Zoster (herpes zoster)

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

Zoster vaccines are recommended for:

• people aged ≥50 years who are immunocompetent
• people aged ≥18 years who are immunocompromised
• people aged ≥50 years who are household contacts of a person who is immunocompromised

How

For Zostavax, a single dose is recommended. For Shingrix, 2 doses are recommended.

There is currently no booster recommendation for either zoster vaccine.

Why

The lifetime risk of reactivation of VZV is about 50%. The risk and severity of outcomes increases with age, affecting half of people who live to 80 years of age. The risk is higher in those who are immunocompromised.

See Infographic. Vaccination for healthy ageing.

Zoster vaccines available in Australia

There are 2 vaccines available in Australia for the prevention of herpes zoster and associated complications — Zostavax and Shingrix.

The Therapeutic Goods Administration website provides product information for each vaccine.

See also Vaccine information and Variations from product information for more details.

Dose and route

The dose of Zostavax is 0.65 mL given by subcutaneous injection.

Shingrix consists of 2 doses of 0.5 mL given 2–6 months apart in immunocompetent people or 1–2 months apart in people who are immunocompromised or shortly expected to be immunocompromised, given by intramuscular injection, preferably in the deltoid muscle.

Co-administration with other vaccines

Zostavax

People can receive Zostavax with other inactivated vaccines (such as tetanus-containing vaccines, influenza vaccine⁴² and pneumococcal polysaccharide vaccine^43-45), 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

Shingrix

People can receive Shingrix with other inactivated vaccines (such as tetanus-containing vaccines, pneumococcal vaccines, influenza vaccines and COVID-19 vaccines), either:^46-48

• at the same time, or
• at any time after

There is the potential for an increase in mild to moderate adverse events when more than one vaccine is given at the same time. Separation of Shingrix from other vaccines is preferable, where possible, particularly for vaccines for which co-administration data are currently limited — for example, adjuvanted influenza vaccine and COVID-19 vaccines.

Contraindications

Anaphylaxis to vaccine components

Zostavax is contraindicated in people who have had:

• anaphylaxis after a previous dose of any live varicella-zoster virus (VZV)–containing vaccine (Zostavax or varicella vaccine)
• anaphylaxis after any component of a live VZV-containing vaccine

Shingrix is contraindicated in people who have had:

• anaphylaxis after a previous dose of Shingrix
• anaphylaxis after any component of Shingrix

People who are immunocompromised or shortly expected to be immunocompromised

Zostavax is not recommended in people who are immunocompromised or shortly expected to be immunocompromised. It is contraindicated in people who are considered severely immunocompromised because it contains live attenuated VZV. Shingrix is the recommended vaccine for people aged ≥18 years who are immunocompromised or shortly expected to be immunocompromised because it is safe and efficacious in this population. See People aged ≥18 years who are immunocompromised or shortly expected to be immunocompromised.

Severe immunocompromise may be from either:

• a primary or acquired medical condition, or
• medical treatment

People who are immunocompromised include those who:

• are receiving high-dose systemic immunosuppressive therapy, such as chemotherapy, radiation therapy or oral corticosteroids (≥20 mg per day of prednisolone 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

Refer to Table. Recommendations for use of Zostavax in people aged ≥50 years on immunosuppressive therapy and see Live zoster vaccine (Zostavax) screening for contraindications tool. If there is uncertainty about the person’s level of immunocompromise and whether vaccination is safe, do not administer Zostavax.

People aged ≥50 years 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 aged ≥50 years on immunosuppressive therapy and Vaccination for people who are immunocompromised. See Live zoster vaccine (Zostavax) screening for contraindications tool.

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 the immune system has recovered and biologic drug levels are low. If there is uncertainty 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.

Managing people who are immunocompromised and who inadvertently receive Zostavax

If an immunocompromised person is inadvertently vaccinated with Zostavax:

• promptly assess them and monitor closely for symptoms or signs of disseminated VZV infection, such as fever or a chickenpox-like rash, within 2–4 weeks of receiving the vaccine
• 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
• consider the use of ZIG in people with severe immunocompromise
• 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.

People can still receive Zostavax if they have a household contact who is pregnant.

See Table. Vaccines 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.

There are no data on the use of Shingrix in pregnant or breastfeeding women.

