Unorthodox H1N1 virus not yielding its secrets easily

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Unorthodox H1N1 virus not yielding its secrets easily

By Kaplan Posted: 09/18/2009 10:01:00 PM PDT

As health officials brace for a new onslaught of illness from the H1N1 virus,

they remain perplexed by one of the most unusual and unsettling patterns to

emerge from this pandemic — the tendency of the so-called swine flu to strike

younger, healthier people.

The initial explanation was that the elderly, who are usually most vulnerable to

the flu, have built-in immunity as a result of their exposure more than 50 years

ago to ancestors of today's pandemic strain. But the limits of the theory are

becoming clearer. For starters, only a third actually have antibodies to H1N1.

" It doesn't quite look as though it's the whole story, " said Dr.

Schaffner, chairman of the department of preventive medicine at Vanderbilt

University School of Medicine in Nashville, Tenn.

Further, the flu's two key genes came directly from pigs and are new to

everyone. That means all age groups should be equally vulnerable since no one

has encountered the genes before. Yet infants seem to be in less danger than

older children and most adults.

Unraveling these mysteries will be critical to designing a strong defense

against this novel and tenacious virus. Tests in animals strongly suggest that

H1N1 will be with us for the foreseeable future, supplanting the strains that

cause seasonal flu within a year or two. Understanding the virus' inner workings

will also help scientists prepare for future influenza pandemics.

H1N1's unorthodox nature became apparent as soon as the virus

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burst onto the scene in early spring: Most of the earliest cases in the United

States and Mexico occurred in children rather than in the elderly.

In the United States, half of all people with confirmed cases of H1N1 infection

have been age 12 or younger, according to the Centers for Disease Control and

Prevention. Until July 24, when the CDC stopped counting new cases, 60 percent

of patients whose ages were known were between 5 and 24 years old. Another 20

percent were in the 25-to-49 age group. Only 1 percent of those sickened had

reached the age of 65.

Younger people also appear to be getting the most severe cases of pandemic flu.

The median age of patients requiring hospitalization is 20, according to the

CDC. In fatal cases, the median age is 37.

Those figures are in stark contrast to the seasonal flu, which is most likely to

sicken people who are elderly, very young or chronically ill. More than 90

percent of fatal cases involve senior citizens.

Scientists theorized that the new H1N1 flu descended from the 1918 Spanish flu,

an H1N1 strain that killed an estimated 50 million people worldwide. Older

people who had been exposed to that virus must have built up immunity that

protected them against the new pandemic strain.

But an analysis published last week in the New England Journal of Medicine found

H1N1 antibodies in blood samples from only 39 of 115 people born before 1950, a

rate of 34 percent. The results supported a similar analysis released in May.

Over the summer, researchers who tested blood samples from Japan found that few

people born after 1918 had antibodies that protected them against the new H1N1.

But most of the people over the age of 90 did.

That suggests immunity came only from the initial versions of Spanish flu, not

the myriad offshoots to which most elderly people were exposed. For them,

protection came from something else.

" Other components of the immune response no doubt also contribute to reduce

disease, " said Katz, chief of immunology and pathogenesis in the

CDC's Influenza Division. But so far, she said, scientists don't know what those

might be.

Then there's the matter of the key " H " and " N " genes in the new H1N1 virus.

Although they have much in common with the corresponding genes from the 1918

strain, both came directly from pigs. No one should have immunity.

It may turn out that prior experience with H1N1 has very little impact on who

will wind up with the most severe cases.

Consider this alternate explanation for the unusually young age of H1N1 victims

from Dr. Wenger, a professor of preventive medicine and community health

at New Jersey Medical School in Newark: Perhaps their more vigorous immune

systems are simply mounting stronger challenges to the flu virus.

If bodies overreact and release too many infection-fighting proteins called

cytokines, the resulting " cytokine storm " can cause severe inflammation that

overwhelms the lungs and respiratory tract. In extreme cases, the reaction can

be fatal.

Many scientists have speculated that this kind of calamitous immune response may

have been at work in 1918. But the theory is difficult to test.

" The immune system is such a finely modulated system, " he said. " When you start

pulling out cells and putting them in test tubes, it gives you some idea, but is

it really what happened? "

Though the overall H1N1 fatality rate remained low over the summer during the

Southern Hemisphere's flu season, deaths continued to be concentrated among

middle-aged adults. For example, in New South Wales, Australia's most populous

state, half of the 48 deaths were in people in their 40s and 50s, according to

figures from the government's health department.

Though children and young adults have higher rates of H1N1 infection, the fatal

cases are more likely to involve middle-aged adults because they have higher

rates of the underlying medical conditions that make H1N1 deadly, such as

asthma, diabetes and heart disease, said CDC spokeswoman Artealia Gilliard.

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