Summary: During a major publicity campaign, shingles vaccine is being marketed as highly effective. It is being recommended for everyone over 60. After looking at the available information, I think it is much less effective than its presentation, because healthy individuals are not at high risk for shingles. I also have concerns about side-effects and long-term protection.
Should I get Zostavax, the Shingles Vaccine?
As with all medical decisions, this is a decision to make with your doctor. It’s also a decision that most older people have already made and said no. “Vaccination
coverage was highest for the ≥ 70 age group (18.3%), followed by age groups
60-69 (8.9%) and 50-59 (1.4%).” (Dermatol Online J. 2012 Aug 15;18(8):2)
Those selling the vaccine think the lack of vaccination is due to ignorance. Here’s the positive outcome info: “Over.. 3.1 years, zoster vaccine reduced…illness by 61%, …incidence of herpes zoster by 51% and …incidence of postherpetic neuralgia by 67%. Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and severity than placebo recipients. Zoster vaccine had continuing efficacy in a Shingles Prevention Study subpopulation followed for 7 years post-vaccination. (Drugs Aging. 2010 Feb 1;27(2):159-76. See below for full abstract.)
Fantastic! Great vaccine! But let’s look at the bigger picture. All the information given is based on one large study.
Here’s another way of looking at the same data: “vaccine
administered to adults 60 years of age or older reduced the incidence of herpes
zoster from 11.12 to 5.42 cases per 1000 person-years.” (Ann
Intern Med. 2006 Sep 5;145(5):317-25) If you notice, the drop is indeed a high one, but running around saying “a fifty percent reduction in risk” means that most of us overestimate the risk.
The biggest reason to get the vaccine is if the risk of getting shingles is enormous. One study says: “The lifetime risk is approximately 25%.” (Expert Rev Vaccines. 2010 Mar;9(3 Suppl):31-5.) Really? One in four people get herpes zoster? The Mayo clinic goes further and says: “Some experts estimate that half the people who live to the age of 85 will experience shingles at some point in their lives.”
Ok, so what really is my risk? Do we have any hard data? Shingles isn’t a reportable disease, so not really. But wouldn’t we expect people who have already had shingles to be at a higher risk? Here’s the effect of vaccinating that population against shingles: “the incidence of recurrent herpes zoster among persons aged <70 years was 0.99 (95% confidence interval [CI], .02-5.54) and 2.20 (95% CI, 1.10-3.93) cases per 1000 person-years in the vaccinated and unvaccinated cohorts, respectively.” (J Infect Dis. 2012 Jul 15;206(2):190-6.) By that estimate, unless you plan to live to be a thousand years old, your chances of getting shingles twice are less than 1%.
Ok, maybe we can’t agree on our risk, but we know the vaccine is effective, yes?
It does seem to lower the risk of shingles by about half initially, but here’s a study watching the decline in effectiveness over five years: “VE (vaccine effectiveness) for incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of VE in each year post-vaccination for all three outcomes showed a decrease in VE after year 1, with further decline in VE thereafter” (Clin Infect Dis. 2012 Jul 24)
After five years, we have declining response rates, which means we need booster shots at some point. In the cost-benefit analysis of the vaccine: “By
reducing incidence and severity of herpes zoster, vaccination can increase
quality-adjusted survival by 0.6 day compared with no vaccination. One scenario
in which vaccination costs less than 100,000 dollars per QALY gained is when 1)
the unit cost of vaccination is less than 200 dollars, 2) the age at
vaccination is less than 70 years, and 3) the duration of vaccine efficacy is
more than 30 years.” (Ann Intern Med. 2006 Sep 5;145(5):317-25.)
So if the vaccine loses effectiveness, it becomes more and more expensive, and doesn’t meet a cost-benefit analysis for governments providing health care. As a whole, the vaccine may not make it into those vaccinations covered by insurance.
But what about the individuals involved?
Here’s the original data from the initial study. Out of 38,546 patients: “A
total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and
642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among
vaccine recipients and 80 among placebo recipients)” (N Engl J Med. 2005 Jun 2;352(22):2271-84.)