Women of child-bearing age who are immunocompromised are recommended to receive Shingrix vaccine either:

• before a planned pregnancy, or
• as soon as practicable after delivery

Precautions

Zoster vaccines should not be used for the prevention of primary varicella infection (chickenpox). Varicella vaccine should be considered (see Varicella). They also should not be used for the treatment of acute herpes zoster illness or post-herpetic neuralgia.

People with mild immunocompromising conditions or who are shortly expected to be immunocompromised

People aged ≥18 years with any level of immunocompromise are recommended to receive Shingrix.

For people aged 18–49 years with any level of immunocompromise, or who are shortly expected to be immunocompromised, Shingrix is the only available vaccine.

Zostavax is not recommended in people who are immunocompromised and is contraindicated in those who are severely immunocompromised. Where Shingrix is not accessible, people aged ≥50 years with mild immunocompromising conditions or who are shortly expected to be immunocompromised may receive Zostavax. They are recommended to:

• be assessed on a case-by-case basis
• undergo serological testing before vaccination to confirm that they are VZV IgG-positive

Appropriate specialist advice should be sought before vaccinating. See Table. Recommendations for use of Zostavax in people aged ≥50 years on immunosuppressive therapy, Live zoster vaccine (Zostavax) screening for contraindications tool and Vaccination for people who are immunocompromised. If uncertain about the person’s level of immunocompromise and whether vaccination is safe, do not administer Zostavax.

People who are shortly expected to be immunocompromised may include those:

• anticipating solid organ transplantation⁴⁹
• 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 they have a high risk of developing zoster in the future, it is recommended to vaccinate them with a zoster vaccine at least 4 weeks before they become immunocompromised.⁵⁰ If a 4-week interval is not possible, Shingrix can be considered. Do not give Zostavax, and seek specialist advice.

See Adverse events in people with immunocompromising conditions or on immunosuppressive therapy.

Serological confirmation of VZV infection

For people aged ≥50 years with mild immunocompromising conditions or who are shortly expected to be immunocompromised, it is recommended 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 Live zoster vaccine (Zostavax) screening for contraindications tool. If uncertain about the person’s level of immunocompromise and whether vaccination is safe, do not administer Zostavax. See Serological testing before and after zoster vaccination and Considerations for timing of zoster vaccination.

People with HIV infection

People with asymptomatic HIV infection are likely to have a higher relative risk of developing herpes zoster in the future.⁵¹ People aged ≥18 years with HIV infection can receive Shingrix, which is the preferred vaccine. Shingrix is safe and immunogenic in people with HIV⁵²infection.

People aged ≥50 years with asymptomatic HIV infection can receive Zostavax, if Shingrix is not accessible, 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 that a CD4+ count >200 per µL is safe.⁵⁰

Before vaccinating a person with asymptomatic HIV infection with Zostavax:

• 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
• see Live zoster vaccine (Zostavax) screening for contraindications tool

See Serological testing before and after zoster vaccination and Considerations for timing of zoster vaccination.

Vaccination before or after administration of immunoglobulin or a blood product

People aged ≥50 years 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.

No precautions are required around immunoglobulins and blood product administration and administration of Shingrix in people aged ≥18 years.

People receiving long-term aspirin or salicylate therapy

People aged ≥18 years receiving long-term salicylate therapy (aspirin) can receive any registered zoster vaccine for their age. 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:^50,53

• stop taking it at least 24 hours before vaccination with Zostavax
• start taking it again at least 14 days after vaccination with Zostavax

See Live zoster vaccine (Zostavax) screening for contraindications tool.

No precautions are required around antiviral medications and administration of Shingrix.

Adverse events after Zostavax

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 people aged ≥50 years.^25,54

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. Injection site symptoms included erythema, pain, swelling and itching at the injection site.^54,55

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.^54,55

Fever of >38.3°C was not more common in vaccine recipients than in placebo recipients, and occurred in <0.1% of clinical trial participants overall.²⁵

Systemic symptoms occurred in vaccine recipients (6.3%) more commonly than in placebo recipients (4.9%). The most common systemic symptoms reported were headache⁵⁴ and fatigue.²⁵

Zostavax is a live attenuated vaccine and is contraindicated in people who are, or are soon to be, severely immunocompromised.

