"Return of the Flu" Everything you ever wanted to know about influenza, but were too sick to ask.

The virus mutates, searching for new and nastier ways to invade your respiratory tract. When it does, sickness arrives with aches. Fever. Cough. Three shades of snot. And, sometimes, death. Hello, flu. Let's welcome the Fujian strain. It's from China and it may do some bad, bad things. Kids dead in Colorado. Nationwide vaccine shortages. Widespread flu activity in New York City. To believe the talking heads, this season's flu is the second coming of the 1918 epidemic, which killed more than 20 million people worldwide. Or, you know, not.

My father's business is infectious disease. The flu, actually. Or "IN-flu-ENZA" as he is wont to correct. Dr. Jack M. Bernstein is a professor of medicine at Wright State University and chief of infectious diseases at the Veteran Affairs Medical Center of Dayton, Ohio. Maybe not the most attractive calling, but you'd want this 53-year-old on your side when hacking up day-glo hunks of lung.

Since I've toddled in Underoos, my father has treated my flu. With pill regimens and bed rest, he's vanquished the heartiest viral invaders. And how I've suffered for my health. I was his pet guinea pig. When I sniffled, he'd scrape mucus from my throat with six-inch cotton swabs. Then he'd nurture my sickness in petri dishes and tissue cultures. And snap my sickly picture, further displayed for his doctor cronies as "Example A: Eight-Year-Old with Influenza."

Embarrassment aside, I always got better. But this year, I'm far from my father's pill purse. Will the Fujian get me? An average flu season kills more than 2000 New Yorkers annually. Would a subway ride make me sick? Or visiting my girlfriend's tenement building? Or buying street-cart shawarma? I ran home to dad, where he assuaged and heightened my fears with talk of mutant strains, sentinel fowl and the benefits of soup.

In I-didn't-go-to-medical-school terms, describe the flu.

It's not the flu?it's influenza. It's a respiratory virus. The unique thing about influenza is it change from year to year. It tries to evade each person's immunity. Influenza undergoes mutations, which changes its character. Every year you get something called antigenic drift. 'Drift' means that there are subtle mutations. The strain that comes out next year is totally different from this year's strain. And the year after that, the same thing. As you go from year one to year two to year three, your immunity to the virus gets less and less and less. If you were infected by influenza AH3 (which is the strain going around), the chance of getting AH3 next year is very low. The chance of your getting it in two years is a little bit higher. The chance of getting it in three years is higher still. In four years, it should be as if you were never infected. You'll have no immunity.

That's unfortunate. And depressing. How much does influenza shift each year?

Drift. 'Shift' is a different word. How much does it drift? A little bit. Enough that you're not quite immune and that every year drug companies make a new vaccine?or think they need to make a new vaccine.

Now, do we need to get jabbed full of fresh vaccine each year? Are the drug companies just trying to make another buck?

Well, since influenza runs around in the winter of each hemisphere, drug companies are looking at what's happening early in the southern hemisphere's flu season. Based upon that, they guess what virus they need to use in a vaccine. It's a relatively slow and laborious process. It takes nine months to make a vaccine.

Babies are made in nine months. A school year is nine months. What takes so long?

Eggs. They're making it in eggs. They're selecting the virus; they're growing it up in eggs. Then they have to remove it from the eggs and purify the vaccine. Some viruses grow slower than others. If you were allowed to use tissue-culture cells?meaning permanent cell lines, not eggs?you could get the vaccine rolling much quicker. Or there's been talk about "reverse genetics," which is just a fancy way of engineering the virus more rapidly. That's all.

Let's backtrack. When you say "eggs," what do you mean?

Cluck-cluck. They grow the virus in embryonated eggs, meaning eggs that would've hatched chickens.

Oh, you're talking about chicken eggs. I was imagining a human female's eggs, which was disturbing, to say the least. So, chickens.

Oh, yeah. They make a window by removing a little piece of shell and inject the virus into the chicken egg. After a couple of days they remove the egg and purify the virus. Now, if people are allergic to eggs, they can't have the vaccine.

Are there chicken farms specifically breeding eggs for flu vaccines?

I'm sure, but I can't tell you where to find them.

Well, maybe we've found our mission: to scour the U.S. for flu vaccine farms. Now, I'm still confused. Does the flu season start in the southern hemisphere?

No, no, no?that's not what I said. When we're trying to decide what strain is prevalent, we're going to start guessing in March what vaccines to have for next year. We need to gear up production for next winter. If I tell you we need a six-to-nine-month lead time to have a vaccine ready for September, I need to start in January. But in January we're still in this hemisphere's flu season.

You're almost like flu oracles.

No, we're just examining the southern hemisphere for the beginning of their flu season. It may not be hitting full, but we have to guess what's coming to this hemisphere next year. Suppose we guess wrong? Then the vaccine is not very good. But if we wait for the virus to hit the northern hemisphere, we're going to be six months too late.

Do strains originate in certain hemispheres?

No, they come from around the world.

Just how many strains are we talking about, Dad? One, two, twenty?

