Zoster (herpes zoster)
Information about herpes zoster (shingles) disease, vaccines and recommendations for vaccination from the Australian Immunisation Handbook.
Recently added
This page was added on 06 June 2018.
Updates made
This page was updated on 19 May 2022. View history of updates
Vaccination for certain groups of people is funded under the National Immunisation Program.
Overview
What
Herpes zoster, commonly known as shingles, is a reactivation of the varicella-zoster virus (VZV) in a person who has previously had varicella (chickenpox). Herpes zoster commonly presents as a painful, self-limiting vesicular rash in a dermatomal distribution.
Who
Zostavax is recommended for:
- adults aged ≥60 years
- adults aged ≥50 years who are household contacts of a person who is immunocompromised
How
A single dose of Zostavax is recommended.
There is currently no booster recommendation for Zostavax.
Why
The lifetime risk of reactivation of VZV is about 50%. It affects half of people who live to 80 years of age.
Recommendations
Adults
Zostavax vaccine is not routinely recommended for adults aged 50–59 years.
The incidence of herpes zoster in people aged 50–59 years is higher than people aged <50 years,4,7 and Zostavax is efficacious in this age group.8 However, the likelihood of developing herpes zoster, post-herpetic neuralgia and other complications of herpes zoster is lower in this age group than in people ≥60 years of age.9,10
People aged 50–59 years who want to reduce their risk of herpes zoster can receive Zostavax. However, the exact duration of vaccine efficacy is not known. Protection after a single vaccine dose wanes over time.2,3 The need for revaccination is not yet determined.
Please refer to the ATAGI clinical statement on the clinical use of Zoster vaccine in Australia.
See Vaccine information and Epidemiology.
View recommendation detailsAdults aged ≥60 years
A single dose of Zostavax is recommended for adults aged ≥60 years who have not previously received Zostavax. A dose is particularly recommended for adults who are 70–79 years of age.
In people aged 60–69 years, the incidence of both herpes zoster and post-herpetic neuralgia is high, and Zostavax is efficacious.1 However, the exact duration of vaccine efficacy is not known. Protection after a single vaccine dose wanes over time.2,3 The need for revaccination is not yet determined.
People aged 70–79 years are expected to benefit the most from routine vaccination with Zostavax. Although Zostavax efficacy against herpes zoster is lower in this age group than in people aged 50–69 years, people ≥70 years of age have a higher risk of both herpes zoster and post-herpetic neuralgia.1,4,5
In people aged ≥80 years, Zostavax is less efficacious. People of this age may still receive some clinical benefit from being vaccinated.6
Please refer to the ATAGI clinical statement on the clinical use of Zoster vaccine in Australia.
See Vaccine information and Epidemiology.
View recommendation detailsHousehold contacts of people who are immunocompromised
People ≥50 years of age who are household contacts of a person who is, or is expected to become, immunocompromised are recommended to receive zoster vaccine. This indirectly protects the immunocompromised household member from exposure to varicella-zoster virus (VZV).
Because the efficacy of zoster vaccines is not 100%, the vaccinated household member may still develop herpes zoster from wild-type VZV.
The rate of VZV-like rashes after Zostavax from the vaccine virus is very low. It is unlikely that vaccine-associated virus would be transmitted from a person recently vaccinated with Zostavax to a susceptible immunocompromised contact.1 VZV from vaccine-associated virus is not possible with Shingrix.
If a vaccinated person develops a varicella- or zoster-like rash after Zostavax, they should:
- cover the rash
- avoid contact with people who are immunocompromised until the rash clears
People who have had a previous episode of herpes zoster
People ≥50 years of age who have had a previous episode of herpes zoster can receive zoster vaccine at the recommended age.
The risk of a repeat episode of zoster is about 5% in immunocompetent people.10-12 In addition, a history of previous zoster may be inaccurate or a mistaken diagnosis.
An episode of herpes zoster boosts cellular and humoral immunity above baseline levels in most people. Studies suggest that this boost persists for at least 1 year and up to 3 years.13
It is suggested that people should wait at least 1 year after an episode of herpes zoster before they receive zoster vaccine. However, this timing is unclear and studies have not established an optimal time.
View recommendation detailsPeople previously vaccinated with varicella vaccine
People who have received varicella vaccine are not recommended to receive zoster vaccine.
Studies of the safety and immunogenicity of zoster vaccine in this setting are limited, and data are insufficient to suggest a benefit from vaccination.
It is unknown whether, in the future, populations vaccinated with varicella vaccine will experience rates of herpes zoster that are sufficient to warrant zoster vaccination. Preliminary information suggests that the incidence of herpes zoster in people who have received varicella vaccine is lower than in people infected with wild-type varicella.14
View recommendation detailsSerological testing before and after zoster vaccination
It is not necessary to have serological evidence of immunity to varicella-zoster virus (VZV) or a history of previous varicella infection before routine administration of Shingrix or routine administration of Zostavax.
However, serological testing before zoster vaccination is recommended if the person receiving Zostavax:
- has HIV (see People with HIV in Contraindications and precautions)
- has an uncertain level of immunocompromise and a potential risk for adverse events is identified in pre-vaccination screening (see People with mild to moderate immunocompromising conditions)
People who are immunocompromised and have negative VZV IgG should not receive Zostavax. See also Contraindications and precautions. If a person who is immunocompromised does not have evidence of previous VZV natural infection and is seronegative, they may have very severe outcomes after receiving Zostavax.15 A cautious approach with detailed individual clinical assessment is required to determine whether it is safe to administer Zostavax.