A thorough assessment of each person’s immune status should be undertaken before administering Zostavax. See Live zoster vaccine (Zostavax) screening for contraindications tool and Adverse events in people with immunocompromising conditions or on immunosuppressive therapy.

In clinical trials, both non-localised and localised (injection site) varicella-like rashes in Zostavax recipients were rare: 0.1% of vaccine recipients developed a rash, and this was more common than in placebo recipients.²⁵

A non-localised varicella-like rash can occur around 2–4 weeks after vaccination with Zostavax.56 This type of rash may be due to disseminated VZV infection from the Oka vaccine strain. Always advise people who have received Zostavax to:

• seek immediate medical attention if they develop a generalised varicella-like rash
• inform their medical practitioner that they have recently received Zostavax

If the person has suspected disseminated VZV infection:

• collect a sample for appropriate diagnostic testing and notify testing laboratory to conduct sequencing for Oka vaccine strain
• 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

Post-marketing surveillance of Zostavax in the United States found that the most common adverse events were injection site reactions and that vaccination did not increase the risk of adverse events such as cerebrovascular events or encephalitis.⁵⁷

Adverse events after Shingrix

Shingrix is a non-live vaccine and is safe for use in both immunocompetent and immunocompromised people. Local and systemic adverse events following vaccination with Shingrix are substantially more common than after placebo but generally do not prevent normal activities. It is important for people to receive the second dose of Shingrix to be adequately protected against herpes zoster.

Injection site reactions were experienced by 82% of trial participants aged ≥50 years who received Shingrix (compared with 12% who received placebo) and 74% of participants aged ≥70 years (compared with 10% who received placebo). ^2,3

Systemic adverse events (such as fever, fatigue, gastrointestinal symptoms, headache, shivering or myalgia) were experienced by 66% of trial participants aged ≥50 years who received Shingrix (compared with 30% who received placebo) and 53% of participants aged ≥70 years (compared with 25% who received placebo). There was no difference in the rates of serious adverse events compared with placebo.^2,3

In a small proportion of people (approximately 10%), reactions may be severe enough to disrupt normal daily activities; these are generally short-lived (1–3 days) and go away without treatment.

Rates of local and systemic reactions appear to be slightly higher after Shingrix than after Zostavax.^25,54,58

Before vaccination with Shingrix, immunisation providers should counsel people about what local and systemic reactions to expect, and the importance of completing the 2-dose schedule for an adequate level and duration of protection.

Guillain–Barré syndrome

Data from the United States suggest a possible but very rare risk of Guillain–Barré syndrome (GBS), a demyelinating neurological condition, following Shingrix (an estimated 3 additional cases per million doses administered).⁵⁹ However, GBS may also be triggered by zoster itself,⁶⁰ and modelling suggests that the overall benefits of vaccination outweigh the risks of GBS.⁶¹

Adverse events in people with immunocompromising conditions or on immunosuppressive therapy

Zostavax is contraindicated in severely immunocompromised people. Administering Zostavax to people who are severely immunocompromised can result in disseminated disease from the Oka vaccine virus.
Without an adequate immune response, the vaccine virus can replicate unchecked.^62,63 There have been 2 case reports, including one in Australia, of disseminated Oka vaccine virus disease, leading to death, in people with chronic lymphocytic leukaemia who were given Zostavax^.41,62,63 They were not receiving immunosuppressive treatment when they were vaccinated. Two further cases of vaccine-related deaths in Australia and one in Canada in people with varying levels of immunosuppression have been reported, occurring several weeks after receiving Zostavax. ^{64,65 66} These cases highlight the difficulty of assessing immunocompromise and the significant consequences that can result from inadvertent administration in an immunocompromised person. It is recommended that all people due to receive Zostavax are screened with the Live zoster vaccine (Zostavax) screening for contraindications tool before vaccination.

The TGA and the Australian Technical Advisory Group on Immunisation continue to monitor global evidence on the safety of Zostavax.

There are no additional safety concerns for people with immunocompromising conditions or on immunosuppressive therapy who receive Shingrix.

Varicella-zoster virus (VZV) is a DNA virus of the Herpesviridae family.

