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| New Details About H5N1 |
| 2005-08-23 |
| ...Why this new virus is so deadly is not entirely understood, although scientists have hints. Influenza viruses invade cells lining the throat and windpipe, where they replicate and cause inflammation but are eventually suppressed by the immune system. In some cases, the microbe invades the lungs and leads to viral or bacterial pneumonia. Some H5N1 strains, however, have two features that make them even more dangerous. Normally, the flu viruses can replicate only in the throat and lungs. With H5N1, however, the protein that triggers replication can be activated in many other organs, including the liver, intestines and brain. What is usually a respiratory infection can suddenly become a whole-body infection. Simultaneously, a second "defect" in the virus unleashes a storm of immune-system chemicals called cytokines. In normal amounts, cytokines help fight microbial invaders. In excessive amounts, they can cause lethal damage to the body's own tissues... ...H5N1's potential as the next pandemic virus is all a matter of probability and opportunity. Influenza A is a simple virus. That is one of the things that makes it so adaptable and potentially dangerous. It flourishes in hundreds of animal species with only 10 genes and a genome of 13,600 nucleotides, or "letters." (The human genetic code, in comparison, has about 25,000 genes and 3 billion nucleotides.) Of course, influenza virus needs more than 10 genes to replicate itself and spread. Like all viruses, it gets what it needs from the cells it invades, hijacking their molecular machinery. Influenza A's adaptability arises, in part, because its genes are carried on eight unconnected strands, called "gene segments." The segments can be traded like cards in a game of hearts, producing new strains of flu, the equivalent of new hands of cards. But that can happen only if two different viruses find themselves in the same cell, which is a very rare event. However, when millions of people, chickens and pigs -- the last animal can be infected by both human and bird influenza viruses -- live close together, as they do in China, rare events happen. This gene-trading is called "reassortment." In the 1960s, Webster hypothesized that something like reassortment -- the process had not yet been discovered -- must explain the really big changes that appeared every once in a while in human flu viruses. This is the theory he tested in his London experiment decades ago. There he asked for a little space at the National Institute for Medical Research at Mill Hill and access to the famous lab's collection of human serum and influenza viruses. He mixed antibody-rich serum from victims of the 1957 flu pandemic with samples of avian flu viruses. In a matter of hours, he saw the human antibodies attack some of the microbes. This showed that the 1957 human virus shared features with some of the bird viruses. "It's the only paper I've ever done based on just one day of experiments," he recalled recently, still both proud and amazed. It turns out that of the Asian flu's eight gene segments, three had recently arrived from birds, according to an analysis of the genes' molecular fingerprints that was done much later. Two of the bird genes were for surface proteins that give a flu virus its immunological identity -- hemagglutinin and neuraminidase (denoted "H" and "N"). Something similar happened in 1968, when the Hong Kong flu strain got a new "H" from birds through reassortment, as well as a bird version of another, less important, gene segment. That strain, too, caused a pandemic. The other way avian flu viruses can adapt to become human viruses is by slowly acquiring mutations. As small changes pile up, the virus's behavior can evolve. One trait that can appear is the capacity to enter human cells easily. That, and the ability to replicate efficiently once inside, are the two requirements for contagiousness. Evolution of flu viruses is inevitable because the microbe is prone to making mistakes as it copies its genes. The more times a virus replicates, the more opportunity there is for a new mutation to arise that allows easy person-to-person transmission. For that reason, suppressing H5N1 outbreaks in birds -- where the microbe is replicating trillions of times a day -- is a crucial tool in preventing a human outbreak. China and Indonesia have vaccinated poultry flocks against H5N1, and Vietnam this month is starting a two-year, $35 million campaign to do so, too. The highly lethal H5N1 viruses isolated from last year's human cases of avian flu were genetically 99 percent identical to each other. The slightly less lethal -- but perhaps more transmissible -- virus taken from patients in northern Vietnam early this year is only 98 percent identical to last year's; more important, it isn't completely inhibited by antibodies to last year's strain. It may be on its way to becoming a new, human-adapted strain. But H5N1 flu isn't evolving just in human hosts. It's also changing in birds in a dangerous way. Decades ago, Webster demonstrated that waterfowl are the true "home range" of influenza A viruses -- another of his key scientific contributions. For nearly 30 years, he and his colleagues have annually sampled wild ducks in the birds' nesting grounds in Alberta, looking for new flu strains. Since 1985, they have also sampled the feces of more than 5,000 migrating shorebirds along Delaware Bay. H5N1 strains with slightly different traits have appeared several times in East Asia since the first one emerged in southern China in 1996. Last fall, while analyzing a strain circulating after an outbreak in Hong Kong in 2002, one of Webster's post-doctoral researchers, Diane Hulse, made an unusually important observation. Many ducks experimentally infected with the virus didn't die, even though the strain was highly lethal to chickens. But one of the duck viruses was highly lethal to ferrets, the animal whose susceptibility mirrors that of people. This meant that killing infected chickens wasn't going to be enough to stop the spread of the microbe. Ducks could serve as a permanent reservoir of H5N1 virus. Webster immediately informed officials at the WHO, who in turn sounded the alarm. They announced that ducks -- there are 2 billion domestic ones in East Asia -- might be "silent carriers" of H5N1 influenza strains potentially fatal to people. The discovery by Hulse and Webster led, in part, to an extreme program Thailand mounted last November. About 70,000 investigators went into every village in the country looking for sick ducks and sampling the feces of healthy-looking ones. Flocks carrying H5N1 influenza virus were killed. The strategy appears to have worked. Last year, Thailand had 12 human deaths from H5N1 flu. So far this year, it has had none. Stretching out before Webster and public health experts is a long list chores the world must complete if it is to abort the bird-to-man transfer of disease he long ago proved could happen. Last month, two teams of scientists based in China, one assisted by Webster, proved that H5N1 is now circulating in several species of migratory birds capable of carrying the virus to India, Australia and Central Asia. Tests announced last week suggest that some of those long-distance fliers have already carried H5N1 into Mongolia, where it hadn't been seen before. A task equal in importance to charting the spread of H5N1 is developing and distributing a good duck vaccine for the billions of those birds in East Asia. Those countries, which collectively are the likely ground zero of pandemic flu, also need to improve their disease surveillance. In particular, they need to develop laboratories capable of safely isolating and testing influenza viruses. And while they are doing that, they -- and the rest of the world, Webster believes -- would be well advised to draw up a plan to limit human movement and distribute vaccine and antiviral drugs should a pandemic flu strain emerge despite the efforts to prevent it. |
| Posted by:Anonymoose |
| #1 A couple of potentially useful "home remedies", as far as prevention go, are first, cranberry juice, which has shown some ability to prevent cell transfer of some viruses. Second, are metallic zinc and silver, which if uptaken by the mucous membranes inhibit pathogen reproduction. The best overall method of limiting exposure remains hand sanitizing at reasonably frequent intervals and staying out of close quarters with other people during a flu outbreak. |
| Posted by: Anonymoose 2005-08-23 19:27 |