Herpes Shingles Research

Shingles poses two immediate challenges to medical research. The first is to develop drugs to fight the disease and to prevent complications. The second challenge is to understand the disease well enough to prevent it, especially in people known to be at high risk.

To protect susceptible patients from a shingles attack scientists need to know much more about the varicella-zoster virus, especially how it remains latent in the body for so long and what induces it to become active again. NIA-supported scientists are studying the biology of the varicella-zoster virus in an effort to gain a better understanding of the molecular basis of viral latency and reactivation.

Although the virus is presumed to hide in the nervous system between bouts of chickenpox and shingles, it has never been recovered from nerve cells at autopsies unless the patient had shingles at the time of death. In contrast, herpes simplex, which causes recurrent infections of cold sores and fever blisters, has been identified in spinal nerve cells during its latent periods.

If the whole varicella-zoster virus does not remain intact in nerve cells, perhaps its core genetic material — the DNA — survives. Scientists suspect that the viral DNA may be inserted into one of the chromosomes of the nerve cell — the larger units that house the cell's own genetic material.

What keeps the varicella-zoster virus quiet during its long latency? Probably the immune system. A healthy immune system protects against all kinds of diseases, but people with depressed immunity are vulnerable to many illnesses, and have a high incidence of shingles. Antibodies, one of the immune system's major defense mechanisms against infection, are not very helpful against shingles. Studies have shown that patients with shingles produce varicella-zoster antibodies but they don't halt the infection. Similarly, injections of antibody-rich blood serum do not prevent the dissemination of shingles in cancer patients or others whose immune systems are depressed. (This is in contrast to the protection conferred by the immunoglobulin given to newborns with chickenpox.)

The components of the immune system that do appear to combat shingles are two types of white blood cells: the T lymphocytes and scavenger cells called macrophages. Scientists are trying to find ways of boosting the activity of these cells — especially in patients at high risk for severe or disseminated shingles (a rare condition in which the virus spreads to other areas of the body, sometimes vital areas such as the blood or the lungs).

Current research is aimed at finding new methods for treating shingles and its complications. In one NINDS-supported study, investigators are studying the effectiveness of a long-acting preparation of morphine (a type of analgesic used to manage pain) as a possible treatment for postherpetic neuralgia. Research from this study could lead to improved treatment for this condition, which complicates many cases of shingles.

Capsaicin ointment (containing less than 1 percent of the active ingredient) is a currently available treatment for the pain of shingles, especially postherpetic neuralgia. In 1998 a group of scientists tested a higher dose capsaicin cream (5 to 10 percent) in a small group of patients suffering from pain caused by a number of different conditions, including diabetes, arthritis, and HIV infection. Seven of ten patients reported a 50 percent reduction in pain after using these higher dose creams. Further studies, using larger groups of patients, will be conducted to establish the safety and effectiveness of this promising treatment, which could bring relief to patients suffering from postherpetic neuralgia.

The development of preventive measures and treatments for shingles has long been hindered by scientists' difficulty in working with the varicella-zoster virus in the laboratory. The virus grows very poorly in laboratory cells and does not infect animals other than man. Recently, however, the Department of Veterans Affairs (VA) concluded a long-term, nationwide trial — the Shingles Prevention Study — that studied an experimental shingles vaccine. At the completion of the study researchers found that the vaccine reduced the incidence of shingles by half. Scientists are now close to offering the public a vaccine capable of preventing this painful condition. In the course of this work on vaccines, scientists expect to uncover important information to use against other diseases, to learn more about the body's immune system, and ultimately to outwit the clever viruses that evade that system.

Source: NIH