Pathogenesis

Primary infection with VZV is known as varicella or chickenpox.⁶⁷ After primary infection, the virus resides in the sensory ganglia.⁶⁷

Herpes zoster, or shingles, occurs when latent VZV reactivates. This could be due, in part, to a decline in cellular immunity to the virus.¹⁵ 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.⁵⁰

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.¹⁵ Associated symptoms may include:^68,69

• 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.^18,67 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.^70,71

Other complications depend on the site of reactivation, and may include:⁷²

• 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.⁶⁹

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.^73-77 However, PHN can be difficult to treat and may persist for years.⁷⁸

Herpes zoster occurs most commonly in people who:

• are older — 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.^67,79-81

For up to 8 years after an initial episode of zoster, the risk of a repeat episode in immunocompetent people is 6–8%.^26,27 Repeat episodes of herpes zoster are more common in people who are immunocompromised.³³

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.²⁵

Herpes zoster in Australia

In Australia, there are about 560 cases of herpes zoster per 100,000 population per year in all age groups.⁸

In comparison, there are about 1174 cases per 100,000 population in people aged ≥50 years.8 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.⁸

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 infection. In the 1st year after haematopoietic stem cell transplantation, up to 30% of patients may develop herpes zoster.^18,51

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.^13,14

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.^26,82,83 The population-based incidence of PHN is 3 times higher in people aged 70–79 years (235 per 100,000) than in people aged 50–59 years (73 per 100,000).⁸²

Two zoster vaccines are available for use in Australia for the prevention of herpes zoster.

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 people who usually remain seropositive for VZV after primary infection, but have declining cellular immunity as they get older.⁸⁴

It is important to review a person’s medical history and medication use before vaccination with Zostavax because it is contraindicated in people who are immunocompromised. See Contraindications and precautions.

Shingrix is a recombinant VZV glycoprotein E (gE) subunit vaccine, with AS01B adjuvant to stimulate the vaccine-related immune response. Shingrix is the preferred vaccine for use in people who are immunocompromised.

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.⁸⁵

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.⁵⁵ Zostavax has since been shown to reduce the incidence of herpes zoster in people 50–59 years of age.⁵⁴

Shingrix

Efficacy

In 2 large clinical trials, Shingrix provided 97% protection against herpes zoster in immunocompetent people ≥50 years of age and 91% protection in immunocompetent people ≥70 years^2,3 of age.

Vaccine efficacy of Shingrix against post-herpetic neuralgia (PHN), a persistent pain syndrome after herpes zoster, was 91% in immunocompetent people ≥50 years of age and 89% in immunocompetent people ≥70 years^2,3 of age.

In a small number of clinical trials of highly immunocompromised populations (autologous haematopoietic stem cell transplantation and haematological malignancy), including patients ≥18 years of age, Shingrix provided good protection against herpes zoster, PHN and herpes zoster–related hospitalisation.^23,24

Although data are lacking on the efficacy of Shingrix in a broad range of immunocompromised groups, trials demonstrate a robust immune response to the vaccine in a sufficient range of immunocompromised populations (HIV infection, renal transplant, solid organ malignancies receiving immunosuppressant/cytotoxic medications) to support a recommendation for the vaccine’s use in immunocompromised populations more generally.^{23,24,52,86,87}

Duration of immunity

High vaccine efficacy (>80%) has been demonstrated for at least 7 years after vaccination with 2 doses of Shingrix,9 and immunogenicity data suggest that protection may persist beyond 10 years.^2-4 In contrast, the effectiveness of Zostavax appears to decrease significantly by 5–10 years after vaccination.^1,5-7

Zostavax

Efficacy

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 people aged ≥60 years. Zostavax significantly reduced the likelihood of developing both herpes zoster and PHN.²⁵ Over a median of more than 3 years follow-up, Zostavax vaccination of people aged ≥60 years reduced the:²⁵

• 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.25 Efficacy against herpes zoster in the ≥80 years age group was lower (18% and not statistically different from placebo). However, there were fewer participants of this age in the study.⁵⁰

In people who developed herpes zoster despite vaccination with Zostavax, the pain associated with the episode was less severe.⁸⁸

Another randomised controlled study in >22,000 people aged 50–59 years showed that compared to placebo, the incidence of herpes zoster was lower in those who received Zostavax over an average follow-up period of 1.3 years (range 0–2 years). The vaccine efficacy for preventing herpes zoster was 69.8%.⁵⁴

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.^7,89

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.⁵

Transport according to National Vaccine Storage Guidelines: Strive for 5.90 Store at +2°C to +8°C. Do not freeze. Protect from light.

