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Title: Flu Fighters
Author: Wina Sturgeon
Date: April 22, 2004

The telephone call comes, as it always does, and Dr. Robert Rolfs springs into action like an athlete, his heart beating faster, his focus narrowing.

He musters his troops. He calls his coordinator, who contacts the local health department and makes sure there's a public health nurse who can quickly get to the patient to find out where that patient has been and to whom or what that person may have been exposed. He gets on the phone to the national Centers for Disease Control and Prevention (CDC) in Atlanta. With a phone pressed to his ear, sometimes one to each ear, Rolfs quickly gathers information and prepares to send it out.

The whole time, his brain is crunching facts as fast as a computer.

"My mind jumps fairly quickly to what we have to do to find out the answers to what needs to be done, on whatever scale. I'm very methodical," Rolfs said.

As state epidemiologist at the Utah Department of Health, he has to be. It's a huge and terrible responsibility, watching for outbreaks, hoping to stop them before they spread.

It doesn't matter whether it's a contagious rash on high school wrestlers or a suspected case of smallpox a few weeks ago in a Salt Lake City hospital (it turned out to be chicken pox), or the detection of anthrax at the Salt Lake City International Airport (it turned out to be a false alarm).

"Every one of those, your adrenaline goes off and you have a startle response," Rolfs said.

Rolfs knows that we are at war. Not just Americans, but the entire human race. The enemy is worse than any human terrorist, because it doesn't belong to our species.

We are at war with an alien world that even humanity's best minds don't fully understand—the near invisible, often inscrutable "microworld."

Our battles have an ironic humor. Who could have thought that the huge population of Asia would suddenly be terrified by, of all things, chickens? The rest of the world is waiting, at the edge of alarm, to see what our old enemy influenza will do this time.

Rolfs and infectious disease experts throughout the world have been expecting a flu pandemic for years, one where millions die.

"It's overdue. Based on history, we will definitely have a pandemic some day. That's as certain as anything can be. Whether avian influenza, or 'bird flu' will be it, is not certain," Rolfs said.

But he admits it is very probable.

"What's scary about this flu strain is that it's gone to humans. The strain, H5N1, affects birds. It has not been found in people before. Humans have no experience with it, so our immune systems aren't prepared for it. That's probably why it's so lethal in the people who get it," Rolfs said.

The mortality rate in known cases is about 70 percent. Nearly every case was contracted directly from a bird.

The big fear, according to Rolfs, is that this strain of the virus will pick up human RNA and mutate. Then it will spread like--well, like the flu.

"It's a type of virus that has been shown in the past to be able to pick up genetic material from the animal it is in. If it acquired characteristics from a human strain of flu virus, it might be able to spread from person to person. Then we could not contain it. We have never been able to contain influenza," he said.

The influenza virus has killed more people than any other microorganism, more than typhoid and cholera combined, more than the medieval black death of bubonic plague.

The flu virus is dangerous because it's a shape-shifter, a mutator that breeds different strains at a ferocious speed. The surface of each strain is coated with two different proteins with very long names: hemagglutinin comprises the "H" part of each strain, while neuraminidase makes up its "N" part or component. It is the subtle variations in both the H and N's that create different strains. There are about 15 different variations of the H protein and nine varieties of the N protein, each of which is numbered. A typical flu year, for example, might give us the strain H1N1, or H1N2.

And, a typical flu year will kill more than 35,000 Americans—more than 10 times the number killed in the Sept. 11 attacks on the World Trade Center.

A new strain of flu comes around like clockwork every year, usually starting in Hong Kong. Again, that microworld humor: migrating birds give it to pigs raised by farmers in the Orient. The new flu does not make the pigs sick, but the pigs give it to humans. Pigs are the vector, the middleman used by the virus, in which it mutates into an infectable form that can be passed from person to person.

A serious worldwide outbreak of flu happens once every 20 to 30 years. But the last serious flu pandemic took place during the late 1960s. Millions died.

Once it was over, everyone more or less forgot about the flu, as they usually do, dismissing it as a slightly more serious cold.

Only people like Rolfs still concern themselves with the most serious outbreak of modern times, the 1918 Spanish Flu pandemic, so called because it first surfaced in the Iberian Peninsula.

