Assessment of the potential public health impact of Herpes Zoster vaccination in Germany.

The aim of this study was to compare the public health impact of introducing 2 Herpes Zoster (HZ) vaccines, Zoster Vaccine Live (ZVL) versus a non-live adjuvanted subunit candidate vaccine (HZ/su), in the German population aged 50+ years split into 3 age cohorts, i.e. 50-59, 60-69 and 70+ years, respectively. A multi-cohort static Markov model was developed following age cohorts over their lifetime. Demographic data were obtained from the German federal statistical office. HZ incidence and the proportion of HZ individuals developing post-herpetic neuralgia (PHN) were derived from German specific sources. Age-specific vaccine efficacy and waning rates were based on published clinical trial data. Vaccine coverage for both vaccines was assumed to be 40%, with compliance of the second dose of the HZ/su vaccine of 70%. Sensitivity analyses were performed to assess the robustness of the results. It was estimated that, over the remaining lifetime since vaccination, the HZ/su vaccine would reduce the number of HZ cases by 725,233, 533,162 and 486,794 in the 3 age cohorts, respectively, compared with 198,477, 196,000 and 104,640, using ZVL. The number needed to vaccinate (NNV) to prevent one HZ case ranged from 8 to 11 using the HZ/su vaccine compared with 20 to 50 using ZVL. Corresponding NNV to prevent one PHN case ranged from 39 to 53 using the HZ/su vaccine compared with 94 to 198 using ZVL. Due to the higher, sustained vaccine efficacy, the candidate HZ/su vaccine demonstrated superior public health impact compared with ZVL.

FV-100 versus valacyclovir for the prevention of post-herpetic neuralgia and the treatment of acute herpes zoster-associated pain: A randomized-controlled trial.

This prospective, parallel-group, randomized, double-blind, multicenter study compared the efficacy and safety of FV-100 with valacyclovir for reducing pain associated with acute herpes zoster (HZ). Patients, ≥50 years of age, diagnosed with HZ within 72 h of lesion appearance who had HZ-associated pain, were randomized 1:1:1 to a 7-day course of either FV-100 200 mg QD (n = 117), FV-100 400 mg QD (n = 116), or valacyclovir 1000 mg TID (n =117). Efficacy was evaluated on the basis of the burden of illness (BOI; Zoster Brief Pain Inventory scores); incidence and duration of clinically significant pain (CSP); pain scores; incidence and severity of post-herpetic neuralgia (PHN); and times to full lesion crusting and to lesion healing. Safety was evaluated on the basis of adverse event (AE)/SAE profiles, changes in laboratory and vital signs values, and results of electrocardiograms. The burden of illness scores for pain through 30 days were 114.5, 110.3, and 118.0 for FV-100 200 mg, FV-100 400 mg, and valacyclovir 3000 mg, respectively. The incidences of PHN at 90 days for FV-100 200 mg, FV-100 400 mg, and valacyclovir 3000 mg were 17.8%, 12.4%, and 20.2%, respectively. Adverse event and SAE profiles of the two FV-100 and the valacyclovir groups were similar and no untoward signals or trends were evident. These results demonstrate a potential for FV-100 as an antiviral for the treatment of shingles that could both reduce the pain burden of the acute episode and reduce the incidence of PHN compared with available treatments.

Incidence of herpes zoster and associated events including stroke--a population-based cohort study.

BACKGROUND: More detailed understanding of herpes zoster (HZ) is called for in the context of an increasing observed frequency of disease, and ongoing discussions regarding potential consequences of the disease. Thus, population-based data on incidence and complications of HZ are needed. METHODS: We conducted a register-based cohort study in Västra Götaland County (population 1.5 million) in Sweden. We collected data on all patients diagnosed with HZ during the years 2008 to 2010 from population-based registers. Incidence rates (IR) of HZ and related complications were calculated and stratified by age and sex. RESULTS: There were 13 269 new HZ cases during the study period. Overall, the IR of herpes zoster in both genders was 3.25 (95% CI: 3.16-3.34) per 1000 person years in 2010. The incidence was consistently higher in women than in men and in older than in young. A history of immunosuppression was more common than in the general population. The incidence was highest in individuals over 80 years of age (IR 9.2 per 1000 person years, 95% CI: 8.8-9.6) during 2008-2010. The most common complications to HZ were ocular engagement and postherpetic neuralgia; risks for stroke and sepsis were significantly elevated during the one year following diagnosis, especially in the youngest age group of patients 0-39 years. CONCLUSIONS: Herpes zoster is more common in women, the elderly and immunosuppressed individuals. We verify a population-based association between herpes zoster and risk for stroke and sepsis, which may merit concern.

Assessment of transcriptomal analysis of Varicella-Zoster-virus gene expression in patients with and without post-herpetic neuralgia.

Varicella-Zoster virus (VZV) is a human herpes virus that reactivates from a latent state in human trigeminal and dorsal root ganglia to cause herpes zoster (shingles) which is a painful vesicular dermatomal skin eruption. The major complication of herpes zoster is post-herpetic neuralgia (PHN) which is a serious condition occurring especially in individuals over 50 years. PHN is extremely painful, may be permanent, and is frequently very refractory to all treatment. The ability to identify those patients with herpes zoster who are likely to develop PHN would be highly beneficial as it would allow pre-emptive anti-viral therapy. We have assessed the potential of using long oligonucleotide VZV microarrays to determine whether MeWo cells infected with VZV isolates obtained from 13 patients with zoster who had subsequently developed PHN showed significant transcriptomal differences from MeWo cells infected with viruses isolated from ten zoster patients who had not developed PHN. We found that viral gene expression from sample to sample within a group (PHN patients or non-PHN patients) varied as much, or more, than the viral gene expression between those groups. Quantitative real-time polymerase chain reaction studies carried out on 11 open reading frames on four representative viral infected MeWo cell lines (two from each group) confirmed the transcriptomal heterogeneity between the two groups. Growth curve analyses of ten representative infected cell lines (five from each group) showed that PHN and non-PHN-associated viruses replicated equally efficiently. Taken together, these findings suggest that viral microarray-based transcriptomal measurements are unlikely to prove of clinical utility in predicting the incidence of PHN.

Varicella zoster vaccines.

In the past, the varicella zoster virus affected virtually the entire population and had substantial morbidity and mortality associated with both primary varicella and herpes zoster reactivation. Since the varicella vaccine was first approved in 1995, there has been a significant decline in incidence, morbidity, and mortality caused by primary varicella. Breakthrough disease with the one-dose vaccine schedule led to the recommendation in 2006 that children receive a two-dose vaccine series. Older adults have also benefited from the development of the zoster vaccine. In 2006, the Food and Drug Administration approved the zoster vaccine, a higher concentration of the same live attenuated virus used in the primary varicella vaccine, for persons 60 years of age or older. It has the potential to help millions of people avoid the pain associated with reactivation of the varicella zoster virus by reducing the incidence and severity of herpes zoster and postherpetic neuralgia.