One Step Ahead

“Ghastly,” says Dr. Ann Vannier--and she could easily be talking about the flu-like thing that knocked her flat this winter. In fact, she’s talking about the sheer volume of other people’s flus and flu-like sicknesses--and the nose and throat swabs and vials of blood pouring into a Kaiser Permanente laboratory in North Hollywood.

It’s a busy year, this year. A seasonal killer--the flu virus--could be skulking in many of these samples.

In the facility’s receiving room, workers are taking specimens out of Igloo coolers and loading them into two delivery robots named Lois and Clark. The robots glide off down the corridors, bossily barking, “Please stand clear!” and commandeering the elevators if they need to go up or down a floor.

Some of Clark’s cargo--swabs from throats and noses, bathed in Kool-Aid-colored fluid--ends up with lab assistant Florenda Son. Son dips her pipette into a sample. Out comes pink broth, which she adds to tubes containing monkey or dog cells. If the flu virus is there, it will multiply. In one to 14 days, the lab will know.

The state will know too. As part of a new program, the Kaiser facility--which performs the bulk of lab tests for the managed care organization’s Southern California patients--sends flu virus samples to California’s Department of Health Services for further study. Its sister lab in the north does the same. Kaiser sends other statistics to the state too: numbers of flu and pneumonia cases, since the flu can lead to pneumonia, and numbers of prescriptions for flu-fighting drugs.

The new state-Kaiser collaboration is one strand of California’s effort to track the flu virus each year. And it is an even smaller strand of a massive national and international public health effort conducted by the World Health Organization, the federal Centers for Disease Control and Prevention and state and county health departments--one that goes on year after year after year.

The goal: to track and head off the beast that kills about 20,000 people annually in the United States alone, and which makes so many more folks feel utterly wretched for a week or so each winter.

It is a huge sleuthing job, dependent on myriad shreds of information: flu reports from state health departments and volunteer doctors, death stats from cities, samples from clinics all over the globe, probed with all the tools of modern molecular biology.

Each seasonal circle on the flu carousel, the steps are the same: Track cases of flu as best you can. Figure out which strains of the virus--for it is constantly, craftily changing--are making people sick now. And then gaze into the crystal ball and predict the future.

Such vigilance gives health workers, in a worst-case scenario, the chance to spot a new, especially deadly strain--one that could cause a pandemic, killing millions. On the here-and-now, routine end, knowledge helps health providers anticipate staffing needs, for instance, or demand for hospital beds.

And then there is the vaccine--next season’s vaccine.

Sure, we’re all still busy contaminating our noses with virus-tainted fingers, coughing flu on colleagues or groaning feebly in bed. Or perhaps we’re feeling smug about that flu shot we got. But already, flu scientists are preparing for a series of meetings--the first at the end of this month--to decide which three strains to recommend for next year’s shot. (The final FDA decision comes in March.)

The vaccine manufacturers aren’t waiting. Already, trucks filled with chicken eggs are rolling into the Swiftwater, Pa., plant of Aventis Pasteur, a leading vaccine producer. Vast quantities of virus will be grown in those eggs and then harvested and killed to make flu shots.

“We want to get started as quickly as possible,” says company spokesman Len Lavenda (who has managed to avoid the flu this season). It takes six months, he says, to make and test the vaccine, so the company makes an educated guess, using all the available data, about a strain likely to be pestering us next season. Then it starts.

“It’s dangerous to do that--we may be guessing wrong, in which case we would have to discard product,” he says. But it’s worth the risk. Production time is tight.

“You’re talking 100 million doses of vaccine that people need to produce, purify, put through quality control testing, package, label, distribute and get into peoples’ arms by October,” says Dr. Carolyn Buxton Bridges, medical epidemiologist at the CDC’s influenza branch in Atlanta. And since a lot can happen in six months, it’s no wonder, she says, that vaccines don’t always hit the mark.

Identified Too Late to Do Much Good

In 1997-98, a moderately bad flu season, the strainown as A/Sydney/5/97 (H3N2) knocked people flat.