"We are concerned about that. [Today] we would have to try to control the spread at a time when people are very mobile," Rolfs said.

That was not the case nearly a century ago, when travel on passenger planes and cross-country highways was less common.

In the span of just one year, more than 21 million people died from the 1918 flu strain. It devastated Western Samoa, killing 20 percent of the population. Millions more were too sick to work, which impacted the economy on an international scale. Only educated guesses gave us any clue about what strain caused the pandemic.

Until now.

On Feb. 4, National Geographic News detailed two new studies by British scientists showing that the 1918 flu virus had jumped from birds to humans. It mutated, and then spread from person to person.

That's what makes Rolf's heart beat faster today. "This is what we are worried about. You could say that the world's public-health systems are on red alert. Not only to find the first cases, but to get information out. Whenever you have an outbreak, there are a lot of calls from media and citizens, so you have to spend a lot of time talking to them. You need to prevent panic by giving out information," said Rolfs.

It has long been medical dogma that the flu strain H5 could not infect humans. But a few years ago there was panic in Hong Kong. Officials killed and burned every bird in the former British Crown Colony, including millions of chickens, because that year's strain of flu was being passed directly to humans without the aid of "vectoring" pigs. It was discovered that the H5 subtype was the viral strain in the Hong Kong birds.

"That's what scared everyone really badly, that there was a new subtype of influenza that people had never gotten before. If it got out of control, we have no immunization for it. The fear of that was so overwhelming that the decision was made to wipe out all the chickens before it had a chance to spread. It was so quickly handled that it was a done deal before it really got out of Hong Kong," said Dr. Larry Reimer, infectious disease specialist and clinical microbiologist at the University of Utah.

But last year, there were outbreaks of an H5 subtype in Norway, Sweden and Germany. "It was a reasonably bad outbreak. Now scientists know that an H5 strain of flu can infect people. The bird flu strain is H5N1," Rolfs said.

And that is not all, he adds. "We are also dealing with an outbreak of a different strain of avian influenza in the United States, as well as a more serious strain of human flu that hit earlier than usual this year. It has changed our traditional method of influenza surveillance. Usually, surveillance has been during the typical flu season, November to March. Now it will be all year round," Rolfs said.

Rolfs has international experience in outbreaks. Before coming to Utah—a place he enjoys because he's an athletic man who skis, bikes and hikes—Rolfs was an epidemiologist at the CDC, America's Pentagon of illnesses.

He hopes people won't panic over screaming headlines when the first case of Bird Flu hits the United States, which he reasons will probably happen.

"Panic is rarely a good response. [Instead], think about what that first case means. If it's a person who was on a chicken farm in Asia, then it's no different from people in Asia who are getting avian flu right now. If this person has acquired this strain of influenza and has had no exposure to birds, then that would cause concern," he said.

Finding a vaccine will be less complicated than getting it out to the public. First, it will have to be tested to see that it works and has no side effects. Then, it will have to be produced, in addition to producing the year's regular flu vaccine. It's going to be difficult. Remember how quickly available supplies of this year's vaccine ran out when there was only a slight and early increase in the number of cases?

But the familiar old devil of the flu is just one thing to worry about. Past the horizon, already among us, are new enemies: Ebola, mad cow, hantavirus, West Nile, SARS, monkey pox. They are scary words, and new.

AIDS, which currently affects 60 million people, appeared in the Western world less than 25 years ago. Over the last two decades, strange diseases have emerged at regular intervals like devilish spawn. They seem to be coming faster and faster.

Why does Ebola always erupt suddenly out of nowhere in Africa, kill a few hundred people, and then disappear? No one knows where it hides between outbreaks, and what makes it strike again.

What about mad cow disease, which is not caused by an actual organism, but by a deformed bit of protein? What's next?

For a brief and blessed portion of time in the late 20th century, modern science seemed to overcome the microworld's clever ways. Penicillin and antibiotics became universal antidotes; sanitation and vaccinations were powerful preventatives. We thought we were safe.

We forgot about airplanes. We forgot about commerce. Now the complaint of epidemiologists everywhere is that modern transportation is the biggest epidemic risk today.

Virulent microorganisms come to us on ships bringing out-of-season produce. Remember how shocking it was when E coli on lettuce and strawberries made people sick enough to die?

