In one of the largest adult vaccine clinical trials ever, researchers have found that an experimental vaccine against shingles (zoster vaccine) prevented about half of cases of shingles--a painful nerve and skin infection--and dramatically reduced its severity and complications in vaccinated persons who got the disease. The findings appear in the June 2 issue of The New England Journal of Medicine.
The Shingles Prevention Study, conducted over 5 ½-years, was led by the Department of Veterans Affairs (VA) and carried out in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and Merck & Co., Inc. (Whitehouse Station, NJ).
"This is very promising news for older persons," says Stephen E. Straus, M.D., an infectious diseases specialist at NIAID and Director of the NIH National Center for Complementary and Alternative Medicine, who participated in the design, oversight and conduct of the trial. "These striking results indicate for the first time that we can use a vaccine to prevent shingles, one of the most common and debilitating illnesses of aging. And among vaccine recipients who did get shingles, the episodes generally were far milder than they otherwise would have been."
"For some people, shingles can result in months or even years of misery," comments study leader Michael N. Oxman, M.D., an infectious disease specialist at the San Diego VA Healthcare System and the University of California, San Diego.
Shingles, also known as herpes zoster, is caused by reactivation of the virus that causes chickenpox. Once chickenpox infection has run its course, the virus is not eliminated; rather, it retreats to clusters of sensory nerve cells usually located near the spinal cord, where the virus persists in a dormant state. As immunity weakens with advancing age, the virus can reactivate, multiply in and damage sensory nerve cells to cause pain. It then migrates to the skin, causing the blistering rash of shingles.
Generally, shingles first manifests as pain, itching or tingling in an area of skin on one side of the body or face. Then a painful blistering rash develops in that same area of skin; the rash can take two to four weeks to heal.
Anyone who has had chickenpox--which includes most adults in the United States--could develop shingles, though not all will. The two major risk factors are increasing age and declining immunity. Half of all people who live to age 85 will get the disease. Experts estimate more than a million new cases of shingles occur in the United States each year.
The trial was conducted at 22 study sites nationwide, including 16 VA medical centers and six clinical research sites outside the VA system coordinated through NIAID. Between November 1998 and September 2001, the multicenter research team enrolled more than 38,500 men and women age 60 or older into the study. Half of the participants received a single injection of the zoster vaccine--a live, weakened form of varicella-zoster virus, the virus responsible for chickenpox; the other half received a placebo vaccine. Neither the researchers nor the participants knew who received vaccine and who received placebo until after the study was over. The zoster vaccine used in the study, manufactured by Merck, is a new, more potent version of the chickenpox vaccine used to prevent chickenpox in millions of American children every year since 1995. The zoster vaccine was developed specifically for study in older adults.
During an average of more than three years of follow-up, the vaccine reduced the incidence of shingles by 51 percent: 642 cases of shingles occurred among those in the placebo group compared with only 315 in the vaccinated group. Among all vaccine recipients, the total burden of pain and discomfort due to shingles was 61 percent lower than in placebo recipients. Moreover, the zoster vaccine reduced the incidence of postherpetic neuralgia (PHN)--a form of chronic nerve pain that is the most common serious complication of shingles--by two-thirds compared with placebo. The vaccine was well tolerated, with the rates of serious adverse events low and local reactions at the vaccination site generally mild.
"As people live longer, and the proportion of older people in our population increases, it is highly likely that the prevalence of shingles will increase. A preventive shingles vaccine would be an enormous boon for the health and quality of life of seniors," says Anthony S. Fauci, M.D., NIAID director. "We are extremely gratified that this public-private partnership has led to these exciting results, which have the potential to greatly benefit seniors in years to come."
Approximately 12 percent of older people with shingles experience pain lasting for 3 months or longer (the definition of PHN used in the study). As people age, however, shingles-associated nerve pain increases in frequency and severity. This complication may occur in nearly one-third of persons with shingles who are 60 years of age or older.
Patients with PHN often describe the pain as burning, throbbing, aching, stabbing or shooting, and it can cause both physical and emotional suffering. What can be most distressing and debilitating, according to these patients, is that at least 90 percent of them have allodynia--pain caused by something that ordinarily is not painful, such as clothing touching the skin, or a cool breeze. Simply dressing and having a shirt touch the side of the body that is affected can be excruciating.
Postherpetic neuralgia is difficult to treat. Antiviral medications can speed the healing of shingles and reduce the severity of nerve damage caused by the disease, but only if these medications are used within 72 hours of the first sign of a shingles rash. Thus, it is important for people to recognize the symptoms of shingles and get to a doctor quickly. Antiviral medications do not help relieve PHN once it has begun.
The researchers emphasize that the zoster vaccine was tested only as a preventive therapy and is not intended as a treatment for those who already have shingles or postherpetic neuralgia. On April 25, Merck announced that it had submitted a license application to the Food and Drug Administration for the zoster vaccine. If approved for use, the research team estimates the vaccine could prevent 250,000 cases of shingles that occur in the United States each year and significantly reduce the severity of the disease in another 250,000 cases annually.
The study was funded by the VA and by Merck, which supplied the vaccine and placebo. The James R. and Jesse V. Scott Fund for Shingles Research provided additional funds.