Herpes zoster (shingles) typically presents as a painful unilateral vesicular rash in the dermatomal distribution
of the affected nerve.1 It is caused by a reactivation of the varicella zoster virus (chicken pox), which
remains latent in neural ganglia for many years after primary infection, until cell-mediated immunity to varicella
zoster virus wanes with age or is otherwise compromised.1
Older people are most likely to develop herpes zoster
Approximately one-third of people will develop shingles in their lifetime; 50% of people will develop shingles
if they reach age 85 years.2 National incidence data is not available for New Zealand, but several regional
studies have been conducted. An analysis of consultations over an 11 year period in 39 general practices in the lower
North Island reported an overall incidence rate of 48.6 cases of herpes zoster per 10,000 patient-years*.3 The
age-adjusted incidence rate for Māori was 38.9 per 10,000 patient-years and 29.1 per 10,000 patient-years for Pacific
peoples;3 this may indicate a lower incidence rate in these ethnic groups, but it may also reflect a lower
rate of presentation to general practice. The highest incidence rate was in the 80–84 years age group, which is an
older age group than many studies have previously reported.2, 3 Females were more likely than males to
present to general practice with herpes zoster (32% higher incidence rate).3
Immunocompromised people, including those undergoing immunosuppressive treatment, are at higher risk of developing
herpes zoster.1 Other risk factors for herpes zoster include rheumatoid arthritis, inflammatory bowel
disease, chronic obstructive pulmonary disease, asthma, chronic kidney disease, depression, sleep disorders and type
1 and 2 diabetes.1,2 N.B. Herpes zoster vaccination is contraindicated in people who are significantly
immunocompromised (see below).
* A patient-year is a standardised way of reporting incidence when the observation period differs
between study groups. For example, if a data set included 100 patients over a period of 10 years, this would be 1000
patient-years. If another data set included 70 patients over 8 years, this would be 560 patient years. The incidence
rate of the outcome in the second data set could be adjusted to a rate per 10,000 patient-years, if the data-sets
were combined.
Valaciclovir is the recommended treatment for herpes zoster
Antiviral medicines given within 72 hours of rash onset may reduce the severity and duration of the pain and rash,
but are unlikely to prevent post-herpetic neuralgia (see below).4 The recommended first-line antiviral
treatment is valaciclovir 1 g, three times daily, for seven days.5
Post-herpetic neuralgia is a common complication of herpes zoster
While herpes zoster is self-limiting, the most common complication occurring in up to 30% of affected people is
post-herpetic neuralgia.1 Like herpes zoster, the risk and severity of post-herpetic neuralgia increases
with age. It is usually experienced as a burning or shooting pain, itch, numbness, tingling, or hypersensitivity
to touch or temperature. Post-herpetic neuralgia can persist for months to years.1, 2
In approximately 10% of patients with shingles, the ophthalmic branch of the trigeminal nerve is affected, and
if the eye becomes involved, permanent visual loss can occur.1
For further information, see “The diagnosis and management of herpes zoster and its complications”.
Available from: www.bpac.org.nz/bpj/2014/march/herpes.aspx
The herpes zoster vaccine Zostavax will be fully subsidised for people aged 65 years*,
from 1 April, 2018.6
A catch-up immunisation programme will be available for two years from 1 April, 2018 to 31 March,
2020, during which time people aged 66 to 80 years will be eligible to receive one fully subsidised dose of Zostavax.6
Funded Zostavax vaccinations will initially only be available at general practices.6
* The vaccine is subsidised for people turning 65 years, i.e. from the date of their birthday. People
who are already aged 65 years as of 1 April, 2018 are also eligible for a subsidised Zostavax vaccination as part
of the catch-up programme.