Interpreting serology for varicella (chickenpox) is difficult, as there is no serological correlate of protection. A positive result indicates past exposure from either natural infection or vaccination. More than 97% of people in Australia are seropositive to VZV by 30 years of age,16 even if they cannot recall having varicella at a younger age. In some small studies, high-dose VZV-containing vaccine (comparable to Zostavax) was given to healthy VZV-seronegative adults and previously infected adults. The limited data suggest that Zostavax was well tolerated and immunogenic in seronegative people.17,18
View recommendation detailsMore than 97% of people in Australia are seropositive to varicella-zoster virus (VZV) by 30 years of age,16 even if they cannot recall having varicella at a younger age.
Adults who are VZV-seronegative on laboratory testing and have no history of age-appropriate varicella vaccination may receive either:
- 2 doses of varicella vaccine (this is preferable — see Varicella), or
- 1 dose of Zostavax (if aged ≥50 years)
In some small studies, high-dose VZV-containing vaccine (comparable to Zostavax) was given to healthy VZV-seronegative adults and previously infected adults. The limited data suggest that Zostavax was well tolerated and immunogenic in seronegative people, but the incidence of self-limited injection site reactions may be slightly higher than in seropositive people.17,18
There are no specific studies of Zostavax safety in VZV-seronegative adults who have mild to moderate immunocompromising conditions. A cautious assessment of risk factors — both underlying disease and medications — is required in these adults.
View recommendation detailsLaboratory testing to check for an immune response after zoster vaccination is not recommended.
Zoster vaccine boosts both humoral and cellular immune responses. It is not necessary to confirm an immune response because it does not predict the level of protection against zoster.
In addition, routinely available serological assays are not designed to detect antibody levels after zoster vaccination, which may be lower than antibody levels after natural infection.
View recommendation detailsVaccines, dosage and administration
Zoster vaccines available in Australia
There are two vaccines available in Australia for the prevention of herpes zoster and associated complications – Zostavax and Shingrix. For clinical guidance on the use of Shingrix please refer to the ATAGI clinical statement on the clinical use of Zoster vaccine in Australia.
The Therapeutic Goods Administration website provides product information for each vaccine.
See also Vaccine information and Variations from product information for more details.
Zoster vaccines
Registered for use in adults aged ≥50 years
Recombinant Varicella Zoster Virus glycoprotein E antigen (ASO1B adjuvanted vaccine)
Powder and suspension
Each 0.5 mL reconstituted dose contains:
- 50 micrograms of gE antigen
- Sucrose
- Polysorbate 80
- Monobasic sodium phosphate dihydrate
- Dibasic potassium phosphate
These are adjuvanted with ASO1B Adjuvant System (Suspension). The adjuvant includes:
- plant extract Quillaja saponaria saponin (QS-21) (50 micrograms)
- 3-O-desacyl-4’-monophosphoryl lipid A (MPL) from Salmonella minnesota (50 micrograms)
- Dioleoylphosphatidylcholine
- Cholesterol Sodium chloride
- Dibasic sodium phosphate
- Monobasic potassium phosphate
For Product Information and Consumer Medicine Information about Shingrix visit the Therapeutic Goods Administration website.
View vaccine detailsRegistered for use in people aged ≥50 years.
Live herpes zoster vaccine
Lyophilised powder in a monodose vial with separate diluent.
Each 0.65 mL reconstituted dose contains:
- ≥19,400 plaque-forming units of live attenuated varicella-zoster virus (Oka/Merck strain)
- 41.05 mg sucrose
- 20.53 mg hydrolysed porcine gelatin
- 8.55 mg urea
- 0.82 mg monosodium glutamate
- residual components of MRC-5 cells
Also contains traces of:
- neomycin
- bovine serum albumin
For Product Information and Consumer Medicine Information about Zostavax visit the Therapeutic Goods Administration website.
View vaccine detailsDose and route
The dose of Zostavax is 0.65 mL given by subcutaneous injection.
Co-administration of Zostavax with other vaccines
Adults can receive Zostavax with other inactivated vaccines (such as tetanus-containing vaccines, influenza vaccine19 and pneumococcal polysaccharide vaccine20-22), either:
- at the same time, or
- at any time after
If a person needs both Zostavax and another live parenteral vaccine (such as measles-mumps-rubella or yellow fever), they can receive the vaccines either:
- on the same day, or
- at least 4 weeks apart
See also Varicella.
Contraindications and precautions
Contraindications to the use of Zostavax
Anaphylaxis to vaccine components
Zostavax is contraindicated in people who have had:
- anaphylaxis after a previous dose of any live varicella-zoster virus (VZV) vaccine
- anaphylaxis after any component of Zostavax vaccine
People who are immunocompromised
In people who are or have recently been immunocompromised due to a medical condition or medical treatment, consider the safety of giving Zostavax on a case-by-case basis. If uncertain about the person’s level of immunocompromise and whether vaccination is safe, do not vaccinate. Seek expert advice from the treating physician or an immunisation specialist. See also Adverse events.
Because Zostavax contains live attenuated VZV, it is contraindicated in people with current or recent severe immunocompromising conditions from either:
- a primary or acquired medical condition, or
- medical treatment
Refer to Table. Recommendations for use of Zostavax in people on immunosuppressive therapy.
This includes people who:
- are receiving high-dose systemic immunosuppressive therapy, such as chemotherapy, radiation therapy or oral corticosteroids (≥20 mg per day of prednisilone equivalent dose)
- are receiving biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs or tsDMARDs)
- have malignant conditions of the reticuloendothelial system (such as lymphoma, leukaemia or Hodgkin disease, even if they are not receiving active treatment)
- have AIDS or symptomatic HIV infection
- have similar immunocompromising conditions due to a disease or treatment
People who have stopped treatment with high-dose systemic immunosuppressive therapy may receive Zostavax after an appropriate time. See Table. Recommendations for use of Zostavax in people on immunosuppressive therapy and Vaccination for people who are immunocompromised.
