/publications/issue/2007/2007-09/2007-09-6766

Prevention of Shingles: The Zostavax Vaccine

Author: Jeegisha T. Patel, PharmD

The same virus that causes chickenpox causes herpes zoster, commonly known as shingles. Herpes zoster is caused by the reactivation of the varicella-zoster virus (VZV) from latency after infection with chickenpox. After an episode of chickenpox, the virus becomes dormant in the body and can reappear many years later to cause a case of shingles.

The annual incidence of herpes zoster ranges from approximately 1.5 to 4.0 cases per 1000 persons.1,2 The cause of the VZV reactivation is unclear.3,4 However, increasing age, altered cell immunity, and immunocompromised state (such as with HIV infection) are risk factors for the development of herpes zoster.1,3,4

Herpes zoster is an acute, localized infection that causes a painful, blistering rash. A shingles rash usually appears on 1 side of the face or body and lasts for 2 to 4 weeks.2 Symptoms include pain or a burning sensation in specific parts of the body, headaches, upset stomach, and chills. The typical rash appears in 2 to 3 days, after the virus has reached the skin. It consists of red patches of skin blisters (vesicles) that look very similar to early chickenpox.5 The rash progresses to clusters of clear vesicles, which continue to form for 3 to 5 days and evolve through stages of pustulation, ulceration, and crusting.3 The crusts fall off in 2 to 3 weeks, leaving behind pink healing skin.

Shingles can be contagious through direct contact in an individual who has not had chickenpox. Shingles is a reactivation of the VZV virus, and this condition is not spread through sneezing, coughing, or casual contact. Anyone who has recovered from chickenpox may develop shingles. Shingles is more common, however, in people aged 50 and older, people who have medical conditions that keep the immune system from working properly, or people who receive immunosuppressive drugs.

Treatment for shingles includes antiviral drug therapy to accelerate the healing of the skin lesions (Table3).

Recommended Oral Antiviral Therapy for Herpes Zoster

Pain medications and steroids may be added for symptomatic relief and to reduce inflammation. Nondrug therapy to reduce the risk of infection may include keeping the lesions clean and dry with soap and water, applying compresses (water, saline, Burow?s solution), and wearing loose-fitting clothing for improved comfort.

Extreme pain and shingles infection can lead to pneumonia, hearing problems, blindness, brain inflammation (encephalitis), or death. Postherpetic neuralgia is a persistent pain syndrome that occurs after resolution of rash and is the most debilitating complication of herpes zoster. Both the incidence and the duration of postherpetic neuralgia are directly correlated with the patient?s age.3 Pain can persist for months and occasionally years.

Prevention

If patients have not had chickenpox or received the chickenpox vaccine, they should be advised to avoid contact with the skin lesions of persons with known herpes zoster infection (shingles or chickenpox), especially if they are immunocompromised.

The chickenpox (varicella) vaccine is a recommended childhood vaccine, and it also can be administered to adults who have never had chickenpox. Two varicella virus?containing vaccines are currently licensed for use in the United States. Varivax is the single-antigen varicella vaccine, and ProQuad, or MMRV, is a combination vaccine of measles, mumps, rubella, and varicella. Due to the increase in cell-mediated immunity in older adults, however, a higher titer of live attenuated virus is required. As a result, herpes zoster can now be prevented with a new VZV vaccine.

Herpes Zoster Vaccine

The FDA approved the first live VZV vaccine, called Zostavax (Oka/Merck) on May 25, 2006, to reduce the risk of shingles for use in people 60 years of age and older.6 The preventive effect of zoster vaccine is thought to be a consequence of its boosting effect on VZV-specific immunity. Each 0.65-mL single-dose vaccine contains 19,400 plaque-forming units of virus, considerably more than the ~1350 plaque-forming units found in the vaccine to prevent varicella in children. On October 25, 2006, the Advisory Committee on Immunization Practices (ACIP) voted to recommend a single dose of zoster vaccine for adults aged 60 years and older, whether or not they report a prior episode of herpes zoster.8 Furthermore, persons with chronic medical conditions may be vaccinated unless a contraindication or precaution exists for their condition.8

A large efficacy study by the Shingles Prevention Study Group evaluated the high-titer, live attenuated zoster vaccine. This was a placebo-controlled double-blind trial in which 38,546 subjects aged 60 and older were randomized to receive a single dose of either Zostavax or placebo. The participants were followed for the development of zoster for a median of 3.1 years. This study excluded people who were immunocompromised or using corticosteroids on a regular basis and anyone with a previous history of herpes zoster.

