First Vaccine for Prevention of Herpes Zoster Infection in Older Adults

A Step Closer to Eliminating Postherpetic Neuralgia

The recent FDA approval of the first-ever attenuated zoster vaccine live (Zostavax; Oka/Merck) may avert a substantial number of the estimated 1 million cases of herpes zoster infection (also known as shingles) that occur in the United States each year and its devastating sequela of postherpetic neuralgia that is common in older adults.

“It’s very simple for primary care physicians to determine which patients should be vaccinated: any adult over the age of 60 who is not immune suppressed.”

—Kenneth E. Schmader, MD

“This is a very valuable and powerful tool to reduce the pain and suffering from shingles and postherpetic neuralgia,” says Kenneth E. Schmader, MD, vice-chief, Division of Geriatrics, Department of Medicine, GRECC, Durham, Va, and Duke University Medical Centers, Durham, NC.

The vaccine is indicated for persons aged ≥60 years whose immune system is intact. It is not indicated for the treatment of herpes infection or for postherpetic neuralgia. Dr Schmader emphasized that the incidence of herpes zoster infection, and therefore postherpetic neuralgia, increases significantly at age 60.

Herpes infection is caused by reactivation of the varicella-zoster virus [VZV], which causes chickenpox. “It gets in our bodies when we’re young, but it’s not cleared,” Dr Schmader explains. Most people who develop shingles are either elderly or immune suppressed.

VZV continues to reside in the sensory ganglia of the cranial nerves and the spinal dorsal-root ganglia long after chickenpox has resolved. “The virus reactivates within nerves, and in destroying the nerves, it causes a huge amount of pain,” says Dr Schmader. “The acute pain is bad enough. But what people really fear is postherpetic neuralgia, pain that goes on for months or years.”

Being one of the most common neuropathic pain syndromes in the United States, he says, postherpetic neuralgia “affects several hundred thousand people. Patients describe it as ‘the worst pain I’ve ever had.’ It completely ruins their quality of life.”

Effects of Aging

Experts are still unsure how the herpes zoster virus is reactivated, although host factors involving waning immunity are suspected. “Cellular immunity is what keeps the virus in check,” says Dr Schmader. “It probably reactivates subclinically in our bodies periodically throughout life, but our cellular immune response contains it. Unfortunately, that weakens as we get older.”

When the VZV vaccine was introduced in 1995 for chickenpox prevention, there were concerns that the resultant reduced circulation of wild-type virus would lead to a rising prevalence of herpes zoster infection. “Although the absolute number of cases is going to continue to increase as the population ages,” Dr Schmader says, “the jury is still out about whether the chickenpox vaccine is going to affect the incidence of shingles in older adults.”

Compelling Evidence

N Engl J Med

Dr Schmader took part in the randomized, double-blind Shingles Prevention Study (SPS), the largest trial with the zoster vaccine, which included 38,546 immunocompetent adults aged ≥60 years (. 2005;352: 2271-2284). “We’ve vaccinated more than 19,000 individuals” with the herpes vaccine, he said. “The vaccine seems to be pretty well tolerated, and it’s clearly effective in preventing shingles.” Age of participants ranged from 60 to >80 years.

In the SPS, vaccination reduced the burden of infection—a combined primary end point encompassing the incidence of herpes zoster, severity of disease, and duration of pain and discomfort—by 61%. It cut the incidence of infection by 51.3% and of postherpetic neuralgia by 66.5% (Table).

“It was much more effective in preventing shingles than we had imagined going into the trial,” Dr Schmader says. He noted that most of the reduction in postherpetic neuralgia was because “if you don’t get shingles, you don’t get postherpetic neuralgia,” but added that there was “an additional benefit on the really severe, long-lasting pain, even in those people who were vaccinated and who got shingles.”

P

In a subgroup analysis in the SPS, which included 6616 placebo and vaccine patients, significantly more treated patients experienced ≥1 adverse event, primarily injection site reactions, compared with placebo (48% vs 17%, respectively). Although there was also a significantly greater incidence of serious adverse events in the vaccine group than in the placebo group (1.9% vs 1.3%, respectively; = .03), post hoc analysis found no clinically meaningful between-group differences.

Who Should Be Vaccinated?

Dr Schmader, who also serves on the Herpes Zoster Working Group that advises the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, says, “We’re in the midst of formulating recommendations now, but universal vaccination for adults aged 60 and older who do not have problems with their immune system is under consideration.” The full recommendations are due to be released in October.

“In the meantime,” he says, “it’s very simple for primary care physicians to determine which patients should be vaccinated: any adult over the age of 60 who is not immune suppressed.” The vaccine is administered as a single-dose injection. Physicians should be aware that it is not indicated for the treatment of shingles, only for prevention.

Individuals with a history of shingles do not need immunization, “because they got their own ‘vaccination’ naturally,” Dr Schmader notes. It is still unknown whether the vaccine will be effective in the very elderly (ie, people who are 85 or 90), even though “they’re also the ones who are at the greatest risk for developing shingles.”

When he first started working in this field in the 1980s, Dr Schmader remembers, “all we had was prednisone. We really do have a lot more tools now to reduce the pain and suffering from this virus. And it’s great, because it’s across the lifespan. With the varicella vaccine, we can prevent VZV infection altogether. And now we have treatments for all these people who are latently infected with the virus and who can develop shingles.”

Sounding upbeat, Dr Schmader added that “with early antiviral therapy, very aggressive pain control, the use of the vaccine, and the newer medicines available for postherpetic neuralgia, we’ve made huge inroads into rendering this virus much less troublesome.”

Vaccinating older adults is now an important prevention strategy that can prevent a lot of severe, long-term pain and suffering. Studies are continuing to investigate the length of protection beyond 4 years, to determine the exact duration of efficacy and whether there is a need for revaccination at any point.

The vaccine is contraindicated in patients receiving immunosuppressive therapy, including high-dose corticosteroids, and in pregnant women.