In some cases, the level of immunocompromise that absolutely contraindicates live attenuated vaccines can last for 1 year or longer after the previous dose of therapy. This can occur after therapy with biologics such as rituximab, which can have long-term effects on the immune system. Blood tests may be needed before considering vaccination with Zostavax to ensure that immune system has recovered and biologic drug levels are low. If you are uncertain about the level of immunocompromise in any person who has received a biologic therapy, do not give Zostavax or any other live attenuated vaccine. Consult with a medical specialist who can help determine the appropriate interval since last treatment and, in some cases, can assess the person’s immunological recovery.
Immunosuppressive therapy | Safe dose to vaccinate | Dose at which vaccine is contraindicated | Acceptable timing of Zostavax if dose is contraindicated |
---|---|---|---|
Corticosteroid monotherapy | ≤20 mg per day of prednisolone or equivalenta | ≥20 mg/day of prednisolone or equivalent for less than 14 days |
|
≥20 mg per day of prednisolone or equivalent for 14 days or longer |
|
||
csDMARD — azathioprine | ≤3.0 mg per kg per day (if used as a single agent, with or without low-dose corticosteroids) | >3.0 mg per kg per day |
|
csDMARD — 6-mercaptopurine | ≤1.5 mg per kg per day (if used as a single agent, with or without low-dose corticosteroids) | >1.5 mg per kg per day |
|
csDMARD — methotrexate | ≤0.4 mg per kg per week (if used as a single agent, with or without low-dose corticosteroids) | >0.4 mg per kg per week |
|
csDMARDs — sulfasalazine or hydroxychloroquine | Any dose | None | Not applicable |
csDMARD — mycophenolate | None | All regimens |
|
Other csDMARDs | None | All regimens |
|
T-cell inhibitors or activators (eg tacrolimus, cyclosporine; except denosumab, for which there is no evidence of significant immunosuppression) | None | All regimens |
|
Other unspecified immunosuppressants (eg chemotherapy, radiotherapy) | None | All regimens |
|
Anti-TNF agents (eg etanercept, infliximab, adalimumab) | None | All regimens |
|
tsDMARDs — Janus kinase inhibitors (eg tofacitinib), phosphodiesterase-4 inhibitors (eg apremilast), or bDMARDs — monoclonal antibodies, IL inhibitors (eg anakinra, tocilizumab), costimulation blockers (eg abatacept), B-cell depleting agents (eg rituximab) | None | All regimens |
|
Haematopoietic stem cell transplant | None | All regimens |
|
b = biologic; cs = conventional synthetic; DMARD = disease-modifying anti-rheumatic drug; IL = interleukin; TNF = tumour necrosis factor; ts = target synthetic a If person is on long-term corticosteroid monotherapy or corticosteroid therapy combined with other disease-modulating or immunosuppressive therapy, consider delaying Zostavax and consulting with both the treating doctor and an immunisation specialist. |
Managing people who are immunocompromised and who inadvertently receive Zostavax
If an immunocompromised person is inadvertently vaccinated with Zostavax:
- promptly assess them
- discuss their appropriate management with an infectious diseases and/or immunisation expert
- notify the relevant state or territory health authority, and the Therapeutic Goods Administration (TGA)
For mechanisms for reporting to the TGA, see Adverse events following immunisation.
It is important to establish the person’s degree of immunocompromise and risk of vaccine-associated adverse effects. Patient management may include:
- pre-emptive or therapeutic use of antiviral medication as soon as possible after inadvertent administration of Zostavax
- clinical investigations, such as laboratory testing for VZV from any rash or other affected sites
Women who are pregnant or breastfeeding
Because Zostavax contains live attenuated VZV, it is contraindicated in pregnant women.
Women should avoid pregnancy for 28 days after vaccination with Zostavax. See also Varicella.
Adults can still receive Zostavax if they have a household contact who is pregnant.
See Table. Vaccines that are contraindicated in pregnancy: live attenuated vaccines in Vaccination for women who are planning pregnancy, pregnant or breastfeeding for more details.
Breastfeeding women can receive Zostavax if they are eligible for vaccination.
Precautions to the use of Zostavax
People with mild to moderate immunocompromising conditions
People ≥50 years of age with mild to moderate immunocompromising conditions may receive Zostavax.
Assess each person individually and, if necessary, seek appropriate specialist advice before vaccinating. See Table. Recommendations for use of Zostavax in people on immunosuppressive therapy and Vaccination for people who are immunocompromised.
For example, people may be suitable to receive Zostavax if they are receiving a single conventional synthetic DMARD in low doses, such as:
- azathioprine ≤3.0 mg per kg per day
- 6-mercaptopurine ≤1.5 mg per kg per day
- methotrexate ≤0.4 mg per kg per week
People who receive these non-biologic DMARDs in combination with low-dose corticosteroids (such as <20 mg per day of prednisolone equivalent) may also be suitable to receive Zostavax and should be individually assessed.23,24 At these doses, the person is not likely to be severely immunocompromised. However, careful pre-screening and a risk-based assessment are recommended before administering Zostavax. This may include medical specialist consultation or screening for pre-existing antibodies to VZV.
If the person is about to start immunotherapy, a 4-week interval is recommended between receiving Zostavax and starting therapy. If this is not possible, do not give Zostavax, and seek specialist advice.
See Adverse events in people with immunocompromising conditions or on immununosuppressive therapy
Serological confirmation of VZV infection
For some people receiving immunosuppressive therapy, or for those whose pre-vaccination assessment shows an uncertain level of immunocompromise, it may be appropriate to confirm previous VZV infection using serological testing before vaccination with Zostavax. Detection of VZV-specific antibody may help confirm previous VZV infection and therefore immune memory. In someone with a mild level of immunocompromise, pre-existing immunity provides additional reassurance about the safe use of Zostavax in that person. See Serological testing before and after Zostavax.