Vaccination may be considered for people aged under 65 years
Zostavax is currently approved for adults aged 50 years and older.5 Although not subsidised, some patients
aged under 65 years may consider vaccination, particularly if they are at increased risk of shingles, e.g. with co-morbidities
such as diabetes, chronic kidney disease or autoimmune disease.1 However, the effectiveness of Zostavax
decreases over time and early vaccination may mean that protection is lost in older age, when there is a higher risk
of developing shingles and its complications.7
There is no clinical reason not to vaccinate people aged under 50 years, except that the original studies on Zostavax
did not include younger age groups and herpes zoster is less common in younger people. If considering vaccination
in high risk people aged under 50 years, the non-approved status of the vaccine for this age group should be discussed
and informed consent gained.
Consider delaying vaccination if herpes zoster has recently occurred
An episode of herpes zoster boosts immunity and therefore reduces the likelihood of it reoccurring in the short-term.
Therefore, patients who have recently had herpes zoster may wish to wait at least one year before vaccination, in
order to increase the overall number of years they are protected.1, 8
Booster doses of Zostavax are not currently recommended
Booster doses of Zostavax are not currently recommended as no studies reporting efficacy for the prevention of herpes
zoster have been performed.1 However, adults who are eligible to receive a funded dose of Zostavax, may
still receive this if they have previously purchased Zostavax.8 It is recommended to allow at least one
year between doses.8
Varicella vaccines do not prevent herpes zoster
Zostavax is a live attenuated vaccine containing the Oka strain of varicella zoster virus.1 Varilrix
and other varicella vaccines are also live attenuated Oka strain vaccines, but do not protect against herpes zoster
due to their lower strength.1
A history of varicella is not a pre-requisite for herpes zoster vaccination
It is not necessary to confirm if the patient has had varicella, prior to considering a herpes zoster vaccination.
Almost every adult will have been exposed to varicella infection at some point in their life, even if they have no
history of clinical infection.
Serology to check varicella immunity is not required except for in adults with asymptomatic HIV infection who have
a CD4+ lymphocyte count ≥ 200 cells/mm3, and in adults who will be significantly immunocompromised in the
near future, e.g. about to commence immunosuppressive treatment.1 The reason for checking serology in these
patients groups is to confirm whether varicella or herpes zoster vaccination is most appropriate.
Zostavax halves the risk of herpes zoster
Zostavax approximately halves the incidence of herpes zoster (51% relative reduction in risk) and reduces the incidence
of post-herpetic neuralgia by two-thirds (67% relative reduction in risk) in adults aged 60 years and over.9 As
shown in Table 1, Zostavax efficacy differs by age group; efficacy declines with increasing
age and it is not significantly effective for the prevention of herpes zoster in people aged 80 years and older.9–13
Zostavax efficacy decreases over time
Long-term follow-up studies have demonstrated that the efficacy of Zostavax for the prevention of herpes zoster
and post-herpetic neuralgia decreases over time.11, 12 In analyses by year since vaccination, Zostavax
significantly reduces the risk of herpes zoster for up to eight years.1, 12
Table 1. Zostavax efficacy by age group and time since vaccination.9–13
|
|
Vaccine efficacy*
(95% confidence intervals) |
|
| Herpes zoster |
Post-herpetic neuralgia† |
Burden of illness‡ |
Age group |
|
|
|
50 to 59 years |
70% (54 to 81) |
No data |
73% (53 to 85) |
60 to 69 years |
64% (56 to 71) |
66% (20 to 87) |
66% (52 to 76) |
70 to 79 years |
41% (28 to 52) |
No data |
No data |
≥ 70 years |
38% (28 to 52) |
67% (43 to 81) |
55% (40 to 67) |
≥ 80 years§ |
18% (–29 to 48) |
No data |
No data |
Time since vaccination |
|
|
|
0.0 to 3.1 years |
51% (44 to 58) |
67% (48 to 79) |
61% (51 to 69) |
3.3 to 7.8 years |
40% (18 to 56) |
60% (−10 to 87) |
50% (14 to 71) |
4.7 to 11.6 years |
21% (11 to 30) |
35% (9 to 56) |
37% (27 to 46) |
* Vaccine efficacy is the percentage reduction of disease in a vaccinated group of people compared
to an unvaccinated group
† Vaccine efficacy for the prevention of post-herpetic neuralgia across all study participants,
not specifically among those who developed herpes zoster
‡ Burden of illness is a composite measure of herpes zoster incidence, and severity and duration
of acute herpes zoster pain
§ Estimates of vaccine efficacy vary in this age group, for further details see: “Evidence
for Zostavax was generated in large randomised controlled trials”.
