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Vaccination for the prevention of shingles (herpes zoster)
Authors:
Mary A Albrecht, MD
Myron J Levin, MD
Section Editor:
Martin S Hirsch, MD
Deputy Editor:
Jennifer Mitty, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Mar 23, 2018.

INTRODUCTION — Varicella-zoster virus (VZV) infection causes two clinically distinct diseases. Primary infection with VZV results in varicella, also known as chickenpox, characterized by vesicular lesions in different stages of development concentrated on the face and trunk, and less so on the extremities. Herpes zoster, also known as shingles, results from reactivation of latent VZV (from the varicella infection) in neurons within the sensory ganglia. Herpes zoster is characterized by a painful, unilateral vesicular eruption that occurs in a restricted dermatomal distribution.

Vaccines are available for prevention of both infections. This topic will address the use of the two vaccines licensed to prevent herpes zoster. A discussion of the vaccine to prevent varicella (chickenpox) is found elsewhere. (See "Vaccination for the prevention of chickenpox (primary varicella infection)".)

IMPORTANCE OF CELL-MEDIATED IMMUNITY — Varicella-zoster virus (VZV)-specific cell-mediated immune responses play a critical role in controlling VZV latency and limiting the potential for reactivation [1]. A decline in cell-mediated immunity has been documented in older individuals and in patients with lymphoproliferative malignancies, both populations that experience higher rates of herpes zoster (figure 1) [2-4]. These epidemiologic observations are supported by in vitro data that demonstrate reduced VZV-specific T cell frequency in aging patients who are more susceptible to virus activation [5]. (See "Epidemiology and pathogenesis of varicella-zoster virus infection: Herpes zoster".)

Immunity and risk of reactivation — A decline in VZV-specific cell-mediated immunity is regarded as the major precipitant for VZV reactivation [4]. Approximately 30 to 40 percent of persons over the age of 55 years do not have any detectable VZV-specific T cell responses by some assay methods [4].

Among those who develop herpes zoster, in vitro data suggest that robust VZV cell-mediated immunity at the onset of rash is correlated with reduced severity of disease and less risk of postherpetic neuralgia [6]. Immunocompromised patients who lack adequate VZV-specific cellular immune responses are at greater risk for prolonged episodes of reactivation and disseminated disease, which can be fatal [7]. (See "Clinical manifestations of varicella-zoster virus infection: Herpes zoster".)

Several observations suggest that a decline in cell-mediated immunity, rather than humoral immunity, is linked directly to reactivated VZV syndromes. As an example, in allogeneic stem cell transplants, both cell-mediated and humoral immune responses are ablated, and although antibody is replaced with intravenous gamma-globulin (which contains VZV antibody), these patients have very high rates of herpes zoster [8]. In addition, children with hypogammaglobulinemia do not experience severely protracted or fulminant primary varicella infection or increased rates of herpes zoster [9].

Boosting of T cell specific immunity to VZV — Cell-mediated immune responses improve with periodic subclinical varicella-zoster virus (VZV) reactivation (endogenous boosting), which may limit virus replication and decrease the risk of developing herpes zoster [4,10]. Environmental boosting of T cell responses has also been documented among VZV-immune healthy adults who have had household exposures to children with primary varicella, which may also decrease the risk of herpes zoster [4,11-13]. The impact of varicella vaccination on the incidence of herpes zoster is discussed elsewhere. (See "Epidemiology and pathogenesis of varicella-zoster virus infection: Herpes zoster", section on 'Impact of varicella vaccine on incidence of herpes zoster'.)

Zoster immunization, with either of the available vaccines, is associated with a boost in VZV-specific T cell immune responses, which contribute to the vaccine's efficacy in preventing or attenuating disease [6,14-18]. Data demonstrating the efficacy of these vaccines are described below. (See 'Efficacy of the different vaccines' below.)

APPROACH TO VACCINATION

Indications for vaccination — Herpes zoster vaccination is indicated for individuals ≥50 years of age to reduce the risk of developing herpes zoster and postherpetic neuralgia. Vaccination is not indicated for the treatment of herpes zoster or postherpetic neuralgia. There are certain precautions and contraindications to vaccination, particularly in immunocompromised hosts. This is discussed in detail below. (See 'Immunocompromised hosts' below and 'Contraindications to RZV' below and 'Contraindications and precautions for ZVL' below.)

