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Stanford Report, June 7, 2000

New vaccine emulates shingles to boost immune system against the virus  

BY KRISTIN WEIDENBACH

People who have had a bout of shingles routinely describe it as one of the most painful experiences of their lives. Researchers conducting the Shingles Prevention Study hope to spare new victims this misery by vaccinating them against the disease.

Shingles is caused by the same virus (varicellazoster) that causes chickenpox. After producing a relatively benign rash in youngsters, the virus can linger for many years in the body before exploding from its internal hiding place in a fury of pain.

A large study is now under way at Veteran's Affairs (VA) hospitals around the country, to test the efficacy of a vaccine designed to prevent shingles. Researchers are hoping to recruit 37,000 people nationwide who are willing to roll up their sleeves and be jabbed in the name of shingles prevention. Jeffery Loutit, MBChB, assistant professor of medicine and chief of infectious diseases at the Palo Alto VA Health Care System, leads the local arm of the project.

According to Loutit, a person will get shingles only once in their lifetime, which is an obvious source of relief for those who have had the disease. "An episode of shingles boosts the immune system so you don't get another episode. With the vaccine, we are trying to emulate an episode of shingles and boost the immune system against the virus," he explained.

Volunteers will be randomly assigned to one of two groups: one will receive the vaccine and the other will receive a placebo. The researchers will then monitor participants for three to five years for evidence of the disease. "It is the same chickenpox vaccine given to kids but in a slightly higher dose," said Loutit. "The idea is that the group that gets the vaccine will have a lower incidence of shingles."

To date, more than 14,000 older Americans have joined the trial -- almost 600 of them at the Palo Alto VA. Researchers can not yet comment on the effectiveness of the vaccine for shingles prevention, but the early results show that the vaccine is safe and side effects are "very minimal," according to Loutit. Studies from Japan, where the vaccine has been distributed to children for chickenpox prevention for the past 15 years, reassure physicians of the vaccine's safety.

People who have never had chickenpox will not get shingles, said Loutit, because the disease is exclusively caused by reactivation of virus that has been lying dormant in the body. But many people have forgotten or are unsure if they have had the childhood illness. For this reason, anyone who has not had shingles, who is at least 60 years old and has lived in North America for at least 30 years is eligible for the trial. The researchers assume that people who have lived in the United States this long are likely to have been previously exposed to the virus. Chickenpox can be mild or asymptomatic in children, so many people have had the disease without realizing it.

After an episode of chickenpox, the virus sequesters in the dorsal root ganglion -- the region where nerves that supply the head, neck and trunk meet and connect to the spinal cord. Researchers still are unsure what triggers reactivation of the virus -- perhaps stress, suggested Loutit. But for some reason the virus stirs and migrates along one or more of these nerves causing a red, blistering rash on the skin overlaying the nerve. The condition will only affect one side of the body and usually occurs on the chest, face or trunk.

According to Loutit, the major motivation for the study is to prevent the pain associated with shingles. The rash that signals flare-up of the virus usually lasts no longer than 10 to 14 days, but half of patients over age 60 will experience prolonged pain that can last for weeks to years, said Loutit, and "chronic pain clearly affects people's quality of life." Just as they do not know what causes shingles, researchers also do not know why the pain lingers but ascribe it to "some type of nerve irritation," said Loutit.

The disease may be more common in the elderly due to their generalized waning immunity. Fifty percent of 80-year-olds will have had an episode of shingles, said Loutit, who predicts that over the next 30 years, as the population ages, physicians are going to see increasing numbers of shingles cases.

Despite the promise of protection from the disease, finding volunteers for the study has not been easy. To drum up support, Loutit has been visiting local nursing homes and explaining the study to those who might benefit. Volunteers receive a single injection and then are monitored by telephone unless they develop symptoms of the disease. "We need to capture all those people who are likely to get shingles. We need to see if they get it, and what their pain is like," he said. In the population they are targeting, the researchers expect to see 10 cases per 1,000 unimmunized people per year. They hope to see fewer cases among those who receive the vaccine.

Volunteers will be enrolled until March 2001. For further information on the Shingles Prevention Study call (650) 849-0293. SR