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      Prevention of shingles: safety and efficacy of live zoster vaccine

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          Abstract

          Primary infection with varicella zoster virus (VZV) causes chickenpox (varicella) after which virus becomes latent in cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. Virus may later reactivate, causing shingles (zoster), characterized by pain and rash restricted to 1–3 dermatomes. More than 40% of zoster patients over age 60 develop postherpetic neuralgia (PHN), pain that persists for months to years. The socioeconomic impact of primary varicella infection has been lessened by introduction of VZV vaccine for children. However, the effect of childhood vaccination on the incidence of zoster is unknown. Virus reactivation correlates with waning cell-mediated immunity (CMI) to VZV with normal aging. Adults exposed to children with varicella may have a boost in CMI to VZV. For at least several more decades, the incidence of zoster may increase as the elderly population grows. The anticipated increase in zoster burden of illness in future decades was a major impetus for the Shingles Prevention Study, a prospective, double-blind, placebo-controlled trial of attenuated VZV vaccine to prevent zoster in older adults. This review discusses clinical and virological aspects of zoster and its complications, current treatment options, and VZV vaccine development along with its future role in disease prevention.

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          Most cited references 59

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          Development of a measure of the burden of pain due to herpes zoster and postherpetic neuralgia for prevention trials: adaptation of the brief pain inventory.

          In preparation for clinical trials of a vaccine against herpes zoster (HZ), we conducted a prospective, observational study to evaluate (1) the Zoster Brief Pain Inventory (ZBPI), an HZ-specific questionnaire to quantify HZ pain and discomfort, (2) an operational definition of postherpetic neuralgia (PHN), and (3) a severity-duration measure of the burden of illness caused by HZ. HZ patients aged 60 years or older (n = 121) were enrolled within 14 days of rash onset and completed ZBPI, McGill Pain Questionnaire Present Pain Intensity (PPI), quality of life (QoL), and activities of daily living (ADL) questionnaires on a predetermined schedule. Reliability, measured by intraclass correlation coefficients within 14 days of rash onset, ranged between 0.63 and 0.78. ZBPI pain scores were strongly correlated with other pain measures, interference with ADL, and worsening QoL. The operational definition of PHN, a ZBPI pain score of 3 or greater occurring 90 or more days after rash onset, had high agreement with pain worse than mild on the PPI (kappa = 0.72). The ZBPI pain severity-duration measure had high correlations with severity-duration measures of ADL interference, worsening QoL, and other pain scales. These findings support the validity and utility of the ZBPI, the definition of PHN, and the severity-duration measure of the burden of HZ illness. Herpes zoster pain, as measured by the ZBPI severity-duration measure, is associated with impairment in daily living activities and quality of life. The ZBPI measure appears useful for quantifying herpes zoster pain, postherpetic neuralgia, and impairment in daily living activities for clinical trials of herpes zoster prevention.
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            The incidence of herpes zoster.

            There are few population-based studies of the natural history and epidemiology of herpes zoster. Although a relatively common cause of morbidity, especially among the elderly, contemporary estimates of herpes zoster incidence are lacking. Herein we describe a population-based investigation of incident and recurrent herpes zoster from 1990 through 1992 in a health maintenance organization. The health maintenance organization's automated medical records contain clinical and administrative information about care rendered to patients in ambulatory settings, emergency departments, and hospitals. Cases of herpes zoster were ascertained by screening the medical record for coded diagnoses. The predictive value of a herpes zoster diagnosis code was determined by review of a sample of patient records. Records from all patients with potential recurrences were also reviewed. The overall incidence, based on 1075 cases in 500,408 person-years, was 215 per 100,000 person-years (95% confidence interval, 192 to 240 per 100,000) and did not vary by gender. Although the rate increased sharply with age, approximately 5% of the cases occurred among children younger than 15 years. Infection with human immunodeficiency virus was documented in 5% of the persons with incident herpes zoster and cancer in 6%. Four persons had confirmed recurrences of herpes zoster (744 per 100,000 person-years; 95% confidence interval, 203 to 1907); three of these persons were infected with the human immunodeficiency virus. The recorded incidence of herpes zoster was 64% higher than that reported 30 years ago; the age-standardized rate was more than twofold higher. Immunosuppressive conditions had little impact on overall incidence, although they were strongly associated with early recurrences.
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              Pain, medication use, and health-related quality of life in older persons with postherpetic neuralgia: results from a population-based survey.

              Persons aged >65 years with pain caused by postherpetic neuralgia (PHN) were recruited via advertisements in 24 US newspapers and were mailed a questionnaire that addressed pain intensity (average, worst, least, current), pain interference (with general activity, mood, relations with other people, sleep, enjoyment of life), and health-related quality of life (using the EuroQoL health measure [EQ-5D] and a global rating scale). Respondents also were asked about their use of medication for shingles pain. A total of 385 persons completed the survey; 61% were >75 years of age. Mean (+/-standard deviation) duration of PHN was 3.3 (+/-4.0) years. Only about one half had taken prescription medication for shingles pain during the prior week; dosages were typically low. Mean average, worst, least, and current pain caused by shingles (0- to 10-point scale) was 4.6 (+/-2.1), 6.0 (+/-2.4), 2.9 (+/-2.3), and 4.0 (+/-2.7), respectively. Mean pain interference with general activity, mood, relations with other people, sleep, and enjoyment of life (0- to 10-point scale) was 3.7 (+/-3.1), 4.3 (+/-2.9), 3.0 (+/-2.8), 3.8 (+/-2.9), and 4.5 (+/-3.1), respectively. The mean EQ-5D health index score was 0.61; respondents rated their overall health as 65.7 (+/-21.1) on a 100-point scale. PHN causes substantial pain, dysfunction, and poor health-related quality of life in older persons, many of whom might be suboptimally treated. Many older persons (age >65 years) with PHN experience longstanding, severe, and debilitating pain and poor health-related quality of life; levels of dissatisfaction with treatment are high. Our study highlights the need for improved management of this disease.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                August 2007
                August 2007
                : 3
                : 4
                : 633-639
                Affiliations
                [1 ]Department of Neurology, University of Colorado Health Sciences Center Denver, Colorado, USA
                [2 ]Department of Microbiology, University of Colorado Health Sciences Center Denver, Colorado, USA
                Author notes
                Correspondence: Donald H Gilden Department of Neurology, Mail Stop B182, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262, USA Tel +1 303 315 8281 Fax +1 303 315 8720 Email don.gilden@ 123456uchsc.edu
                Article
                2374947
                18472986
                © Dove Medical Press Limited. All rights reserved
                Categories
                Review

                Medicine

                zoster, zoster vaccine, shingles

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