Prevention of Shingles

Shingles, also known as herpes zoster, is caused by the reactivation of the varicella-zoster virus (VZV) in people who have previously had chickenpox. The incidence of shingles increases with age and is most commonly seen in people 60 years of age or older. One in three people will develop shingles in their lifetime, with those who are immunocompromised at greater risk.

Shingles can cause a rash that is characterised by blisters that appear in a dermatomal distribution. Acute pain is often associated with shingles and may develop before the first blisters appear. Pain intensity generally reduces and resolves completely over a period of a few weeks. However, persistent pain can occur. Postherpetic neuralgia is the most common complication of shingles. This condition is defined as pain that persists for at least three months after shingles infection. It occurs in around 10% of all cases, but its incidence increases significantly with patient age.

In 2016, shingles was responsible for over 2,600 hospital admissions and 27 deaths in Australia. Indications for hospitalisation may include:

• Severe symptoms;
• Immunosuppression;
• Atypical presentation;
• Involvement of more than one dermatome;
• Significant facial bacterial superinfection;
• Disseminated disease;
• Ophthalmic involvement; or
• Meningoencephalopathic involvement.

Vaccination reduces the risk of shingles and its complications. Shingles vaccination has been available on the National Immunisation Program (NIP) since 2016 in the form of Zostavax®. Zostavax® is a live attenuated zoster vaccine indicated for the prevention of shingles in people 50 years of age and older, and for the prevention of postherpetic neuralgia and the reduction of acute and chronic zoster-associated pain in people 60 years of age and older.

The safety and efficacy of Zostavax® were demonstrated in the Shingles Prevention Study. This large randomised, placebo-controlled trial investigated whether VZV vaccination reduces the incidence, severity, or both of shingles and postherpetic neuralgia in older adults. The VZV vaccine was associated with a 51.3% reduction in the incidence of shingles, a 61.1% reduction in the burden of illness due to herpes zoster, and a 66.5% reduction in the incidence of postherpetic neuralgia. The most commonly reported adverse events included injection site reactions and headache.

While clinical trials demonstrate that Zostavax® is generally safe and effective in older age groups, it is contraindicated in people with current or recent severe immunocompromising conditions. The Therapeutic Goods Administration (TGA) has published a number of safety alerts regarding the risk of disseminated vaccine strain varicella-zoster infection. In Australia, deaths have been reported due to this adverse event, including in people on low dose immunosuppressive medication. A boxed warning was recently added to the product information and consumer medicine information documents regarding this issue. The Department of Health provide a tool that can be used to screen for contraindications to Zostavax®.

There is now an alternative VZV vaccine available in Australia. Shingrix® contains the VZV glycoprotein E and is produced by recombinant DNA technology. It is formulated with an adjuvant to enhance the immune response. Shingrix® does not contain live virus and, therefore, cannot cause disseminated vaccine strain varicella-zoster infection.

Clinical trials for this vaccine demonstrate a 97.2% reduced risk of shingles in patients 50 years of age or older and an 89.8% reduced risk for patients 70 years of age and older. While Shingrix® and Zostavax® have not been compared in head-to-head clinical trials, studies against placebo suggest that Shingrix® may be significantly more efficacious.

Shingrix® is associated with moderately high rates of local and systemic adverse effects, including injection site reactions, fatigue, myalgia, headache, and fever. Patients should be advised of the potential for local and systemic reactions and encouraged to complete the recommended two-dose schedule even if they experience a non-serious reaction with the first dose.

The use of Shingrix® in people with immunocompromise is currently under investigation. Limited safety and efficacy data are available for people with human immunodeficiency virus (HIV) or haematopoietic stem cell transplant. Shingrix® was shown to be immunogenic and well-tolerated in this population. The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that immunocompromised adults 50 years of age and older may receive the Shingrix® vaccine for the prevention of shingles and its complications.

The safety and efficacy of Shingrix® coadministration with the adjuvanted influenza vaccine (Fluad Quad®) or COVID-19 vaccines has not been evaluated. However, non-adjuvanted influenza vaccines may be given concurrently. ATAGI routinely suggests a minimum of seven days between COVID-19 vaccines and other vaccines. However, coadministration is acceptable in some situations. Current recommendations on this issue can be found at the Department of Health.

The current ATAGI advice is that Shingrix® is preferred over Zostavax® for ages 50 years and above. However, Shingrix® is not funded on the NIP and availability is expected to be limited. Zostavax® remains a readily available and effective option that can be considered for immunocompetent people who wish to reduce their risk of shingles.

A brief comparison of the two vaccines is shown in Table 1.

Table 1. Comparison of Shingrix® and Zostavax®