It is not necessary to determine whether patients have a history of varicella or herpes zoster prior to vaccination because waning antibodies in previously exposed patients (particularly older adults) may lead to negative results despite past infection. In addition, a self-reported history of shingles is often of questionable reliability [19]. More than 96 percent of individuals who have resided 30 years in the United States have serologic evidence of prior varicella, and a majority of people claiming no prior varicella have varicella-zoster virus (VZV) antibody [20]. Moreover, inadvertent administration of zoster vaccine live (ZVL) to VZV-naïve individuals has been well tolerated in immune competent individuals [21]. (See "Diagnosis of varicella-zoster virus infection", section on 'Serologic testing'.)

Choice of vaccine — There are two types of zoster vaccine:

A non-live recombinant glycoprotein E vaccine (designated recombinant zoster vaccine [RZV]; sold as Shingrix). RZV contains varicella-zoster virus glycoprotein E in combination with an adjuvant (AS01B).

A live attenuated vaccine (designated zoster vaccine live [ZVL]; sold as Zostavax). ZVL contains 18,700 (at expiry) to 60,000 plaque-forming units of virus, considerably more than the approximately 1350 plaque-forming units found in the Oka/Merck vaccine for prevention of varicella. (See "Vaccination for the prevention of chickenpox (primary varicella infection)".)

We suggest RZV rather than ZVL for most immunocompetent patients. Special considerations for immunocompromised hosts and other patient groups, as well as information on vaccine administration, are discussed below. (See 'Patients aged 50 to 59' below and 'Comorbid conditions' below and 'Patients who received live attenuated herpes zoster or varicella vaccine' below and 'Vaccine administration' below.)

We generally prefer RZV based upon evidence that it has greater efficacy, especially among people in their seventh to ninth decade (table 1) (see 'Efficacy of the different vaccines' below). In addition, there is less concern for waning immunity with RZV [22]. Although long-term data are not available for RZV, protection has extended to four years [23], and immune responses are elevated for at least six years [24]. With ZVL, protection appears unchanged through year 5 [25], but wanes significantly after about eight years (from approximately 50 percent to 20 to 30 percent) [25-31]. In one study, there was no benefit from ZVL in reducing herpes zoster after year 8, but prevention of postherpetic neuralgia was better preserved [28].

There are a few advantages of ZVL as compared with RZV. As an example, ZVL requires administration of one dose of the vaccine, versus two for RZV. In addition, ZVL has a lower incidence of side effects that prevent everyday activities. Systemic side effects such as myalgia, fatigue, headache, shivering, and fever typically occur in <1 percent of those who receive ZVL [32], but developed in approximately 11 percent of those who received RZV (table 1) [23,33]. However, these side effects usually resolve in one to three days [23,33,34], and rarely prevent patients from completing the RZV vaccine series. A more detailed discussion of the side effects of RZV and ZVL is presented below. (See 'Adverse events associated with RZV' below and 'Adverse events associated with ZVL' below.)

The choice of RZV as the preferred type of vaccine is consistent with recommendations from the Advisory Committee on Immunization Practices (ACIP), which were accepted by the United States Centers for Disease Control and Prevention [22]. However, not all members of the ACIP agreed with this preferential recommendation (vote split eight to seven), citing concerns about the lack of data on its performance among minority groups, relatively limited data on long-term vaccine safety and efficacy, including limited data when administered in a nonclinical trial setting, and issues related to a two-dose schedule.

Efficacy of the different vaccines — While the two vaccines have not been compared head-to-head, the efficacy of RZV observed in two randomized trials appears superior to that observed for ZVL.

Efficacy of ZVL – The efficacy of zoster vaccination for reducing the risk of herpes zoster and postherpetic neuralgia was first demonstrated in the Shingles Prevention Study (SPS), a placebo-controlled clinical trial that evaluated the ZVL in 38,546 adults 60 years of age or older [35]. More than 95 percent of the subjects completed three years of surveillance with the following results:

Confirmed herpes zoster occurred in 957 patients (2.5 percent). ZVL reduced the incidence of herpes zoster over approximately three years by 51 percent compared with placebo (1.6 versus 3.3 percent, respectively), but vaccine efficacy was significantly greater in individuals aged 60 to 69 years compared with those ≥70 years (63.9 versus 37.6 percent).

