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Primary Care Today 2008

Toronto, Ontario / May 8-10, 2008

Arguments supporting widespread uptake of the herpes zoster (HZ) vaccine can be readily marshalled when confronted with the prevalence of painful acute HZ. As the population ages, the risk of frequently intractable and excruciatingly painful post-herpetic neuralgia (PHN) will inevitably increase as well.

Pathophysiology

As explained by Dr. Peter Watson, Assistant Professor of Medicine, Division of Neurology, University of Toronto, Ontario, primary varicella zoster viral (VZV) infection induces chickenpox in children but once the lesions crust over, the virus enters nerve cell bodies in the dorsal root ganglion where it becomes latent.

With age, VZV-specific cell-mediated immunity declines and the virus reactivates, traveling to the skin where the infection appears as a rash in a dermatomal pattern. At the same time, the virus also travels centrally into the spinal cord where it causes hemorrhagic inflammation in one dorsal ganglion and nerve as well as the dorsal horn of the spinal cord, Dr. Watson indicated. The inflamed dorsal horn then sends out pain messages that are likely a mixture of inflammatory and neuropathic pain.

Antiviral compounds, including valacyclovir, famciclovir and acyclovir, have been shown to have modest effects at reducing acute and prolonged pain as well as rash. Moreover, as Dr. Watson noted, “They have to be started within 72 hours of rash onset, so patients have to recognize they have shingles; there may be a delay between rash onset and a visit to the doctor. Pain can also precede the rash for several days during which time patients may not be aware of underlying viral activity. PHN, in turn, results from damage to the dorsal horn and to the dorsal root ganglion, where the neurons that do survive are often damaged and irritable, and which can give rise to the terrible pain of PHN.”

Structures within the dorsal horn are also permanently destroyed by prior inflammation from the acute episode, reducing the number of receptors for analgesics, “which may be why analgesic drugs may not work,” Dr. Watson observed. Thus primed and hyperexcitable, the nervous system sends pain signals to the brain that register as the characteristic steady, burning pain of PHN, often accompanied by electric shock sensations and pain upon the lightest touch, including contact with clothing or even a breeze on the skin.

Aggressive management of the acute zoster episode may help prevent PHN. But as Dr. Watson confirmed, randomized controlled trials of antivirals, antidepressants and gabapentin have only a modest effect at preventing PHN. Approximately half of those over the age of 60 who suffer an acute episode of zoster will have PHN at one month, which increases to 70% for patients over the age of 80. Randomized controlled trials of antidepressants, anticonvulsants and opioids indicate that about 50% of patients either do not respond at all to treatment or are poorly relieved, Dr. Watson observed. “The generalizability of these results will be less in office practice, where patients with comorbidities are less likely to respond,” he added. Furthermore, the incidence of zoster is poised to increase not only because an aging population is more susceptible to zoster flares, but also because widespread childhood varicella vaccination programs are depriving older individuals from receiving an immunological boost against zoster when exposed to children with chickenpox. In Alberta, for example, the incidence of HZ has steadily climbed from 1986 to 2002 and this increase is accelerating.

“I have been working in this [therapeutic] area for many years and have a personal interest in zoster after seeing so many patients with PHN and often failing to relieve them,” Dr. Watson told delegates. “To me, vaccination against zoster appears to be a very important advance in this disease.”

Target Population

Vaccinating to the currently recommended target population of patients <u>></u>60 years of age falls largely to the family physician, who is most likely to be in repeated contact with this patient group. The first step towards optimal implementation of the zoster vaccine is education. As family practitioner Dr. Vivien Brown, Associate Staff, Mount Sinai Hospital, Toronto, emphasized, patients need to understand that unlike childhood vaccines, adult vaccines do not necessarily always prevent infection but rather attenuate the severity of illness should a patient become infected.

For example, the SPS (Shingles Prevention Study) showed that among almost 39,000 adults who were enrolled in the trial, the vaccine reduced the incidence of HZ by over 50% relative to placebo, and the incidence of PHN by 66.5% (Oxman et al. N Engl J Med 2005; 352(22):2271-84). As importantly, the vaccine reduced the frequency, severity and duration of the infection by over 60%, Dr. Brown noted. Patients therefore need to understand that like the influenza vaccine, the zoster vaccine may not prevent every episode of shingles but it will decrease the frequency, severity and duration of illness. “For anybody who has ever experienced HZ, decreasing the frequency, severity and duration of the disease is a huge step forward,” Dr. Brown told delegates.

Physicians also need to endorse the vaccine and recommend it to patients, as medical recommendation of any vaccine dramatically increases the likelihood that patients will accept it. According to a 2006 Canadian survey of adult national immunization, over 90% of at-risk adults received the pneumococcal vaccine when recommended by their family physician compared with only a fraction of those when the vaccine was not medically recommended. Physicians also need to encourage patients to become more involved with their own immunization status and be aware of what vaccines they would benefit from.

Strategies that raise awareness of adult immunization needs could include having patients fill out an adult immunization questionnaire during any scheduled medical visit and carrying the Canadian Coalition for Immunization Awareness and Promotion (CCIAP) adult immunization card in their wallet so that each time they receive a vaccine, whether it is in a clinic, emergency room or doctor’s office, the vaccination can be documented and their own personal immunization record kept up to date (the card can be downloaded from the CCIAP Web site).

Every office visit represents an opportune time to discuss vaccination needs, Dr. Brown suggested, but one appropriate opportunity is to offer the HZ vaccine at the same time as patients receive the influenza vaccine, as studies indicate concomitant administration does not compromise immune response to either of them. Patients are eligible for the HZ vaccine at the age of 60 onward, including those who have had a previous episode of zoster, she added.

Primary Prevention

The major contraindication to the HZ vaccine is a history of either primary or acquired immunodeficiency states, including hematologic malignancies, AIDS or the need for immunosuppressive therapy. Patients can also be reassured that only 0.1% of patients in the vaccine arm of the SPS had a documented serious adverse event, the same percentage as was observed in the placebo arm. “The value of a vaccine to prevent or attenuate disease across the lifespan cannot be overstated,” Dr. Brown emphasized, “and we now have the tools to practice primary prevention.”