Outpatient healthcare utilization and prescribing patterns for herpes zoster in United States adults.

Little is known about health resource utilization and treatment patterns for herpes zoster (HZV) after the introduction of HZV virus vaccination. The objective of this study is to characterize trends in HZV utilization, racial disparities, and treatment patterns in the United States. Data from the 1993-2015 National Ambulatory Medical Care Survey were analyzed, including 15,400,000 weighted primary acute HZV visits in adults. Overall, the weighted frequency (95% confidence interval) of HZV visits increased from 1993-1998 to 2007-2015 (1,269,815 [565,455-1,974,175]-8,017,911 [6,424,491-9,611,331], P = 0.0001). HZV visits were associated with African-American (38.8% [35.8-41.7%] vs. 8.2% [7.4-9.0%]) and Hispanic race/ethnicity (12.6% [6.6-18.5%] vs. 8.0% [7.3-8.5%]), public insurance (42.7% [36.6-49.2%] vs. 33.7% [32.2-35.2%]) in comparison with all other visits. Oral antiviral agents were prescribed in 64.3% (58.1-70.1%) of HZV visits. HZV visits were associated with higher rates of opioid prescriptions compared to all other visits (18.4% [14.0-23.9%] vs. 6.1% [5.6-6.6%], P < 0.0001). The limitation is no data on HZV severity. HZV visits increased over time, even after introduction of HZV vaccines. There were significant racial/ethnic and healthcare disparities of, and high rates of opiate and corticosteroid prescriptions at HZV visits. Future efforts are needed to address these practice gaps, and encourage vaccination and evidence-based prescribing in HZV.

Inhibitory effect of amenamevir on acute herpetic pain and postherpetic neuralgia in mice infected with herpes simplex virus-1.

BACKGROUND: Amenamevir (AMNV) is a helicase-primase inhibitor with antiviral activity against herpesviruses [herpes simplex viruses (HSV)-1 and -2, and varicella-zoster virus], which are associated with the development of acute herpetic pain (AHP) and postherpetic neuralgia. However, the inhibitory effects of helicase-primase inhibitors on AHP and postherpetic neuralgia remain incompletely understood. OBJECTIVE: In this study, we investigated the effects of AMNV on AHP and postherpetic pain (PHP) in HSV-1-infected mice accompanied by zosteriform-like skin lesions. METHODS: HSV-1 was percutaneously infected on the femoral region of mice. AMNV was orally administered twice a day for 5 days. Pain-related response in the hind paw was evaluated using a paintbrush. The infiltration of inflammatory cells in dorsal root ganglion (DRG) and spinal cord (SC) was evaluated by hematoxylin and eosin staining. The viral load in DRG and the expression of pain-related genes in SC were measured by real-time PCR. RESULTS: Pain response was begun to be observed from day 3 post-infection (pi) in HSV-1-infected mice. AMNV administered repeatedly from day 3 pi or day 4 pi, but not day 5 pi, showed an inhibitory effect on the development of AHP and the transition to PHP. Repeated AMNV administration inhibited inflammatory cell infiltration and increases in the viral load and the expression of pain-related genes (ATF-3, TNF-α, COX-2). CONCLUSION: These results demonstrate that AMNV potently suppresses the development of AHP and the transition to PHP as a consequence of decreased viral load in DRG and reduced expression of pain-related genes in SC.

Long-term effectiveness of zoster vaccine live for postherpetic neuralgia prevention.

BACKGROUND: Postherpetic neuralgia (PHN) occurs in 5-30% of individuals with herpes zoster (HZ) and is characterized by long-lasting pain. Zoster vaccine live (ZVL) is licensed for people 50 years and older to prevent HZ and PHN. This study evaluated vaccine effectiveness (VE) of ZVL against PHN. METHODS: We conducted an open cohort study within Kaiser Permanente Northern California with continuous accrual of people as they became age-eligible for ZVL. We defined PHN using a PHN diagnosis between 90 and 365 days after an incident episode of HZ. We estimated VE against PHN using Cox regression with a calendar timeline stratified by year of birth and adjusted for sex, race, influenza vaccination, outpatient visit frequency, comorbidities, and immune compromise status. RESULTS: From 2007 to 2016, 1·5 million people entered the study population and 33% received ZVL. During 7·6 million person-years of follow-up, there were 62,205 HZ cases, 4150 (6·7%) of which went on to develop PHN. Overall VE for PHN was 64·8% (95% CI 61·3, 68). VE was 82·8% (95% CI 77·6, 86·7) during the first year after vaccination, 58·3% (95% CI 50.1, 65.2) during the third year, and then waned more gradually to 48·7% (95% CI 30·2, 62·3) during the eighth year. VE in persons vaccinated when aged 80 years or older was similar to VE in younger vaccinees. VE in persons vaccinated when immune compromised was similar to VE in immune competent. CONCLUSIONS: Overall, ZVL was 65% effective against PHN. It was effective in all age groups and provided moderate protection through 8 years.

