Key information

Mode of transmission

Zoster is a reactivation of the varicella-zoster virus in someone who has previously had varicella disease (most often as chickenpox).

Direct contact with zoster vesicles has a low risk of causing varicella in non-immune individuals – can be prevented by covering the rash.

There is potential for aerosol transmission from some immunocompromised cases with viraemia.

Period of communicability

Until lesions have crusted.

Incidence and burden of disease

Increasing incidence with age; lifetime risk about 1 in 3. For those aged over 85 years, the risk is 1 in 2. Complications include post-herpetic neuralgia and herpes zoster ophthalmicus.

Funded vaccine

Recombinant zoster vaccine – rZV; Shingrix

Dose, presentation, route

  • 0.5 ml per reconstituted dose
  • vial of vaccine powder and vial of suspension for one dose. The vaccine must be reconstituted prior to injection.
  • Intramuscular injection only

Funded vaccine indications and recommended schedule

Two doses of rZV are funded for individuals at age 65 years.

Recommended, not funded

  • for use from age 50 years, including those aged 66 years and older, due to older age and comorbidity
  • for individuals aged 18 years or older with increased risk of zoster due to immunocompromise.

Vaccine efficacy/ effectiveness

rZV showed efficacy against both zoster and post herpetic neuralgia of over 90 percent in participants aged over 50 years and over 70 years, including those with comorbidities, maintained at 84 percent for at least 7 years and at 70 percent for up to 10 years.

Contraindications

For contraindications and precautions see section ‎23.6.1. Use in pregnancy is limited and not routinely recommended.

23.1. Virology

Varicella-zoster virus (VZV) is a DNA virus from the herpesvirus family. The virus is usually acquired in childhood and primary infection with VZV causes varicella disease (chickenpox). Herpes zoster (zoster), or ‘shingles’, is a clinical syndrome caused reactivation of latent VZV, which resides in the dorsal root or trigeminal nerve ganglia after primary infection. VZV is usually acquired in childhood, but it is often many decades before the virus reactivates, at times when cellular immunity is compromised and is unable to maintain suppression of the virus.

23.2. Clinical features

Herpes zoster (shingles) occurs when the cell-mediated immune response is impaired and unable to maintain suppression of latent varicella-zoster virus reactivation (see chapter ‎22). Zoster occurs only by loss of suppression and reactivation of the patient’s own virus – which is often acquired in childhood; it is not acquired from other patients with zoster or varicella.[1]

VZV, present at low levels in lesions of zoster rash, is transmissible via direct contact with fluid in the rash vesicles to VZV-naïve or other susceptible individuals (causing chickenpox). Episodes of zoster in older individuals provide a constant mechanism for reintroducing the virus, causing varicella in non-immune individuals who are in close contact, who then spread the virus to other susceptible individuals. Covering the rash can reduce this risk of transmission.

Zoster presents clinically as a unilateral vesicular rash, which in most cases is in a dermatomal distribution. The dermatomal distribution of the rash is the key diagnostic feature. In 70–80 percent of zoster cases in older adults, prodromal pain and/or itching occurs three to four days before the appearance of the rash.[2] In the majority of patients, zoster is an acute and self-limiting disease, with the rash lasting 10–15 days. However, complications can occur, especially with increasing age.

Although most zoster cases occur in adults aged 40 years or older, it may be seen less commonly in infants and children. In those aged under 2 years may reflect in utero chickenpox, with the greatest risk arising following exposure between 25 and 36 weeks’ gestation, and reactivation in early life. Infants who get varicella at a young age have a higher change of having zoster before the age 20 years.

A common complication of zoster is post-herpetic neuralgia (PHN), a chronic, often debilitating pain condition that can last several months or even years. A systematic review of the incidence and complications of zoster found that the risk of developing post-herpetic neuralgia ranges between 5 percent and about 30 percent (depending on the type of study design, age distribution of the study populations and definition).[3] The risk rises with age, and it is uncommon in healthy children and young people.

