Zoster (herpes zoster)
Information about herpes zoster (shingles) disease, vaccines and recommendations for vaccination from the Australian Immunisation Handbook
Vaccination for certain groups of people is funded under the National Immunisation Program.
What's changed
More detailed guidance provided on the use of Zostavax in patients who are immunocompromised or on immunosuppressive therapy
- Further information on pre-vaccination screening (including serology for past varicella-zoster virus infection where relevant)
- List of immunosuppressive therapies where administration of Zostavax is considered safe expanded
Adverse events section updated to include detailed information on varicella - or zoster-like rash that could rarely occur following Zostavax, including relevant advice to vaccine recipients, and management and reporting of such an episode.
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
Zoster vaccine 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 zoster vaccine is recommended.
There is currently no booster recommendation for zoster vaccine.
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
Adults aged ≥60 years are recommended to receive zoster vaccine
A single dose of zoster vaccine is recommended for adults aged ≥60 years who have not previously received zoster vaccine. 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 the vaccine 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 zoster vaccination. Although vaccine 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, vaccination is less efficacious. People of this age may still receive some clinical benefit from being vaccinated.6
See Vaccine information and Epidemiology.
Adults aged 50–59 years are not routinely recommended to receive zoster vaccine, but they can receive it if they want to reduce their risk of herpes zoster
Zoster 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 zoster vaccine 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 zoster vaccine. 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.
See Vaccine information and Epidemiology.
Household contacts of people who are immunocompromised
People aged ≥50 years who are household contacts of a person who is immunocompromised are recommended to receive zoster vaccine
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). However, because the efficacy of zoster vaccine is around 40–65%, the vaccinated household member may still develop herpes zoster from wild-type VZV.
The rate of VZV-like rashes from the vaccine virus is very low. It is unlikely that vaccine-associated virus would be transmitted from a recently vaccinated person to a susceptible immunocompromised contact.1
If a vaccinated person develops a varicella- or zoster-like rash, 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 who have had a previous episode of herpes zoster can receive zoster vaccine
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.
People previously vaccinated with varicella vaccine
People who have received varicella vaccine are not recommended to receive zoster 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
Serological testing before and after zoster vaccination
Serological testing before zoster vaccination is recommended for some people
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 zoster vaccine.
However, serological testing before zoster vaccination is recommended if the person receiving the vaccine:
- has HIV (see People with HIV in Contraindications and precautions)
- has an uncertain level of immunocompromise and there is potential risk for adverse events identified in pre-vaccination screening (see People with mild to moderate immunocompromising conditions)
People who are immunosuppressed and have negative VZV IgG should not receive Zostavax. See also Contraindications and precautions.
The interpretation of serology for varicella (chickenpox) is difficult, as there is no serological correlate of protection, but a positive result indicates past exposure (from either natural infection or vaccination) and more than 97% of people in Australia are seropositive to VZV by 30 years of age,15 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 the vaccine was well tolerated and immunogenic in seronegative people,16,17 If an individual does not have evidence of previous VZV natural infection and is seronegative, very severe outcomes may occur in immunocompromised individuals.18 A cautious approach with detailed individual clinical assessment is required prior to administration of the Zostavax vaccine.
Adults who are seronegative to varicella-zoster virus are recommended to receive either varicella or zoster vaccine
More than 97% of older people in Australia are seropositive to varicella-zoster virus (VZV) from previous natural infection,15 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 zoster vaccine (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 the vaccine 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.16,17 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 in these adults, both underlying disease and medication(s), is required.
Serological testing after zoster vaccination is not recommended
Laboratory 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.
Vaccines, dosage and administration
Zoster vaccine available 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
Zostavax
Registered 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
Dose and route
The dose of Zostavax is 0.65 mL given by subcutaneous injection.