Medical conditions at enrollment do not impact efficacy and safety of the adjuvanted recombinant zoster vaccine: a pooled post-hoc analysis of two parallel randomized trials.

In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ).Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment.At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4-97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3-99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant.As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.

Patient report of herpes zoster pain: Incremental benefits of zoster vaccine live.

INTRODUCTION: Pain following herpes zoster (HZ) can persist for months and negatively impact quality of life. To evaluate the effect of zoster vaccine live (ZVL) on progression of pain following HZ, we conducted a prospective cohort study of HZ cases at Kaiser Permanente Southern California. METHODS: ZVL vaccinated and unvaccinated members aged ≥60 years with laboratory-confirmed HZ from January 18, 2012 to February 26, 2015 were followed up within 5 days of HZ diagnosis, and at 30, 60, and 90 days after diagnosis. Pain was assessed with the Zoster Brief Pain Inventory (ZBPI) on a 0-10 scale, using cut-points of ≥3, ≥5, and ≥7, with postherpetic neuralgia (PHN) defined as pain ≥3 at 90 days. Log binomial regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) associated with pain, comparing vaccinated versus unvaccinated HZ patients. RESULTS: We interviewed 509 vaccinated and 509 unvaccinated HZ patients. ZVL was associated with significantly lower risks of HZ-related pain at all time-points. The risk of PHN in vaccinated and unvaccinated patients, respectively, was 9.2% and 15.4% (aRR = 0.594, 95% CI: 0.413, 0.854); 2.0% and 4.8% of these patients reported pain ≥7 (aRR = 0.332, 95% CI: 0.153, 0.721). Irrespective of vaccination, the risk of PHN was lower in adults aged <70 years versus those ≥70 years and was similar or lower in females versus males. CONCLUSION: We used laboratory confirmation of HZ cases and patient survey to show that aside from preventing HZ, ZVL reduced HZ-related pain and prevented PHN among vaccine recipients who experienced HZ. Observational studies will be needed to evaluate long-term effectiveness of the new recombinant zoster vaccine and its benefits in protecting patients against PHN.

The comparative efficacy and safety of herpes zoster vaccines: A network meta-analysis.

BACKGROUND: We estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials. METHODS: A systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age. RESULTS: RZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VERZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VEZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VERZV = 0.91 (95%CI: 0.87, 0.94), VEZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VERZV = 0.89 (95%CI: 0.70, 0.96), VEZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VERZV = 0.89 (95%CI: 0.69, 0.96), VEZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs. CONCLUSION: RZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL.

Zoster Vaccination in Older Adults: Efficacy and Public Health Implications.

Shingles and its most common disabling complication, post-herpetic neuralgia, represent a serious public health challenge in the older population. The decline in the T-cell-mediated immune response to varicella zoster virus after age 50 is clearly associated with increased risk of viral reactivation, causing an acutely painful zoster rash, which may have a severe prodrome of dermatomal pain and persist as seriously debilitating post-herpetic neuralgia well beyond the resolution of the rash. However, new vaccines and adjuvants are being developed and trialed and are now more effective in preventing shingles and the sequelae of post-herpetic neuralgia. Those vaccines that possess the ability to enhance antigen presentation and reverse memory T-cell exhaustion, as well as diminish the immune suppressive effects of regulatory T cells, are most likely to be effective in older adults.

A post hoc analysis utilizing the FDA toxicity grading scale to assess injection site adverse events following immunization with the live attenuated Zoster Vaccine (ZVL).

BACKGROUND: ZOSTAVAX (ZVL; Zoster Virus Live), is a single dose, live, attenuated vaccine licensed for the prevention of herpes zoster (HZ) and post herpetic neuralgia (PHN) in adults ≥50 years of age. Injection site adverse events (AEs) of erythema, swelling and pain were solicited within 5 days post vaccination in the 2 pivotal studies of ZVL; ZEST (ZOSTAVAX Efficacy and Safety Trial) and SPS (Shingles Prevention Study). Protocol specified criteria were used to report the frequency and intensity of injection site AEs in ZEST and SPS studies. Subsequently, the FDA Toxicity Grading Scale provided guidance for uniform assessment of AEs across all adult vaccine clinical trials. The objective of this post-hoc analysis was to categorize the previously reported injection site AEs in two pivotal trials of ZVL according to the current FDA Toxicity Grading Scale. METHODS: The current FDA Toxicity Grading Scale provides a measure for classifying injection site AEs by four grades [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe) and Grade 4 (life threatening)]. Injection site erythema, swelling, and pain intensity gradings were assigned to the respective FDA Toxicity Grade based on this appropriation. A descriptive analysis of the proportion and risk difference (within 95% confidence intervals) of injection site AEs per the FDA Toxicity Grading Scale is provided. RESULTS: The frequency of injection site AEs (erythema, swelling, pain) after subcutaneous vaccination with ZVL were higher in recipients of ZVL compared with placebo. Majority of the injection site AEs observed were Grade 1 (mild) or Grade 2 (moderate) in intensity. Additionally, Grade 3 (severe) injection site AEs were observed infrequently. CONCLUSIONS: Application of the FDA Toxicity Grading Scale provides a uniform AE assessment tool across different adult vaccines. This post hoc summary of injection site AEs using FDA Toxicity Grading Scale provides further evidence of low frequency of severe injection site AEs post ZVL vaccination.