People with HIV
People ≥50 years of age with asymptomatic HIV infection can receive Zostavax if they are:
- on antiretroviral therapy and
- have a very low or undetectable viral load and
- have a CD4+ count ≥350 per µL
If there is a strong indication to vaccinate, some experts suggest a CD4+ count >200 per µL is safe.6
Before vaccinating a person with asymptomatic HIV infection:
- seek expert advice from the treating physician and/or an immunisation specialist (see also People with HIV in Vaccination for people who are immunocompromised)
- check for previous VZV infection using serological testing before vaccination with Zostavax
See Serological testing before and after Zostavax.
People with asymptomatic HIV infection are likely to have a higher relative risk of developing herpes zoster in the future.25 It is possible that both the efficacy and the safety of Zostavax may be lower in these people than in uninfected people.
People who are anticipating to be significantly immunocompromised in the future
Seek specialist advice before administering Zostavax to an immunocompetent person ≥50 years of age whose immune status may change because of an existing illness.6 This may include people:
- anticipating solid organ transplantation26
- with solid tumours that will require future chemotherapy or radiation therapy
- with inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease or psoriasis that may need further immunosuppressive medical treatment
These people may have a functioning immune system now, but may be significantly immunocompromised in the future because of their disease or treatment.
Because these people have a high risk of developing zoster in the future, it may be appropriate to vaccinate them at least 1 month before they become immunocompromised.6 Seek specialist advice.
Serological confirmation of previous VZV infection is recommended before vaccination with Zostavax. See Table. Recommendations for use of Zostavax vaccine in people on immunosuppressive therapy and Serological testing before and after Zostavax.
Vaccination before or after immunoglobulin or blood product administration
People ≥50 years of age can receive Zostavax at any time before or after receiving immunoglobulin or any antibody-containing blood product. This is because Zostavax is indicated in people who, because of their age, are assumed to have had previous infection with VZV. This means they already have serum antibody levels that are comparable to those found in blood products. See also Vaccination for people who have recently received normal human immunoglobulin and other blood products.
People receiving long-term aspirin or salicylate therapy
People ≥50 years of age receiving long-term salicylate therapy (aspirin) can receive Zostavax. Natural varicella infection and salicylate use has been associated with an increased risk of developing Reye syndrome. There have been no reports of an association between Reye syndrome and varicella vaccination.
People receiving antiviral medicines
Antivirals with anti-VZV activity may interfere with the replication of the Zostavax live attenuated virus. These antivirals include:
- aciclovir
- famciclovir
- valaciclovir
People taking an antiviral medicine should:6,24
- stop taking it at least 24 hours before vaccination with Zostavax
- start taking it again at least 14 days after vaccination with Zostavax
Contraindications and precautions to the use of Shingrix
Please refer to the ATAGI clinical statement on the clinical use of Zoster vaccine in Australia.
Adverse events
The Shingles Prevention Study was a very large clinical trial on live attenuated zoster vaccine (Zostavax). Together with other smaller studies, it demonstrated that Zostavax is safe and generally well tolerated among adults ≥50 years of age.1,8
Zostavax is contraindicated in people who are severely immunocompromised. It is important to monitor for a disseminated (non-localised) varicella-zoster virus (VZV)-like rash as a potential adverse event after Zostavax administration in these people. VZV-like rash after Zostavax administration has also very rarely been reported to occur in people who are immunocompetent or on low-dose immunosuppressive therapy. See Adverse events in people with immunocompromising conditions or on immunosuppressive therapy.
Injection site reactions
Injection site reactions occurred in 48% of clinical trial participants who received Zostavax, regardless of their history of herpes zoster, compared with 17% of participants who received placebo. These reactions included:8-27
- erythema
- pain
- swelling
- itching at the injection site
Mild to moderate adverse events, particularly injection site reactions, were more common in vaccine recipients aged 50–59 years than in those aged ≥60 years.8,27
Varicella-like rashes at the injection site were rare. 0.1% of vaccine recipients developed a rash, and this was more common than in placebo recipients.1
Varicella-like rashes that were not localised to the injection site were also rare. This occurred in vaccine and placebo recipients at the same incidence (0.1%).1
Clinical trials for Zostavax analysed rashes in the vaccine (and placebo) recipients for the presence of VZV using PCR. Most rashes, in both groups, were due to wild-type virus. Only 2 participants in 1 early trial reported rashes due to the Oka VZV vaccine strain. See also Vaccine information.
Post-marketing studies of Zostavax in the United States found a 2-fold increased risk in the 1st week after vaccination for events coded as ‘allergic reactions’. However, on more detailed review, most of these were injection site reactions.28
Systemic symptoms
Fever of >38.3°C was not more common in Zostavax recipients than placebo recipients, and occurred in <0.1% of clinical trial participants overall.1
Systemic symptoms occurred in Zostavax recipients (6.3%) more commonly than in placebo recipients (4.9%). The most common systemic symptoms reported were headache8 and fatigue.1
Post-marketing surveillance of Zostavax in the United States in a cohort of almost 200,000 adults found that vaccination did not increase the risk of adverse events such as cerebrovascular events or encephalitis.28
Very rarely, a non-localised VZV-like rash occurs around 2–4 weeks after vaccination with Zostavax.29 This type of rash may be due to the Oka vaccine VZV strain. Always advise people who have received Zostavax to:
- seek immediate medical attention if they develop a generalised VZV-like rash
- inform their medical practitioner that they have recently received Zostavax.
