Battle against flu focuses on Chinese farms

5/13/2001

ZHOU CHENG, China - Mention Chinese threats to America, and people think of spy-plane incidents and conflicts over Taiwan - not pigs, ducks, and farmers such as Yang Jing Huau.

To Mr. Yang and thousands of other villagers in China, livestock are bank accounts on four feet. These investments measure a rural family's wealth and get tender-loving care.

That is why litters of squealing porkers often spend cold nights inside the farmhouse, sleeping near family members. In some areas, livestock occupy the first floor of the family house and people the second.

“My ancestors have done so for centuries,'' Mr. Yang explained on a bright spring day in this village in China's Yunnan Province. “We have pigs, ducks, and chickens.''

However, experts on infectious diseases have said this close contact between people, pigs, and ducks has a deadly effect 7,000 miles away in the United States. It has made southern China the breeding ground for influenza viruses that assault the United States and other countries each year.

Could relatively simple changes in traditional farming practices in China and other countries prevent future pandemics?

Preventing or reducing the severity of annual flu epidemics could have enormous health benefits.

In 1999, a U.S. Centers for Disease Control and Prevention team headed by Dr. Martin I. Meltzer used data from previous flu outbreaks to estimate the effect of the next flu pandemic in the United States. The study concluded that 89,000 to 207,000 Americans will die; 314,000 to 734,000 will need hospitalization; 18 million to 42 million will flock to doctors' offices, and 20 million to 47 million will get sick but treat themselves at home.

The economic cost, including days lost at work and other disruptions to the economy, would range between $71 billion and $167 billion.

Knowledge that could form the basis for a new prevention strategy - focused on changing agricultural practices in China and elsewhere - does exist, according to a number of flu experts.

Dr. Kennedy Shortridge, an international authority on flu viruses at the University of Hong Kong, said flu pandemics will continue so long as farmers such as Yang Jing Huau continue to live in close quarters with ducks and pigs.

All around southern China, people have the same unusually close contact with these animals. It happens on tiny farms, in crowded village markets, and sprawling big city bazaars that sell live birds and pigs direct to consumers.

“This part of the world is the epicenter for influenza epidemics,” Dr. Shortridge said. “It's the place where epidemics are most likely to originate. The ingredients are here - ducks, pigs, people - in close contact.”

Dr. Shortridge explained that ducks are the reservoir for avian, or bird, flu viruses. Duck droppings litter the soil on hundreds of thousands of small farms throughout China. Pigs constantly snort in the soil for food and inhale avian flu viruses from duck feces.

Then pigs act as what scientists describe as the flu “mixing bowl,'' combining avian viruses with the human flu viruses they already harbor from contact with people.

Pigs shuffle the genes of human and bird flu viruses like two decks of playing cards. It creates the new strains of influenza that march around the globe each year.

The genetic card shuffle usually means only a moderately bad deal for the public. In most instances, it results in “genetic drift,” a slight change in the flu virus' ability to sneak past humans' immune defenses and infect people. The result is just your typical flu season. In the United States, that means hundreds of thousands of people stricken and 20,000 deaths.

Periodically, however, humanity gets stuck with a really bad hand. Major shifts occur in flu viruses' genetic makeup, leading to the sudden emergence of strains to which most humans have no immunity.

“The resulting pandemics vary from serious to catastrophic,'' noted Dr. Robert G. Webster, a flu expert at St. Jude Children's Research Hospital in Memphis.

During the past 250 years, 10 to 20 flu pandemics - worldwide epidemics - have swept the globe. The so-called “Spanish” flu epidemic of 1918-19 was by far the worst. It sickened 200 million people and killed 20 million, including 500,000 in the United States.

The origin of other terrible epidemics - Asian flu in 1957, Hong Kong flu in 1968, and Russian flu in 1977 - have been traced to traditional Chinese agricultural practices.

“Each of these new subtypes first appeared in China, and anecdotal records suggest that previous epidemics also had their origin in China,” Dr. Webster said.

Although China has the reputation as an epicenter for flu epidemics, viruses can and do emerge in other countries where conditions are right.

“Anywhere in the world where humans, birds, and pigs live in proximity would be a fertile breeding ground for pandemic viruses,” Dr. Shortridge said.

Flu has stalked humanity for thousands of years. Hippocrates wrote a clear description of influenza in 421 B.C. - including the fever, shaking chills, muscle aches, headache, dry cough, and other symptoms that can put victims in bed for a week or more.

Scientists isolated the first human flu virus in 1933 and named it simply Type A. It is one of three families of flu virus, called A, B, and C. The A family causes the great epidemics, and the B family causes smaller, more localized outbreaks. Type C viruses cause little disease in humans.

This is not a stable family. Flu viruses constantly undergo genetic changes, with their genes mutating into different forms.

The great ancestor of this annual wave of misery and death is an avian, or bird, influenza virus that emerged in the ancient past. It evolved into five lineages specialized to infect different animals: an ancient equine, or horse, virus not observed in more than 15 years; a modern equine virus; an aquatic bird virus; a swine virus, and a human virus.

“The ancestral viruses that caused the Spanish flu in 1918, as well as the viruses that provided gene segments for the Asian/1957 and Hong Kong/1968 pandemics, are still circulating in wild birds,” Dr. Webster noted.

What's the possible threat to people, since avian flu viruses are specialized to infect birds?

That's where Mr. Yang's porkers enter the picture.