Effectiveness of herpes zoster vaccination in an older United Kingdom population.

BACKGROUND: Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. METHODS: In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. RESULTS: Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. CONCLUSION: This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK.

[Update on anti-N-methyl-D-aspartate receptor encephalitis]. / Update Anti-N-Methyl-D-Aspartat-Rezeptor-Enzephalitis.

Autoimmune encephalitis is a group of autoimmune inflammatory disorders affecting both grey and white matter of the central nervous system. Encephalitis with autoantibodies against the N­methyl-D-aspartate receptor (NMDA-R) is the most frequent autoimmune encephalitis syndrome presenting with a characteristic sequence of psychiatric and neurological symptoms. Treatment necessitates a close interdisciplinary cooperation. This article provides an update on the current knowledge on diagnostic standards, pathogenesis, and treatment strategies for anti-NMDA-R encephalitis from psychiatric and neurological perspectives.

Decreased absolute numbers of CD3+ T cells and CD8+ T cells during aging in herpes zoster patients.

Herpes zoster (HZ) is an infectious dermatosis with high incidence worldwide. Age is a key risk factor for HZ, and postherpetic neuralgia (PHN) is the main sequelae. Until now, no index has been available to predict the pathogenesis of PHN, and rare reports have focused on the immune response during aging and PHN. In this study, we selected immunoglobulin and complement proteins as markers for humoral immunity, while T lymphocyte subsets and natural killer (NK) cells were selected as markers for cell immunity, to systematically study the characteristics of immune responses in the peripheral blood of HZ patients. Our data showed that the absolute number of CD3+ T cells and CD8+ T cells decreased during aging and PHN. This implies that more attention should be paid to prevent the occurrence of PHN, especially in the aged population.

Neuroimmune-Glia Interactions in the Sensory Ganglia Account for the Development of Acute Herpetic Neuralgia.

Herpetic neuralgia is the most important symptom of herpes zoster disease, which is caused by Varicella zoster Nevertheless, the pathophysiological mechanisms involved in herpetic neuralgia are not totally elucidated. Here, we examined the neuroimmune interactions at the sensory ganglia that account for the genesis of herpetic neuralgia using a murine model of Herpes Simplex Virus Type-1 (HSV-1) infection. The cutaneous HSV-1 infection of mice results in the development of a zosteriform-like skin lesion followed by a time-dependent increase in pain-like responses (mechanical allodynia). Leukocytes composed mainly of macrophages and neutrophils infiltrate infected DRGs and account for the development of herpetic neuralgia. Infiltrating leukocytes are responsible for driving the production of TNF, which in turn mediates the development of herpetic neuralgia through downregulation of the inwardly rectifying K+ channel Kir4.1 in satellite glial cells. These results revealed that neuroimmune-glia interactions at the sensory ganglia play a critical role in the genesis of herpetic neuralgia. In conclusion, the present study elucidates novel mechanisms involved in the genesis of acute herpetic pain and open new avenues for its control.SIGNIFICANCE STATEMENT Acute herpetic neuralgia is the most important symptom of herpes zoster disease and it is very difficult to treat. Using a model of peripheral infection of mice with HSV-1, we have characterized for the first time the neuroimmune-glia interactions in the sensory ganglia that account for the development of acute herpetic neuralgia. Among these mechanisms, leukocytes composed mainly of macrophages and neutrophils infiltrate infected sensory ganglia and are responsible for driving the production of TNF. TNF, via TNFR1, mediates herpetic neuralgia development through downregulation of the inwardly rectifying K+ channel Kir4.1 in satellite glial cells. This study elucidates novel mechanisms involved in the genesis of acute herpetic neuralgia and open new avenues for its control.

The herpes zoster subunit vaccine.