Herpes zoster ophthalmicus (HZO) is another complication of zoster, which occurs when VZV reactivation affects the ophthalmic branch of the trigeminal nerve. HZO can occur with or without eye involvement, and can result in prolonged or permanent pain, facial scarring and loss of vision. About 10 percent of zoster patients develop HZO, if that dermatome is affected, and the risk is similar across all age groups.[3]

The incidence of zoster is highest in immunocompromised individuals,[45] including:

  • following HSCT
  • solid organ transplants[6]
  • haematological malignancy[7]
  • immunomodulatory treatments and immune-mediated inflammatory diseases including treatments for
    • rheumatoid arthritis[8]
    • systemic lupus erythematosus
    • inflammatory bowel disease
    • cancer
  • those living with HIV infection.[9]

Up to 10 percent of children treated for a malignant neoplasm may develop zoster. In immunocompromised patients, extensive viraemia in the absence of a vigorous immune response can result in a disseminated form of zoster that includes severe multi-organ disease.[2, 10] There is an increased risk of airborne transmission of VZV for immunocompromised individuals with viraemia.

Other factors associated with an increased risk of developing zoster include splenectomy, chronic pancreatitis, chronic kidney disease, chronic inflammatory skin disease,[11] anxiety and depression,[12, 13] sleep disorders[14] and type 1 and type 2 diabetes,[15, 16, 17] chronic obstructive pulmonary disease and adult asthma.[18] Environmental factors such as exposure to high ambient temperature, UV radiation[19, 20] and high altitudes[21] have also been proposed as potential triggers. There is some evidence that a family (sibling or parent) history of zoster is also a potential risk factor in elderly individuals[22] Incidence of zoster is higher in women than men.[4]

23.3. Epidemiology

23.3.1. Global burden of disease

Zoster is a sporadic disease occurring as a reactivation of the VZV in individuals who have previously had chickenpox. Approximately one in three people will develop zoster during their lifetime with the incidence rising as cell-mediated immunity to VZV declines with age;[23] 50 percent of those aged 85 years or over will suffer zoster.[24, 25] A systematic review documented an incidence rate between 3 and 5 per 1,000 person-years in North America, Europe and Asia-Pacific.[3] The incidence rate was about 6–8 per 1,000 person-years at age 60 years and 8–12 per 1,000 person-years at age 80 years.

Recurrence is greater in females than males (about 7 percent after eight years compared with 4 percent for males), and in those who are immunocompromised. Third episodes are rare. In those who have zoster at a younger age (45–54 years) the time from the first episode to recurrence is shorter than for those who are aged over 55 years (mean time 2 years [IQR 1.0–2.3] vs 3 years [1.4–4.2], respectively).[26]

VZV is present in lesions of zoster and is transmissible via direct contact with the vesicles to other susceptible individuals (causing chickenpox). Airborne transmission can occur from immunocompromised individuals with disseminated zoster. Episodes of zoster in older individuals provide a constant mechanism for reintroducing the virus, causing varicella in non-immune individuals who are in close contact, who then spread the virus to other susceptible individuals.

Following the introduction of VV onto the childhood schedule, exposure to wild-type virus decreases. It has been theorised that a lack of boosting may lead to an increase in zoster in older adults. However, several studies that have investigated this issue, observed an increase in zoster prior to VV programme introductions and have been unable to attribute any increase in incidence of zoster to childhood VV programmes.[1112, 13, 14] Such increases have been observed in countries both with and without childhood varicella immunisation.

23.3.2. New Zealand epidemiology

Zoster hospitalisations by age group during 2018/2019 are shown in Figure 23.1, with around 60 percent occurring in adults aged 60 years and older. Hospitalisations are predicted to account for only a very small proportion of the overall zoster cases as most are managed in primary care. Interrogation of general practice electronic records found the incidence of zoster in New Zealand to be similar (approximately 5 per 100,000 patient-years rising to 12.8 per 100,000 in those aged 80–90 years) to the global incidence estimates described in section 23.3.1.[27] In 2018/2019, there were 483 hospitalisations associated with herpes zoster.

Figure 23.1: Hospitalisations with herpes zoster as primary diagnosis by age group, 2018/2019

Figure 23.1: Hospitalisations with herpes zoster as primary diagnosis by age group, 2018/2019 Figure 23.1: Hospitalisations with herpes zoster as primary diagnosis by age group, 2018/2019 Figure 23.1: Hospitalisations with herpes zoster as primary diagnosis by age group, 2018/2019
Source: Ministry of Health.

