Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial.

BACKGROUND: The herpes zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However, its safety has not been described in depth. OBJECTIVE: To describe local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults. DESIGN: Randomized, placebo-controlled trial with enrollment from November 1998 to September 2001 and follow-up through April 2004 (mean, 3.4 years). A Veterans Affairs Coordinating Center generated the permutated block randomization scheme, which was stratified by site and age. Participants and follow-up study personnel were blinded to treatment assignments. (ClinicalTrials.gov registration number: NCT00007501) SETTING: 22 U.S. academic centers. PARTICIPANTS: 38 546 immunocompetent adults 60 years or older, including 6616 who participated in an adverse events substudy. INTERVENTION: Single dose of herpes zoster vaccine or placebo. MEASUREMENTS: Serious adverse events and rashes in all participants and inoculation-site events in substudy participants during the first 42 days after inoculation. Thereafter, vaccination-related serious adverse events and deaths were monitored in all participants, and hospitalizations were monitored in substudy participants. RESULTS: After inoculation, 255 (1.4%) vaccine recipients and 254 (1.4%) placebo recipients reported serious adverse events. Local inoculation-site side effects were reported by 1604 (48%) vaccine recipients and 539 (16%) placebo recipients in the substudy. A total of 977 (56.6%) of the vaccine recipients reporting local side effects were aged 60 to 69 years, and 627 (39.2%) were older than 70 years. After inoculation, herpes zoster occurred in 7 vaccine recipients versus 24 placebo recipients. Long-term follow-up (mean, 3.39 years) showed that rates of hospitalization or death did not differ between vaccine and placebo recipients. LIMITATIONS: Participants in the substudy were not randomly selected. Confirmation of reported serious adverse events with medical record data was not always obtained. CONCLUSION: Herpes zoster vaccine is well tolerated in older, immunocompetent adults. PRIMARY FUNDING SOURCE: Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development; grants from Merck to the Veterans Affairs Cooperative Studies Program; and the James R. and Jesse V. Scott Fund for Shingles Research.

Reducing the incidence and severity of herpes zoster and PHN with zoster vaccination.

The results of the Shingles Prevention Study, a Cooperative Studies Program conducted through the US Department of Veterans Affairs, are summarized. Also provided are general recommendations and contraindications for the use of zoster vaccine live among patients aged 60 years or older.

A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses.

A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human beta-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results.

Varicella zoster virus redux.

In May 2008, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention in the USA recommended the routine administration of a live-attenuated high-potency varicella zoster vaccine to all adults over 60 years of age without specific contraindications, for the prevention and attenuation of herpes zoster (HZ). Nevertheless, many physicians still consider this vaccine to be of marginal value. This is not a reasonable conclusion. This short article reviews available data.

Preventing herpes zoster through vaccination.

TOPIC: The role of the zoster vaccine in the prevention of herpes zoster and its sequelae, including postherpetic neuralgia (PHN) and herpes zoster ophthalmicus. CLINICAL RELEVANCE: Wide administration of the herpes zoster vaccine in accordance with the recommendations of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) will lead to a decline in the incidence and morbidity of herpes zoster and its complications, including PHN. METHODS: The key study leading to the approval of the zoster vaccine for use, the Centers for Disease Control and Prevention ACIP's recommendations for appropriate use of the zoster vaccine, and predictions regarding the cost efficacy of a zoster vaccination program are reviewed. RESULTS: The Shingles Prevention Study established that the zoster vaccine was safe, well tolerated, and effective in reducing the burden of illness due to herpes zoster and the incidence of PHN. The ACIP recommended that the zoster vaccine be given to adults 60 and older for the prevention of herpes zoster. Cost-efficacy analyses suggest that the greatest gain in quality-adjusted life-years can be gained by vaccinating individuals at the younger end of the ACIP-recommended age range. CONCLUSION: The zoster vaccine promises to reduce the morbidity and mortality of herpes zoster. Administering the vaccine at the younger end of the age range may offer a greater cost benefit.