If the person has suspected disseminated VZV infection:
- conduct appropriate diagnostic testing
- start empirical antiviral treatment
- consult with an infectious diseases specialist
- stop immunosuppressive therapy, if relevant
- notify the relevant state or territory health authority, and the Therapeutic Goods Administration (TGA) - see Reporting AEFIs
Adverse events in people with immunocompromising conditions or on immunosuppressive therapy
Zostavax is contraindicated in severely immunocompromised people. Administering Zostavax to people with severe immunocompromise can result in disseminated disease from the Oka vaccine virus. Without an adequate immune response, the vaccine virus can replicate unchecked.30,31 2 people with chronic lymphocytic leukaemia who were given Zostavax died from disseminated Oka vaccine virus disease.15,30,31 They were not receiving immunosuppressive treatment when they were vaccinated. Another person, who at the time of vaccination was taking prednisolone and had also recently been taking checkpoint inhibitors, died a few weeks after receiving Zostavax.33
People on multiple medications associated with low level immunosuppression may also be at risk. In Australia, 1 person died from infection with the Oka VZV vaccine strain 3 weeks after receiving Zostavax. The person was taking long-term hydroxychloroquine and low-dose prednisolone (5 mg per day).32
The TGA and the Australian Technical Advisory Group on Immunisation (ATAGI) continue to monitor global evidence on the safety of Zostavax. To date, there have been no other reports of a fatal outcome from vaccine-related VZV infection in people who were either mildly immunocompromised or not known to be immunocompromised.
Nature of the disease
Varicella-zoster virus (VZV) is a DNA virus of the Herpesviridae family.
Pathogenesis
Primary infection with VZV is known as varicella or chickenpox.33 After primary infection, the virus resides in the sensory ganglia.33
Herpes zoster, or shingles, occurs when latent VZV reactivates. This could be due, in part, to a decline in cellular immunity to the virus.34 Virus-specific cellular immunity most commonly declines with ageing or with immunocompromising medical conditions or immunosuppressive treatment.
Transmission
VZV spreads through direct contact with fluid from the rash blisters caused by herpes zoster. This can cause primary varicella in exposed susceptible people.6
Clinical features
Most cases present with a unilateral vesicular rash in a dermatomal distribution.
80% of cases have a prodromal phase 48–72 hours before the rash appears.34 Associated symptoms may include:35,36
- headache
- photophobia
- malaise
- itching, tingling or severe pain in the affected dermatome
In most people, herpes zoster is an acute and self-limiting disease. The rash usually lasts 10–15 days.33,37 However, complications can occur, especially with increasing age.
PHN and other complications
Post-herpetic neuralgia (PHN) is the most frequent debilitating complication of herpes zoster. PHN is a neuropathic pain syndrome that persists or develops after the dermatomal rash has healed.
PHN is most commonly defined as the persistence of pain for longer than 3 months after the onset of the rash. But definitions can vary by the period of persistent pain.38,39
Other complications depend on the site of reactivation, and may include:40
- ophthalmic disease, such as keratitis and chorioretinitis
- neurological complications, such as meningoencephalitis and myelitis
- secondary bacterial skin infection
- scarring
- pneumonia
Rarely, some people may develop disseminated herpes zoster. This is characterised by widespread vesicular rash, and visceral, central nervous system and pulmonary involvement. Disseminated disease is more common in people who are immunocompromised, and may be fatal.36
Some people may also experience dermatomal pain without a rash. This is known as zoster siné herpéte.
Treating herpes zoster
Antiviral therapy can reduce the severity and duration of herpes zoster if therapy starts within 3 days of onset.
Antiviral therapy may also reduce the risk of developing PHN.41-45 However, PHN can be difficult to treat and may persist for years.46
Epidemiology
Herpes zoster occurs most commonly in people who:
- are of older age — particularly >50 years
- are immunocompromised
- had varicella in the 1st year of life
The lifetime risk of reactivation of varicella-zoster virus is about 50%. It affects half of people who live to 80 years.33,47-49
Second attacks of herpes zoster occur in approximately 5% of immunocompetent people, but are more common in people who are immunocompromised.11,12,34,37
In a large clinical trial of Zostavax in the United States (the Shingles Prevention Study), active surveillance in the unimmunised (placebo) participants estimated the herpes zoster incidence at 1112 cases per 100,000 person-years in people ≥60 years of age.1
Herpes zoster in Australia
In Australia, there are about 560 cases of herpes zoster per 100,000 population per year in all age groups.50
In comparison, there are about 1174 cases per 100,000 population in people aged ≥50 years.50 Herpes zoster incidence increases with age, from an estimated rate of 630 per 100,000 population in people aged 50–59 years, to 1531 per 100,000 population in people aged 70–79 years.50
Herpes zoster in people who are immunocompromised
People who are immunocompromised have an increased risk of herpes zoster compared with non-immunocompromised people. Rates of herpes zoster are up to 15 times higher in people who are immunocompromised due to HIV. In the 1st year after haematopoietic stem cell transplantation, up to 30% of patients may develop herpes zoster.25,37
Rate of complications from herpes zoster
Overall, 13–26% of patients with herpes zoster develop complications. Complications occur more often in older people and people who are immunocompromised.51,52
Post-herpetic neuralgia (PHN) is the most common complication of herpes zoster, but it occurs very infrequently in children and young adults. PHN occurs in approximately 1 in 5 herpes zoster cases in people aged >80 years, compared with approximately 1 in 10 cases in people aged 50–59 years.4,5,9 The population-based incidence of PHN is 3 times higher in people 70–79 years of age (235 per 100,000) than in people 50–59 years of age (73 per 100,000).4
Vaccine information
Zostavax is a live attenuated vaccine formulated from the same varicella-zoster virus (VZV) strain (Oka) as the registered varicella (chickenpox) vaccine Varivax. But Zostavax has higher potency (on average, at least 14 times greater) than Varivax. The higher viral titre in Zostavax is needed to boost the immune response in adults who usually remain seropositive to VZV after primary infection, but have declining cellular immunity as they get older.53
Zostavax is used to prevent herpes zoster in people >50 years of age. It is important to note that:
- registered varicella vaccines should not be used to prevent herpes zoster in older people
- Zostavax is not indicated for use in younger people who have not been previously immunised or infected with VZV
- Zostavax is not indicated for use for therapeutic benefit during an acute herpes zoster episode, nor to treat post-herpetic neuralgia (PHN)
It is important to review a person’s medical history and medication use before vaccination. Zostavax is contraindicated in people who are immunocompromised. See Contraindications and precautions.