There are three major types of influenza used in the vaccine. Two of them are usually influenza A and one is influenza B, which is a different virus. With influenza A, in the last 15 years?including when you and your brother and sister were tortured as children?two major strains have circulated. They are designated influenza A H3N2 and influenza A H1N1. What the H and N stand for are two surface projections (or proteins) on the virus that cause it to stick to cells. H1 is different from H3. N1 is different from N2. H3 and N2 happen to go together. H1 and N1 happen to go together. Drift, as I mentioned, is when H3N2 changes from year to year. It's still the same virus. But let's suppose something catastrophic happens and new viruses come in. With influenza, each gene?which codes for a single protein?is on a different segment. So we're talking about a deck of cards. You take two decks of cards and shuffle them, what do you get?

Well, if I could actually shuffle a deck of cards, I'd get a random assortment.

Right. If, say, an H3N2 and H1N1 simultaneously infect a cell, the Hs and Ns are going to reassort?or shuffle?in a random manner. You're going to get all sorts of different combinations of external and internal proteins.

Is that what happened to Jon [my brother] when he was infected with two types of flu? He always did get the shaft.

No, Jon was just infected with two viruses at once. When the genes shuffle, you have antigenic shift. Something entirely new is introduced. When people were worried about the swine flu coming in, that would've been a shift. Luckily, it didn't happen. The concern about bird flu in Hong Kong would've been an antigenic shift. When that happens you get pandemics [worldwide influenza epidemics]. No one's immune.

Like World War I's rampant flu epidemic? That sure was a whole lot of dying.

Theoretically, yes.

Can this happen today, modern practices notwithstanding?

Sure.

So where are super flus incubating? Insects? Rain forests? Animals?

Ducks can have the flu. Horses can have the flu. Whales, seals? flu affects many animals. Some get sicker than others.

Which animals get sickest?

It's hard to say. Ducks frequently don't get that sick. In ducks, I believe, flu lives in the gut. It doesn't live in the respiratory tract; it's in the stool. In any case, there was a famous sea lion epidemic years ago in which a virus from a seagull and a virus from a duck infected a walrus, I think. The virus reassorted?an antigenic shift. When this new virus came out, it was really, really bad. There was a flu epidemic among sea lions, causing a big die-off in the Arctic. It was probably not good to be on an iceberg and have the flu. [Laughs] That virus was transmitted to humans and pigs. But the seagull and duck virus normally couldn't infect a human; only when the strains reassorted in the sea lion could the virus infect people.

I'm never going to look at sea lions the same way. Just how often do viruses reassort?

It's happening quite a bit in China. On Chinese farms, you have ducks and pigs living together directly beneath people. If the ducks and pigs both get flu, the virus can reassort and infect loads of people. From there, it spreads into the general population. This may be one of the reasons why a lot of the strains you have heard of have had Chinese names. A Beijing; B Shanghai; things like that. It's because the epidemics are first noticed in China.

Another reason not to visit China. So, this new strain causing all the hoopla, what is it?

It's an H3N2, with the designation "Fujian." Fujian is a province in China, which is the first place it was recognized.

Why is the Fujian so ooga-booga scary?

We've been dealing with H3N2 for a long time, but this one has drifted a bit further away than we would've liked. So the vaccine strain wasn't as good of a match for this as we would've liked. We're also seeing deaths in children. That's something we usually don't see. We usually see flu deaths in people with underlying illnesses or in the elderly. Nevertheless, we still have not seen a huge increase in mortality. When we look at this winter's epidemic curve, we see that, as of right now, there is no significant excess mortality. So, in spite of the newspaper articles you have seen, to date, there has not been an influenza epidemic associated with a significant increase in deaths.

Are people being irrational? Like with SARS, when paranoiacs started wearing hospital masks around the city?

If you're healthy, you're probably overly worried. If you do have underlying diseases, you should've been vaccinated already.

Us New Yorkers, are we more at risk?

Yes. Flu is transmitted in close quarters. I was just in close quarters last weekend?at your house, and riding the subway. There's a good chance that you could get sick. Hold on. I'm going to get some numbers for you. [Sounds of keyboard clacking] Here it is: the Center for Disease Control and Prevention's [CDC] website.

Oh, yeah. I tried reading that, but it was like hieroglyphics. All those numbers and lines. I did not inherit your scientific mind. What happened to the good old days of the pie chart?

Well, you should have read this graph: Pneumonia and Influenza Mortality Surveillance. This is an important stat. We know in the winter that more elderly people contract colds and pneumonia and die. In years of bad flu, we have what's known as "excess mortality." This means that we're having more deaths from respiratory diseases than we expected. Let's look at this graph: In 2000, there's a huge peak above the baseline. That means we have respiratory deaths way in excess of what we would have predicted in an average winter. In 2001 the deaths were average, while in 2002 the deaths peak slightly above the median. 2003, though, slices right down the middle. So far in 2004, we're below excess mortality. Yes, the numbers are increasing, but they're not yet in excess. When you look at the spikes, they correlate highly with isolation of influenza. In essence, excess mortality is influenza deaths. On the same web page, the graph of the U.S. gives you widespread regional influenza activity etc., etc., etc. That's very nice, but that's influenza-like illness. That's someone saying, "Oh, yeah, you have the flu." That's not isolation. And since we're not culturing everybody, we don't really know the extent of the flu.

