Shingles: Zoster Virus Vaccination - Who should vaccinate?

Herpes zoster is a condition caused by the varicella zoster virus. Infection with this virus is also known as chickenpox. This usually occurs in children, but the virus may remain 'dormant' to re-establish symptoms later in life. This condition in adulthood is often known as shingles. Shingles is characterised as varicella zoster infection that presents with symptoms such as:

• Pain in an area of skin, usually on one side of the body
• A raised, red rash in the same area
• Itching
• Increased sensitivity to pressure
• Vesicles (or blisters) that may break open

The symptoms as above can be resolved especially if antiviral therapy is administered. However, some patients may experience chronic pain even after the skin complaints have abated. This is due to nerve damage associated with varicella zoster infection, and is known as post-herpetic neuralgia.

Up to 50% of patients may be left with this neuralgia following a case of shingles, although this risk is influenced by age. Post-herpetic neuralgia is associated with significant effects on the life quality of patients.

Risk Factors for Varicella Zoster Infection

Some age groups or people of other demographics may be more susceptible to varicella zoster infection, and to the resulting conditions (including post-herpetic neuralgia). Risk factors include:

• Age: There is some evidence that older people are at a higher risk of neuralgia.
• Genetic factors: A recent genome-wide analysis with approximately 23,000 participants found that the gene HCP-5 is associated with the increased risk of herpes zoster
• Gender: Women are thought to be at an increased risk of herpes zoster development.
• Immune suppression: This may also be associated with the re-emergence of an infection.
• Family history of the condition.

Administration of the Varicella Zoster Vaccine

Currently, vaccination against the varicella zoster virus is recommended to reduce the risk of shingles and/or post-herpetic neuralgia in the groups mentioned above. Some vaccines (e.g. Zostavax®) are specifically developed for people aged 50 years or more, to prevent recurrent infections in this group. Nursing guidelines in the United Kingdom suggest that this vaccine is recommended to patients when they reach the age of 70, and also to those aged 79. European health professionals prefer to deliver these vaccines via intramuscular injection, although those in the U.S. usually do so using a subcutaneous route. Vaccination against this virus is also recommended for children.

Safety and Efficacy of Zoster Virus Vaccination

Some members of the research community argue that there is no evidence that vaccinations have reduced the risk of shingles or neuralgia.

However, the Shingles Prevention Study found that vaccination significantly reduced conditions associated with varicella zoster in older recipients. Some researchers also claim that the rates of severe adverse events and death in trial subjects who received vaccines are comparable to those in corresponding placebo groups, and that vaccinated patients who developed shingles experienced a reduction in symptoms.

Despite these findings, and the incidence of shingles in vulnerable populations (approximately 3-4 in every thousand), the rates of vaccine uptake in those over 60 increased by only 4.1% in one year (2012-13) in the U.S.On the other hand, the U.S. Centre for Disease Control-sponsored Antelope Valley (a community of approximately 300,000 residents) Varicella Surveillance Project reported a decrease in vaccine efficacy of over 80% in 200113. This study concluded that vaccination was inferior to natural acquired immunity to varicella zoster in this population.

Zostavax® is a one-dose vaccine. There have been some doubts about whether this remains effective after the fifth year post-inoculation. A study on varicella zoster vaccine persistence, including over 6800 vaccinated patients, was conducted. This study demonstrated that the vaccine significantly reduced disease burden associated with the virus for 10 years, but also reported that it significantly reduced the incidence of shingles for only eight years14. This may indicate the need for 'booster shots' or repeat administrations.

The injection of varicella zoster vaccinations may be associated with some adverse effects, particularly within the skin or tissue injected. These reactions include:

• Pain
• Swelling
• Skin redness

The efficacy and risks of these side-effects associated with a particular vaccine is thought to be influenced by a number of factors. These may include:

• Vaccine type: Some vaccines contain live or live-attenuated (weakened) forms of the virus to be inoculated against. Alternatively, they may contain dead viral particles, adjuvants or viral proteins relevant to the process of host infection or cellular invasion.
• Route of administration (i.e. subcutaneous, etc.)
• Prior symptomatic infections

The Shingles Prevention Study excluded patients with prior herpes zoster symptoms, meaning that the data on the effects of a pre-existing episode of disease on vaccine safety was lacking. However, a subsequent study included over 13,000 patients, 420 of whom had a history of symptomatic recurrent infection. The rate of severe adverse events in this group was not significantly different from that of patients without a history of shingles.

Another cohort study on the safety of Zostavax® including 29,000 people over 60 years found no evidence of increased adverse events. However, the subjects of this study were in good health, which gives no indication of the effect of immune suppression on the safety of vaccination. Studies on this are currently lacking.

There are rare cases of symptomatic shingles found to be associated (by analysing the presence of vaccine-specific viral genes) with vaccination with Zostavax®. An open-label trial of Zostavax® (a live-attenuated vaccine) including 354 people of the target age group (see above) compared the tolerability and efficacy of this vaccine. The subjects were randomised to either subcutaneous or intramuscular vaccinations. Measures of efficacy such as geometric mean antibody titres and immune (interferon-gamma) response were used in this trial.

Intramuscular injections were found to be comparable in these measures to subcutaneous administration, and also resulted in fewer adverse reactions. Another form of varicella zoster vaccination is the v-Oka vaccine. This is also a live-attentuated virus, but is associated with an increased risk of re-establishing virulence in nervous tissue. This may result in neuralgia. However, other studies conclude that this vaccine results in a reduction of approximately 50% in the incidence of shingles, 60% in disease burden and 70% in the incidence of post-herpetic neuralgia. A new polyvalent (or virus that also carries the genes of other lifeforms) form of vOka that also vaccinates against mumps is currently under evaluation.

References

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