The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1%, reduced the incidence of postherpetic neuralgia by 66.5%, and reduced the incidence of herpes zoster by 51.3%.9 The vaccine was more efficacious in preventing herpes zoster among persons aged 60 to 69 than among those 70 and older.9 The vaccine did prevent postherpetic neuralgia to a greater extent, however, among those aged 70 and older than among those aged 60 to 69.9 This study concluded that the vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.9

Zostavax is not indicated for the treatment of zoster or postherpetic neuralgia. It should not be used in children, and it is not a substitute for Varivax (chickenpox vaccine). Zostavax should not be used by women who are or may be pregnant and people who are allergic to neomycin or gelatin. People with a history of immunodeficiency conditions or those receiving immunosuppressive therapy, including corticosteroids, and active tuberculosis should not receive the vaccine.

Zostavax is administered subcutaneously as a single dose in the upper arm. The vaccine is stored frozen and should be reconstituted using only the diluents supplied. It should be administered immediately after reconstitution and discarded if not used within 30 minutes. It is supplied as a package of 1 single- dose vial or 10 single-dose vials of lyophilized vaccine and diluents.

Some common side effects reported were headache and redness, pain and tenderness, itching, and swelling at the injection site. Adequate treatment provisions, including epinephrine injection, should be available for immediate use, should an anaphylactic reaction occur.

Conclusion

Now that the vaccine is available, patients who are 60 years of age and older should be advised about immunization. For those who develop shingles, it is important to provide education on what to expect. Patients should be educated both on how to manage the chronic pain and about the potential infection risk to others. Health care workers should be advised to use standard precautions and gloves when examining lesions.

Herpes zoster can occur in anyone who has had varicella. The vaccine gives health care providers an important tool that can help prevent an illness that affects many older Americans.

It is anticipated that zoster vaccine will not be covered under Medicare Part B.10 The vaccine instead will be reimbursed through the Medicare Part D program.10 Beneficiaries should contact their Part D plan for more information.

Studies have concluded that the vaccine would increase quality-adjusted lifeyears, compared with no vaccination.4,11 An ongoing analysis of cost-effectiveness and efficacy in those for whom the vaccine is not indicated needs to be evaluated. This evaluation will probably influence future recommendations for herpes zoster immunizations.

Immunizations for the elderly are crucial, and health care professionals need to be informed on recent changes or additions to recommendations made by the ACIP. New vaccines are on the horizon for various conditions such as genital herpes, HIV/AIDS, human papillomavirus, Alzheimer?s disease, cancer, the common cold, malaria, and many more. For updated information, visit the Centers for Disease Control and Prevention Web site at www.cdc.gov.

References

1. Donahue JG, Choo PW, Manson JE, Platt R. The incidence of herpes zoster. Arch Intern Med. 1995;155:1605-1609.

2. Advisory Committee on Immunization Practices. Considerations for shingles vaccine recommendations in the US: record of the proceedings. Atlanta, Ga: Centers for Disease Control and Prevention; 2006. Available at: http://cdc.gov/nip/acip. Accessed June 13, 2007.

3. Gnann JW Jr, Whitley RJ. Clinical practice: herpes zoster. New Engl J Med. 2002;347 (5):340-346.

4. Kimberlin DW, Whitley RJ. Varicella-zoster vaccine for the prevention of herpes zoster. New Engl J Med. 2007;356(13):1338-1343.

5. National Institute of Health Medline Plus. Herpes Zoster. Available at: www.nih.gov/. Accessed June 13, 2007.

6. US Food and Drug Administration. FDA licenses new vaccine to reduce older American?s risk of shingles. Available at: www.fda.gov. Accessed June 13, 2007.

7. Zostavax package insert. Available at: www.fda.gov/cber/label/zosmer052506pi.pdf. Accessed June 13, 2007.

8. CDC. ACIP provisional recommendations for the use of zoster vaccine. Available at: www.cdc.gov/vaccines/recs/provisional/downloads/zoster-11-20-06.pdf. Accessed June 13, 2007.

9. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Eng J Med. 2005;352:2271-2284.

10. CDC. National Immunization Program (NIP). Herpes Zoster Vaccine (Shingles). Available at: www.cdc.gov/nip/vaccine/zoster/faqs-vacc-zoster.htm. Accessed June 13, 2007.

11. Hornberger J, Robertus K. Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Ann Intern Med. 2006;145:317-325.