Vaccine formulation
In Australia, a refrigerated form of Zostavax is registered based on comparable immunogenicity and safety to the frozen vaccine formulation that was used in the Shingles Prevention Study.54
Zostavax is also registered for use in people 50–59 years of age based on a study that demonstrated similar immunogenicity in this age group compared with those ≥60 years of age.27 Zostavax has since been shown to reduce the incidence of herpes zoster in people 50–59 years of age.8
Efficacy studies
The Shingles Prevention Study was a single large, randomised, double-blind, placebo-controlled efficacy study of the frozen formulation of Zostavax. The study included 38,546 adults aged ≥60 years. Zostavax significantly reduced the likelihood of developing both herpes zoster and PHN.1 Over a median of more than 3 years follow-up, Zostavax vaccination of people aged ≥60 years reduced the:1
- incidence of herpes zoster by 51.3%
- incidence of PHN by 66.5%
- burden of illness associated with herpes zoster by 61.1%
Zostavax was better at reducing herpes zoster in people aged 60–69 years (64% efficacy) than in those aged 70–79 years (41% efficacy). However, efficacy against PHN was similar in both age groups.1 Efficacy against herpes zoster in the ≥80 years age group was lower (18% and not statistically different to placebo). However, there were fewer participants of this age in the study.6
In people who developed herpes zoster despite vaccination with Zostavax, the pain associated with the episode was less severe.55
Another randomised controlled study in >22,000 people aged 50–59 years showed that the incidence of herpes zoster was lower over an average follow-up period of 1.3 years (range 0–2 years). The vaccine efficacy for preventing herpes zoster was 69.8%.8 In these clinical trials, many participants received antiviral and pain medicines for their herpes zoster. This suggests that the effect of Zostavax was in addition to any benefit from medical therapy.1,8
Duration of immunity
A single dose of Zostavax appears to lose efficacy over time. One short-term follow-on study of Shingles Prevention Study participants showed a decline in vaccine efficacy. However, estimates remained statistically significant for up to 5 years after vaccination, with uncertain efficacy beyond that.2,56
A longer-term study of Shingles Prevention Study participants suggested that Zostavax significantly protected against herpes zoster for up to 8 years after vaccination. However, the study’s methods limit confidence in this result.3
One large observational study investigated vaccine effectiveness among community-dwelling adults aged ≥60 years. Vaccine effectiveness decreased with each year of follow-up (from 69% in the 1st year to 4% in the 8th year).57
Co-administration with other vaccines
In one study, participants received Zostavax at the same time as inactivated influenza vaccine, in different syringes and at different injection sites. Immunogenicity and safety were comparable to giving the vaccines at different times.19
In another study, participants received Zostavax at the same time as 23vPPV (23-valent pneumococcal polysaccharide vaccine; Pneumovax 23). Co-administration had no effect on the immunogenicity of 23vPPV. However, the immunogenicity of Zostavax (indicated by VZV antibody levels) may be lower than if the 2 vaccines were given 4 weeks apart.58
However, VZV antibody levels do not directly correlate with clinical protection. Also, a large observational study from the United States reported that co-administration of Zostavax and 23vPPV did not affect the effectiveness of Zostavax against herpes zoster.20-22
Use in people with a history of herpes zoster
People with a history of herpes zoster were excluded from the Shingles Prevention Study (see Vaccine information), so there are no data on vaccine efficacy in this group.
One small clinical trial studied the safety and immunogenicity of Zostavax in people with a history of herpes zoster. Zostavax was well tolerated and immunogenic.59
Transporting, storing and handling vaccines
Transport according to National vaccine storage guidelines: Strive for 5.60 Store at +2°C to +8°C. Do not freeze. Protect from light.
Zostavax must be reconstituted. Add the entire contents of the diluent container to the vial and shake until the powder completely dissolves. Reconstitute immediately after taking the vaccine out of the refrigerator. Use the reconstituted vaccine within 30 minutes.
Public health management
Herpes zoster is a notifiable disease in most states and territories in Australia.
State and territory public health authorities can provide advice about the public health management of herpes zoster, including management of cases and their contacts.
Variations from product information
Co-administration with influenza vaccine and 23vPPV
The product information for Zostavax states that the vaccine can be given concurrently with inactivated influenza vaccine but not with 23-valent pneumococcal polysaccharide vaccine (23vPPV).
The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that Zostavax may be given concurrently with other vaccines, including 23vPPV.
Administration in people with HIV
The product information for Zostavax states that the safety and efficacy of Zostavax have not been established in adults with known HIV infection with or without evidence of immunosuppression.
ATAGI recommends that Zostavax may be given to people who have HIV but are not immunocompromised, after confirming pre-existing immunity to varicella-zoster virus.
References
- Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. New England Journal of Medicine 2005;352:2271-84.
- Schmader KE, Oxman MN, Levin MJ, et al. Persistence of the efficacy of zoster vaccine in the Shingles Prevention Study and the Short-Term Persistence Substudy. Clinical Infectious Diseases 2012;55:1320-8.
- Morrison VA, Johnson GR, Schmader KE, et al. Long-term persistence of zoster vaccine efficacy. Clinical Infectious Diseases 2015;60:900-9.
- Stein AN, Britt H, Harrison C, et al. Herpes zoster burden of illness and health care resource utilisation in the Australian population aged 50 years and older. Vaccine 2009;27:520-9.
- Gauthier A, Breuer J, Carrington D, Martin M, Rémy V. Epidemiology and cost of herpes zoster and post-herpetic neuralgia in the United Kingdom. Epidemiology and Infection 2009;137:38-47.