INTRODUCTION: Herpes zoster (HZ) causes severe pain and rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN). AREAS COVERED: HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age related or other causes of decreased T cell immunity. A concentrated live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 5-8 years. The new HZ subunit (HZ/su or Shingrix) vaccine combines a key surface VZV glycoprotein (E) with T cell boosting adjuvant (AS01B). It is highly efficacious in protection (97%) against HZ in immunocompetent subjects, with no decline in advancing age and protection maintained for >3 years. Phase I-II trials showed safety and similar immunogenicity in severely immunocompromised patients. Local injection site pain and swelling can be severe in a minority (9.5%) but is transient (2 days). EXPERT OPINION: The HZ/su vaccine appears very promising in immunocompetent patients in the ZoE-50 controlled trial. The unblinding of the current ZoE-50 trial and publication of results from the accompanying ZoE-70 trial will reveal more about its mechanism of action and its efficacy against PHN, particularly in subjects >70 years. Phase III trial results in immunocompromised patients are eagerly awaited.

Anti-cytokine autoantibodies in postherpetic neuralgia.

BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN.

Zoster Vaccine and the Risk of Postherpetic Neuralgia in Patients Who Developed Herpes Zoster Despite Having Received the Zoster Vaccine.

BACKGROUND: Although it is evident that zoster vaccination reduces postherpetic neuralgia (PHN) risk by reducing herpes zoster (HZ) occurrence, it is less clear whether the vaccine protects against PHN among patients who develop HZ despite previous vaccination. METHODS: This cohort study included immunocompetent patients with HZ. The vaccinated cohort included 1155 individuals who were vaccinated against HZ at age ≥60 years and had an HZ episode after vaccination. Vaccinated patients were matched 1:1 by sex and age with unvaccinated patients. Trained medical residents reviewed the full medical record to determine the presence of HZ-related pain at 1, 2, 3, and 6 months after HZ diagnosis. The incidence of PHN was compared between vaccinated and unvaccinated -patients. RESULTS: Thirty vaccinated women (4.2%) experienced PHN, compared with 75 unvaccinated women (10.4%), with an adjusted relative risk of 0.41 (95% confidence interval, .26-.64). PHN occurred in 26 vaccinated men (6.0%) versus 25 unvaccinated men (5.8%), with an adjusted relative risk of 1.06 (.58-1.94). These associations did not differ significantly by age. CONCLUSIONS: Among persons experiencing HZ, prior HZ vaccination is associated with a lower risk of PHN in women but not in men. This sex-related difference may reflect differences in healthcare-seeking patterns and deserve further investigation.

[Zoster and postherpetic neuralgia: vaccine prevention is available]. / Zona et douleurs post-zostériennes : la prévention vaccinale est possible.

Herpes zoster (HZ) infection is a common condition in the elderly. Immunosuppression involving cellular immunity favors its occurrence. The pain is the most frequent complications of HZ. It occurs in about 30% of people aged over 70 years. The virological diagnosis of typical HZ is not useful, and the diagnosis is mainly based on clinical data. Skin care is essential to limit cutaneous damage. Antiviral drugs will reduce the risk of post-herpetic neuralgia, if they are early prescribed within 72 hours after the rash onset. Analgesia is essential and should be conducted in relation evolution. Vaccination is the most effective way to prevent the occurrence of HZ complications in the elderly, in particular post-herpetic neuralgia.

Varicella-zoster virus-derived major histocompatibility complex class I-restricted peptide affinity is a determining factor in the HLA risk profile for the development of postherpetic neuralgia.

UNLABELLED: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster and is typified by a lingering pain that can last months or years after the characteristic herpes zoster rash disappears. It is well known that there are risk factors for the development of PHN, such as its association with certain HLA alleles. In this study, previous HLA genotyping results were collected and subjected to a meta-analysis with increased statistical power. This work shows that the alleles HLA-A*33 and HLA-B*44 are significantly enriched in PHN patients, while HLA-A*02 and HLA-B*40 are significantly depleted. Prediction of the varicella-zoster virus (VZV) peptide affinity for these four HLA variants by using one in-house-developed and two existing state-of-the-art major histocompatibility complex (MHC) class I ligand prediction methods reveals that there is a great difference in their absolute and relative peptide binding repertoires. It was observed that HLA-A*02 displays a high affinity for an ∼7-fold-higher number of VZV peptides than HLA-B*44. Furthermore, after correction for HLA allele-specific limitations, the relative affinity of HLA-A*33 and HLA-B*44 for VZV peptides was found to be significantly lower than those of HLA-A*02 and HLA-B*40. In addition, HLA peptide affinity calculations indicate strong trends for VZV to avoid high-affinity peptides in some of its proteins, independent of the studied HLA allele. IMPORTANCE: Varicella-zoster virus can cause two distinct diseases: chickenpox (varicella) and shingles (herpes zoster). