Understanding the Zoster Vaccine

July 13, 2011

Allergy/Immunology Class Act ID 5 min read

By Michael Cohen

Faculty Peer Reviewed

The varicella-zoster virus (VZV) is well known to the majority of the population. In children, it strikes as varicella (chickenpox), characterized by pruritic, vesicular lesions in different stages of development dispersed over the body. A self-resolving and generally limited disease, this form of VZV infection is considered to be a nuisance more than a debilitating affliction, but rarely can have severe sequelae. In adults and the elderly VZV more commonly takes the form of zoster (shingles). This disease results from the eventual reactivation of latent VZV from the sensory neuron ganglia, where it remains dormant, and clinically manifests as a very painful, vesicular rash that follows a dermatomal distribution on the body. Unlike chickenpox, however, zoster has several severe sequelae, including postherpetic neuralgia,[1] or pain persisting for at least 3 months in the area of the skin eruption after resolution of the rash; herpes zoster ophthalmicus,[2] a crippling and sight-threatening condition; and Ramsay Hunt syndrome,[3] characterized by facial paralysis, ear pain, and auditory canal and auricular vesicles. Given the potential morbidity of VZV in adults, combined with the 32% lifetime risk of developing herpes zoster, the appropriate utilization of the herpes zoster vaccine is critically important.[4]

The Herpes Zoster Vaccine: How and Why it Works

Both the incidence of herpes zoster (HZ) and its complications increase with age. Seventy percent of cases occur in adults aged 50 years and older, and the debilitating sequelae of HZ develop more frequently in those aged 79 and older.[4] This is not surprising given that the incidence of HZ has shown to be directly correlated with one’s cell-mediated immunity (CMI).[5] As CMI against VZV declines below a certain threshold, whether due to normal aging or an immunocompromised state, the risk for VZV reactivation increases.[6] Conversely, maintaining high levels of CMI against VZV through re-exposure to the virus ultimately provides a defense against it.[7]

In the past, adults over 50 were frequently re-exposed to VZV by children with chickenpox, stimulating their CMI to stay above the crucial threshold.[8] It is hypothesized that the current widespread use of the chickenpox vaccine significantly reduces that avenue of exposure and allows one’s immunity to VZV to decrease slowly over time. This may potentially alter the natural course of HZ [9] and lead to a substantial increase in the number of HZ cases in adults in the years to come. It is estimated that in the adult population currently under 50 years of age, an additional 14.6 million cases of HZ (a 42% increase) [8] may develop over the next 50 years, resulting in substantial medical costs and morbidity.[10]

Administration of the live, attenuated zoster vaccine, also known as Zostavax, works by increasing CMI against VZV in immunocompetent adults, providing protection against the reactivation of VZV.[7, 11] The only major contraindication to the zoster vaccine is an immunocompromised state, as is true for all live, attenuated vaccines.[12]

Where We Stand

In 2006, Zostavax was approved by the Food and Drug Administration for use in individuals aged 60 and over. However, despite impressive evidence published in 2005 that the vaccine decreases the incidence of HZ by 51% and postherpetic neuralgia by 67% in immunocompetent adults over the age of 60,[11] and is extremely safe [13], vaccination rates remain abysmally low, documented at 2% in 2007 [14] and at 7% in 2008.[15] Some of the identified barriers to its use include lack of patient awareness, lack of physician recommendation, difficulty and expense related to storing the frozen vaccine, trouble with re-imbursement, and concern about the cost.[14, 16]

In March 2011, Zostavax was approved by the Food and Drug Administration for use in those aged 50 to 59 years old as well, a decision based on a multicenter study of 22,000 individuals aged 50 to 59 in which administration of the vaccine decreased the risk of herpes zoster by 70% over the course of one year.[17]

Conclusion

Administration of Zostavax to immunocompetent adults over the age of 50 has been proven to significantly reduce the incidence of HZ and its associated morbidities. It is important that physicians are aware of the beneficial effects of the zoster vaccine, the rationale for its use, and its few contraindications. It is hoped that the recent expansion of the age recommendations for the vaccine will increase patient and physician awareness of the vaccine’s efficacy, thus helping to increase the use of this powerful preventive tool.  Moreover, increasing education regarding the potential devastating complications of HZ and the substantial benefit derived from the low-risk vaccine needs to be the primary prevention strategy against the development of HZ disease.

Michael Cohen is a 4th year medical student at NYU School of Medicine.

Reviewed by Elisabeth J. Cohen, MD, Professor, Department of Ophthalmology, NYU Langone Medical Center

Image courtesy of Wikimedia commons

References

  1. Dworkin RH, Portenoy RK. Pain and its persistence in herpes zoster. Pain. 1996;67(2-3):241-251.
  2. Pavan-Langston D. Herpes zoster ophthalmicus. Neurology. 1995;45(12 Suppl 8):S50-51.
  3. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001;71(2):149–154.
  4. Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc. 2007;82(11):1341-1349.
  5. Hope-Simpson R. The nature of herpes zoster: a long-term study and a new hypothesis. Proc R Soc Med. 1965;58:9-20.
  6. Oxman MN. Immunization to reduce the frequency and severity of herpes zoster and its complications. Neurology. 1995;45(12 Suppl 8):S41-46.
  7. Weinberg A, Zhang JH, Oxman MN, et al. Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine. J Infect Dis. 2009;200(7):1068–1077.
  8. Schuette MC, Hethcote HW. Modeling the effects of varicella vaccination programs on the incidence of chickenpox and shingles. Bull Math Biol. 1999;61(6):1031-1064.
  9. Reynolds MA, Chaves SS, Harpaz R, Lopez AS, Seward JF. The impact of the varicella vaccination program on herpes zoster epidemiology in the United States: a review. J Infect Dis. 2008;197 Suppl 2:S224-227.
  10. Goldman GS. Cost benefit analysis of universal varicella vaccination in the U.S. taking into account the closely related herpes-zoster epidemiology. Vaccine. 2005;23(25):3349-3355.
  11. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. New Engl J Med. 2005;352(22):2271-2284.
  12. Harpaz R, Ortega-Sanchez IR, Seward JF. Advisory Committee on Immunization Practices (AICP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2008; 57(RR-5):1-30. Accessed at http://www.cdc.gov/mmwr/PDF/rr/rr5705.pdf 11 April 2011.
  13. Simberkoff MS, Arbeit RD, Johnson GR, et al. Safety of herpes zoster vaccine in the shingles prevention study. Ann Intern Med. 2010;152(9):545-554.
  14. Lu PJ, Euler GL, Jumaan AO, Harpaz R. Herpes zoster vaccination among adults aged 60 years or older in the United States, 2007: uptake of the first new vaccine to target seniors. Vaccine. 2009;27(6):882-7.
  15. Schiller JS, Euler GL. Vaccination coverage estimates from the National Health Interview Survey: United States, 2008. Atlanta: Centers for Disease Control and Prevention; 2009 at http://www.cdc.gov/nchs/data/hestat/vaccine_coverage/vaccine_coverage.pdf Accessed 10 April 2011.
  16. Hurley LP, Lindley MC, Harpaz R, et al. Barriers to the use of herpes zoster vaccine. Ann Intern Med. 2010;152(9):555-560.
  17. Food and Drug Administration Web site. http://http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm248390.htm Accessed 11 April 2011. (referencing clinical trial NCT00534248).