"The importation of fruits and vegetables from other countries, where animal manure or even human manure might be used as fertilizer, has created a greater number of organisms on food products than there used to be," explained Dr. Reimer.

Microscopic organisms hitch rides wherever they can. Take one new virus on the block, West Nile. How did it get here? Was it a bird? Was it a plane? Was it a horse? It may have been all three.

Horses are transported throughout the world by passenger planes. The back wall of most airplanes is adjustable, and can easily be moved forward by removing a few seats. The resulting empty compartment stables horses for transatlantic flights to shows, competitions or sales.

It may have been one of these horses, bitten by one little mosquito overseas, that brought the unwelcome immigrant of West Nile to America four years ago. Like influenza, West Nile passes through birds. The first sign of West Nile virus are dead birds lying around. A mosquito sucks blood from a bird infected with West Nile, and the virus multiplies inside the insect's digestive system. When the mosquito takes its next meal—biting an animal, human, or another bird—it also transmits robust throngs of virus.

West Nile might have been stopped in its tracks in 1999 had the disease been immediately identified. But during those early, golden, stoppable hours, it was misdiagnosed as Eastern Equine Encephalitis (EEE). The alarm was all about horses. Early news reports covered the rising fear among breeders in New York about a strange epidemic of EEE killing horses, even though they'd been vaccinated against the disease.

Very soon, a sudden rash of human encephalitis cases puzzled New York doctors. The brain inflammation, which can be fatal and has many causes, did not respond to any treatment.

It took valuable time for veterinarians and physicians to compare notes through the CDC and recognize that the same new-to-the-area perpetrator caused both the horse and human encephalitis cases. The delay was understandable. Symptoms of EEE, for which there is an equine vaccine, are almost exactly like those of West Nile, for which no human vaccine exists. More than half of all horses with EEE die.

When the virus was finally identified, mosquitoes had eaten and eaten again, then buzzed away. Three years later, by 2002, West Nile had been identified in 44 states with 4,156 human cases serious enough to be reported to public health agencies.

"It is here now. It's been established in four years, and every year, it's gotten bigger. This year, it was bigger than last year," Reimer said.

This year, according to medical experts, could be even worse as the virus moves west.

Then there is another new villain, SARS. This one sports the most frightening aspect of emerging diseases—the ability of viruses to jump to another species. That's a pretty neat survival trick for a virus: a little adaptation and, suddenly, there's a whole new source of easy food and shelter.

SARS is a corona virus, an organism common in livestock and pets. It never did anything worse than cause colds in humans. But the SARS strain is so different from other identified varieties of corona virus, it is suspected of having mutated in some unknown animal host before making the jump to humanity.

The SARS epidemic is a poster child for worldwide public health cooperation. It has its origins in southern China, but medical authorities there took no steps to control it, nor did they tell public health officials in other countries that they had a problem. That gave those microorganisms a free ride to a whole world of new hosts.

But SARS and West Nile are fairly small concerns compared to what's on the horizon. Hemorrhagic fever viruses are on the move. Ebola rules for fear factor, but Rift Valley fever, though not as fatal, is far more frightening. So violent is Ebola that it quickly kills off available hosts and burns itself out. Rift Valley fever, like West Nile, is spread by mosquitoes and is only dangerous when complications occur. But those complications can produce the same gruesome symptoms as Ebola.

According to worldwide mortality reports, in September 2000 Rift Valley fever spread out of its home in Africa and Madagascar for the first time ever, causing outbreaks in Saudi Arabia and Yemen.

Dr. Woody Spruance, an infectious diseases specialist at the University of Utah, warns, "There's a very reasonable chance it could come to the United States. It has emerged into Saudi Arabia for the first time. Where is it going next?"

Another hemorrhagic threat is Lassa Fever, a virus in West Africa infecting between 100,000 and 300,000 people annually, killing approximately 5,000 who develop complications. Like hantavirus, it's spread through the air by rat droppings.

Then there is our familiar old enemy, herpes. One strain, Herpes virus simiae, causes minimal or undetectable chronic infection in monkeys. But when monkeys pass that strain to humans, as they sometimes do, it may cause fatal encephalitis, an inflammation of the brain.