- Centers for Disease Control and Prevention (CDC), Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Recommendations and Reports 2008;57(RR-5):1-30.
- Araújo LQ, MacIntyre CR, Vujacich C. Epidemiology and burden of herpes zoster and post-herpetic neuralgia in Australia, Asia and South America. Herpes 2007;14 Suppl 2:40-4.
- Schmader KE, Levin MJ, Gnann JW, Jr., et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50–59 years. Clinical Infectious Diseases 2012;54:922-8.
- Yawn BP, Saddier P, Wollan PC, et al. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clinic Proceedings 2007;82:1341-9.
- Hope-Simpson RE. The nature of herpes zoster: a long-term study and a new hypothesis. Proceedings of the Royal Society of Medicine 1965;58:9-20.
- Ragozzino MW, Melton LJ, III, Kurland LT, Chu CP, Perry HO. Population-based study of herpes zoster and its sequelae. Medicine 1982;61:310-6.
- Yawn BP, Wollan PC, Kurland MJ, St Sauver JL, Saddier P. Herpes zoster recurrences more frequent than previously reported. Mayo Clinic Proceedings 2011;86:88-93.
- Arvin A. Aging, immunity, and the varicella-zoster virus. New England Journal of Medicine 2005;352:2266-7.
- Centers for Disease Control and Prevention (CDC), Marin M, Guris D, et al. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Recommendations and Reports 2007;56(RR-4):1-40.
- Alexander KE, Tong PL,Macartney K, et al. Live zoster vaccination in an immunocompromised patient leading to death secondary to disseminated varicella zoster virus infection. Vaccine 2018;36:3890-3.
- Gidding HF, MacIntyre CR, Burgess MA, Gilbert GL. The seroepidemiology and transmission dynamics of varicella in Australia. Epidemiology and Infection 2003;131:1085-9.
- Diaz C, Dentico P, Gonzalez R, et al. Safety, tolerability, and immunogenicity of a two-dose regimen of high-titer varicella vaccine in subjects ≥13 years of age. Vaccine 2006;24:6875-85.
- Macaladad N, Marcano T, Guzman M, et al. Safety and immunogenicity of a zoster vaccine in varicella-zoster virus seronegative and low-seropositive healthy adults. Vaccine 2007;25:2139-44.
- Kerzner B, Murray AV, Cheng E, et al. Safety and immunogenicity profile of the concomitant administration of ZOSTAVAX and inactivated influenza vaccine in adults aged 50 and older. Journal of the American Geriatrics Society 2007;55:1499-507.
- Tseng HF, Smith N, Sy LS, Jacobsen SJ. Evaluation of the incidence of herpes zoster after concomitant administration of zoster vaccine and polysaccharide pneumococcal vaccine. Vaccine 2011;29:3628-32.
- Baylor NW. Perspective of the U.S. Food and Drug Administration on concomitant administration of Zostavax and Pneumovax [letter]. Vaccine 2011;29:8771.
- Centers for Disease Control and Prevention (CDC). Update on herpes zoster vaccine: licensure for persons aged 50 through 59 years. MMWR. Morbidity and Mortality Weekly Report 2011;60:1528.
- Shingles (herpes zoster). In: Ramsay M, ed. Immunisation against infectious disease: the green book. London: Public Health England; 2016.
- Kroger AT, Duchin J, Vázquez M. General best practice guidelines for immunization. Best practices guidance of the Advisory Committee on Immunization Practices (ACIP). Atlanta, GA: Centers for Disease Control and Prevention; 2017.
- Vafai A, Berger M. Zoster in patients infected with HIV: a review. American Journal of the Medical Sciences 2001;321:372-80.
- Gourishankar S, McDermid JC, Jhangri GS, Preiksaitis JK. Herpes zoster infection following solid organ transplantation: incidence, risk factors and outcomes in the current immunosuppressive era. American Journal of Transplantation 2004;4:108-15.
- Sutradhar SC, Wang WW, Schlienger K, et al. Comparison of the levels of immunogenicity and safety of Zostavax in adults 50 to 59 years old and in adults 60 years old or older. Clinical and Vaccine Immunology: CVI 2009;16:646-52.
- Tseng HF, Liu A, Sy L, et al. Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study. Journal of Internal Medicine 2012;271:510-20.
- Simberkoff MS, Arbeit RD, Johnson GR, et al. Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial. Annals of Internal Medicine 2010;152:545-54.
- Australian Government Department of Health, Therapeutic Goods Administration. Zostavax vaccine: Safety advisory – not to be used in patients with compromised immune function. 7 March 2017.
- Costa E, Buxton J, Brown J, et al. Fatal disseminated varicella zoster infection following zoster vaccination in an immunocompromised patient. BMJ Case Reports 2016; May 4: doi:10.1136/bcr-2015-212688.
- Therapeutic Goods Administration (TGA). Safety advisory - not be used in people with compromised immune function. Therapeutic Goods Administration (TGA); 2020. (Accessed 11 January 2020). https://www.tga.gov.au/alert/zostavax-vaccine-0
- Levin MJ. Zoster vaccines. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM, eds. Plotkin's vaccines. 7th ed. Philadelphia, PA: Elsevier; 2018.
- Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clinical Infectious Diseases 2007;44 Suppl 1:S1-26.
- Whitley RJ. Varicella-zoster virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 7th ed. Philadelphia: Churchill Livingstone; 2010.
- Gnann JW, Jr., Whitley RJ. Clinical practice. Herpes zoster. New England Journal of Medicine 2002;347:340-6.
- Whitley RJ. Chickenpox and herpes zoster (varicella-zoster virus). In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015.
- Dworkin RH, Portenoy RK. Proposed classification of herpes zoster pain. The Lancet 1994;343:1648.
- Kost RG, Straus SE. Postherpetic neuralgia – pathogenesis, treatment, and prevention. New England Journal of Medicine 1996;335:32-42.