Ok, the vaccine doesn’t really do all that much, but is there any reason not to get vaccinated? I went and looked at the VAERS data for adverse event reports. According to VAERS, in the same time period as the study we had 85 reports of life threatening side effects from the shingles vaccine. (Data search for Zostavax on VAERS website). That compares with the number of postherpetic neuralgia patients in the initial study. For those unfamiliar, shingles hurts for a while, postherpetic neuralgia just keeps on hurting. If the possible serious side effects of getting the vaccine are comparable to the possible serious side effects of getting shingles, that means we’re giving the vaccine with the hopes of preventing pain and suffering without affecting serious illness rates.
In sum, I can’t make your decision for you, but I don’t see a vaccine does all that much overall for a healthy population. Please, don’t take my word for it, nor even my quotes. Here are the abstracts I used.
Dermatol Online J. 2012 Aug 15;18(8):2.
Herpes zoster vaccine awareness among people ≥ 50 years of age and its implications on immunization.
Javed S, Javed F, Mays RM, Tyring SK.
University of Texas Medical School at Houston, Houston, Texas.
Herpes zoster (HZ) vaccine was recently approved for adults ≥ 50 years of age and has been shown to reduce the incidence of zoster, postherpetic neuralgia (PHN), and associated healthcare costs. However, currently HZ immunization is sub-optimal. We examined awareness of HZ and of the HZ vaccine. Information was gathered via a one-page survey given to patients ≥ 50 years of age presenting at the dermatology clinic. From the surveyed population of 1000 individuals, the HZ vaccination rate was 11.9 percent. Vaccination coverage was highest for the ≥ 70 age group (18.3%), followed by age groups 60-69 (8.9%) and 50-59 (1.4%). Individuals with female gender, older age (≥ 70 years), higher level of education (college and beyond), retired employment status, memory of chickenpox, knowledge of shingles, and history of shingles and influenza vaccination in the past year all were more likely to have heard of and have received the HZ vaccine (except female gender, education level, and awareness of shingles). Our study suggests lack of awareness to be a significant factor in non-immunization with zoster vaccine. Targeting adults in younger age groups and minorities would be beneficial towards increasing zoster vaccine awareness and thus preventing herpes zoster and its many complications.
Ann Intern Med. 2006 Sep 5;145(5):317-25.
Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
Hornberger J, Robertus K.
SPHERE Institute and Acumen LLC, Burlingame, California 94010, USA. email@example.com
The Shingles Prevention Study showed that a varicella-zoster virus (VZV) vaccine administered to adults 60 years of age or older reduced the incidence of herpes zoster from 11.12 to 5.42 cases per 1000 person-years. Median follow-up was 3.1 years, and relative risk reduction was 51.3% (95% CI, 44.2% to 57.6%).
To assess the extent to which clinical and cost variables influence the cost-effectiveness of VZV vaccination for preventing herpes zoster in immunocompetent older adults.
Decision theoretical model.
English-language data published to March 2006 identified from MEDLINE on herpes zoster rates, vaccine effectiveness, quality of life, medical resource use, and unit costs. Target Population: Immunocompetent adults 60 years of age or older with a history of VZV infection. Time Horizon: Lifetime. Perspective: U.S. societal. Interventions: Varicella-zoster virus vaccination versus no vaccination. Outcome Measures: Incremental quality-adjusted survival and cost per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: By reducing incidence and severity of herpes zoster, vaccination can
increase quality-adjusted survival by 0.6 day compared with no vaccination. One scenario in which vaccination costs less than 100,000 dollars per QALY gained is when 1) the unit cost of vaccination is less than 200 dollars, 2) the age at vaccination is less than 70 years, and 3) the duration of vaccine efficacy is more than 30 years. Results of Sensitivity Analysis: Vaccination would be more cost-effective in “younger” older adults (age 60 to 64 years) than in “older” older adults (age > or =80 years). Longer life expectancy and a higher level of vaccine efficacy offset a lower risk for herpes zoster in the younger group. Other factors influencing cost-effectiveness include quality-of-life adjustments for acute zoster, unit cost of the vaccine, risk for herpes zoster, and duration of vaccine efficacy.
The effectiveness of VZV vaccination remains uncertain beyond the median 3.1-year duration of follow-up in the Shingles Prevention Study.