In those who developed herpes zoster, the median duration of pain and discomfort was modestly reduced in the vaccine group compared with the placebo group (21 versus 24 days, respectively).

The incidence of postherpetic neuralgia was reduced by 67 percent in the vaccine group (0.46 versus 1.38 cases per 1000 person-years). Unlike the incidence of herpes zoster, the benefit was greater in patients ≥70 years of age (0.71 versus 2.13 per 1000 person-years). (See "Postherpetic neuralgia".)

An immunology substudy of 1395 patients demonstrated increases in VZV-specific antibody and cell-mediated immunity at six weeks after vaccination compared with placebo [14]. These increases persisted during the three years of follow-up, although the magnitude of T cell responses declined over time.

A 2016 systematic review and meta-analysis confirmed the benefits observed in the earlier definitive SPS study and calculated that 50 people need to be vaccinated to protect one person [36].

A post-licensure observational study of ZVL effectiveness reinforced the potential of the vaccine to reduce significant morbidity in patients 60 years of age or older. This retrospective study evaluated immunocompetent patients (75,761 patients were vaccinated and 227,283 matched patients were unvaccinated) during a two-year period [37]. A total of 5434 cases of herpes zoster were identified; in an adjusted analysis, vaccination was associated with a significantly reduced risk of herpes zoster (hazard ratio, 0.45; 95% CI 0.42-0.48). This risk reduction occurred in all age strata (60 to >80 years of age) and among individuals with chronic diseases (eg, diabetes, liver disease, coronary artery disease). The risk of ophthalmic herpes zoster and hospitalization was also reduced by approximately two-thirds among vaccine recipients. An even larger effectiveness trial confirmed these findings for herpes zoster and postherpetic neuralgia [26].

The efficacy of vaccination among patients 50 to 59 years of age was evaluated in the Zostavax Efficacy and Safety Trial (ZEST). In this trial, 22,439 patients aged 50 to 59 years from the United States and Europe were randomly assigned to vaccine or placebo and followed for a mean of 15 months for the development of herpes zoster [38]. The vaccine efficacy for preventing herpes zoster was 70 percent (95% CI 54.1-80.6); zoster vaccine reduced the incidence of herpes zoster from 99 cases in the placebo group (6.6 per 1000 person-years) to 30 cases in the vaccine group (2 per 1000 person-years).

Efficacy of RZV – Two randomized controlled trials have evaluated the efficacy of RZV. In both trials that evaluated RZV, participants received the recombinant vaccine or placebo at zero and two months [23,33].

In one trial, 15,411 individuals ≥50 years old were evaluated [33]. During a mean follow-up of approximately three years, RZV reduced the risk of developing herpes zoster by 97.2 percent (95% CI 93.7-99.0); herpes zoster was confirmed in six individuals in the RZV group and 210 individuals in the placebo group. In addition, no cases of postherpetic neuralgia were reported in the RZV group compared with 18 cases reported in the placebo group.

RZV was subsequently evaluated in 13,900 adults 70 years or older who were followed for a mean of 3.7 years [23]. The efficacy of RZV in preventing herpes zoster was 90 percent (95% CI 84.2-93.7); herpes zoster developed in 23 patients who received the vaccine versus 223 who received placebo. In addition, the vaccine efficacy against postherpetic neuralgia was 89 percent (95% CI 68.7-97.1).

Special considerations

Patients aged 50 to 59 — Although both vaccines are approved for patients ≥50 years old, the ACIP does not recommend ZVL for patients aged 50 to 59 years [39], in part because of the limited long-term protection provided by ZVL [25-31]. Moreover, because of the lower rate of herpes zoster in this age group compared with persons ≥60 years old, routine vaccination with ZVL was not supported in a cost-effectiveness analysis [40].

Comorbid conditions

Patients with prior herpes zoster infection — Patients age 50 years or older with a history of herpes zoster should receive zoster vaccine. However, it is unclear when after infection patients should be vaccinated. We typically delay vaccination for approximately three years, since herpes zoster itself will boost VZV-specific immunity for several years.