- Gross G, Doerr HW. Herpes zoster guidelines of the German Dermatological Society [letter]. Journal of Clinical Virology 2003;27:308-9.
- Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Archives of Family Medicine 2000;9:863-9.
- Johnson RW, Dworkin RH. Treatment of herpes zoster and postherpetic neuralgia. BMJ 2003;326:748-50.
- Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia: a meta-analysis. Archives of Internal Medicine 1997;157:909-12.
- Meister W, Neiss A, Gross G, et al. Demography, symptomatology, and course of disease in ambulatory zoster patients: a physician-based survey in Germany. Intervirology 1998;41:272-7.
- Simmons A. Management of shingles and post-herpetic neuralgia. Current Therapeutics 2000;41:61-6.
- Dworkin RH, Schmader KE. Treatment and prevention of postherpetic neuralgia. Clinical Infectious Diseases 2003;36:877-82.
- Schmader K. Herpes zoster in older adults. Clinical Infectious Diseases 2001;32:1481-6.
- Brisson M, Edmunds WJ, Law B, et al. Epidemiology of varicella zoster virus infection in Canada and the United Kingdom. Epidemiology and Infection 2001;127:305-14.
- Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? The Lancet Infectious Diseases 2004;4:26-33.
- MacIntyre R, Stein A, Harrison C, et al. Increasing trends of herpes zoster in Australia. PLoS One 2015;10(4):e0125025.
- Edmunds WJ, Brisson M, Rose JD. The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales. Vaccine 2001;19:3076-90.
- Scott FT, Johnson RW, Leedham-Green M, et al. The burden of herpes zoster: a prospective population based study. Vaccine 2006;24:1308-14.
- Oxman MN. Vaccination to prevent herpes zoster and postherpetic neuralgia. Human Vaccines 2007;3:64-8.
- Gilderman LI, Lawless JF, Nolen TM, et al. A double-blind, randomized, controlled, multicenter safety and immunogenicity study of a refrigerator-stable formulation of Zostavax. Clinical and Vaccine Immunology: CVI 2008;15:314-9.
- Schmader KE, Johnson GR, Saddier P, et al. Effect of a zoster vaccine on herpes zoster–related interference with functional status and health-related quality-of-life measures in older adults. Journal of the American Geriatrics Society 2010;58:1634-41.
- Hales CM, Harpaz R, Ortega-Sanchez I, Bialek SR. Update on recommendations for use of herpes zoster vaccine. MMWR. Morbidity and Mortality Weekly Report 2014;63:729-31.
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Page history
There is updated clinical guidance on the use of both zoster vaccines, Zostavax and Shingrix, that is relevant for people aged ≥18 years. Please refer to the ATAGI clinical statement on the clinical use of Zoster vaccine in Australia.
More detailed guidance provided on the use of Zostavax in people who are immunocompromised or on immunosuppressive therapy, including:
- more details on pre-vaccination screening, including serological testing for past varicella-zoster virus (VZV) infection when relevant
- expanded list of immunosuppressive therapies that are considered safe for administration of Zostavax
Adverse events section updated to include:
- detailed information on VZV-like rash that could rarely occur following Zostavax administration
- relevant advice to vaccine recipients
- management and reporting of these episodes
Changes to 4.24.7 Recommendations, 4.24.9 Contraindications, 4.24.10 Precautions, and 4.24.11 Adverse events
4.24.7 Recommendations
Addition of text reiterating importance of obtaining a medical history in patients prior to vaccination, to reiterate the contraindications regarding use of zoster vaccine in immunocompromised individuals and to provide further detail on what constitutes immunocompromise and how to manage inadvertent vaccination in these individuals.
4.24.9 Contraindications
Addition of text and table to reiterate the contraindications regarding use of zoster vaccine in immunocompromised individuals and to provide further detail on what constitutes immunocompromise and how to manage inadvertent vaccination in these individuals.
4.24.10 Precautions
Addition of text providing more specific detail of CD4 levels at which a person infected with HIV can receive zoster vaccine. (Refer also Chapter 3.3 Groups with special vaccination requirements).
4.24.11 Adverse events
Addition of text providing details of select serious outcomes where immunocompromised individuals have received zoster vaccine.
There is updated clinical guidance on the use of both zoster vaccines, Zostavax and Shingrix, that is relevant for people aged ≥18 years. Please refer to the ATAGI clinical statement on the clinical use of Zoster vaccine in Australia.
More detailed guidance provided on the use of Zostavax in people who are immunocompromised or on immunosuppressive therapy, including:
- more details on pre-vaccination screening, including serological testing for past varicella-zoster virus (VZV) infection when relevant
- expanded list of immunosuppressive therapies that are considered safe for administration of Zostavax
Adverse events section updated to include:
- detailed information on VZV-like rash that could rarely occur following Zostavax administration
- relevant advice to vaccine recipients
- management and reporting of these episodes
Changes to 4.24.7 Recommendations, 4.24.9 Contraindications, 4.24.10 Precautions, and 4.24.11 Adverse events
4.24.7 Recommendations
Addition of text reiterating importance of obtaining a medical history in patients prior to vaccination, to reiterate the contraindications regarding use of zoster vaccine in immunocompromised individuals and to provide further detail on what constitutes immunocompromise and how to manage inadvertent vaccination in these individuals.
4.24.9 Contraindications
Addition of text and table to reiterate the contraindications regarding use of zoster vaccine in immunocompromised individuals and to provide further detail on what constitutes immunocompromise and how to manage inadvertent vaccination in these individuals.
4.24.10 Precautions
Addition of text providing more specific detail of CD4 levels at which a person infected with HIV can receive zoster vaccine. (Refer also Chapter 3.3 Groups with special vaccination requirements).
4.24.11 Adverse events
Addition of text providing details of select serious outcomes where immunocompromised individuals have received zoster vaccine.