Varicella-zoster virus vaccination to prevent herpes zoster in older adults would increase QALYs compared with no vaccination. Resolution of uncertainties about the average quality-of-life effects of acute zoster and the duration of vaccine efficacy is needed to better determine the cost-effectiveness of zoster vaccination in older adults.
Shingles vaccine: effective and costly or cost-effective? [Ann Intern Med. 2006]
Summary for patients in
Ann Intern Med. 2006 Sep 5;145(5):I14.
J Infect Dis. 2012 Aug 21. [Epub ahead of print]
A Phase 1/2 Clinical Trial Evaluating Safety and Immunogenicity of a Varicella Zoster Glycoprotein E Subunit Vaccine Candidate in Young and Older Adults.
Leroux-Roels I, Leroux-Roels G, Clement F, Vandepapelière P, Vassilev V, Ledent E, Heineman TC.
Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium.
Background. An adjuvanted recombinant varicella zoster virus (VZV) subunit vaccine is being developed for the prevention of herpes zoster and its complications.Methods. In a phase I/II, open-label, randomized, parallel-group study, older adults (50-70 years) received 2 doses 2 months apart of an adjuvanted recombinant glycoprotein E vaccine (HZ/su; n = 45), a live attenuated Oka strain VZV vaccine (OKA; n = 45), or HZ/su and OKA administered concomitantly (n = 45). To evaluate safety prior to administration in older adults, young adults (18-30 years) were vaccinated with 2 doses 2 months apart of HZ/su (n = 10) or OKA (n = 10). Safety and immunogenicity were assessed up to 42 months for older adults immunized with HZ/su and up to 12 months for all others.Results. Few grade 3 events and no severe adverse events were reported. Fatigue, myalgia, headache, and injection site pain were the most common solicited reactions for HZ/su and occurred more frequently than with OKA. CD4(+) T-cell and humoral immune responses were much higher with HZ/su than with OKA and remained elevated until 42 months. Addition of OKA to HZ/su did not increase immunogenicity.Conclusions. In this study, HZ/su adjuvanted subunit vaccine was well tolerated and more immunogenic than a live attenuated VZV vaccine.Clinical Trial registration. NCT00492648 and NCT00492648.
Vaccine. 2000 Feb 25;18(16):1700-6.
Vaccination of immunocompetent elderly subjects with a live attenuated Oka strain of varicella zoster virus: a randomized, controlled, dose-response trial.
Trannoy E, Berger R, Holländer G, Bailleux F, Heimendinger P, Vuillier D, Creusvaux H.
Pasteur Mérieux Connaught (PMC), Lyon, France.
After primary infection in childhood, varicella zoster virus (VZV) remains latent in the dorsal route ganglia. Its reactivation later in life can lead to a zoster episode. VZV-specific, T-cell-mediated immunity (VZV-CMI) is likely to be important in preventing symptomatic reactivation. As CMI declines with age, a vaccine enhancing VZV-CMI might be effective in decreasing the incidence or severity of zoster in elderly subjects. A randomized, double blind controlled trial assessing CMI responses of elderly subjects immunized with a live attenuated, VZV-Oka vaccine was conducted. Two hundred healthy volunteers (55-75 years of age) received either a single injection of the VZV vaccine (PMC), containing 3200 (Oka 3200), 8500 (Oka 8500), or 41,650 (Oka 41650) PFU of live VZV, or a pneumococcus vaccine control group (Pneumo 23((R)). The immune response to VZV was assessed by measuring the T-cell response to VZV antigens, i.e. proliferation (stimulation index, SI), precursor cell frequency (PCF), cytokine secretion, and antibody titers. Six weeks post-vaccination, VZV-specific SI (adjusted mean values) was significantly greater (P<0.0001) in the 3 vaccine groups (with SI=5. 6 for Oka 3200; SI=5.0 for Oka 8500, and SI=7.2 for Oka 41,650) than in the control group (SI=2.9). The increase in PCF was striking, with 72.4, 91.2 and 85.1 precursors per million cells respectively in these 3 vaccine groups, vs 26.3 in the control group. No significant IL-4 secretion was observed in any subject, whereas the presence of IFN-gamma secretion was found to correlate with good responder status. The increase of these CMI parameters did not depend upon the titer of virus injected. Geometric mean titers of VZV antibodies increased in all vaccine groups and remained unchanged in the control group. Nevertheless, no correlation between the antibody response and the cell-mediated response was found. Live attenuated VZV vaccine caused a significant increase in VZV-CMI in a healthy, elderly population. No relationship between vaccine dose and the intensity of the specific response was found.