It is the possibilities from the mysterious microworld that are most disturbing to medical scientists. Spruance said, "If by some chance Ebola combined with Rift Valley fever to make a new, third organism we would then have the possibility of a highly lethal mosquito-borne infection. But that's completely speculative. The combination of the two is just an example."

Like the possibility of bubonic plague in the Middle Ages.

It is almost a spiritual thing, this deadly, ongoing war of competition. There is only one kind of human, but many, many kinds of viruses. Some are so alien they do not even have DNA. Measles is one example.

And humanity is alien to the microworld. We have a mind. They have mutation. We evolve externally, creating machines like cars and planes to transport us faster and further than feet, satellites and microphones to give us louder voices, telescopes and microscopes and night-vision goggles to give us better eyes, bombs and bullets to give us bigger fists. Microorganisms evolve internally, mutating, changing their abilities, reproductive patterns and even their basic makeup to more precisely achieve their purpose, which is the same as ours: survival and reproduction. To accomplish it, each species must kill members of the other.

Humanity has some protection from an unexpected source: our DNA. Spruance explains that our genetic diversity is important, and that this DNA diversity is individual.

"Take two blonde-haired, blue-eyed people that look alike, breathe on one and he dies, breathe on the other and nothing happens. It goes down to a cellular level. That means some of us will be susceptible to a microorganism and some won't. Humanity will never be wiped out, because of our genetic diversity," he said.

But Spruance points out how this can be a setup for disaster if agricultural advances like genetically modified plants, in which every plant is exactly the same, take over in factory farms. "Normally, in the plant kingdom, there is incredible diversity, and we moved to eliminate that in the name of greater productivity. You can imagine the problems."

They won't necessarily be new ones.

"Emerging diseases have actually been emerging forever," Spruance said. "If you look back over time, you'll see it. We brought smallpox and measles to the New World, we got syphilis there and brought it back to the Old World. So the idea of emerging infections is not a new thing, it's a new term we've applied to a fact of life."

The situation is not helped by media sensationalism. Something like Ebola is so frightening and fascinating that even the smallest outbreak makes headlines. But Ebola kills only a few hundred people each year, and has not spread. Less reported is a cholera pandemic currently exploding in Africa and South America, infecting about 150,000 people each year, or the 170 million people in the world estimated to be chronic carriers of hepatitis C, which can eventually cause cirrhosis or cancer of the liver.

When a new disease emerges, medical scientists go into the same kind of frenzy that news reporters do in a breaking story. Impressions and guesses are reported as fact, while corrections come later. Sometimes, medical misperception boggles the mind.

When AIDS debuted in America, doctors announced at first that it infected only gay men, and others did not have to worry. It was an amazing violation of simple common sense. No infectious organism on earth is gender specific. In addition, basic research by medical or public health officials would have uncovered the fact that AIDS was already endemic in Africa, where it was called "skinny," and both men and women were already dying from it in equal numbers. Such mistakes probably won't happen again. If every cloud has a silver lining, the last two decades of emerging diseases, as well as the 9/11 terrorist attacks, have created one. Public-health programs are now much more organized and efficient. Doctors are much more aware today, Dr. Rolfs believes.

"No question, yes. The public-health system today, in terms of the level of alert and amount of attention being paid, is dramatically different than it was even two years ago," he explained.

In the Intermountain Area, the University of Utah is considered the nerve center of infectious-disease knowledge. If laboratories in other states have a problem, they phone Dr. Reimer for a solution. Dr. Rolfs still works closely with the CDC, and was part of the medical staff that helped create the current model of more efficient public-health reporting. After 9/11, biological terrorism was taken much more seriously.

A new chapter in the old war with the microworld is about to begin. This time it has ethical implications. Will medical practitioners forgo profit to provide lifesaving vaccines to the uninsured and indigent if a pandemic hits? Who will get the hospital beds? And do we have the resources to fight SARS, West Nile and a lethal influenza epidemic all at once?

Somewhere, at some time, unsuspected microorganisms may discover that tiny change, that barely noticeable mutation that opens up a brand new garden of susceptible hosts. And, as has always been the case throughout history, there will be birds, mosquitoes, pigs, horses, fleas, rats, and who knows what else, just waiting to take them in.