However, after the blisters and shingles pain have subsided, patients (especially older people) can develop PHN (Post-herpetic Neuralgia) which can be extremely painful. As most people know, shingles can return with a vengeance and that especially applies to people living with HIV, when a weakened immune system can lead to re-occurrence. However, the good news is that there is a vaccine called Zostavax which can significantly reduce the risk of shingles reappearing and the length of time suffering from PHN. This article discusses it in depth and wonders why there has been such a low up-take of the vaccination.
When an Ounce of Prevention Is the Cure for Chronic Neuropathic Pain
by Raji Edayathumangalam on 26 Feb 2013
Shingles vaccine proven to reduce painful postherpetic neuralgia, but vaccination rates lag behind.
For many chronic or neuropathic pain conditions, the causes are obscure and treatments equally elusive. That is not the case for shingles and its sequelae, postherpetic neuralgia (PHN). The advent of a vaccine to prevent shingles in 2006 presented for the first time a chance to make a substantial dent in the prevalence of this always painful and sometimes disabling condition.
There is just one problem: Too few people are being vaccinated. According to the US Centers for Disease Control and Prevention (CDC), in the US only around 14 percent of eligible adults over age 60 were immunized against shingles in 2010, compared to approximately two-thirds of older citizens who received the flu vaccine in that same year. In other countries, vaccination rates are even lower, leaving the majority who would benefit from the vaccine unprotected.
However, the tide may be turning. The vaccine’s manufacturer, Merck, has resolved supply problems, and the company, physicians, pharmacies, and professional organizations are all working to educate the public with the goal of increasing vaccination rates.
Meanwhile, in the US, states have recently put policies in place to make it easier for older adults to get the vaccine. Public health and medical experts are optimistic that these efforts will transform PHN from a common affliction, especially of elderly people, into a far rarer condition.
One virus, two diseases
Shingles, also known as herpes zoster or zoster, is predominantly an adult disease, but it has its roots in childhood, when the first exposure to the varicella zoster virus (VZV) in an unvaccinated person leads to chickenpox. During that first infection, the virus travels along nerve fibers from the skin to sensory nerves in spinal and cranial sensory ganglia, where it establishes a dormant infection. When reactivation of VZV occurs, usually in adulthood, patients develop shingles, which appears as a painful and itchy skin rash localized to one area of the body. The rash commonly consists of blisters that occur on one side of the torso or the face in a band-like pattern that follows the distribution of the nerves from the affected sensory ganglia.
Herpes zoster rash. ©iStockphoto.com/franciscodiazpagador
Reactivation of the virus occurs in people with weakened immune systems. Because immune function progressively declines with age, it is no surprise that age is the biggest risk factor for shingles. Shingles will afflict one in two people who live to 85. A million new cases occur in the US every year, and more than half are in people over 60. Those with immune systems made fragile by organ transplantation, cancer, HIV/AIDS, rheumatoid arthritis, or asthma are also at significantly increased risk for shingles.
While the pain during the acute stage of shingles can range from mild to severe and can be hard to control, it only lasts a week or two. But for about one-third of older adults, the pain does not end when the blisters heal. Instead, these people may develop the chronic pain of PHN. Again, the elderly are most at risk: Up to half of people over age 70 who get shingles will end up with PHN for at least a year.
Michael Oxman, an infectious disease specialist, learned about PHN early in his career. In the 1960s, he witnessed the devastating impact of PHN on a classmate’s mother, who developed shingles shortly after receiving radiation therapy for cancer. “The last three years of her life were made miserable, not by her cancer, but by her chronic PHN pain, which was not relieved by any available therapy,” said Oxman, a staff physician at the Department of Veterans Affairs (VA) Medical Center in San Diego, California, US, and a professor of medicine and pathology at the University of California, San Diego.
PHN pain can diminish quality of life and ability to function to the same extent as congestive heart failure, myocardial infarction, type 2 diabetes, and major depression. Over half of PHN patients require more than one prescription drug to relieve pain. Unfortunately, those drugs, which include anticonvulsants, tricyclic antidepressants, topical lidocaine or capsaicin, and opioids, are effective in only half of the patients, and side effects are especially problematic for older patients.
Despite the fact that PHN has been extensively studied in clinical trials of new pain medications, many patients are still unable to find adequate pain relief even after trying all available medications, said Anne Louise Oaklander, a neurologist and expert on shingles and neuropathic pain at Massachusetts General Hospital, Boston, Massachusetts, US.
Progression of herpes zoster. A cluster of small bumps (1) turns into blisters (2). The blisters fill with lymph, break open (3), crust over (4), and finally disappear. Postherpetic neuralgia can sometimes occur due to nerve damage (5). Image: FDA
A vaccine for shingles and PHN
Roughly 45 years after his first encounter with PHN in medical school, Oxman and his colleagues published the results of a landmark clinical trial involving nearly 40,000 adults age 60 and older showing that a vaccine containing live attenuated VZV was effective in preventing shingles and PHN (Oxman et al., 2005).
The vaccine, produced by Merck and marketed as Zostavax®, is a high-potency reformulation of the company’s previously approved chickenpox vaccine. In the study, a single dose of vaccine reduced the incidence of shingles by 51 percent compared to placebo, after a mean follow-up of three years. Although some vaccine recipients did get shingles, when they did, the severity of illness and the incidence of PHN were both markedly reduced compared to unvaccinated controls. Overall, vaccination resulted in a two-thirds’ reduction in the incidence of PHN. Oxman’s vaccine trial and subsequent studies showed that the vaccine is safe and well tolerated (Gagliardi et al., 2012).