Evidence for Zostavax was generated in large randomised controlled
trials
In the Shingles Prevention Study, more than 38,500 adults aged 60 years and over were randomised to receive
either Zostavax or placebo and followed up for 3.12 years.9 A second randomised controlled trial investigated
the efficacy of Zostavax in more than 22,000 adults aged 50 to 59 years over 1.3 years follow-up.10 Long-term
follow-up studies of the original Shingles Prevention Study cohort were conducted at 3.3 to 7.8 years post-vaccination
or post-placebo (14,000 participants) and at 4.7 to 11.6 years post-vaccination (7000 participants).11,
12
A more recently published study reports different rates for vaccine efficacy than the Shingles Prevention Study.19 Of
particular note is a higher, and significant, rate of efficacy for preventing herpes zoster in people aged over
80 years of 42%. However, this study was an observational cohort study which means that the results are more
likely to be affected by confounding than a randomised controlled study. What it does show is that vaccine efficacy
data can be variable and should not be the only factor used to determine whether or not a vaccine is useful for
a particular patient group.
Adverse effects of Zostavax are typically limited to local injection site reactions
In clinical trials, 48% to 64% of participants experienced a local injection site reaction following Zostavax administration
compared with approximately 15% of those who received a placebo vaccination.9, 10 The most frequent injection
site reactions following Zostavax administration were erythema (36%), pain or tenderness (35%), swelling (26%) and
pruritus (7%), and the most commonly reported systemic adverse event was headache, occurring in 9% of the vaccine
group and in 8% of controls.9, 10 The overall risk of serious adverse events was similar between Zostavax
and placebo groups.9, 10
In post-licensure studies, Zostavax has been found to be safe and well-tolerated, with no increased risk of cerebrovascular
events, cardiovascular events, meningitis, encephalitis, encephalopathy, Ramsay Hunt syndrome or Bell’s palsy.1,
14
Zostavax is contraindicated in people who are significantly immunocompromised
Zostavax is a live attenuated vaccine and can cause disseminated infection in immunosuppressed people. It is contraindicated
in people with current or recent severe immunocompromise due to:1
- Immunosuppressive therapy
- Primary and acquired immunodeficiency states, such as leukaemia, lymphoma, other conditions affecting the bone
marrow or lymphatic system, immunosuppression due to AIDS, and cellular immune deficiencies. For patients with HIV
infection, check with their treating physician.
Zostavax is not contraindicated in people who use only topical/inhaled corticosteroids, low-dose
systemic corticosteroids, corticosteroids as a replacement therapy (e.g., adrenal insufficiency) or low-dose weekly
methotrexate or azathioprine.15
For detailed information on the use of Zostavax in patients taking immunosuppressive treatment, see: www.health.govt.nz/publication/immunisation-handbook-2017
Further discussion on Zostavax in people taking immunosuppressive
treatment
As Zostavax is a live vaccine, it is generally contraindicated in people taking immunosuppressive treatment.
However, there are some exceptions to this for patients considered to be only mildly immunosuppressed.
The Ministry of Health Immunisation Handbook has further details on this, which can be found in Sections 4.3.3
and 22.6.2: www.health.govt.nz/publication/immunisation-handbook-2017
The Handbook states that:
“As a general guide, low-level immunosuppression
includes treatment with prednisone <2 mg/kg with a maximum of 20 mg/day; methotrexate ≤0.4 mg/kg/week; azathioprine
≤3 mg/kg/day; or 6-mercaptopurine ≤1.5 mg/kg/day. High-level immunosuppression regimens include treatment regimens
with higher than the above doses, and those on biological agents such as tumour necrosis factor antagonists or
rituximab. Combination therapies increase the level of immunosuppression.”