Drugs Aging. 2010 Feb 1;27(2):159-76. doi: 10.2165/10489140-000000000-00000.
Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults.
Sanford M, Keating GM.
Adis, a Wolters Kluwer Business, Auckland, New Zealand. firstname.lastname@example.org
Individuals who have been infected with varicella zoster virus (VZV) are at risk for developing herpes zoster and this risk appears to be related to a decline in VZV-specific cell-mediated immunity (CMI). Zostavax (zoster vaccine) is a one-dose, high-potency, live, attenuated VZV vaccine that boosts VZV-specific CMI and this is its presumed mechanism of action. Zoster vaccine is registered in the EU for use in adults aged >or=50 years for the prevention of herpes zoster and herpes zoster-related postherpetic neuralgia. In the Shingles Prevention Study, a placebo-controlled trial in adults aged >or=60 years (n = 38 546), zoster vaccine led to a sustained boost of VZV-specific CMI. Over a mean herpes zoster surveillance period of 3.1 years, zoster vaccine reduced the herpes zoster-related burden of illness by 61%, reduced the incidence of herpes zoster by 51% and reduced the incidence of postherpetic neuralgia by 67%. Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and severity than placebo recipients who developed herpes zoster. Zoster vaccine had continuing efficacy in a Shingles Prevention Study subpopulation followed for 7 years post-vaccination. Zoster vaccine was generally well tolerated in older adults. While cost-effectiveness estimates in pharmacoeconomic analyses varied widely according to vaccine and herpes zoster parameter cost/benefit estimates, an analysis from a UK perspective found a zoster vaccine immunization programme in adults aged 65 years to be cost effective. In older adults, the zoster vaccine has the potential to significantly reduce the herpes zoster burden of illness by decreasing the incidence of herpes zoster or reducing its severity.
Clin Infect Dis. 2012 Jul 24. [Epub ahead of print]
Persistence of the Efficacy of Zoster Vaccine in the Shingles Prevention Study and the Short-Term Persistence Substudy.
Schmader K, Oxman M, Levin M, Johnson G, Zhang J, Betts R, Morrison V, Gelb L, Guatelli J, Harbecke R, Pachucki C, Keay S, Menzies B, Griffin M, Kauffman C, Marques A, Toney J, Keller P, Li X, Chan I, Annunziato P; for the Shingles Prevention Study Group.
GRECC,Durham VA Med. Ctr and Duke University, Durham, NC.
Background. The Shingles Prevention Study (VA Cooperative Study #403, SPS) demonstrated efficacy of zoster vaccine (VE) through 4 years post-vaccination. A Short-Term Persistence Substudy (STPS) was initiated after SPS to further assess persistence of VE.Methods. STPS re-enrolled 7329 vaccine and 6950 placebo recipients from the 38,546-subject SPS population. Surveillance, case determination, and follow-up were analogous to SPS. VE for herpes zoster (HZ) burden of illness (BOI), incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, the combined SPS and STPS populations, and for each year through year 7 post-vaccination.Results. In the STPS compared to the SPS, VE for HZ BOI decreased from 61.1% to 50.1%; VE for incidence of PHN decreased from 66.5% to 60.1%; and VE for incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of VE in each year post-vaccination for all three outcomes showed a decrease in VE after year 1, with further decline in VE thereafter. VE was statistically significant for incidence of HZ and HZ BOI through year 5.Conclusion. VE for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of VE through year 5 post-vaccination but VE is uncertain beyond that point.
Expert Rev Vaccines. 2010 Mar;9(3 Suppl):31-5.
Vaccination: a new option to reduce the burden of herpes zoster.
