreed in May 2005 by the UN's Food and Agriculture Organization (FAO) and the World Animal Health Organization (OIE), in collaboration with the World Health Organization (WHO). The money would go to reinforcing veterinary surveillance and laboratories, to keep emerging diseases in check.

But so far, countries have pledged just $16.5 million: Germany ($6 million), Switzerland ($4 million), the United States ($6 million) and Japan ($0.5 million). The FAO has put in $2 million itself.

23 September 2005 Representatives from the financial services industry received a briefing today in New York from avian flu experts, who hope that the private sector will take the initiative to prepare for a pandemic.

The event, coordinated by the Center for Biosecurity, a not-for-profit organization based at the University of Pittsburgh Medical Center, also involved talks from current and former government officials.

"We don't need any spies to tell us about the pandemic that's coming," noted James Pavitt, the former deputy director of operations of the US Central Intelligence Agency.

If — or as many experts say, when — a pandemic hits, small countries will face the biggest economic challenge, said Robert Shapiro, who served as the US undersecretary of commerce and economic affairs in the late 1990s. He added that because the pandemic would likely strike in waves rather than a single hit, businesses will suffer from severe absenteeism and an uncertain financial climate.

What can companies do to keep the economy running and avoid a breakdown of commerce under such circumstances? Isaac Weisfuse, who leads New York city's pandemic flu planning as deputy commissioner the Division of Disease Control, urged businesses to build up the technical capacity to let employees telecommute. Should a pandemic strike and vital services such as transportation shut down, these people could continue working from home. "We're not stuck in 1918 is my mantra," he told listeners, referring to the year that a Spanish flu killed millions of people.

22 September 2005 Two studies published in The Lancet spell more bad news for the prospect of preventing and treating a pandemic flu outbreak, which would likely be started by a bird flu.

The first study finds that resistance to two antiviral drugs, amantadine and rimantidine, is rampant around the world. The authors studied genetic sequences of flu strains isolated during the past decade. They found that resistance has skyrocketed since the mid-90s, especially during the past two years: 84% of all viruses sequenced since 2003 bear the telltale signature of drug resistance. Public health officials already knew that resistance is a problem with these older drugs, and have been stockpiling newer drugs as a result. But the authors of The Lancet survey , led by the US Centers for Disease Control and Prevention in Atlanta, Georgia, say their work should definitively silence anyone who thought these drugs might be a cheap alternative to prevent pandemic strains of flu from spreading.

The second paper is perhaps more worrying, because it throws up concerns about vaccines, our surest line of defense against pandemic flu. The report finds that flu vaccines are not very effective in elderly people who live outside nursing homes. The authors, based at the Cochrane Vaccines Field in Rome, analysed 15 studies, and found that taken together, the studies found that flu vaccines were not significantly effective for preventing flu, flu-like illness or pneumonia in people 65-years-old and older who don't live in nursing homes. The vaccines seemed to work better in populations that live in long-term care facilities. It's not entirely clear why. But in the face of the data, the authors suggest that public health officials concentrate vaccination efforts on nursing homes - and mix up a more effective vaccine for the remaining elderly, who are one of the most vulnerable populations in flu epidemics. Figuring out why these vaccines are not effective in older people might contribute to better vaccine design for pandemic influenza, too.

21 September 2005 Vietnam state officials say they will begin stockpiling the anti-viral drug Tamiflu, importing some 600,000 tablets before the winter hits. They also plan to boost monitoring at 800 hospitals nationwide, and improve their early detection of cases in humans.

Though there have been no new cases recently reported in Vietnam, the government this week retrospectively confirmed a fatal case of H5N1 that struck in July 2005. This brings the confirmed number of cases in Vietnam since mid-December 2004 to 64 cases, 21 of which were fatal.

19 September 2005 Three children have been hospitalized in Jakarta, Indonesia, with suspected avian flu. Two of them have tested positive in preliminary tests for the H5N1 virus.

On 16 September, Indonesia's health ministry confirmed that a 37-year-old woman who died in the capital on 10 September was positive for H5N1, bringing the country's death total to four from the disease.

Meanwhile, the Ragunan Zoo zoo in Souther Jakarta has been closed for three weeks as of today, after the death over the weekend of 19 exotic birds, including eagles, mynahs, peacocks, and pigmy chickens.

