CSP News: Shingles vaccine proves effective in large VA trial

[VA R&D Communications/ 10 a.m.. May 24, 2005]

A stronger version of the chickenpox vaccine cuts incidence and severity of painful nerve and skin infection in older adults

In one of the largest adult vaccine trials ever, researchers from the Department of Veterans Affairs and colleagues have shown that an experimental vaccine against shingles prevented about 51 percent of cases of shingles, a painful nerve and skin infection, and dramatically reduced its severity and complications in vaccinated persons who got shingles. The findings appear in the June 2, 2005, New England Journal of Medicine.

The medical term for shingles is herpes zoster. Shingles is caused by reactivation of the virus that caused chickenpox, which persists in a dormant state within nerve cells in everyone following this childhood infection. Shingles is characterized by pain in one area of skin on one side of the body or face, and by a painful, blistering rash in the same area of skin. It can afflict anyone who has had chickenpox - which includes most adults in the United States. Half of people who live to age 85 will get shingles, and it is estimated that more than a million new cases of shingles occur in the United States each year.

"For some people, shingles can result in months or even years of misery" said study leader Michael N. Oxman, MD, an infectious disease specialist at the San Diego VA Healthcare System and the University of California, San Diego. Shingles and a complication called postherpetic neuralgia (PHN), consisting of pain originating in damaged nerves that can persist for months or years, can diminish the quality of life and functional capacity of older adults, and markedly reduce their enjoyment of life.

The Shingles Prevention Study involved more than 38,000 men and women, age 60 or older at 22 study sites across the United States - 16 VA medical centers and six clinical sites outside of the VA system coordinated through the National Institute of Allergy and Infectious Diseases (NIAID). The vaccine used in the study is called "zoster vaccine." Half of the subjects received a placebo and the other half received a single injection of the zoster vaccine- containing a live, attenuated (weakened) form of varicella-zoster virus, the virus responsible for chickenpox and shingles. The zoster vaccine, manufactured by Merck & Co., Inc., is a new, higher potency version of the vaccine that has been used to prevent chickenpox in children since 1995. The new zoster vaccine was developed for and studied in older adults.

During an average of more than three years of follow-up, 642 cases of shingles occurred in the placebo group, compared to only 315 in the vaccinated group. The total burden of pain and discomfort caused by shingles was reduced by 61 percent in vaccine recipients compared with placebo recipients. Moreover, vaccinated subjects were only a third as likely as placebo recipients to develop postherpetic neuralgia, a form of chronic nerve pain that is the most common serious complication of shingles.

"The zoster vaccine was able to prevent shingles, or convert it to a minor illness," said Myron Levin, MD, an infectious disease specialist at the University of Colorado and one of the study's authors.

When a young person recovers from chickenpox, the virus doesn't disappear. It lies dormant in nerve cells in sensory ganglia located near the spinal cord. As immunity to the varicella-zoster virus weakens with age, the virus can reactivate, multiply in and damage the sensory ganglion, and then migrate to the skin, causing the blistering rash of shingles. When people suffer from shingles, they generally first feel pain, itching, or tingling in one area of skin on one side of the body or face. They then develop a painful blistering rash in that same area of skin. The shingles rash takes two to four weeks to heal. .

Approximately 12 percent of older people with shingles experience PHN. At least 90 percent of these patients have allodynia - pain caused by something that is not ordinarily painful, such as clothing touching the skin or a cool breeze - one of the most distressing and debilitating types of pain. "If the side of your body is affected by shingles, just the touch of a shirt can be painful," said Oxman. "If you have shingles on your head, even a breeze can be intolerable."

Postherpetic neuralgia is notoriously difficult to treat," said Oxman, noting that patients with PHN often describe the pain as burning, throbbing, aching, stabbing, or shooting. Antiviral medications have been shown to speed the healing of shingles and reduce the severity of nerve damage caused by the disease, but only if they were used within 72 hours of the first sign of the 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 zoster vaccine reduced the incidence of PHN by 66 percent compared to placebo.

The researchers emphasized that the zoster vaccine was tested only as a preventive therapy. It is not intended as a treatment for those who already have shingles or postherpetic neuralgia.

"The zoster vaccine had an excellent safety profile," commented Oxman. The only adverse experiences reported significantly more often by vaccine recipients than placebo recipients were headaches and injection-site reactions such as redness, tenderness, swelling, and rash. Most of these adverse experiences were reported as mild in intensity.

The Shingles Prevention Study was a VA Cooperative Study carried out in collaboration with the NIAID and Merck & Co., Inc. The study was funded by the VA and Merck & Co., Inc., which supplied the vaccine and placebo. Additional funds were provided by the James R. and Jesse V. Scott Fund for Shingles Research.