Studies have found that ZVL can be safely administered to patients ≥50 years of age with a prior history of herpes zoster, although efficacy in this situation has not been established [41,42]. Studies of RZV in such patients are currently underway, but there is no reason to believe that there would be any safety concerns.

Immunocompromised hosts — There are insufficient data to make definitive recommendations regarding zoster vaccination in immunocompromised hosts ≥50 years old. Vaccination is not indicated for people <50 years old.

As with immunocompetent hosts, RZV is generally preferred. However, in certain patients, such as those with autoimmune conditions and transplant recipients, there are theoretical risks due to the immune response elicited by the adjuvant (eg, a flare of the underlying condition, rejection of the graft). Studies to answer these questions are underway.

The approach to vaccination in immunocompromised patients depends upon when immunosuppression is planned, the patient's underlying condition, and the choice of vaccine.

Planned immunosuppression – Patients ≥50 years of age should ideally be vaccinated prior to receiving immunosuppressive therapy. Since RZV requires two doses, the interval would be two months, plus an additional two to four weeks after the second dose for an optimal response to develop. If ZVL is used, it should be administered ≥4 weeks before the initiation of immunosuppressive therapy [43].

Patients receiving low-dose immunosuppressive therapy – Patients receiving low-dose immunosuppressive therapy would be expected to respond to vaccination. These therapies include [43]:

Low-dose prednisone (<2 mg/kg: maximum ≤20 mg/day) or equivalent

Methotrexate (≤0.4 mg/kg/week)

Azathioprine (≤3 mg/kg/day)

6-mercaptopurine (≤1.5 mg/kg/day)

The ACIP recommends RZV in such patients [22]. ZVL can also be used in patients receiving low-level immunosuppression, but disseminated herpes zoster with vaccine type virus has occurred rarely in such patients who have received ZVL [44].

Patients with underlying immunodeficiency and/or receiving moderate- to high-dose immunosuppressive therapy – We generally avoid vaccinating immunocompromised hosts who have an underlying immunodeficiency or are receiving moderate- to high-dose immunosuppressive therapy. This includes [39,43,45,46]:

Patients who have primary or acquired immunodeficiency – These disorders include leukemia, lymphoma, or other malignancies affecting the bone marrow or lymphatic system. (See "Immunizations in adults with cancer", section on 'Zoster vaccine' and "Primary immunodeficiency: Overview of management".)

Solid organ and hematopoietic stem cell transplant patients – The use of antiviral medications to prevent herpes zoster in transplant candidates and recipients is discussed elsewhere. (See "Immunizations in solid organ transplant candidates and recipients" and "Prophylaxis of infections in solid organ transplantation" and "Immunizations in hematopoietic cell transplant candidates and recipients" and "Prevention of infections in hematopoietic cell transplant recipients".)

HIV-infected patients with a CD4 cell count <200 cells/microL. (See "Immunizations in HIV-infected patients", section on 'Zoster vaccine'.)

Patients receiving immunomodulatory therapies such as disease-modifying anti-rheumatic, anti-multiple sclerosis, or biologic therapies (eg, corticosteroid therapy with a dose ≥20 mg/day of prednisone or equivalent for ≥14 days, rituximab, tofacitinib, tumor necrosis factor (TNF)-alpha, or Janus kinase inhibitors) [43,46]. (See "Overview of immunosuppressive and conventional (non-biologic) disease-modifying drugs in the rheumatic diseases".)

ZVL is contraindicated in these patients since they are at risk for developing disseminated VZV infection. ZVL can be administered to those who have completed immunosuppressive therapy after a certain period of time, provided that there is no evidence of ongoing immune compromise. As an example, patients who have received chemotherapy or radiation, and are in remission, should wait at least three months before receiving ZVL [45]. Among patients receiving other immunosuppressive agents (eg, high-dose corticosteroids, TNF-alpha inhibitors), vaccination should be deferred at least one month after completion of the treatment course.

There are no contraindications to administering RZV in immunocompromised hosts who have an underlying immunodeficiency or are receiving moderate- to high-dose immunosuppressive therapy, but there are insufficient data at this time to recommend routine vaccination with RZV [22]. Early studies suggest that RZV is safe and immunogenic in autologous hematopoietic stem cell populations [47], and additional data and guideline recommendations for these patients are forthcoming.

