If you have the stomach for it, go to www.who.int/csr/disease/avian_influenza/en/ and click on “frequently asked questions”. Here, courtesy of the World Health Organisation (WHO), you will find everything you ever wanted to know about H5N1, the avian influenza virus — and plenty that you wished you didn’t. That the potential for H5N1 to fuel a human influenza pandemic “is serious and has increased” ; that once a pandemic is under way it is “considered unstoppable”; that the best way to prevent one is to eliminate H5N1 in birds but that this is seen as “increasingly doubtful”.
There have been more deaths from bird flu — 73 — in 2006 than in any previous year of the current outbreak, which kicked off in 2003. The virus is creeping closer to Europe, with several countries — Azerbaijan, Djibouti, Egypt, Iraq and Turkey — reporting human cases for the first time this year. And now winter lies around the corner. Cold weather brings a sharp rise in human influenza, heightening the possibility that bird flu could infect a person already infected with human flu. The resulting viral brew may permit H5N1 to snatch from human flu the ability to jump from person to person (at present, infection requires close contact with an infected bird). In WHO parlance, the emergence of a transmissible virus takes us from phase 3 to phase 4, just two phases away from showtime.
But if you want to get a real feel for how the influenza community perceives the threat, you have to join doctors and researchers on the front line of the war against H5N1. For the past ten years Professor Jeremy Farrar has been director of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City (formerly Saigon) in Vietnam. Many of the country’s 93 confirmed H5N1 cases have spent their final, suffocating hours here in the hospital, built in the 19th century. Along with a Vietnamese medical team headed by Dr Tran Tinh Hien, Farrar has cared for many victims and is tracking the survivors.
“I don’t necessarily share all the doom and gloom of the global community,” he says, as we sit down to green tea in his large office. “But I do think influenza is probably the only infectious disease we know about that has the potential to cause a global nightmare.
“There are very few infectious diseases that can affect everybody, whether you’re rich or poor, whether you live in San Francisco, London, or Ho Chi Minh City, that can potentially kill a lot of people, and that in reality you can’t do much about.” For the moment, H5N1 — or, to give its full name, HPAI A(H5N1): highly pathogenic avian influenza virus of type A of subtype H5N1 — remains very much a local nightmare, plaguing few people but tormenting them terribly. The virus ravages the lungs — X-rays show the black of the lungs replaced by a ghostly white cloud — to cause pneumonia. The virus can also spread elsewhere in the body, even to the brain, to cause multiple organ failure.
The pathogen appears to latch on to receptors in the lower lung. This part of the body is relatively inaccessible — which may explain why, even though the virus is endemic in poultry, human infection is so rare. Human flu, in contrast, hooks on to receptors in the upper respiratory tract, meaning that coughs and sneezes disperse the virus easily. Scientists have warned that H5N1 could mutate and begin to favour receptors in the upper tract, which would raise the threat level.
“Avian influenza is a horrible disease, and people can deteriorate incredibly quickly,” says Farrar, 45. “I remember one patient having breakfast and talking and by the next morning she was dead. Seeing fit healthy young people, and especially children, go from being very well to very sick and then dying in a short space of time, is always traumatic.” But to see Hn (a bird flu survivor, see opposite) coming in every six months — she always remembers you and has got that gorgeous smile — makes life worthwhile. She should have died.”
Each person that the virus infects — 256 worldwide since 2003, of whom 151 have died — acts as a reservoir in which H5N1 can replicate and mutate. What scientists fear most is that the virus maintains its lethality — it kills around 60 per cent of people it infects — while acquiring the capability to jump from person to person. Were this to happen, the resulting pandemic could relegate the Spanish flu outbreak of 1918 to the footnotes of history. The 1918 virus, H1N1, killed only 1 per cent of those it infected. This is why clusters of H5N1 victims within families or neighbourhoods cause palpitations among scientists — fortunately, outbreaks within families have been due to common exposure rather than to transmission between relatives.
Reassuringly, it is predicted that a rise in transmissibility will go hand-in-hand with a decrease in virulence — as happened with later milder pandemics, such as the 1957 episode of H2N2 that killed two million people, and the 1968 outbreak of H3N2 that killed one million. The logic is that a virus that wipes out its host also wipes out its main vehicle for replication and transmission, so for a virus to be “successful” — such as HIV, which is still with us 25 years after emerging — it cannot be too virulent.
Farrar, though, sees no reason to smile: “The fear factor has gone a little bit but my guess is that if a pandemic were to happen it would happen explosively anyway. The virus would gain this transmissibility, and if the climate was right, say in urban Manila, or Shanghai, or Jakarta, then I think it would take off explosively.”
His unit has produced a wealth of research about H5N1, much of which has earned global headlines. One of the most promising projects, a collaboration between the unit and the National Institutes of Health in Maryland, involves isolating antibodies to H5N1 in the blood of bird-flu survivors. Mice that are first immunised with these antibodies and then infected with the virus survive the ordeal, raising the prospect that the antibodies could form the basis of a future vaccine. The Wellcome Trust, which is fast-tracking influenza research and has funded much of the unit’s work, has awarded the project £385,000.
“We believe that part of surviving H5N1 involves individuals making antibodies capable of killing the virus,” explains Dr Cameron Simmons, who is leading the unit’s involvement with the project.
But, Simmons says, antibodies are not the only key to survival: “It’s partly how soon you get medical care and Tamiflu, how much virus you got initially, how old you are, and what your flu infection history is. Although H5N1 is very different from human flu, parts of it are very similar. So adults who have a long history of flu exposure could potentially have an immune response that helps them to fight H5N1.”
