http://www.feer.com/_0106_07/p034innov.html A Deadly Flu Ready To Strike
The world's next flu pandemic will probably originate in southern China, then transit through Hong Kong and on to the world. How ready are we?
THE FEAR IS THAT when Hong Kong sneezes, the world catches the flu. The world's leading influenza experts are virtually unanimous in their suspicion that Hong Kong will be close to the epicentre of the next pandemic of a contagion that swept the globe three times last century, most lethally in 1918-19 when a particularly vicious flu virus claimed up to 40 million lives.
It is this lurking dread that history will repeat itself that lies behind the slaughter in Hong Kong this month of more than 1.2 million chickens, the second mass cull in four years. "The chances of a pandemic are very high," says Graeme Laver, a professor of biochemistry and molecular biology at the Australian National University. "Whether the next virus will be a killer or just make people sick is not clear at this stage. If it does happen, it will almost certainly come out of China."
Researchers believe that most influenza pandemics in recorded history originated in bird populations in southern China. So, when chickens in Hong Kong's crowded markets begin to die from influenza as they did earlier this month, the death squads in rubber boots and protective clothing begin clearing out the cages in a bid to halt the infection in its tracks.
Kennedy Shortridge, a professor of microbiology at the University of Hong Kong is a leading influenza researcher. Like most researchers, he believes that teeming, tropical southern China, where man and domestic animals, particularly pigs and poultry, live in close contact, is a primary source of new influenza strains. These viruses are believed to then pass through Hong Kong and into the human population. "In a way, in Hong Kong we are a sentinel post," he says.
The city's importance as a trans-shipment centre for southern China's booming manufacturing industry is mirrored by its suspected role in exporting influenza around the world. Hong Kong has the world's fifth busiest airport, so a new strain picked up from a cough on a crowded subway could reach another continent within hours.
Even slight changes in influenza viruses each year take a serious toll on the sick, elderly or very young. In addition to contributing to thousands of deaths, the debilitating infection of millions imposes substantial economic losses on almost all communities.
However, it is the potential for new, deadly viruses like those that caused the 1918 pandemic and the less serious 1957 and 1968 outbreaks that has the ex-perts worried.
So serious is the threat that the World Health Organization has drawn up a plan to deal with the next influenza pandemic. Alan Hampson, the deputy director of the WHO's centre for influenza research in Melbourne, says that it is the "enormous speed" at which influenza infections can travel that poses one of the biggest challenges to public-health authorities.
"In an ideal situation for a virus, you can go from the first case to about a million cases in about a month," he says. "Pandemics have gone around the world and touched most parts within six months."
Despite widespread advances in public health and disease control, it appears that mankind is unwittingly giving influenza unprecedented opportunities to flourish and spread. "We have probably created a better environment for viruses," Hampson says. "We travel more and travel en masse and our world is increasingly more urbanized."
The grim reality is that an outbreak of a deadly new virus would probably overwhelm public-health defences. In the worst case--that a virulent and deadly new virus similar to the 1918 influenza emerges--vaccines and new anti-viral drugs will be unable to check the disease, at least in the early stages.
It takes more than three months to prepare significant amounts of vaccine to counter a new influenza strain, according to industry specialists.
The newest and most promising anti-viral drugs, Glaxo-Wellcome's Relenza and Tamiflu from Roche Holdings Ltd. and Gilead Sciences, which inhibit an enzyme crucial to viral reproduction, have proved effective when administered early in an infection. It is thought that they could also be effective in blocking infection if administered as a preventative.
"These drugs will almost certainly form the first line of defence against any new virus," says Laver, a pioneer in establishing that influenza strains infecting humans originate in animals. "However, it is perfectly clear that in the event of a new pandemic, they will be woefully inadequate. Even a couple of tonnes would not go very far."
There is no evidence that the influenza virus that killed more than 700 chickens in Hong Kong markets this month has spread to humans or is even capable of infecting humans, but the local authorities are taking no chances.
Hong Kong Secretary for the Environment and Food Lily Yam told reporters the latest chicken cull was a "precautionary measure . . . endorsed by the World Health Organization."