Co-administration 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
Anaphylaxis to vaccine components
Zoster vaccine is contraindicated in people who have had:
- anaphylaxis after a previous dose of any varicella-zoster virus (VZV)–containing vaccine
- anaphylaxis after any component of a VZV-containing 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 zoster vaccine 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 zoster vaccine 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 zoster vaccine 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 zoster vaccine after an appropriate time. See Table. Recommendations for use of zoster vaccine 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 after the previous dose of therapy. This can include biologics like Rituximab, which can have long-term effects on the immune system. Blood tests may be required to ensure that immune system recovery has occurred and biologic drug levels are low before contemplating vaccination. If you are uncertain about the level of immunosuppression in any person who has received a biologic therapy, do not give Zostavax or any other live attenuated vaccines. Consult with a medical specialist who can help determine the appropriate delay since last treatment and, in some cases, as noted above, can assess the patient’s immunological recovery.
| Immunosuppressive therapy | Safe dose to vaccinate | Dose vaccine contraindicated | Acceptable timing of vaccination if dose is contraindicated |
| Dose | Timing of vaccination | ||
| corticosteroid monotherapy |
≤20 mg per day of prednisilone or equivalent a |
≥20 mg/day of prednisilone or equivalent for less than 14 days |
|
| Anti-TNF — (Etanercept Infliximab Adalimumab) | None | All regimens |
|
| csDMARD | |||
| Azathioprine | ≤3mg/kg/day (if used as a single agent, with or without low-dose corticosteroid) |
>3.0 mg/kg/day |
|
| Mercaptopurine |
≤1.5mg/kg/day |
>1.5 mg/kg/day |
|
| Methotrexate | ≤0.4mg/kg/week (if used as a single agent, with or without low-dose corticosteroid) |
>0.4 mg/kg/week |
|
| Sulfasalazine, Hydroxychloroquine | Any dose | None | Not applicable |
| 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 |
|
| tsDMARDs - Janus kinase inhibitors (eg Tofacitinib), phosphodiesterase-4 inhibition (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 corticosteriod monotherapy or corticosteriod therapy combined with other disease-modulating or immunosuppressive therapy, consider delaying vaccination and consulting with both the treating doctor and an immunisation specialist.
For more information, please refer to the Zostavax screening tool.
Managing people who are immunocompromised and who inadvertently receive zoster vaccine
If an immunocompromised person is inadvertently vaccinated with zoster vaccine:
- 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
- clinical investigations, such as laboratory testing for VZV from any rash or other affected sites
Women who are pregnant or breastfeeding
Because zoster vaccine contains live attenuated VZV, it is contraindicated in pregnant women.
Women should avoid pregnancy for 28 days after vaccination. See also Varicella.
Adults can still receive zoster vaccine 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 zoster vaccine if they are eligible for vaccination.
Precautions
People with mild to moderate immunocompromising conditions
People ≥50 years of age with mild immunocompromising conditions may receive zoster vaccine.
Assess each person individually and, if necessary, seek appropriate specialist advice before vaccinating. See Table. Recommendations for use of zoster vaccine in people on immunosuppressive therapy and Vaccination for people who are immunocompromised.
For example, patients may be suitable to receive zoster vaccine if they are receiving a single conventional synthetic DMARDs 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 either on their own or in combination with low-dose corticosteroids (such as <20 mg per day of prednisone equivalent dose) may also be suitable to receive zoster vaccine following an individual assessment.23,24 At these doses, the person is not likely to be severely immunocompromised. However, careful pre-screening and a risk-based assessment prior to Zostavax administration are recommended. If necessary, this may include medical specialist consultation. Screening for pre-existing antibodies to VZV may be indicated and detection of VZV-specific antibody may assist in confirming previous VZV infection and thus immune memory. In someone with a mild level of immunocompromise, the presence of pre-existing immunity provides additional reassurance regarding the safe use of vaccine at the individual patient level. If immunotherapies are about to be commenced a 4-week interval between Zostavax vaccine administration and initiation of therapy is recommended. If this is not possible the vaccine should be withheld and specialist advice sought.
See Adverse events in people with immunocompromising conditions or on immununosuppressive therapy
Serological confirmation of VZV infection
For some people receiving immunosuppressive therapy or whose level of immunocompromise is uncertain following pre-vaccination assessment, it may be appropriate to confirm previous VZV infection using serological testing before vaccination. See Serological testing before and after zoster vaccination.
People with HIV
People ≥50 years of age with asymptomatic HIV infection can receive zoster vaccine 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
See Serological testing before and after zoster vaccination.
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 zoster vaccination 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 vaccinating 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. See Table. Recommendations for use of zoster vaccine in people on immunosuppressive therapy and Serological testing before and after zoster vaccination.