Therefore, Zostavax is considered safe to administer in patients taking < 20 mg/day prednisone. However,
some rheumatologists would recommend a lower threshold for safe administration of Zostavax vaccination, e.g. < 10
mg/day prednisone. A pragmatic solution is to routinely offer Zostavax vaccine to patients taking < 10 mg/day
prednisone, and for patients taking 10 – 20 mg/day prednisone, consider their specific clinical scenario before
deciding to vaccinate, e.g. duration of prednisone treatment, co-morbidities.
Patients taking a methotrexate dose of ≤ 0.4 mg/kg/week can safely receive Zostavax. Therefore, this would
encompass most adults taking a standard once-weekly dose of <15-20 mg methotrexate.
Patients taking combination treatment, e.g. methotrexate with leflunomide, should not receive Zostavax vaccine
as taking two treatments at once increases the level of immunosuppression.
Patients taking other DMARDS* and biologic medicines, such as the “mab” medicines, tacrolimus and
cyclosporin, will not be able to receive a Zostavax vaccine until at least three to 12 months after treatment
has stopped – in some cases immunisation with a live vaccine is absolutely contraindicated (discuss with the
patient’s rheumatologist or other treating clinician).
Sulfasalazine, hydroxychloroquine and sodium aurothiomalate (gold injection) are not considered to be significantly
immunosuppressive, so patients taking these treatments at any dose may still receive Zostavax vaccine, unless
they are taking it in combination with another immunosuppressive medicine.
Patients should not receive Zostavax vaccine within four weeks of the start of planned chemotherapy or radiotherapy
and for at least three to six months after treatment has finished. Patients who have undergone stem cell or bone
marrow transplant should not receive Zostavax until at least two years after treatment.
* Disease Modifying Anti-Rheumatic Drugs
| Zostavax vaccine may be given to patients taking: |
Zostavax vaccine is contraindicated in patients taking: |
Prednisone < 10-20 mg/day
Methotrexate ≤ 0.4 mg/kg/week
Azathioprine ≤ 3.0 mg/kg/day
Mercaptopurine ≤ 1.5 mg/kg/day
Sulfasalazine
Hydroxychloroquine
Sodium aurothiomalate (gold injection)
Topical or inhaled corticosteroids |
Prednisone ≥ 20 mg/day
Methotrexate > 0.4 mg/kg/week
Azathioprine > 3.0 mg/kg/day
Mercaptopurine > 1.5 mg/kg/day
Other DMARDs and biologic medicines, e.g. abatacept, adalimumab, anakinra, cyclophosphamide, cyclosporin,
etanercept, infliximab, leflunomide, mycophenolate, rituximab, tacrolimus, tocilizumab, ustekinumab
Chemotherapy, radiotherapy
Any of the above medicines used in combination at any dose. |
Zostavax may be a new vaccine for many patients
Zostavax has been available to purchase from general practices and some pharmacies in New Zealand since 2014. However,
for many patients, it will be new vaccine for a condition that they may not be familiar with. Prior to administering
the vaccine, patients are likely to require time to discuss herpes zoster, including its incidence, symptoms and
potential complications, and Zostavax, including its efficacy and safety. Patients can then make an informed decision
as to whether they would like to proceed with vaccination.
While it is considered clinically safe to administer seasonal influenza vaccination at the same time as Zostavax,
for some patients there may be insufficient time to address questions about both vaccinations, and therefore vaccinations
may have to be done on two separate occasions.
For further reading, see: Immunisation Advisory Centre. Zostavax. Available from: www.immune.org.nz/vaccines/available-vaccines/zostavax
Another shingles vaccine on the horizon
Shingrix is a newly developed shingles vaccine recently registered for use in the USA. It is a subunit vaccine,
meaning that it does not contain live virus particles.16, 17 Trials have demonstrated a high efficacy
of Shingrix for the prevention of herpes zoster (90%) and post-herpetic neuralgia (89%).17, 18 As Shingrix
is unlikely to be available in New Zealand for some time, shingles vaccination should not be postponed, and vaccination
with Zostavax is not expected to be a contraindication for future Shingrix administration.6, 16