Influenza viruses might rank low on the scale of life--they are basically a minuscule bundle of genes wrapped in protein, so small that millions can fit on a pinhead--but they move in large numbers and are capable of rapid change or genetic shifts that can catch immune systems unawares with sometimes deadly consequences.
Their relatively primitive method of reproduction--they essentially invade a cell and trick it into making new virus copies--also allows them to readily swap genetic information with other viruses.
"It is because we have such a comprehensive surveillance system that we were able to detect the presence of viruses in our markets and therefore to take corresponding action," Yam told reporters on May 19.
Allowing an infection to rage unchecked in the chicken population is clearly damaging to the poultry business. But it also increases the likelihood that the virus will mutate sufficiently to make a leap to humans.
This is far from academic speculation. In March 1997, a virulent influenza virus struck chickens on a farm in Yuen Long in Hong Kong's rural New Territories, near the border with the mainland.
In humans, most influenza viruses attack the cells lining the respiratory tract. But in birds, they can attack other tissue. The 1997 version was plain nasty. After an incubation period of about six hours, the virus spread through the blood and tissues of the chickens. Soon the internal organs, including the brain, heart, lungs and kidneys, were bleeding. Experts say that within 48 hours the chickens had virtually dissolved into a mass of bloody feathers.
Two months later, a three-year old boy died in a Hong Kong hospital of lung, liver and kidney failure. Medical reports said his blood had coagulated in his arteries and veins.
Researchers were shocked when they discovered that it was a human strain of the avian virus that had killed the boy. This marked the first time that a strain of influenza had been observed crossing directly from birds to humans.
By October, 18 others had been similarly infected. By the time six of these patients died, the experts were thoroughly alarmed. With a mortality rate of one in three, this virus could have devastated human populations had it been able to spread from person to person. Till then, it seemed that the new virus was only contracted through contact with infected birds or with their faeces.
There are three prerequisites for a viral pandemic in humans: A population without enough exposure to develop immunity; sufficient virulence to lead to deadly disease; and the ability to jump easily from person to person.
TRAGEDY AVERTED Fortunately, the 1997 virus scored only two out of three. However, experts speculate that this could have changed if, say, it had remained in the human population long enough to gain the ability to spread through coughing or sneezing.
In retrospect, Laver believes the 1997 move to kill all chickens in Hong Kong could have averted a sweeping global tragedy. "If that virus had learned to transmit between people, it would have been round the world and killed millions of people," he says.
Shortridge and his fellow researchers believe that the vast domestic duck population in southern China is a reservoir of avian influenza virus. This has probably been the case since ducks were first domesticated about 4,500 years ago.
"What we have done is bring the viruses of nature onto our doorsteps," he says. The theory is that these viruses shuffle genes with human influenza viruses when both types infect pigs, sometimes giving rise to a new virus that can infect humans. Analysis of viral genetic material suggests that this is what happened in the 1957 and 1968 pandemics.
Shortridge and the WHO's Hampson believe that surveillance, particularly in China and Hong Kong, is a crucial tool in any effort to curb the emergence and spread of new viruses. Early detection, such as in the 1997 outbreak in Hong Kong, holds the key to saving millions of lives. "That is the only time in history that such an intervention has been possible," says Hampson.
However, there is less confidence among experts about the scope and effectiveness of surveillance in China, where the huge numbers of people and animals would challenge the most well-equipped and funded monitoring effort.
In the meantime, research continues on understanding the genetic changes that makes influenza such a formidable enemy. There is no doubt that researchers are making headway in unravelling the secrets of influenza viruses, but much remains unknown, including why some viruses are readily transmitted and others are not.
Even the leading experts are perplexed about why suddenly, out of all the influenza viruses in circulation, a dangerous strain can emerge. "If we have all these viruses in nature, why don't we have a pandemic every year?" asks Shortridge. "Your guess is as good as mine."
For others, the arrival of a new pandemic is simply a question of time.
"Most people in the field think it is going to happen. But when? Nobody knows," says Laver.