Lyon University Hospital, Lyon, France. email@example.com
There is a strong correlation between the incidence of herpes zoster (HZ) and increasing age, with a marked rise in incidence from approximately the age of 50-60 years. The lifetime risk is approximately 25% and the disease is associated with acute and sometimes persistent pain, which substantially reduces the day-to-day functioning and quality of life of affected individuals, particularly older adults. The disease most commonly occurs as a result of an age-related decline in cell-mediated immunity. A live attenuated zoster vaccine has been developed to boost the varicella-zoster virus-specific cell-mediated immunity of older adults and, via this mechanism, protect the individual against HZ and its complications. Evidence that the vaccine is effective in older patients comes from the pivotal Shingles Prevention Study. This was a randomized, double-blind, placebo-controlled trial involving approximately 40,000 adults aged 60 years or more. The HZ vaccinated group had a 51% lower incidence of HZ, a 67% reduction in postherpetic neuralgia (defined as pain rated at three or more on a scale ranging from zero [no pain] to ten [pain as bad as you can imagine], persisting or occurring 3 months or more after rash onset), and a 61% lower burden of illness (a composite measure of the incidence, severity and duration of pain and discomfort caused by HZ), indicating that the vaccine decreased both the incidence of HZ and the average severity of HZ in vaccinees who developed HZ. Moreover, there was a 73% reduction in the number of cases of HZ with severe and long-lasting pain. Overall, the vaccine was well-tolerated with the most common adverse events being mild injection site reactions and headache. A continuation trial from the Shingles Prevention Study involving over 14,000 patients approximately 7000 in the HZ vaccine and placebo groups) confirmed that the efficacy of vaccination against HZ is durable through 7 years in terms of a significantly reduced incidence of HZ, a reduced incidence of postherpetic neuralgia and a markedly lower burden of illness. Although significant improvements have been made, available treatment options are only partially effective, and once postherpetic neuralgia is established, management is difficult. Therefore, the introduction of the zoster vaccine is a promising strategy to reduce morbidity associated with HZ, a particular concern in older adults.
N Engl J Med. 2005 Jun 2;352(22):2271-84.
A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group.
Shingles Prevention Study (Mail code 111F-1), VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161,USA. firstname.lastname@example.org
The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults.
We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine (“zoster vaccine”). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia.
More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild.
The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.
Copyright 2005 Massachusetts Medical Society.
Aging, immunity, and the varicella-zoster virus. [N Engl J Med. 2005]
Varicella-zoster virus vaccine–grown-ups need it, too. [N Engl J Med. 2005]
A vaccine to prevent herpes zoster. [N Engl J Med. 2005]
A vaccine to prevent herpes zoster. [N Engl J Med. 2005]
A varicella-zoster virus vaccine reduced the burden of illness of herpes zoster in older adults. [ACP J Club. 2005]
Can vaccinating older adults against varicella zoster virus prevent herpes zoster and postherpetic neuralgia? [Nat Clin Pract Neurol. 2005]
Varicella-zoster vaccine. [N Engl J Med. 2007]
J Infect Dis. 2012 Jul 15;206(2):190-6. Epub 2012 Jun 4.
Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population.
Tseng HF, Chi M, Smith N, Marcy SM, Sy LS, Jacobsen SJ.
Department of Research and Evaluation, Southern California Kaiser Permanente, Pasadena, CA 91101, USA. email@example.com
The benefit of vaccinating immunocompetent patients who have had shingles has not been examined. The study assessed the association between vaccination and the incidence of herpes zoster recurrence among persons with a recent episode of clinically diagnosed herpes zoster.
This is a matched cohort study in Kaiser Permanente Southern California. Study populations were immunocompetent elderly individuals ≥ 60 years old with a recent episode of herpes zoster. Incidence of recurrent herpes zoster was compared between the vaccinated and the unvaccinated matched cohorts.
A total of 1036 vaccinated and 5180 unvaccinated members were included. On the basis of clinically confirmed cases, the incidence of recurrent herpes zoster among persons aged <70 years was 0.99 (95% confidence interval [CI], .02-5.54) and 2.20 (95% CI, 1.10-3.93) cases per 1000 person-years in the vaccinated and unvaccinated cohorts, respectively. The adjusted hazard ratio was 0.39 (95% CI, .05-4.45) among persons aged <70 years and 1.05 (95% CI, .30-3.69) among persons aged ≥ 70 years.
The risk of herpes zoster recurrence following a recent initial episode is fairly low among immunocompetent adults, regardless of vaccination status. Such a low risk suggests that one should evaluate the necessity of immediately vaccinating immunocompetent patients who had a recent herpes zoster episode.