Some Lessons, and Concerns

Fear of a Swine Flu Epidemic in 1976 Offers Some Lessons, and Concerns, Today

By ANDREW POLLACK
Published: May 8, 2009

With fears of swine flu engulfing the nation in 1976, Janet Kinney got vaccinated to make sure she would be able to take care of her children. Instead, her children ended up taking care of her.

About a week after getting the swine flu shot, she recalled, “I was so weak I couldn’t push down the toaster button.” She spent a month in the hospital, paralyzed from the neck down, before gradually recovering.

With health authorities now gearing up for what could be a huge vaccination campaign against a new strain of swine flu, the experience of 1976 is raising a note of caution.

The feared swine flu epidemic of 1976 never materialized. And several hundred people, including Ms. Kinney, who is now 68 and lives in Gig Harbor, Wash., developed Guillain-Barré syndrome, a rare neurological condition that causes temporary muscle weakness or paralysis. More than 30 of those people died.

Many experts say they do not think a vaccine for the new flu strain, called H1N1, would raise a similar risk for Guillain-Barré. But answering that question is difficult because to this day, no one has figured out why the 1976 vaccine caused the disease, in which the body’s immune system mistakenly attacks the nerves.

Indeed, some researchers still question whether the vaccine did cause Guillain-Barré, particularly since flu vaccines in other years have been linked to little or no risk of the disease.

“It doesn’t make sense that one flu strain would cause Guillain-Barré syndrome where none of the others have,” said Dr. Paul A. Offit, a vaccine expert at Children’s Hospital of Philadelphia.

Still, many experts consider the matter settled. The Institute of Medicine of the National Academy of Sciences concluded after an extensive review in 2003 that the “evidence favored acceptance of a causal relationship” between the 1976 vaccine and the syndrome. It stopped short, however, of saying the evidence “established” a causal relationship.

“It’s really not all that controversial anymore,” said Dr. Lawrence B. Schonberger, who as a young epidemiologist at the Centers for Disease Control and Prevention in 1976 gathered the initial evidence that led to the vaccination program being halted that December. Dr. Schonberger, who is still with the agency, found that for people who got vaccinated, the rate of getting a diagnosis of Guillain-Barré in the next six weeks was more than seven times as high as for those who did not get the vaccine.

In all, the vaccination resulted in nearly one extra case of Guillain-Barré for every 100,000 people immunized, which would translate into roughly 450 cases for the 45 million people who got the shot.

Some critics challenged the findings, arguing that some diagnoses were mistaken and that vaccinated people were more likely to self-report having Guillain-Barré than others because it was in the news.

But some studies canvassed health records for all diagnosed cases and had the diagnoses confirmed by experts. One of the leading critics worked on his own study, which confirmed the magnitude of the increased risk.

The more intriguing question is how the vaccine triggered the syndrome. One hypothesis was that the vaccine, rushed into production, was contaminated with Campylobacter, a type of bacterium that does cause Guillain-Barré. The Institute of Medicine said this was unlikely but could not be totally excluded.

A more likely explanation is that something in the vaccine resembled something in the nerve cells. When the body’s immune system mounted an attack on that component of the vaccine, it also then attacked the lookalike in the nerves.

Irving Nachamkin, a professor of pathology and laboratory medicine at the University of Pennsylvania, examined some 1976 vaccine that had been saved by a scientist in Texas. In a paper published last year in The Journal of Infectious Diseases, he and colleagues reported that mice given the vaccine made antibodies that reacted with gangliosides, which are components of nerve cells. An antibody attack on gangliosides is part of the disease mechanism of Guillain-Barré.

But when Dr. Nachamkin tested two flu vaccines from other years which were not linked to the syndrome, the mice also made those antibodies. So the mystery remains about what was unique, if anything, about the 1976 vaccine.

In particular, the most important question now would be whether the unique factor was that it was a vaccine against a swine flu rather than a human flu. If so, that could raise concern about a vaccine for the new flu strain, which is made mostly of swine virus.

Dr. Nachamkin plays down such worries. “There’s no evidence to suggest it’s a swine-derived-virus problem,” he said.

Others say there are lessons to be learned even without solving the mystery. One is that any medicine or vaccine given to tens of millions of people is likely to have side effects, so surveillance systems need to be in place.

Another is that risks have to be weighed against benefits. Had there been a swine flu epidemic in 1976, the number of lives saved by a vaccine would have dwarfed the small number of cases of Guillain-Barré. But in 1976, the vaccine was given even though the epidemic did not materialize.

“The math is overwhelmingly in favor of vaccine if there’s an epidemic,” said Dr. Harvey V. Fineberg, the president of the Institute of Medicine and co-author of “The Epidemic That Never Was,” a book about the 1976 episode. “It’s in the absence of disease that this rare effect looms large.”

This time, officials say the decision to make the vaccine will be divorced from the decision to use it. The manufacturing decision is likely in the next couple of weeks and will probably be yes. But the decision on using the vaccine will probably not be made until the fall.

For her part, Ms. Kinney, who says the syndrome left her unable to run down stairs, said she would not take the vaccine if offered. “I’m just not willing to take that chance,” she said.

Would she even need to? One intriguing idea is that if the new flu strain is similar to the 1976 strain, people who got vaccinated then might, possibly, have some protection now.

The C.D.C. says it will eventually study that question. Peter Palese, a flu expert at Mount Sinai School of Medicine, said he doubted that would be the case because the two viruses appear quite different.

Still, if it were the case, the oft-maligned 1976 vaccination campaign might end up having done some good after all.

http://www.nytimes.com/2009/05/09/health/09vaccine.html?hp