Other conditions — RZV is preferred for patients with diabetes mellitus; chronic heart, lung, liver, or kidney disease; functional or anatomical asplenia; or complement deficiencies who meet the age criterion [39], although either vaccine can be used. The safety and efficacy of vaccination in these populations has not been specifically evaluated; however, such patients were not excluded from the clinical trials of ZVL and RZV described above, and additional studies are underway. (See 'Efficacy of the different vaccines' above.)

The safety of RZV in patients with other comorbid conditions, such as multiple sclerosis, rheumatoid arthritis, and other autoimmune diseases, is less clear. Until more data are available, the benefits of using RZV must be weighed against the theoretical risks, such as a flare of underlying condition due to the immune response elicited by the adjuvant.

Household contacts of immunocompromised hosts — The RZV is preferred for household contacts of immunocompromised patients. ZVL is not contraindicated in this group, but immunocompromised patients should avoid contact with household contacts who develop skin lesions resulting from ZVL until the lesions clear [43]. Transmission of vaccine virus has not been reported in clinical trials [48]; however, the vaccine package insert mentions the possibility that transmission of vaccine virus to immunocompromised contacts may occur rarely from vaccine recipients who develop a varicella-like rash [49].

Patients who received live attenuated herpes zoster or varicella vaccine — We suggest that patients who previously received ZVL receive the two-dose series of RZV (see 'Vaccine administration' below). Data support that RZV can be safely administered to patients who have previously received ZVL [50].

The optimal timing of revaccination is unclear. However, for patients who received ZVL, the ACIP recommends that the first dose of the RZV be given at least eight weeks after ZVL [22].

Revaccination for patients who received ZVL is warranted given the reduced efficacy of ZVL compared with RZV (particularly in patients ≥70 years), as well as waning immunity, which is seen within five to eight years of receiving ZVL. Data supporting these findings are described above. (See 'Choice of vaccine' above and 'Efficacy of the different vaccines' above.)

The ACIP states that RZV may also be used in patients irrespective of prior receipt of varicella vaccine [22]. However, there are no data on the efficacy of the RZV in reducing vaccine strain herpes zoster in older people.

VACCINE ADMINISTRATION

Non-live recombinant glycoprotein E vaccine (RZV) — The non-live recombinant glycoprotein E vaccine (designated recombinant zoster vaccine [RZV]) was approved for use in the United States in October of 2017 [51]. The Advisory Committee on Immunization Practices (ACIP) recommends RZV as the preferred zoster vaccine for most patients because it provides greater protection, especially among people in their seventh to ninth decade (figure 2 and figure 3) [22]. (See 'Efficacy of the different vaccines' above.)

Dose and route of RZV — The recombinant zoster vaccine (RZV) requires two doses administered intramuscularly (IM) for protection. The second dose should be administered two to six months after the first [52].

This schedule should be used for all patients, including those with a history of prior herpes zoster and those who previously received zoster vaccine live (ZVL). The timing of vaccination in these patients is discussed above. (See 'Patients with prior herpes zoster infection' above and 'Patients who received live attenuated herpes zoster or varicella vaccine' above.)

If there is a deviation from the recommended schedule, the ACIP provides the following guidance [22]:

If there is a delay in administering the second dose, the series does not need to be restarted; however, the efficacy of the vaccine in this setting is unclear.

If the second dose is received less than four weeks after the first, the second dose should be repeated.

Administration of RZV with other vaccines — Although data are limited, the Centers for Disease Control and Prevention advises that recombinant vaccines, such as recombinant zoster vaccine (RZV), can be administered at the same time as other adult vaccines, but at different anatomic sites [22]. (See "Standard immunizations for nonpregnant adults".)

One study found that RZV can be safely administered with the quadrivalent influenza vaccine without affecting the immune response of either vaccine [53]. Studies evaluating the safety of RZV administered with other commonly used vaccines (eg, pneumococcal vaccines, and Tdap) are ongoing.

Adverse events associated with RZV — RZV can cause injection site and systemic reactions.

Injection site reactions – The most common side effect after RZV administration is pain at the injection site in 78 percent of subjects in the two trials [23,33]. Reactions that prevented normal everyday activities (pain, redness, and swelling) occurred in 9.4 percent of vaccine recipients.

