Vaccines for preventing herpes zoster in older adults

The virus responsible for chickenpox, varicella zoster virus (VZV), can remain dormant inside nerve cells. Years later, when a person's immunity declines, for example because of aging, the virus may reactivate and travel through the nerve to the skin surface, producing clusters of blisters distributed along the path of the affected nerve, a condition called herpes zoster or shingles. Itching, numbness, tingling or localised pain precede the appearance of skin lesions. The virus causes inflammation of sensory nerves and can cause severe pain which impacts patients' quality of life. The annual incidence of herpes zoster is currently 5.22 episodes per 1000 older adults. This incidence is increasing, in part due to longer lifespan.

Since this disease can be prevented by a vaccine, our objective was to evaluate the effectiveness and safety of vaccines used to prevent herpes zoster in older adults.

We identified eight randomised controlled trials which enrolled 52,269 participants. The vaccine was effective in reducing herpes zoster by almost 50%. The only adverse effects caused by the vaccine were mostly mild to moderate symptoms at the injection site. The vaccine was more effective in people aged 60 to 69 years, but individuals in this age group were also more susceptible to adverse effects compared to those 70 years or over.

Injection site adverse effects were less frequent in participants receiving refrigerated herpes zoster vaccine than frozen vaccine. The incidence of adverse effects was higher at the second vaccination compared to the first. Participants receiving zoster vaccine had significantly lower rates of one or more injection site adverse effects and pain at injection site than those receiving the 'pneumo 23' vaccine.

The impact of vaccination on quality of life was poorly reported in the included trials. The vaccine reduced the number of participants with severe quality of life impairment caused by acute pain from herpes zoster. Only one of the eight included trials was of high quality, with a low risk of bias. The results currently described in the review may be underestimated. The results of ongoing trials may add relevant data to this interesting and important field of investigation.

The effectiveness of vaccines with lower concentrations of VZV should be tested in order to optimise the viral load used in each dose.

Authors' conclusions: 

Herpes zoster vaccine is effective in preventing herpes zoster disease. Although vaccine benefits are larger in the younger age group (60 to 69 years), this is also the age group with more adverse events. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse effects of mild to moderate intensity.

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Background: 

Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations.

Objectives: 

To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.

Search strategy: 

We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies.

Selection criteria: 

Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years).

Data collection and analysis: 

Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias.

Main results: 

We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated zoster vaccine and one study compared zoster vaccine versus pneumococcal polysaccharide vaccine (pneumo 23).

Confirmed cases of herpes zoster were less frequent in patients who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49 (95% confidence interval (CI) 0.43 to 0.56), with a risk difference (RD) of 2%, and number needed to treat to benefit (NNTB) of 50. Analyses according to age groups indicated a greater benefit in participants aged 60 to 69 years, RR 0.36 (95% CI 0.30 to 0.45) and in participants aged 70 years and over, RR 0.63 (95% CI 0.53 to 0.75). Vaccine-related systemic adverse effects were more frequent in the vaccinated group (RR 1.29, 95% CI 1.05 to 1.57, number needed to treat to harm (NNTH) = 100). The pooled data risk ratio for adverse effects for participants with one or more inoculation site adverse effect was RR 4.51 (95% CI 2.35 to 8.68), and the NNTH was 2.8 (95% CI 2.3 to 3.4). Side effects were more frequent in younger (60 to 69 years) than in older (70 years and over) participants.