Drugs in development for herpes simplex and varicella zoster virus.

The alpha-herpesviruses varicella zoster virus (VZV) and herpes simplex virus (HSV) share common features including lifelong persistence in sensory ganglia and the risk of recurrences. For both HSV and VZV, standard-of-care (SoC) is based on nucleoside analogs (NAs), which require specific activation in infected cells. These existing drugs exhibit substantial limitations, warranting the development of new and more effective drugs.

Healthcare Resource Utilisation Associated with Herpes Zoster in a Prospective Cohort of Older Australian Adults.

BACKGROUND: Herpes zoster (HZ) is a common condition that increases in incidence with older age but vaccines are available to prevent the disease. However, there are limited data estimating the health system burden attributable to herpes zoster by age. METHODS: In this study, we quantified excess healthcare resource usage associated with HZ during the acute/sub-acute period of disease (21days before to 90 days after onset) in 5952 cases and an equal number of controls matched on age, sex, and prior healthcare resource usage. Estimates were adjusted for potential confounders in multivariable regression models. Using population-based estimates of HZ incidence, we calculated the age-specific excess number of health service usage events attributable to HZ in the population. RESULTS: Per HZ case, there was an average of 0.06 (95% CI 0.04-0.08) excess hospitalisations, 1.61 (95% CI 1.51-1.69) excess general practitioner visits, 1.96 (95% CI 1.86-2.15) excess prescriptions filled and 0.11 (95% CI 0.09-0.13) excess emergency department visits. The average number of healthcare resource use events, and the estimated excess per 100,000 population increased with increasing age but were similar for men and women, except for higher rates of hospitalisation in men. The excess annual HZ associated burden of hospitalisations was highest in adults ≥80 years (N = 2244, 95%CI 1719-2767); GP visits was highest in those 60-69 years (N = 50567, 95%CI 39958-61105), prescriptions and ED visits were highest in 70-79 years (N = 50524, 95%CI 40634-60471 and N = 2891, 95%CI 2319-3449 respectively). CONCLUSIONS: This study provides important data to establish the healthcare utilisation associated with HZ against which detailed cost-effectiveness analyses of HZ immunisation in older adults can be conducted.

Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States.

BACKGROUND: Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. METHODS AND FINDINGS: The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥ 65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75-1.74) and unvaccinated (IR 1.78, 95% CI 1.68-1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study's power to assess the role of vaccination. CONCLUSIONS: Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events.

[Economical effectiveness of vaccination of cohort of children aged 2 years against chickenpox in the Russian Federation].

AIM: Perform calculation of the economical effectiveness of realization of a program of vaccination of children aged 2 years against chickenpox (CP) in the Russian Federation. MATERIALS AND METHODS: Data of Federal service on customers rights protection and human well-being surveillance on evaluation of morbidity and losses caused by CP in the Russian Federation in 2008 - 2010 were used. A cohort of children (1 760 000) aged 2 years subject to vaccination against CP in 2011, evaluation of cost of 1 case of the infection, the amount of losses per vaccination of 1 child were approximately determined; analysis of prevented losses by implementation ofvaccination program by using mathematical modeling methods was performed. RESULTS: Without vaccination program in the Russian Federation the cost of losses per 1 case of CP related to hospitalization and outpatient visits as well as temporary disability of one of the parent in various age groups was: for children aged 1 - 2 years--8 333 RUB (Russian rubles), 3 - 6 years--21 171 RUB, 7 - 14 years--21 295 RUB. The cost of vaccination against CP of 1 child including 2 doses of vaccines with physician examination and vaccination procedure would be 1600 RUB. In the case of realization of vaccination program against CP in 2011 of children aged 2 years its cost would be 2 488.9 million RUB. Cost prevention already exceeds the cost of vaccination in 1 age cohort of children at year 2 and in 5 years the amount of prevented losses would exceed 15 billion RUB per 1 vaccinated cohort and would continue to increase steadily. CONCLUSION: The performed calculations show that vaccination against CP in the Russian Federation is a highly efficient investment. Self-sufficiency of a program implemented in 2011 may be obtained already at the start of year 2 after the realization and by 2016 the net economical benefit would be around 8 milliards RUB.

Herpes zoster: daily marking of new vesicles in therapeutic studies. A clinical method for objective assessment of the end of the eruptive phase.

BACKGROUND: The efficacy of a therapeutic agent must be evaluated by objective criteria. However, in herpes zoster (HZ) studies there has been no generally accepted objective clinical criterion. OBJECTIVE: Our purpose was to establish a clinical method for determining objectively the point in time at which the eruptive phase of HZ is completed (no new vesicle formation). This point is said to be a clinical criterion for the end of viral replication in the skin and thus for measuring the efficacy of a virustatic agent. METHODS: Newly formed vesicles were marked with differently colored permanent marker pens each day. This method was evaluated by comparing the results of acyclovir therapy in two groups of patients with HZ. (Group A, no underlying malignancy; n = 9. Group B, underlying malignancy; 64% of these patients were undergoing cytostatic polychemotherapy or had immunodeficiency; n = 22). RESULTS: In both groups, acyclovir stopped the eruption of new vesicles within 1.8 and 2.8 days, respectively (not statistically significant). Group B showed a tendency toward more protracted hematogenous dissemination and a longer duration of therapy. The total duration of the eruptive phase depended solely on the length of the interval between the onset of the HZ and the beginning of therapy. CONCLUSION: The method of marking new vesicles is independent of laboratory facilities, simple, and cost effective; in addition, this method is suitable for statistical evaluation. It is thus superior to other clinical methods for objective assessment of the progression of HZ.