23.4. Vaccine

23.4.1. Available vaccines

Funded vaccine

The funded vaccine is an adjuvanted recombinant subunit zoster vaccine (Shingrix, GSK) containing recombinant VZV glycoprotein E and a proprietary AS01B adjuvant system that is designed to specifically boost T-cell immunity against VZV.[28]

Each 0.5 ml dose contains:

  • 50 µg of recombinant VZV glycoprotein E
  • AS01B liposome-based adjuvant containing two immunostimulants: 50 µg of Quillaja saponaria (soapbark tree) saponin fraction 21 (QS-21) with 50 µg detoxified lipopolysaccharide fraction, 3-O-desacyl-4’-monophosphoryl lipid A (MPL), from Salmonella minnesota
  • It also contains dioleoylphosphatidylcholine, cholesterol, sodium chloride, dibasic sodium phosphate, monobasic potassium phosphate and water.

Other vaccines

A live attenuated varicella-zoster virus vaccine (Zostavax, MSD) is approved for use from the age of 50 years and used as part of the Schedule at age 65 years from 2018 to August 2022. It is no longer available in New Zealand. This higher titre formulation of the varicella vaccine is designed to protect against zoster in those already immune to varicella.[29] By mimicking the immune response seen following a zoster episode and boosting cell-mediated immunity in older adults, the incidence and severity of zoster is reduced. Efficacy against zoster is around 60 percent in adults aged from 50 years and 67 percent against post-herpetic neuralgia in clinical trial settings.[29] Vaccine effectiveness in adults aged 70–79 years in the UK was estimated to be 64 percent (95% CI: 60–80) against zoster and 81 percent (95% CI: 61–91) against PHN. Vaccine effectiveness was lower in those who had a history of zoster (47 percent; 95% CI: 31–58).[30] Clinical effectiveness declined beyond five years post-vaccination.[31] The use of this live vaccine was limited due to a risk of disseminated VZV infection in severely immunocompromised individuals.

23.4.2. Efficacy and effectiveness

Efficacy in adults aged 50 years and over

Two phase III clinical trials (ZOE-50 and ZOE-70) demonstrated vaccine efficacy of over 90 percent in adults aged from 50 years and aged over 70 years, and those with medical conditions that increase their risk of zoster.[32, 33, 34, 35, 36] Pooled data gave vaccine efficacy of 91 percent (95% CI 87–95 percent) against the incidence of zoster overall, and 91 percent (86–98 percent) against post-herpetic neuralgia across all age groups. No decline in efficacy was observed with increasing age; in those aged over 80 years efficacy was 91 percent (80–97 percent) against zoster.[37]

Immunogenicity of rZV was shown to be similar in adults aged 65 or over who have previously received live zoster vaccine compared with those who were live ZV naïve. A strong humoral and polyfunctional cell-mediated immune response was shown to persist for at least 1 year after dose 2 of rZV.[38]

Post-hoc analysis, long term follow-up of trial participants found rZV efficacy against zoster plateaued after four to six years and was sustained overall at 84 percent for at least seven years and 70 percent at up to ten years post-vaccination, including in individuals aged 70 years and over and people with pre-existing medical conditions.[33, 37, 39]

Effectiveness in adults aged 50 years and over

Most effectiveness studies of recombinant ZV have been conducted in the US, as of July 2022. One study involving 1.74 million people found the vaccine effectiveness of two doses of rZV against zoster overall was 85.5 percent (95% CI 83.5–87.3 percent), 86.8 percent (84.6–88.7 percent) in those aged 50 to 79 years and 80.3% (75.4–84.3 percent) for those aged 80 years and over. In those who received live ZV within 5 years, vaccine effectiveness of recombinant ZV was 84.8 percent (75.3–90.7 percent) compared with unvaccinated people. Adjusted effectiveness of two doses rZV against herpes zoster ophthalmicus was 89.1 percent (82.9–93.0 percent).[40] Another real-world study found that administering the second dose beyond six months after the first dose did not impair effectiveness in community-dwelling adults aged over 65 years (approximately 1.5 million participants received one dose and 1.0 million received two doses, compared with 15.6 million unvaccinated controls).[41] One dose was 59.5 percent (57.4–61.4 percent) effective for up to six months and 43.5 percent (37.9–48.7 percent) after six months; whereas, two doses were 70.0 (68.4–71.5 percent) effective for up to six months after the second dose, and effectiveness was maintained beyond six months.[41]