15 September 2005 The United States today bolstered its stockpile of countermeasures against an H5N1 influenza pandemic. Health secretary Mike Leavitt announced that they have bought $100 million worth of pandemic influenza vaccine from Sanofi Pasteur, and 84,300 treatment courses of the anti-viral drug zanamivir (Relenza) from GlaxoSmithKline. They already have a small stockpile of the antiviral drug Tamiflu.

US officials have said they intend to buy enough vaccine to protect 20 million people, and enough drugs to treat 20 million more. It's not clear how many people $100 million worth of vaccine will protect at high doses - earlier this summer, the H5N1 generated a protective immune response in trials with healthy adult volunteers, but only at very high doses (see 'Bird flu vaccine not up to scratch'). US officials are also scrambling to test lower-dose versions of the vaccine.

14 September 2005 In the United States, top scientists plan to meet with heads of the finance industry and White House officials in New York on 23 September for a symposium on Preparing the Financial Industry for a Pandemic .

14 September 2005 President George Bush says he will create "a new international partnership on avian and pandemic influenza". Addressing a high-level UN meeting in New York, Bush gave no details of the proposed coalition, but said that it would "require countries that face an outbreak to immediately share information and provide samples to the World Health Organization". As Nature revealed last May, affected countries are failing, or refusing, to share their human samples with the WHO, the UN agency responsible for coordinating international pandemic flu efforts (see '"Refusal to share' leaves agency struggling to monitor bird flu": ).

13 September 2005 Delegates at the European Influenza Conference largely spent the day pledging money.

Canada reported that it has put aside C$34 million for supporting development of prototype pandemic vaccines.

And Germany reported a fund of €24 million for development of a type of vaccine known as low-antigen, adjuvented, full-virus vaccine. (The inclusion of an adjuvant promotes a stronger immune reaction to the antigen itself and is a favoured strategy in Europe. It should help to protect more people with a limited amount of antigen.)

The European Health Commission also announced a €1 billion fund, which had been approved in early summer, to reimburse member states for expenditure on 'unexpected threats'. The details of who would get paid for what remained unclear to many delegates. But the Commission's general intention was clear: that member states who pledge to buy stockpiles of antivirals, or invest in pandemic vaccine preparedness, will get some level of financial support.

Klaus Stöhr, head of the WHO's Influenza team, warned that preparedness for flu pandemics must also prepare for the distant future. Pandemics come along every few decades. So the best thing would be to develop a single vaccine to protect against all pandemics - along with normal seasonal flu viruses. But there is no money available for the long-term research that would be required for the development of such a vaccine.

Stöhr proposed that European governments should turn as a group to an agency like the World Health Organization to negotiate a single deal with companies for flu vaccines. Such bulk deals should lower the price, said Stöhr, and the money saved could be put into a special fund supporting the development of a general vaccine. There was no public response to this suggestion, which seems to have been discussed in the numerous behind-doors meetings running throughout this congress.

12 September 2005 Scientists at the European Influenza Conference report that the H5N1 virus has become much more virulent and pathogenic since began circulating in 1997. Several mutations are probably implicated, they add - not just changes to the genes encoding the surface haemagluttinin (H) and neuraminidase (N) proteins that give the flu strains their code names, but also the genes encoding internal proteins such as polymerase enzymes. These enzymes control the virus's growth rate; mutations, it seems, can allow growth to far outstrip that which a person's immune system can handle.

The researchers also present improved animal models for flu infections in cats and ferrets, showing how H5N1 can be easily transmitted between animals, infecting the brain and gut as well as the lungs. So far, the more than 100 human cases of H5N1 have not been in a form easily transmitted between people. What molecular changes would be required to make human-to-human transmission as easily as cat-to-cat? That's a crucial question in anticipating a pandemic, and scientists are not close to understanding it.

In gloomy discussions with policy-makers and health workers, scientists broach the contentious subject of who should be first in line for treatment with the scarce supplies of vaccines and drugs such as Tamiflu. The unhappy bottom-line message, as voiced by Claude Hannoun, former head of the Influenza National Reference Centre in France, is: don't expect any vaccine to be available during the first pandemic wave. Governments still need to beef up their national stockpiles of Tamiflu.

It will take 4 to 12 months after identifying the pandemic strain for the first batch of vaccines to appear, by which time the virus will have circled the globe. Scientists have some strategies that could eventually shave a few weeks off different parts of the process, but long-term alternatives to avoid such a delay are not being seriously investigated, they complain. Meanwhile, one company is offering meeting delegates free flu jabs to protect against this year's regular flu strain. Not that they will help against a bird flu pandemic.