In 2006, regulatory agencies in the US and Europe approved the zoster vaccine for people 60 and older. Currently, the CDC’s Advisory Committee on Immunization Practices recommends vaccination for all adults 60 years of age and older who do not have any contraindications. Some other countries, including Austria, the UK, and Germany, also recommend vaccination.
Lagging trend
Since 2006, the uptake of the vaccine in adults over 60 in the US has increased only at a glacial pace, from 6.7 percent in 2008 to around 14 percent in 2010, much to the frustration of experts like Oaklander and public health officials and advocates. “Except for a few categories of people for whom the vaccination is not recommended, all people in America beyond the age of 50 should at least review the vaccine with their physicians, regardless of whether they remember having had chickenpox or not,” Oaklander said.
The impact of full vaccination would be considerable. According to Oxman, if every eligible adult over 60 received the vaccine, as recommended by the CDC, the annual number of new cases of PHN in the US would drop by at least 50,000. Because some cases of PHN persist for longer than a year, the cumulative reduction in the number of PHN cases would be even greater.
Delivery issues
From the beginning, a supply shortage was the stumbling block to widespread vaccination. VZV is very difficult to grow in the large quantities that are needed for varicella-containing vaccines. Until as late as December 2011, Zostavax was available only in very limited quantities and Merck, challenged to meet even moderate demands for the product, did little to promote the vaccine. The company has since solved production issues and ramped up the supply of vaccine. With increased supply, Merck distributed a record volume of Zostavax in 2012, and has shipped the product with a standard 48-hour shipping time since December 2011, said Eddy Bresnitz, Merck’s medical director for Adult Vaccines, Medical Affairs and Policy. In 2013, the company plans additional launches in countries that have so far lacked the vaccine.
With supply issues resolved, Merck and drugstores began direct-to-consumer advertising in the US in April 2012 to encourage older adults to ask their doctors and pharmacists about shingles, PHN, and the vaccine. The company is also working with the CDC to coordinate communication and outreach efforts. Meanwhile, many researchers and physicians like Oaklander and Oxman are also reaching out to the public through radio and other media outlets.
Because Merck is the only global manufacturer of the vaccine, the shortage was worldwide. The company has been selling zoster vaccine to Canada for the past few years in limited quantities, but just recently begun supplying the vaccine to the UK, South Korea, Australia, and New Zealand. Most of those countries now recommend shingles vaccination and will likely see an uptick in vaccination rates as supplies increase over time.
Additional challenges
Beyond supply questions, in the US, cost and reimbursement issues hindered efforts to increase vaccination rates. The shingles vaccine costs up to 10 times more than the flu vaccine, and older people, including Medicare users, often had to pay out of pocket and wait for reimbursement. A 2008 survey of doctors revealed that primary care and family physicians were trying to promote vaccination, but felt hampered by financial issues (Hurley et al., 2010; Donahue and Belongia, 2010).
Storage of the vaccine posed another obstacle. Zostavax must be kept frozen, and because of its cost and storage issues many primary care offices do not offer the vaccine on site.
States have been working to overcome these obstacles. For example, in May 2012 the Massachusetts Department of Public Health issued a new policy granting trained pharmacists the authority to administer the shingles vaccine, without the need for a prescription. Experts view pharmacy-provided vaccinations as a positive development, but urge that pharmacists be very careful. “Pharmacists must take a detailed medical history and make sure that the adult is not severely immunocompromised before administering the shingles vaccine,” Oxman told PRF.
The future
With the supply improving and other obstacles to vaccination being overcome, several research questions linger. For example, although immunocompromised people, including HIV/AIDS patients, those receiving immunosuppressive drugs, and cancer patients undergoing radiation or chemotherapy, are most susceptible to VZV reactivation, the CDC does not recommend Zostavax for people with weakened immune systems. In that regard, a recent study found that the vaccine was effective at reducing shingles in a group of older adults receiving immunosuppressive therapies for arthritis or other inflammatory conditions with few complications (Zhang et al., 2012); preliminary data from the same trial suggest that the vaccine also greatly decreased PHN in the group (Lambert, 2012). Also, Merck and GlaxoSmithKline are both conducting clinical trials with new vaccines containing either inactivated virus or recombinant protein in an effort to develop a vaccine suitable for immunocompromised elders.
It is also uncertain how long the first dose of vaccine will remain effective, and whether booster doses may ultimately be required. A follow-up to the 2005 trial found that the vaccine was still working after five years (Schmader et al., 2012). An ongoing study is watching these same subjects for up to 10-12 years post-vaccination to measure the long-term persistence of immunity from a single dose of vaccine.
Nor is the long-term risk for shingles in children who have received the chickenpox vaccine currently understood. That answer will be forthcoming only decades from now when those children get older.
Though experts say a vaccine approach is unlikely to benefit other neuropathic pain conditions, for PHN, the success of Zostavax brings optimism. At least for this one common condition, prevention is at hand to vastly reduce the burden of pain for older adults. In the US, childhood vaccination programs have all but erased chickenpox. Maybe one day, an adult zoster vaccine might succeed in relegating PHN, too, to the category “remember when?”
Raji Edayathumangalam is an instructor in Neurology at Harvard Medical School, Boston, Massachusetts, US, and a freelance science writer.
http://www.painresearchforum.org/news/24915-when-ounce-prevention-cure-chronic-neuropathic-pain
No comments:
Post a Comment
All comments welcome but advertising your own service or product will unfortunately result in your comment not being published.