Severely immunocompromised adults

Good immunogenicity was also shown in immunocompromised participants, including those aged from 18 years with solid organ transplants, solid organ tumours, haematopoietic stem cell transplants or living with HIV infection.[42, 43, 44, 45, 46] In HSCT recipients, efficacy of 72 percent (39–88%) was shown in those aged 18–49 years and 67 percent (53–78 percent) in those aged 50 or older with 21 months follow-up; in those aged from 18 years with haematological malignancies, efficacy was estimated at 87.2 percent (44.3–98.6 percent) up to 13 months post vaccination.[43]

23.4.3. Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017 (2nd edition).

The recombinant rZV (Shingrix) must be reconstituted before use with supplied diluent. Once reconstituted, if not used promptly, can be store in a refrigerator (+2°C to +8°C) for up to 6 hours. Do not freeze. Protect from light.

23.4.4. Dosage and administration

Two doses of 0.5 ml are administered intramuscularly from two to six months apart.

This recombinant zoster vaccine can be given safely to individuals who are immunocompromised and/or receiving immunosuppressive agents. If a shortened schedule is required, the second dose can be given optimally at two months after the first dose.

Serological testing for previous VZV infection is not necessary prior to administration of this rZV to individuals with immunocompromise. 

Individuals who are receiving antiviral medications, such as acyclovir, can be given rZV at any time without discontinuing their treatment. This vaccine does not contain live VZV.

Co-administration with other vaccines

Recombinant ZV (rZV) can be co-administered with most vaccines, including seasonal influenza vaccine, COVID-19 vaccines (mRNA-CV), 23PPV and Tdap. rZV can also be given at any time with other adjuvanted vaccines such as rCV (Nuvaxovid) and aQIV (FluAd Quad), preferably in a different limb.

Table 23.1: Herpes zoster vaccine (rZV) recommendations

Note: Neither history of previous varicella infection nor evidence of prior immunity to VZV is required prior to the routine administration of rZV. Funded individuals are shown in the shaded row. See the Pharmaceutical Schedule for any changes to funding decisions.

Recommended and funded

2 doses of recombinant rZV at age 65 yearsa

For consideration, but not funded

Two doses of recombinant rZV are recommended but not funded for all individuals aged from 50 years, including those aged over 66 years; and for individuals aged from 18 years who are at increased risk of zoster[5, 6, 9, 46, 47] including:

  • prior to planned, receivingb or post immunosuppressive therapy
  • with HIV infection
  • with end-stage kidney disease (CKD stages 4–5)
  • prior to or post solid organ transplantation
  • prior to or post HSCT
  • with immune-mediated inflammatory disease receiving immunomodulatory agents (eg, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Crohn’s disease, ulcerative colitis).

Other conditions that can increase risk of zoster in older adults include:[11, 13, 15]

  • diabetes
  • chronic obstructive pulmonary disease
  • chronic inflammatory skin diseases
  • splenectomy
  • chronic pancreatitis
  • psychiatric disorders, including depression and anxiety
  • sleep disorders.

a.     The second dose is funded at age 66 years if the first dose was given at age 65 years. 

b.     Ideally, vaccinate prior to planned immunosuppression. If rZV is given during treatment regimen, take timing of treatment and level of immunosuppression into consideration when timing vaccinations. If a shortened schedule is required, the second doses can be given optimally at two months after the first dose.

23.5.1. Other considerations

Recommended not funded

Adjuvanted recombinant zoster vaccine (rZV; Shingrix) is approved for use in New Zealand for all individuals aged 50 years or older (including those aged 66 years and over not eligible to funded vaccine).

It is also available (unfunded) for individuals aged 18 years and older at increased risk of zoster, particularly those who are at increased risk of zoster due to comorbidities[4, 7, 47] such as those who are immunocompromised due to an existing illness and/or its treatment or prior to planned immunosuppression. This includes individuals due to receive or following solid organ transplant, chemotherapy or systemic radiotherapy, and individuals with IMIDs (autoimmune disease) or living with HIV infection (see Table ‎23.1)

This vaccine can be given safely to individuals who are immunocompromised and/or receiving immunosuppressive agents. It is recommended to discuss the optimal timing for vaccination with a specialist before the vaccine appointments for those who are severely immunocompromised. Ideally, vaccination should be conducted prior to any planned immunosuppression (see section ‎4.3.7). If a shortened schedule is required, the second doses can be given optimally at two months after the first dose.