Systemic reactions – The most common systemic effects in the trials were myalgia (44.7 percent), fatigue (44.5 percent), headache (37.7 percent), shivering (26.8 percent), fever (20.5 percent), and gastrointestinal symptoms (17.3 percent). Systemic effects that prevented normal everyday activities were reported by 10.8 percent of vaccine recipients versus 2.4 percent in those who received placebo [22].

In the clinical trials of RZV, combined local and systemic reactions that prevented everyday activities were more common among those who received RZV compared with placebo (16.5 versus 3.1 percent) [22,23,33]. However, most of these reactions only lasted one to three days, and the frequency and severity of these reactions rarely resulted in refusal of the second vaccine dose. There were no significant differences in the percentage of participants who experienced serious adverse events, immune mediated diseases, or death in the vaccine and placebo groups.

Contraindications to RZV — RZV should not be given to patients with a known allergy to the components of the vaccine.

Zoster vaccine live (ZVL) — ZVL may not continue to be widely available as the herpes zoster subunit vaccine (RZV) becomes increasingly available. However, since RZV was licensed only in October 2017 and was not readily available until early 2018, some providers may prefer to immunize with ZVL given the long-term experience with that vaccine. Other obstacles to early uptake of RZV include the side effect profile and the requirement for two doses. (See 'Non-live recombinant glycoprotein E vaccine (RZV)' above.)

Dose and route of ZVL — ZVL is administered as a one-time subcutaneous injection.

Administration of ZVL with other vaccines — ZVL may be administered at the same visit as other vaccines. However, other live vaccines (eg, measles, mumps, and rubella) should be separated by at least 28 days if they are not given on the same day.

There have been concerns that coadministration of PPSV23 may reduce the immunogenicity of ZVL [54-56]. Although the manufacturer states that clinicians should consider administering these two vaccines at least four weeks apart, the United States Centers for Disease Control and Prevention recommends that they be administered at the same visit to eligible patients [57,58]. This approach avoids barriers to receiving indicated vaccines. This is supported by an observational study that did not find a difference in the rate of herpes zoster among those who received both vaccines concurrently compared with those who received them four weeks apart [59]. (See "Pneumococcal vaccination in adults".)

Adverse events associated with ZVL — Zoster vaccine live (ZVL) is generally well tolerated [32,60,61].

Injection site reactions – The most common side effect after ZVL administration is pain at the injection site. In the randomized placebo-controlled pivotal trial, injection site pain was reported in 48 and 16 percent of vaccine and placebo recipients, respectively; the median duration was three days [32]. For most patients, the erythema, swelling, and pain were described as mild.

Acute retinal necrosis – Six cases of optic neuritis, acute retinal necrosis, uveitis, or keratitis following vaccination with ZVL have been reported; the patients developed loss of vision from six days to two months following vaccination, respectively [62]. Most were over 75 years of age and one was immunocompromised, having undergone renal transplantation. Although varicella-zoster virus (VZV) was detected from the vitreous or aqueous fluid by polymerase chain reaction in two patients, it was identified as the Oka strain of VZV (the viral strain used in both the varicella and zoster vaccines) only in the vitreous aspirate and core vitrectomy specimen of the immunosuppressed patient who developed retinitis approximately one month after receiving the varicella vaccine [63].

Vaccine-associated zoster – Vaccine-associated VZV can establish latency and, in rare cases, can reactivate to cause clinical herpes zoster. In a single immunocompetent patient, localized herpes zoster infection occurred nine months after vaccination with ZVL, and virologic studies confirmed that the infection was caused by the vaccine strain of virus [64].

Contraindications and precautions for ZVL — Contraindications to the administration of zoster vaccine live (ZVL) include:

Allergy – Patients with anaphylactic reactions to gelatin or neomycin [60]. (See "Allergic reactions to vaccines".)

Immunocompromise – ZVL should be avoided in populations that are at high risk for developing disseminated VZV infection. This is discussed in detail above. (See 'Immunocompromised hosts' above.)

Pregnancy – ZVL should not be administered to pregnant women; however, this scenario is unlikely since it is not indicated for women of childbearing age. (See "Immunizations during pregnancy", section on 'Immunizations to avoid during pregnancy'.)