“It showed up in June--too late to be incorporated into the vaccine,” Bridges says. But even in June, it would have been impossible to predict it would spread so fast.

Last year, predictions were good. A/Sydney was in the vaccine, and much of the virus was so similar to the strain used that the vaccine appeared to work well.

That probably contributed to the fact that last season was a light one for the flu. Doctors and hospitals have been much busier this year.

“Our members are reporting a bad year,” says Andy Weisser, spokesman for the American Lung Assn. of California, who’s getting over the flu himself.

“Compared with last year, it’s a nightmare,” says Jim Lott, spokesman for the Healthcare Assn. of Southern California, a trade group that represents about 95% of Southern California’s hospitals. As widely reported, various hospital emergency rooms in the region have been so crammed at times that ambulances have been diverted to other facilities.

And Vannier, who directs the microbiology lab at Kaiser’s North Hollywood facility, says the lab has been inundated with samples from sick Kaiser patients. Not long ago, the lab’s blood-testing equipment, which has one of the largest capacities in the world, filled up, forcing the lab to bring in more instruments.

Dr. Carol Glaser, medical officer in the viral diseases laboratory at the California Department of Health Services, agrees that it’s tough this year. But that doesn’t mean this year is remarkable. When the season’s over and the numbers crunched, it will probably turn out to be moderate to heavy, no more. But “two weeks from now, if this escalates, we’ll be changing our tune,” she says.

The severity of the season has led some doctors to suspect that some new strain has cropped up and the vaccine isn’t protecting people. But there’s no reason yet to think so, say Glaser and Bridges.

So far, more than 90% of the analyzed flu specimens have been strain-typed as A/Sydney. Since A/Sydney was one of the three strains in this year’s vaccine, the shot should protect people well by priming their immune systems against that kind of virus.

Many ‘Ifs’ Involved in the Flu Battle

But it’s no surprise, flu experts say, that people are nonetheless getting sick. The vaccines, they point out, only work if you get them, and most people don’t. They work only against flu, but other viruses cause flu-like maladies. And under the best of circumstances, a flu shot is 70% to 90% effective. That number is much lower in the elderly, whose immune systems aren’t as feisty.

Flu sufferers may wonder why they have to go through this every winter--why can’t everyone get a hjab in the arm and be free of all flu, forever? It works for measles and mumps, doesn’t it?

They may wonder why, for that matter, the flu virus can’t simply be eradicated. (They got rid of smallpox, didn’t they?)

Fat chance of ever getting rid of the flu, says Dr. Peter Katona, an infectious disease specialist at UCLA.

“To eradicate a disease, you need certain things,” he says. You need to be able to identify every case. With flu, you can’t. The virus should have no nonhuman reservoirs in the wild, and flu infects myriad other species: birds, pigs, seals, you name it. (Care to vaccinate all the birds of the world?)

Finally, he says, you need a vaccine that’s really effective, and the flu vaccine is “iffy.” For whatever reason, the immunity it confers wanes over the months, even against the right strain of virus. And then there’s the strain issue.

“The smallpox vaccine never changed; every year it was the same vaccine--boring,” Katona says.

But with flu, the virus is constantly mutating as it reproduces, changing the shape of the little protein blobs that stud the outside. Our immune systems, which recognize and attack the virus from the shape of those blobs, can’t keep up. No sooner has it learned to recognize one type of flu than that flu changes into a form it no longer knows--one it can’t fight off.

New strains are always cropping up. So new vaccines are always needed.

There are two primary kinds of flu virus: A and B. Both can change their protein blobs slowly, over time, in a process known as drift. Type A is particularly drifty.

And, as the virus drifts, our immune systems slowly lose the ability to recognize it.

The A virus can also make sudden, large leaps in the structure of its blobs. This is called shift--and it’s the kind of sudden change that leads to pandemics. In 1918, such a pandemic killed more people than World War I.