The only positive way to ascertain the flu is through culturing? Is that why you started shoving swabs down our throats and scraping out our gunk? Gagging on a cotton swab is hardly a party for an eight-year-old.

Why was I doing it? We know that when flu enters a community, it usually affects kids first. And then, in my experience, it will reach the adults several weeks later. A couple weeks after adults get sick you'll start to see bacterial pneumonia, too. Basically, you were the pigeons in the coal mine. [Laughs]

I thought they were canaries.

Pigeons, canaries, whatever?There was actually something they were using for West Nile called the "sentinel chicken." Did you hear about that?

No. It sounds like something out of a barnyard Matrix.

Scientists would put chickens in cages. Then they would bleed them and check them for West Nile antibodies. The ones that had antibodies were obviously infected by mosquitoes. So when a sentinel chicken comes down with West Nile, you know the disease is in the area. You were my sentinel chicken.

Is that a term of endearment? It's a sight better than "my little mistake."

Whenever you got sick, I swabbed you. If you were positive, that told me flu was in the community. That means we could be alert and treat people earlier.

By "swabbing," do you mean growing the virus in a petri dish?

I used to swab your noses, then grow the virus in tissue culture. It was in tubes. Nowadays, I have more rapid antigen tests that give me answers in a couple minutes.

Are tissue cultures a relic of the 80s?

Not really, but results from tissue cultures take a minimum of 24 hours. If you do the antigen tests, they're quicker but not quite as specific. They can't tell you what the strain is: only A or B, nothing else. With tissue culture you can see if it's H3 or H1, a vaccine strain or not a vaccine strain. There are great utilities in tissue cultures.

Back to New Yorkers. You remember my last apartment, the cockroach pit? You could not walk into the kitchen at night barefoot for threat of crunching something brown and unfortunate. How else can we prevent the flu?

There's nothing you can do on the subways. If you are high risk?chronic lung disease or heart disease?the most important thing is vaccination. It may not prevent illness in some cases, but it frequently prevents death. If your major goal is to prevent death, the vaccine works for that. If you're allergic to eggs and you can't take the vaccine, people sometimes take medicine throughout the period the flu is in the community. There are four medicines: rimantadine, amantadine, Oseltamivir (Tamiflu) and Zanamivir (Relenza)?that's the one you inhale. Oseltamivir and Zanamivir work against influenza A and B, while rimantadine and amantadine only work against influenza A. But the problem this year is A, not B. Any of those drugs provides a suitable treatment or prevention regimen. The important thing, though, is to treat the flu within the first 48 hours, and preferably the first 24.

Whenever we got sick as kids, you shoved pills down our throats as soon as we got all achy. It kind of took all the fun out of being sick. I had no motherly pampering, no daytime tv, no hot tea?

You were treated with amantadine within six hours of symptom onset. Almost uniformly, you were back in school by the next day.

I always hated you for that. While my friends were shivering balls of snot, I was reciting multiplication tables. I couldn't fake being sick, either. You saw through every thermometer-on-the-lamp ruse. In elementary school, I could count my number of sick days on one hand.

There were a couple days. When the drugs failed, you either had influenza B or another virus. But when the medicine did work, your mother and I noticed your fevers broke almost immediately. There was a very nice study a number of years ago that looked at the use of amantadine for flu. They wanted to see, "Will Tylenol bring down the flu faster than amantadine?" Amantadine has nothing to do with temperature; it's just by getting rid of the flu it brought people's temperature down. The critical thing is early treatment; if you wait around two days to see what's going to happen, it's too late.

You said that Adrianne [my girlfriend] didn't have a "flu face" when we had dinner last week. She thought she was dying, but you told her she just had a minor cold. If I told her that, I wouldn't have a girlfriend anymore. Tell me, Dad, what is this illustrious "flu face"?

You look like you're sick as stink. You're wiped out, pale. You usually have a bad headache, all your muscles ache. You have a pretty high fever and a hacking, dry cough. People that have bad flu don't walk out to dinner with her boyfriend's parents. They're in bed, they feel terrible, they're bundling; it's very difficult to function when you have full-blown flu.

So when was the last time you had the flu?

It's been a very long time.

Say I'm sick with the flu. What can I do?

Stay hydrated and drink lots of fluids. There is anecdotal evidence that chicken soup may be a benefit. Chicken soup, from a standpoint of electrolytes, is pretty balanced. Some people also believe it promotes nasal mucus flow. Tylenol is pretty reasonable, too. Besides antivirals, taking it easy and treating your symptoms are the best bets.

Did you ever wish I'd become a viral specialist so we could be a father-son flu combo? You know, traveling the world, eradicating the flu with our patented antiviral punch. You're not harboring dashed dreams, are you?

No, you couldn't have been a doctor. We tortured you too much.