Duck, chicken, and other avian flu viruses cannot infect people, according to the traditional scientific view. Human cells lack the right docking port where avian viruses can attach and inject their genetic material. That transfer allows a virus to infect a cell, commandeer the cell's genetic machinery, and start making copies of itself. The newly produced viruses then infect other cells, and the unfortunate person takes sick and spreads the virus through coughs and sneezes to others.

Pig cells, however, do have the docking ports for bird flu viruses along with docking ports for human influenza viruses. Once inside the pig, avian viruses reproduce and make billions of copies of the original virus. At the same time, human influenza viruses, which pigs caught from people such as Mr. Yang and his family, are reproducing.

Imagine shuffling two decks of cards - one red, one blue. As human and avian viruses reproduce inside pigs, their genes get shuffled and mixed together.

If the virus is only a little different from existing flu strains, however, many people will have some immunity from past infections. The result usually is a run-of-the-mill flu season. On some sad occasions, the result is a totally new avian flu virus to which people have little or no immunity. That is when there is a possibility of a pandemic.

This traditional view of the flu took on a new wrinkle in a 1997 episode that set off alarms of another pandemic.

It began in May when a 3-year-old boy in Hong Kong died from a strange respiratory illness. Scientists isolated a virus from the boy but could not match it with any known virus. Dr. Shortridge solved the mystery. He showed that it was an avian flu virus that apparently could infect humans directly, without first passing through a pig.

The virus, known as Type A H5N1, turned out to be the same microbe that had killed thousands of chickens on farms around Hong Kong early in 1997. Although it caused only 18 confirmed human cases of flu and 6 deaths, H5N1 set off alarms among flu experts.

Each new strain of flu virus usually bears some resemblance to its predecessors that have caused outbreaks in previous years. Because of that similarity, most people's immune systems are primed to provide some defense, no matter what form of virus circulates each flu season.

H5N1, however, was unlike any previous flu virus, meaning that humans would have little natural defense against infection.

Dr. Nancy Arden of the Centers for Disease Control and Prevention summarized the concerns in comments published in the journal Science.

“When you have a virus that's so easily transmissible and the entire world population is susceptible to it, that's a recipe for a pandemic,'' she said.

Scientists divide flu viruses into groups based on the kind of proteins that exist on the virus surface. Like other viruses, flu consists of an outer layer of sugar and protein wrapped around a core of genes.

The coating of flu viruses carries different combinations of two proteins, hemagglutinin (H) and neuraminidase (N). Scientists thought that types H1, H2, and H3 were human flu viruses because their hemagglutinin could dock with receptors on human cells.

Types H4 and H5, in contrast, were strictly avian flu viruses because human cells lack docking ports for those forms of hemagglutinin. Pig cells have docking ports for both groups of viruses.

Pigs create flu strains by combining genes from the H1, H2, and H3 viruses with genes from the H4 and H5 viruses. But H5N1 showed that that idea may be too simplistic. It left scientists with the unsettling conclusion that some bird flu viruses apparently can pass directly from birds to humans.

Dr. Shortridge said that such viruses - although capable of causing severe disease - may be very difficult to transmit from one person to another. He suspects that H5N1 was not the first avian virus transmitted directly to people. Rather, avian viruses may have been infecting handfuls of people and then dying out for centuries.

Public health officials in Hong Kong may have averted a pandemic of H5N1-type flu because they are constantly on the alert for new flu viruses, which can be identified in special labs like the one run by Dr. Shortridge. Markets in Hong Kong now segregate live animals to reduce contact between people, pigs, and poultry, Dr. Shortridge pointed out.

Detection of H5N1 led to swift measures to control the virus before it could get into pigs and mutate into an easily transmitted form. Public health officials in Hong Kong ordered the mass slaughter of domestic ducks and chickens, closed live-bird markets, and instituted other measures.

Yet scientists will keep a sharp lookout for H5N1. H5N1 could, for example, be spread to pigs, where a shuffle of the virus genetic cards could yield a highly infectious flu strain.

“If it gets into a human once and dies out, fine,” Dr. Webster said, referring to H5N1's limited spread in 1997. “But next time, will it?”

But agricultural practices are changing as China modernizes and adopts approaches such as industrial pig and duck farming, in which big farms, run by few people, raise huge numbers of one animal.

“Hog farms are likely to become larger and more concentrated,'' said Dr. Meltzer. “This concentration should notably lower the farmer-to-pig ratio. This may, in turn, reduce the risk of transmission from pigs to farmers of a new virulent strain.”

Another possible target for change is aquaculture, or fish farming, which has been spreading so fast in Asia and other areas that it often is termed “the blue revolution.”

Increasingly, small-scale farmers supplement their incomes by raising fish in ponds. They use fresh pig and duck manure to fertilize the ponds to encourage growth of plants for fish to feed on. Wild ducks also land in the ponds.

Scientists know that avian flu viruses in wild birds spread globally during north-south migrations.

Christopher Scholtissek and Ernest Naylor in a 1998 study argued that use of fecal material may transform fish farms into flu factories, where pig and avian flu viruses mix and spread.

There are other targets for preventing the emergence of flu viruses.

One involves discouraging the age-old practice in China, and other countries, of feeding pigs untreated table scraps and other garbage that often contains human virus. Pigs likewise often are used as general purpose trash disposals, being fed carcasses of dead chickens and ducks - which may have died from avian flu.

Raising pigs under poultry houses, where they feed on wastes, should be stopped, experts say.

That practice caused the terrible 1983 poultry flu outbreak among chickens and turkeys in Pennsylvania. The virus was not transmitted to humans, so far as experts know. It eventually was eradicated by the extermination of 17 million birds at a cost of more than $310 million.