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February 27, 2003 Previous
Genetic analysis of bird flu
Latest avian flu virus to cause human deaths doesn't contain human flu sequences but could still be dangerous. | By Tabitha M Powledge
The new bird flu virus that has killed at least one person in South China is genetically different from the avian flu strain that infected 18 people in Hong Kong and killed six of them in 1997. But, like the 1997 virus, the new strain does not appear to contain sequences from human flu viruses that would speed its spread from person to person, lessening fears that a lethal pandemic flu may be imminent.
"The bottom line is that we do not know enough about influenza viruses to predict which virus will be transmissible efficiently from human to human," Malik Peiris, a microbiologist at the University of Hong Kong who is studying the new virus, told The Scientist.
Peiris says he is reassured by the fact that the bird virus has not reassorted with a human influenza virus, which probably hampers its ability to infect people. "However, it is not possible to say with certainly that this virus will not transmit human to human, purely from genetic data. The epidemiological data is important. The key will be to enhance surveillance in humans to ascertain whether there are further human cases. So far, there are none."
There are none in Hong Kong, but an unsettled question is whether an epidemic of atypical pneumonia that appeared in Guangdong province early in February might also be avian flu. At least five people have died and more than 300 others have reportedly been infected, more than 100 of them medical workers. The province's population is about 80 million.
Guangdong health authorities have attributed the disease to Mycoplasma pneumoniae. Beijing health authorities examined lung tissue from two dead patients and declared that the culprit was Chlamydia. Rumors about the disease have been rife, causing a run on herbal medicines and price-gouging on white vinegar, heralded as deadly to the infective agent, whatever it is.
Flu researchers note that they have no direct evidence about the cause of the Guangdong pneumonia. "We are dependent on the Guangdong authorities for that information," Peiris points out. "The information is just not available to us," says Robert Webster, of St. Jude Children's Research Hospital in Memphis, Tennessee. "We don't have samples to analyze. The World Health Organization have a team in China now working with the Chinese to determine whether there's anything else going on there," he told The Scientist.
Adding to the uncertainties, the mainland government has clamped down on information about the pneumonia. Two days ago a spokesman for the Guangdong health department told reporters that all further information would be disseminated by the party propaganda unit.
Speculation about the source of the Guangdong pneumonia is fueled by geography. Guangdong lies between Hong Kong and Fujian province, where the man who died of bird flu in Hong Kong on February 17 had visited during the Chinese New Year early this month. He and his family were exposed to chickens in Fujian, and his young daughter died of an unspecified pneumonia during that trip. His nine-year-old son was infected with avian flu also, but has recovered.
A closely related virus has, however, been found in wild ducks and egrets in Hong Kong in the past few months. "The virus comes from wild birds and could have come from anywhere. I think it's a mistake to try to say where this occurred," says Webster, who has been studying the avian flu virus since 1997 and is working with WHO to develop a vaccine against the new strain.
Of the four types of influenza virus, only two trouble Homo sapiens. Most regional epidemics are due to type B. But human pandemics such as the notorious 1918 flu, said to have killed twice as many people as World War I, are caused by type A. These have avian lineages, according to Webster, author of a new flu review appearing in the March–April issue of American Scientist.
The flu virus is made up of eight RNA segments that code for at least 10 proteins; they can reassort easily when two viruses (even from different host species) infect the same cell. Type A viruses are classified by subtypes of their two cell-surface proteins, hemagglutinin and neuraminidase, which cause epidemics when they mutate in ways that permit them to evade the host immune system. The villain in the 1918 epidemic is known as H1N1. Both the 1997 bird flu and the new outbreak are examples of H5N1, although they are not identical.
"The first virus strain from the nine-year-old boy is completely sequenced. The six internal genes of the virus, as well as the neuraminidase gene, are derived from a different genetic lineage from that of the 1997 virus. Only the haemagglutinin derives from the same lineage as 1997. In addition, we also can establish that the virus has not acquired any human influenza internal genes," Peiris told The Scientist. Additional genetic data are being gathered for publication, he said.
Although similar, this year's hemagglutinin "has undergone change so that the '97 and '03 viruses, while related, can be distinguished serologically. In addition to being antigenically different the '03 virus appears to be more pathogenic for ducks than its predecessor," Ian Gust told The Scientist. "The factors which control infectivity seem to lie on genes other than those coding for the H5 and N1 surface proteins." Gust, at the University of Melbourne in Australia, is collaborating with the WHO flu research team.
Although the Hong Kong death occurred less than two weeks ago, researchers were able to move quickly with genetic studies because they set up an early warning system after the 1997 outbreak and had already been studying the recent infections in Hong Kong birds. "The precursors of these viruses are all over Asia. It's not as though this thing came out of left field again. We've been waiting to see when it would happen," says Webster.
Webster has argued emphatically that a replay of 1918 is on the way, and that it will be worse this time. He is not alone. "A pandemic strain will certainly appear, will spread widely and will be lethal," WHO spokesman Dick Thompson told The Scientist. However, "there have been a half dozen pandemic 'false alarms' in the last 30 years," Thompson says. A false alarm is an outbreak in which a novel strain has jumped the species barrier but has been confined to one or two people and often has not been lethal.
Whether the new avian flu is another false alarm remains to be seen. Webster points out that in 1997 the first case occurred early in the summer and the next one didn't appear until November. "You don't trust influenza. The virus is continually mutating and changing, and we fundamentally don't understand transmissibility of viruses. Unless we can point to molecular changes in the different genes that are responsible for spreadability, don't trust the beast. That's the safest way."
Links for this article
University of Hong Kong
http://www.hku.hk/
St. Jude Children's Research Hospital
http://www.stjude.org/newhp/research.html
World Health Organization
http://www.who.int/
American Scientist
http://www.sigmaxi.org/amsci/amsci-text.html
University of Melbourne
http://www.unimelb.edu.au/
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Sagittarius: Sagittarius seeks adventure, lives to roam the planet and thrives in flirtatious social settings. Impress this Fire Sign by throwing a rousing, foreign culture-themed birthday party. Try an all-Japanese cuisine get-together, complete with sushi, hot tea or sake and green tea ice cream. Or else gather some friends and head out for a day trip in the birthday Sag's honor!
by Kelli Fox, Astrology.com
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