Precautions to administration of ZVL include receipt of acyclovir, famciclovir, or valacyclovir 24 hours before vaccination and for 14 days after vaccination, as these antiviral agents may interfere with the vaccine [39].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Varicella-zoster virus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Vaccines for adults (The Basics)" and "Patient education: Vaccines (The Basics)" and "Patient education: Shingles (The Basics)")

Beyond the Basics topic (see "Patient education: Shingles (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Herpes zoster (shingles) results from reactivation of varicella-zoster virus (VZV) infection latent in sensory ganglia and is characterized by a painful, unilateral vesicular eruption in a dermatomal distribution. (See 'Introduction' above.)

A decline in VZV-specific cell-mediated immunity, which occurs in immune compromised and older individuals, is regarded as the major precipitant for VZV reactivation. (See 'Importance of cell-mediated immunity' above.)

Herpes zoster vaccination decreases the risk of developing herpes zoster and postherpetic neuralgia. It is not necessary to determine whether patients have a history of prior varicella (chickenpox) or herpes zoster, or to check antibodies prior to vaccination. (See 'Indications for vaccination' above.)

There are two types of vaccines, a non-live recombinant glycoprotein E vaccine (designated recombinant zoster vaccine [RZV]; approved for use in the United States in October 2017) and a live attenuated vaccine (designated zoster vaccine live [ZVL]). (See 'Efficacy of the different vaccines' above and 'Non-live recombinant glycoprotein E vaccine (RZV)' above and 'Zoster vaccine live (ZVL)' above.)

We consider vaccination in the following groups of patients:

For immunocompetent patients ≥60 years of age, we recommend zoster vaccination to prevent herpes zoster (Grade 1A). We also suggest zoster vaccination for such individuals who are 50 years of age or older (Grade 2A). (See 'Indications for vaccination' above and 'Patients aged 50 to 59' above.)

For patients with prior herpes zoster infection, we suggest vaccination against herpes zoster (Grade 2C). We delay vaccination for approximately three years since herpes zoster itself will boost VZV-specific immunity. However, the efficacy and appropriate timing of vaccination has not been studied in this setting. (See 'Patients with prior herpes zoster infection' above.)

For patients ≥50 years old who are planning immunosuppressive therapy (eg, transplant patients, chronic autoimmune disease), we recommend zoster vaccination as long as vaccination can be completed within a certain period of time prior to immunosuppression (Grade 1B). The timing of vaccination depends upon which type of vaccine is used. (See 'Immunocompromised hosts' above.)

If vaccination prior to immunosuppression is not possible, we suggest vaccination for patients receiving low-level immunosuppression (Grade 2B). However, for most other immunocompromised patients (eg, those who have a primary immunodeficiency or are receiving moderate- to high-dose immunosuppressive therapy), there are insufficient data to recommend routine vaccination with RZV, and ZVL is contraindicated. (See 'Immunocompromised hosts' above.)

We suggest RZV rather than ZVL for most patients (Grade 2B). RZV appears to provide greater protection against herpes zoster. In addition, there is less concern for waning immunity. Disadvantages of RZV are the need for two doses (versus one with ZVL), and an increased risk of mild to moderate side effects (including those that prevent everyday activities). However, the side effects typically resolve in one to three days, and these factors rarely prevent patients from completing the RZV series. (See 'Choice of vaccine' above and 'Vaccine administration' above.)

The only contraindication to RZV is hypersensitivity to the vaccine components. However, the safety of RZV in patients with comorbid conditions, such as multiple sclerosis, rheumatoid arthritis, and other autoimmune diseases, as well as transplant recipients, is still to be determined. Until more data are available, the benefits of using RZV in such patients must be weighed against the theoretical risks (eg, a flare of the underlying condition, rejection of the graft) due to the immune response elicited by the adjuvant. (See 'Contraindications to RZV' above and 'Other conditions' above.)

ZVL is contraindicated in most immunocompromised patients, as well as in patients with anaphylactic reactions to gelatin or neomycin and pregnant women. (See 'Contraindications and precautions for ZVL' above and 'Immunocompromised hosts' above.)

For patients who previously received ZVL, we suggest revaccination with RZV (Grade 2C). Such patients should receive the two-dose series, which should be initiated at least eight weeks after ZVL. (See 'Patients who received live attenuated herpes zoster or varicella vaccine' above.)

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