Vaccination before or after immunoglobulin or blood product administration
People ≥50 years of age can receive zoster vaccine at any time before or after receiving immunoglobulin or any antibody-containing blood product. This is because zoster vaccine 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 zoster vaccine. 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:
- acyclovir
- famciclovir
- valaciclovir
People taking an antiviral medicine should:6,24
- stop taking it at least 24 hours before vaccination
- start taking it again at least 14 days after vaccination
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 with high levels of immune suppression. Monitoring for a disseminated varicella-zoster virus (VZV)-like rash following Zostavax is an important component of adverse event following immunisation (AEFI) surveillance. See Adverse events in people with severe immuocompromise.
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 analysed rashes in the vaccine (and placebo) recipients for the presence of varicella-zoster virus (VZV) using PCR. Most rashes, in both groups, were due to wild-type virus. Only 2 participants in one early trial reported rashes due to the Oka VZV vaccine strain. See also Vaccine information.
Post-marketing studies 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 vaccine recipients than placebo recipients, and occurred in <0.1% of clinical trial participants overall.1
Systemic symptoms occurred in vaccine 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 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 varicella-zoster virus (VZV)-like rash occurs around 2–4 weeks post vaccination.29 This type of rash may be due to the Oka vaccine VZV strain. Zostavax recipients should be advised to seek immediate medical attention if this occurs and to inform the medical practitioner of recent vaccine receipt. Suspicion of disseminated VZV infection should prompt appropriate diagnostic testing, initiation of empirical antiviral treatment, consultation with an infectious diseases specialist and, where relevant, cessation of immunosuppressing medication. The relevant state or territory health authority, and the Therapeutic Goods Administration (TGA) should also be notified. (See How to report AEFIs)
Adverse events in people with immunocompromising conditions or on immunosuppressive therapy
Zostavax is contraindicated in severely immunocompromised people. Administering zoster vaccine 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 Two people with chronic lymphocytic leukaemia who were given Zostavax died from disseminated Oka vaccine virus disease.18,30,31 They were not receiving immunosuppressive treatment when they were vaccinated.
There has been one report in Australia of death of a patient who was on long-term hydroxychloroquine and a low-dose prednisolone (5 mg per day), from infection by the Oka (vaccine) strain varicella-zoster virus 3 weeks after receiving Zostavax vaccine. (See Therapeutic Goods Administration alert)
There is ongoing monitoring of global evidence on the safety of Zostavax by both the Therapeutic Goods Administration and the Australian Technical Advisory Group on Immunisation (ATAGI). To date, there has not been any other report of 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.32 After primary infection, the virus resides in the sensory ganglia.32
Herpes zoster, or shingles, occurs when latent VZV reactivates. This could be due, in part, to a decline in cellular immunity to the virus.33 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.33 Associated symptoms may include:34,35
- 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.30,34 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.37,38
Other complications depend on the site of reactivation, and may include:39
- 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.35
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.40-44 However, PHN can be difficult to treat and may persist for years.45
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.32,46-48
Second attacks of herpes zoster occur in approximately 5% of immunocompetent people, but are more common in people who are immunocompromised.11,12,33,36
In a large clinical trial of zoster vaccine 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.49
In comparison, there are about 1174 cases per 100,000 population in people aged ≥50 years.49 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.49
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.25,36
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.50,51
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.50
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. Zoster vaccine 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.53
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.26 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%
The vaccine 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, the pain associated with the episode was less severe.54
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 vaccine’s effect was in addition to any benefit from medical therapy.1,8
Duration of immunity
A single dose of zoster vaccine 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.2,55
A longer-term study of Shingles Prevention Study participants suggested that the vaccine 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).56
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. 18
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.57
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 zoster vaccine in people with a history of herpes zoster. The vaccine was well tolerated and immunogenic.58
Transporting, storing and handling vaccines
Transport according to National vaccine storage guidelines: Strive for 5.57 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
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Page history
Definitions
- AIDS
- acquired immunodeficiency syndrome
- PCR
- polymerase chain reaction
- ATAGI
- Australian Technical Advisory Group on Immunisation
- DNA
- deoxyribonucleic acid
- PHN
- post-herpetic neuralgia
- 23vPPV
- 23-valent pneumococcal polysaccharide vaccine
- SC
- subcutaneous
- WA
- Western Australia
- JE
- Japanese encephalitis