Zostavax and Shingrix 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.

For Zostavax, the reconstituted vaccine must be used within 30 minutes.

For Shingrix, the reconstituted vaccine can be kept up to 6 hours if refrigerated at +2°C to +8°C.

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.

Co-administration of Zostavax 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 of Zostavax in people with HIV infection

The product information for Zostavax states that the safety and efficacy of Zostavax have not been established in people with known HIV infection, with or without evidence of immunosuppression.

ATAGI recommends that Zostavax may be given to people who have HIV infection but are not immunocompromised, after confirming pre-existing immunity to varicella-zoster virus.

Co-administration of Shingrix with influenza vaccine

The product information for Shingrix states that the vaccine can be given concurrently with unadjuvanted seasonal influenza vaccine.

ATAGI recommends that Shingrix may be given concurrently with any influenza vaccine.

Administration of Shingrix to people with immunosuppression or immunodeficient conditions

The product information for Shingrix states that immunogenicity data for use of Shingrix in people with HIV infection or haematopoietic stem cell transplantation are available. Immunogenicity is still under investigation for people with other confirmed or suspected immunosuppressive or immunodeficient conditions.

ATAGI recommends that Shingrix is the preferred vaccine for people aged ≥50 years who are, or are soon to be, immunocompromised. Shingrix is the only vaccine available for use in people aged 18–49 years who are immunocompromised.

Administration of Shingrix to people previously vaccinated with a live attenuated zoster vaccine

The product information for Shingrix states that clinical trial data on the use of Shingrix in people who were previously vaccinated with a live attenuated zoster vaccine was in people aged ≥65 years, with an interval of ≥5 years between a live attenuated zoster vaccine and Shingrix.

ATAGI recommends that Shingrix can be administered to people aged ≥50 years who have previously received a live attenuated zoster vaccine when the interval between the live attenuated vaccine and the 1st dose of Shingrix is at least 12 months.