Available Weapons Aren’t Perfect

Antiviral drugs such as amantadine and rimantadine--plus the newly approved Relenza and Tamiflu, which fight all strains of the virus--interfere with the virus’ ability to spread from cell to cell.

But those drugs have their drawbacks. The older drugs, which can be taken preventively, don’t protect against Influenza B. The new pair fight both A and B but are expensive and will cut down on duration and severity of an illness only if treatment starts within a day or so of infection.

The best weapon against the flu, then, is public health vigilance--and a vaccine every year, especially for those at highest risk for complications. People age 65 or older, and those who have diabetes, chronic diseases of the lung, heart or kidneys, are among those advised to get the vaccine. So are health care and nursing home workers.

Getting that vaccine made is a production and a half. At Aventis Pasteur, it takes a million fertilized chicken eggs a week.

After arriving at the plant, the eggs are loaded onto conveyer belts. As they trundle along, they’re jabbed with needles containing one of the three viruses chosen for next season’s vaccine.

Snug under the shells, the viruses grow happily in the chick embryos inside warm rooms for a few days--and then it’s harvest time.

The eggs get loaded onto conveyer belts again. Eggs by the thousands are cracked (OK, sliced by automated blades) into stainless steel vats. The egg whites, swimming with virus, are separated from the embryo and yolk, which are collected and trucked out of the plant again to be made into other products.

To make a vaccine, the virus is extracted from the egg whites, then killed, concentrated and tested to make sure it works against the right strain of virus.

Then the next virus for the shot goes through the process.

And, as soon as the Northern Hemisphere vaccine is all prepared, guess what? It’s time to start making the Southern Hemisphere shot. Flu is seasonal, after all, though nobody quite knows why. Flu season, in the south, comes in summer.

Flu experts are working hard to figure out ways to cut down on the manufacturing process so vaccine decisions could be made a little later. They’re developing new, live vaccines that might be more effective or be deliverable in a nasal spray. They want faster, better diagnostic tests for the flu. And they yearn to know more about how flu moves through the world, and how better to predict--and, they hope, prevent--a dreaded pandemic.

All the while, though, the yearly cycle continues. More than just death and taxes are certain in this world.

Be it mild, or bad, or really bad, there will always be a flu season.

“Every year since I’ve been doing this job there have been lots of reports: ‘Oh, it’s a bad season, all the emergency rooms are closing.’ I used to get excited,” Glaser says. “Every year people act like this is something new. But influenza hits every year. It should be expected.”

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Ever-Shifting Shapes

Why do we catch the flu more than once? Because the influenza virus is constantly changing shape. Our immune system senses and attacks the virus if it recognizes two proteins (H and N) stuck on the outside of the virus. But if the proteins are too different from the ones on the last flu virus we caught, the immune system can’t recognize them. And we get sick.

How a virus invades, multiplies

When the flu virus enters someone’s airways--via droplets from a sneeze or cough or via virus-covered fingers--it invades the epithelial cells that line the airway walls. It forces the cell to make many more viruses, which then go on to invade new cells.

The familiar symptoms of flu are caused by direct effects of the virus as well as the immune system’s attempts to fight infection, causing aches, inflammation and fever.

1) Receptors on the surface of the virus allow it to stick to the cell. The cell engulfs the virus, bringing it inside.

2) Once inside the cell, the virus’ genetic material and some of its proteins enter the nucleus. They force the cell to make many more copies of the viral proteins and genes.

3) The new pieces of virus come together to make new virus particles, which bud off from the cell.

4) The viruses are released from the surface of the cell and go on to invade additional cells.

Combating the virus

Through vaccines, a body can be “taught” to recognize a virus even if it has never encountered it before. This allows the body’s immune system to launch a rapid attack against that virus should it invade. Because of the influenza virus’ changeable nature, the flu vaccine is updated annually.

Other drugs, such as the new medications Relenza and Tamiflu, fight the virus directly. They make it harder for new viruses to “un-stick” themselves from cells and go on to new ones, thus slowing the spread of the virus.