A June 2 article incorrectly said that patients in a clinical trial of a vaccine to prevent shingles were cared for through the Department of Veterans Affairs medical system. Six of the 22 hospitals that recruited volunteers for the study were outside the VA system and contributed 27 percent of the 38,546 participants. (Published 6/9/2005)
An experimental vaccine cuts in half the risk of developing shingles, a painful skin disease that about 1 million Americans contract each year, according to an extensive new study.
Even when it does not prevent the disease, the vaccine still reduces by two-thirds the chance that a shingles sufferer will be left with tormenting chronic pain that can make even the touch of clothing unbearable.
Those are among the conclusions of an expensive experiment that tested the vaccine in more than 38,000 men and women cared for through the Department of Veterans Affairs' health system. The findings are published in today's New England Journal of Medicine, 13 years after the study was conceived. The project's initial cost estimate was $31 million, but its final cost is assumed to be much higher. The leaders of the research did not know its final price tag.
Shingles is a reawakening of the virus that causes chickenpox in childhood and then lies dormant for decades in nerve cells. The condition is most common in old age, when immunity declines. Half of people who live to 85 develop shingles.
The new vaccine, if approved by the Food and Drug Administration, is likely to find a huge market in the burgeoning population of people older than 60, the group in which it was tested. It is part of a growing effort to make vaccines that protect against the diseases of adulthood, not just childhood.
The vaccine may turn out to be a boost for its maker, Merck & Co., which is facing financial losses from the withdrawal of its blockbuster analgesic Vioxx. The new product is an ultra-potent version of Merck's 10-year-old chickenpox vaccine, now one of the routine immunizations of childhood.
"Shingles is rarely a life-threatening disease. But it is frequently a quality-of-life-threatening disease," said Stephen E. Straus, an infectious diseases physician at the National Institutes of Health, who helped run the study. "We estimate that if all individuals over 60 in the United States and who are otherwise healthy were vaccinated, we would prevent a quarter of a million cases."
One problem with the long-lasting pain known as postherpetic neuralgia is "that it is so isolating. People have the fear that anything they do may trigger it," said Paula W. Annunziato, a physician and official at Merck Research Laboratories, which provided vaccine for the study.
Someone with shingles develops small, painful blisters on red, inflamed skin on a part of the body's surface that is served by one nerve. Typically, the rash begins at the spinal column and fans out in a wedge across the face, chest or an arm or a leg. If the affected nerve is the one serving the surface of the eye, the blisters can cause blindness.
Antiviral drugs can help suppress the eruption, whose medical name is herpes zoster. (The inciting microbe is called varicella-zoster virus, a member of the large family of herpesviruses.) That treatment, however, doesn't decrease the risk of long-lasting pain. About 40 percent of shingles sufferers in their sixties and about 50 percent in their seventies experience pain lasting more than a year.
The researchers found that although the vaccine did not prevent shingles in very old people as often as in younger subjects, it was more effective in the old in preventing the feared complication of long-lasting pain.
"Although we didn't reduce the incidence [of shingles] as much, we reduced the severity. We all know that you can put up with almost anything if it doesn't last too long," said Michael N. Oxman, an infectious diseases specialist at the VA San Diego Healthcare System, in California.
The researchers, led by Oxman, enrolled 38,546 volunteers at 22 VA hospitals. The volunteers' average age was 69; 7 percent were older than 80 and 40 percent were women. They were randomly assigned to get a single injection of vaccine or a placebo shot. They were followed, on average, for just over three years, with every rash even remotely suspicious evaluated for shingles.
Over the course of the experiment, 3.3 percent of the people who got placebo shots developed shingles -- a rate of about 1 percent of the population a year. Among the vaccine recipients, 1.6 percent -- or about one-half of 1 percent annually -- developed the condition.
The vaccine prevented only half the cases of shingles that otherwise might have occurred, but it reduced the rate of postherpetic neuralgia by 66 percent, and slightly more in people older than 70.
The vaccine is a "live" but extremely weakened strain of varicella-zoster virus. It contains about 14 times as much virus per dose as the childhood chickenpox vaccine.
Less than 5 percent of people who get shingles once get it again. That's because the reappearance of the virus stimulates the immune system to suppress it once again. The shingles vaccine does the same thing. It boosts the immune system through a mild, controlled infection.
People with clearly weakened immunity (such as people with cancer or AIDS) were excluded from the trial. However, people with diabetes, emphysema and other chronic illnesses that can cause mild suppression of the immune system were not. There were no major complications from the vaccine.
The FDA will probably decide early next year whether to license the vaccine for sale. Merck has not yet announced a price for it. The company sells the chickenpox vaccine to physicians for about $70.
An analysis by the research firm A.G. Edwards & Sons last month estimated that the vaccine, which would be sold as Zostavax, could generate $150 million in revenue by 2009.