1. Tricco AC, Zarin W, Cardoso R, et al. Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis. BMJ 2018;363:k4029.
2. Cunningham AL, Lal H, Kovac M, et al. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. New England Journal of Medicine 2016;375:1019-32.
3. Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. New England Journal of Medicine 2015;372:2087-96.
4. Hastie A, Catteau G, Enemuo A, et al. Immunogenicity of the adjuvanted recombinant zoster vaccine: persistence and anamnestic response to additional doses administered 10 years after primary vaccination. Journal of Infectious Diseases 2020.
5. Morrison VA, Johnson GR, Schmader KE, et al. Long-term persistence of zoster vaccine efficacy. Clinical Infectious Diseases 2015;60:900-9.
6. 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.
7. Tseng HF, Harpaz R, Luo Y, et al. Declining effectiveness of herpes zoster vaccine in adults aged ≥60 years. Journal of Infectious Diseases 2016;213:1872-5.
8. MacIntyre R, Stein A, Harrison C, et al. Increasing trends of herpes zoster in Australia. PLoS One 2015;10(4):e0125025.
9. Boutry C, Hastie A, Diez-Domingo J, et al. The adjuvanted recombinant zoster vaccine confers long-term protection against herpes zoster: Interim results of an extension study of the pivotal phase 3 clinical trials ZOE-50 and ZOE-70. Clinical Infectious Diseases 2022;74:1459-67.
10. Liu B, Heywood AE, Reekie J, et al. Risk factors for herpes zoster in a large cohort of unvaccinated older adults: a prospective cohort study. Epidemiology and Infection 2015;143:2871-81.
11. Qian J, Heywood AE, Karki S, et al. Risk of Herpes Zoster Prior to and Following Cancer Diagnosis and Treatment: A Population-Based Prospective Cohort Study. Journal of Infectious Diseases 2019;220:3-11.
12. Forbes HJ, Bhaskaran K, Thomas SL, et al. Quantification of risk factors for herpes zoster: population based case-control study. BMJ 2014;348:g2911.
13. 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.
14. Scott FT, Johnson RW, Leedham-Green M, et al. The burden of herpes zoster: a prospective population based study. Vaccine 2006;24:1308-14.
15. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clinical Infectious Diseases 2007;44 Suppl 1:S1-26.
16. 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.
17. 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.
18. 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.
19. Australian Technical Advisory Group on Immunisation (ATAGI). The Australian Immunisation Handbook 10th ed. Canberra: The Australian Government Department of Health and Ageing; 2018.
20. Therapeutic Goods Administration. Zostavax vaccine safety advisory – not to be used in patients with compromised immune function. The Therapeutic Goods Administration,; 2017. (Accessed 3 July 2020). https://www.tga.gov.au/alert/zostavax-vaccine
21. Therapeutic Goods Administration. Zostavax vaccine safety advisory July 2020 - not to be used in people with compromised immune function. Therapeutic Goods Administration,; 2020. (Accessed 8 September 2022). https://www.tga.gov.au/alert/zostavax-vaccine-0
22. Therapeutic Goods Administration. Zostavax vaccine safety advisory December 2020 - risk of infection with the vaccine virus. Therapeutic Goods Administration; 2020. (Accessed 8 September 2022). https://www.tga.gov.au/news/safety-alerts/zostavax-vaccine-0
23. Bastidas A, de la Serna J, El Idrissi M, et al. Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial. JAMA 2019;322:123-33.
24. Dagnew AF, Ilhan O, Lee WS, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infectious Diseases 2019;19:988-1000.
25. 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.
26. 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.
27. Tseng HF, Bruxvoort K, Ackerson B, et al. The Epidemiology of Herpes Zoster in Immunocompetent, Unvaccinated Adults ≥50 Years Old: Incidence, Complications, Hospitalization, Mortality, and Recurrence. Journal of Infectious Diseases 2020;222:798-806.
28. Arvin A. Aging, immunity, and the varicella-zoster virus. New England Journal of Medicine 2005;352:2266-7.
29. Mills R, Tyring SK, Levin MJ, et al. Safety, tolerability, and immunogenicity of zoster vaccine in subjects with a history of herpes zoster. Vaccine 2010;28:4204-9.
30. Godeaux O, Kovac M, Shu D, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit candidate vaccine in adults ≥ 50 years of age with a prior history of herpes zoster: A phase III, non-randomized, open-label clinical trial. Human Vaccines and Immunotherapeutics 2017;13:1051-8.
31. Yanni EA, Ferreira G, Guennec M, et al. Burden of herpes zoster in 16 selected immunocompromised populations in England: a cohort study in the Clinical Practice Research Datalink 2000-2012. BMJ Open 2018;8:e020528.
32. Imafuku S, Matsuki T, Mizukami A, et al. Burden of herpes zoster in the Japanese population with immunocompromised/chronic disease conditions: Results from a cohort study claims database from 2005-2014. Dermatol Ther (Heidelb) 2019;9:117-33.
33. Muñoz-Quiles C, López-Lacort M, Díez-Domingo J, Orrico-Sánchez A. Herpes zoster risk and burden of disease in immunocompromised populations: a population-based study using health system integrated databases, 2009-2014. BMC Infectious Diseases 2020;20:905.
34. Weinmann S, Naleway AL, Koppolu P, et al. Incidence of herpes zoster among children: 2003-2014. Pediatrics 2019;144.
35. Hardy I, Gershon AA, Steinberg SP, LaRussa P. The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group. New England Journal of Medicine 1991;325:1545-50.
36. 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.
37. Gidding HF, MacIntyre CR, Burgess MA, Gilbert GL. The seroepidemiology and transmission dynamics of varicella in Australia. Epidemiology and Infection 2003;131:1085-9.
38. 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.
39. 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.
