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http://www.washingtonpost.com/wp-dyn/content/article/2009/05/16/AR2009051601850.\

html?hpid=moreheadlines

Age of Flu Victims Has Big Implications

Scientists Say Relative Youth of Ill People Is Evidence of Pandemic Potential

By Brown

Washington Post Staff Writer

Sunday, May 17, 2009

The swine-origin influenza A (H1N1) virus that burst into public consciousness a

month ago is starting to behave like a mixture of its infamous, pandemic-causing

predecessors.

It seems to have a predilection for young adults, as did its notorious ancestor,

the 1918 Spanish influenza. Many of the young victims who have become deathly

ill turned out to have other medical problems -- a phenomenon first clearly seen

with the 1957 Asian flu. H1N1 is spreading easily in North America but

sputtering in Europe, just as Hong Kong flu did in 1968. And as in the

mini-pandemic of Russian flu in 1977, some people appear to have a degree of

immunity.

Exactly how swine flu fits into the pantheon of flu pandemics will not be known

for a while. It will take months -- and many more victims -- for its full

personality and behavior to emerge. But one thing is clear: This is a lot more

than just seasonal flu out of season.

After a brief moment when news of the outbreak in Mexico made swine flu look

like a horseman of the apocalypse, public health officials have spent much

effort reassuring people that most of the time, the virus causes a mild illness

that can be ridden out at home. Yet, officials at the World Health Organization,

the Centers for Disease Control and Prevention and elsewhere do not want the

public to get blase.

Pandemic flu strains -- and this new H1N1 strain is all but certain to cause the

21st century's first pandemic -- are unpredictable. Any contagious disease that

most of the world's 6.8 billion people can catch is inherently dangerous.

" Our message to everybody is, of course, do not over-worry about these things,

[but] it is important to know it is serious, " the WHO's Keiji Fukuda said last

week.

Perhaps the most worrisome features so far are the number and severity of cases

in teenagers and young adults. This was noticed early, and the pattern has not

changed much now that there are 5,000 laboratory-confirmed infections and

probably more than 100,000 overall. The average age of the confirmed and

probable cases is 15 years. Two-thirds are younger than 18.

There are two theories for what is happening.

One is that students visiting Mexico on spring break were the chief " vectors "

bringing the virus to the United States, where they then infected schoolmates

and friends. The other is that young people are especially vulnerable for some

reason.

" As we get farther and farther in, are we going to be able to choose between

these two hypotheses? Sure we are, " ph Bresee, the CDC's chief flu

epidemiologist, said late last week. But, he added, it may take two or three

months.

Determining the true age distribution is crucial, as it will help set the policy

for who should be first in line for vaccines and how to ration antiviral drugs

if they are in short supply. " It really does have big implications, " Bresee

said.

A closely related question is whether the illness tends to be more serious in

younger age groups as well as more common.

In the United States, the familiar seasonal influenza causes about 8,100 deaths

a year directly and contributes to about 36,000 more in people with lung or

heart problems. Ninety percent of those deaths occur in people 65 and older. The

risk of a healthy person older than 65 dying directly from flu is about 100

times that of a healthy person 5 to 49 years old.

Compared with seasonal outbreaks, all flu pandemics cause a higher percentage of

severe cases and deaths in younger groups. Although the overall mortality rate

from the current swine flu is low, this trend is already apparent.

Last Thursday, when Fukuda announced that the global death total was 65, he

noted that " half of them are healthy people who have no predisposing conditions.

This is a pattern different from what we see with normal influenza. "

There have been too few deaths in the United States to draw any conclusions. But

of the 173 people who have been sick enough to be hospitalized, more than half

are in the 5-to-24 age group.

In the 1918 pandemic, which killed at least 50 million people, nearly half the

deaths were of people 20 to 40 years old. More than 95 percent were of people

younger than 65. In comparison, 36 percent of the deaths in the 1957 pandemic

were of people younger than 65, and 48 percent in the 1968 pandemic.

The 1918 pattern has led many experts to speculate that older people may have

had immunity from a " Spanish-like " virus that circulated in their youth,

sometime before about 1885. Something similar may be happening this time.

The H1 and N1 in the name of the new strain refer to proteins on the virus's

surface. The human immune system " sees " them and tailor-makes antibodies to

attack the bug. Flu vaccines work by priming the immune system with harmless

versions of the same H and N proteins.

A variety of H1N1 strains circulated from 1918 to 1957, then disappeared for two

decades. In 1977, however, an H1N1 strain surfaced that was nearly identical to

the previous one, so much so that scientists suspect it was an accidental

release from a lab freezer. It caused a pandemic -- Russian flu -- that was

largely limited to people younger than 25, whose immune systems had never

experienced H1N1.

Strains of H1N1 have continuously circulated since then. While the new one is

very different -- the H and N proteins are from pig, not human, viruses --

decades of exposure to H1N1s may be providing older people with some protection.

Some young people may have had essentially no exposure.

" My first speculation is that this younger population has somehow missed contact

with H1N1 or with vaccine, " said Edwin D. Kilbourne, an emeritus professor at

New York Medical College and, at 88, flu virology's elder statesman in the

United States.

Differences in background immunity may also exist across geographical areas.

This is the reason for the big difference in North America's and Europe's

experience with the 1968 Hong Kong flu, a pandemic that spanned two winters.

In the United States, nearly three-quarters of all deaths that were ultimately

attributed to that flu came in the first winter (1968-1969). In England and

France, more than three-quarters were in the second winter (1969-1970).

In that virus, one old surface protein, the H, was switched out for a new one in

a process called reassortment. The strain went from H2N2 to H3N2.

Epidemiologists now believe that Europeans had had more recent and intense

exposure to H2N2 viruses than North Americans. Consequently, Europeans had

developed antibodies and were partially protected when the " half-new " H3N2

strain arrived.

By the second winter, however, the N2 part of the virus had also changed

somewhat through mutations and was no longer very recognizable to the immune

system. The antibodies that had protected a lot of Europeans the previous winter

no longer worked against this " drifted " strain of H3N2. Cases of flu -- and

deaths -- went way up.

Whether a similar difference in continent-wide susceptibility explains why swine

flu is spreading in the United States but standing still in Europe will take a

while to figure out.

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