Individuals with a history of zoster (shingles)

Individuals with a history of zoster episodes can be given rZV. It is possible that a history of previous zoster may be inaccurate or a mistaken diagnosis.[47] In addition, the risk of a repeat episode of zoster has been estimated at approximately 5 percent in immunocompetent individuals.[26, 47] The incidence of recurrence is higher in women than men, in people who are immunosuppressed, and in younger people, aged 45–64 years compared with those aged over 65 years at the time of the first episode.[26]

There are no recognised safety concerns in giving zoster vaccines to people with prior history of zoster.[49, 50] The length of time following an episode of zoster after which it may be beneficial to vaccinate has not been established.[51] Recombinant ZV is recommended to be given from 12 months after zoster has resolved from which time the rate of recurrence is increased.[26, 51] Caution is required for individuals who have previously experienced ocular complications of zoster, such as herpes zoster ophthalmicus and uveitis, in this case vaccination is not recommended until at least 12 months after the inflammation has completely resolved.

Individuals with a history of zoster vaccination

The optimal time for administration of recombinant zoster vaccine following live ZV vaccination is not yet established.[51] Effectiveness of live ZV wanes significantly within three to five years of vaccination in adults aged 60 or older.[38] Individuals who previously received live ZV (Zostavax) can receive two doses of recombinant ZV (funded only at aged 65 years). Spacing of at least 12 months after live zoster vaccine is recommended but timing may be shortened to at least three months for the use of rZV in individuals who are immunocompromised with an increased risk of zoster recurrence or prior to planned immunosuppression.

Household contacts of immunocompromised individuals

See also section ‎4.3.1 for general recommendations for vaccination of household members of immunocompromised individuals. Household members aged 50 years or over (funded at age 65 years) are recommended to receive two doses of rZV to reduce the risk contact with a zoster rash and the fluid in the vesicles being a source of VZV infection to immunocompromised individuals.

23.6. Contraindications and precautions

See section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

23.6.1. Contraindications

Recombinant rZV (Shingrix) is contraindicated to individuals with a history of hypersensitivity to a previous dose or to any component of the vaccine.

23.6.2. Precautions

There is limited data on the use of rZV in human pregnancy however, since it is a non-live vaccine, there are no theoretical safety concerns should it be inadvertently administered during pregnancy.

23.7. Potential responses and AEFIs

23.7.1. Potential responses

During clinical trials, rZV was generally well tolerated. The most commonly responses were injection-site pain, myalgia and fatigue; other responses included headache, shivering, fever and gastrointestinal symptoms. These were mild to moderate and lasting for one to three days post vaccination, with higher incidence in those aged under 70 years than in the older age groups.[35] Adverse events were also more frequently reported in younger age groups (ages 18 to 49 years compared with those aged over 50 years). In clinical studies in those aged 50 years and over, a higher incidence of fever and shivering was reported when rZV was co-administered with 23PPV.[52]

23.7.2. AEFIs

Injection-site reactions (eg redness or swelling) were more common after vaccination with rZV than live ZV according to a meta-analysis of clinical trial data (risk difference of 30 percent; 95% CI 2 to 51 percent). There was no statistical difference between serious adverse events or study withdrawal due to adverse events.[53] No safety concerns in immunocompromised populations were associated with rZV across six clinical trials; most adverse events reported were consistent with the underlying diseases or treatments and similar between vaccinated and placebo controls.[54] A post-market surveillance study in adults aged 65 years or over observed a slightly increased risk of Guillain-Barré syndrome (estimated three excess cases per million doses) during 42 days following vaccination with rZV.[52]

There have been rare reports of flares of pre-existing inflammatory eye disease including uveitis and herpes zoster ophthalmicus following rZV administration.[55] It is recommended to allow at least 12 months after ocular zoster episode had resolved prior to administering rZV.

23.8. Variations from the vaccine data sheet

None.

References

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