40. Cunningham AL, Heineman TC, Lal H, et al. Immune responses to a recombinant glycoprotein E herpes zoster vaccine in adults aged 50 years or older. Journal of Infectious Diseases 2018;217:1750-60.
41. 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.
42. 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.
43. 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.
44. Baylor NW. Perspective of the U.S. Food and Drug Administration on concomitant administration of Zostavax and Pneumovax [letter]. Vaccine 2011;29:8771.
45. 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.
46. Maréchal C, Lal H, Poder A, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine co-administered with the 23-valent pneumococcal polysaccharide vaccine in adults ≥50 years of age: A randomized trial. Vaccine 2018;36:4278-86.
47. Strezova A, Lal H, Enweonye I, et al. The adjuvanted recombinant zoster vaccine co-administered with a tetanus, diphtheria and pertussis vaccine in adults aged ≥50 years: A randomized trial. Vaccine 2019;37:5877-85.
48. Schwarz TF, Aggarwal N, Moeckesch B, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine coadministered with seasonal influenza vaccine in adults aged 50 years or older. Journal of Infectious Diseases 2017;216:1352-61.
49. 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.
50. 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.
51. Vafai A, Berger M. Zoster in patients infected with HIV: a review. American Journal of the Medical Sciences 2001;321:372-80.
52. Berkowitz EM, Moyle G, Stellbrink HJ, et al. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled study. Journal of Infectious Diseases 2015;211:1279-87.
53. 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. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html
54. 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.
55. 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.
56. 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.
57. 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.
58. Hata A, Inoue F, Hamamoto Y, et al. Efficacy and safety of live varicella zoster vaccine in diabetes: a randomized, double-blind, placebo-controlled trial. Diabetic Medicine 2016;33:1094-101.
59. Goud R, Lufkin B, Duffy J, et al. Risk of Guillain-Barré syndrome following recombinant zoster vaccine in Medicare beneficiaries. JAMA Intern Med 2021;181:1623-30.
60. Kang JH, Sheu JJ, Lin HC. Increased risk of Guillain-Barré Syndrome following recent herpes zoster: a population-based study across Taiwan. Clinical Infectious Diseases 2010;51:525-30.
61. Janusz CB, Anderson TC, Leidner AJ, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US adults. Human Vaccines and Immunotherapeutics 2022;18:2060668.
62. 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. https://www.tga.gov.au/alert/zostavax-vaccine
63. 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.
64. Dubey V, MacFadden D. Disseminated varicella zoster virus infection after vaccination with a live attenuated vaccine. CMAJ Canadian Medical Association Journal 2019;191:E1025-e7.
65. Therapeutic Goods Administration (TGA). Safety advisory - not to be used in people with compromised immune function. Therapeutic Goods Administration (TGA); 2020. (Accessed 21 July 2020). https://www.tga.gov.au/alert/zostavax-vaccine-0
66. Therapeutic Goods Administration (TGA). Safety advisory - risk of infection with the vaccine virus. Canberra, Australia: TGA; 2020. (Accessed 11 January 2020). https://www.tga.gov.au/alert/zostavax-vaccine-1
67. Levin MJ. Zoster vaccines. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM, eds. Plotkin's vaccines. 7th ed. Philadelphia, PA: Elsevier; 2018.
68. 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.
69. Gnann JW, Jr., Whitley RJ. Clinical practice. Herpes zoster. New England Journal of Medicine 2002;347:340-6.
70. Dworkin RH, Portenoy RK. Proposed classification of herpes zoster pain. The Lancet 1994;343:1648.
71. Kost RG, Straus SE. Postherpetic neuralgia – pathogenesis, treatment, and prevention. New England Journal of Medicine 1996;335:32-42.
72. Gross G, Doerr HW. Herpes zoster guidelines of the German Dermatological Society [letter]. Journal of Clinical Virology 2003;27:308-9.
73. 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.
74. Johnson RW, Dworkin RH. Treatment of herpes zoster and postherpetic neuralgia. BMJ 2003;326:748-50.
75. 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.
76. 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.
77. Simmons A. Management of shingles and post-herpetic neuralgia. Current Therapeutics 2000;41:61-6.
78. Dworkin RH, Schmader KE. Treatment and prevention of postherpetic neuralgia. Clinical Infectious Diseases 2003;36:877-82.
79. Schmader K. Herpes zoster in older adults. Clinical Infectious Diseases 2001;32:1481-6.
80. 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.
81. Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? The Lancet Infectious Diseases 2004;4:26-33.
82. 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.
83. 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.
84. Oxman MN. Vaccination to prevent herpes zoster and postherpetic neuralgia. Human Vaccines 2007;3:64-8.
85. 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.
86. Vink P, Delgado Mingorance I, Maximiano Alonso C, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: A randomized trial. Cancer 2019;125:1301-12.
87. Vink P, Ramon Torrell JM, Sanchez Fructuoso A, et al. Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clinical Infectious Diseases 2020;70:181-90.
88. 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.
89. 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.
90. National vaccine storage guidelines: Strive for 5. 2nd ed. Canberra: Australian Government Department of Health and Ageing; 2013. https://beta.health.gov.au/resources/publications/national-vaccine-stor…