11 September 2005 The Second European Influenza Conference opens in Malta. Bird flu experts confirm that the virus is still sweeping its way across the globe, and still threatens to cause a major and deadly human pandemic for which we remain insufficiently prepared.

Conference organizer Albert Osterhaus notes a small recent turning point, however: some governments are at last beginning to take the issue seriously - almost 50 countries now have provided draft pandemic preparedness plans.

11 September 2005 Indonesian authorities have reported what may be the country's fourth victim of avian flu. The 37-year old woman from the country's capital Jakarta died on 10 September. The health minister has said that an initial test was positive for the highly pathogenic H5N1 virus. Samples have been sent to a Hong Kong laboratory for confirmation.

The woman was an immigration official, with little contact with poultry, and the source of infection remains unknown. Health authorities aim to track down and test the woman's contacts.

The first deaths from avian flu in Indonesia were reported in July (see 'Bird flu: crossing borders' ).

26 August 2005 Bird flu spreads to another species: it is confirmed in civets (the animal that famously spread SARS to humans) in Vietnam. Bird flu has previously been found in other mammals, including tigers.

25 August 2005 The president of the British Veterinary Association says that bird flu is "inevitably" going to arrive in the UK. Various European officials have decided that poultry flocks should be brought indoors to prevent the possible transmission of the H5N1 virus from migratory birds. Others say this is not necessary.

7 August 2005 The US National Institutes of Health (NIH) announce preliminary results for a vaccine against H5N1, showing that two large doses should protect adults from infection. But critics point out that the large amounts needed mean the hundreds of millions of doses needed to tackle a pandemic could never be produced.

See Bird flu vaccine not up to scratch

August 2005 Pharmaceutical giant Roche pledges to make three million courses of its anti-viral drug Tamiflu available to the World Health Organization.

August 2005 A Maine biotechnology company that makes vaccines for poultry diseases is fined US$500,000 for smuggling a chicken flu virus into the US. The company hoped to use the virus sample to develop a vaccine.

See Maine company falls a-fowl for smuggling bird flu

August 2005 Poultry flocks in Russia and Kazakhstan are hit by H5N1. A suspected human case is also investigated. The outbreak hints that the disease is moving towards Europe.

Bird flu moves towards Europe

July 2005 At the end of a three-day conference in Malaysia, World Health Organization officials announce that $150 million is needed to fight the spread of the disease in people and another $100 million to stop its spread in animals in Asia.

The Philippines, so far the only Asian country unaffected by bird flu, reports its first case in a town north of the capital, Manila, but officials do not confirm whether it is the H5N1 strain.

June 2005 Indonesia confirms that a man exposed to sick chickens has been infected with a deadly strain of avian flu virus. The man, a farm labourer, shows no symptoms, but his blood carries antibodies against the H5N1 strain.

Bird flu becomes resistant to the low-cost amantadine family of antiviral drugs. Chinese farmers' use of the compound in chickens is blamed, a claim formally denied by Chinese authorities who pledge to investigate the situation.

May 2005 Rumours of human deaths in China from H5N1 remain unconfirmed, while the virus has killed more than 1,000 migratory birds. Indonesia's government confirms reports of H5N1 infection in pigs.

The WHO reports 97 cases and 53 deaths from bird flu in Vietnam, Cambodia and Thailand since January 2004.

April 2005 Vietnam reports a total of 60 laboratory-confirmed human cases of H5N1 avian flu since the outbreaks began, with 35 deaths. Thailand confirms a total of 17 infections of which 12 have been fatal, whereas Cambodia has confirms two fatal cases.

March 2005 15 additional cases of H5N1 infection in Vietnam, and one additional case in Cambodia, are reported.

Bird flu has spread to 10 countries, including the Democratic People's Republic of Korea, and killed around 50 million chickens.

February 2005 First report of a bird flu case from Cambodia.

A report of probable person to person transmission of bird flu in Vietnam is published (New Engl. J. Med. 352, 333-340)

The WHO makes prototype H5N1 vaccine strains available to several institutions and companies, and a range of vaccines is submitted for clinical testing.

January 2005 13 additional cases of bird flu have occurred in Vietnam since December 2004, 12 of which have proved fatal.

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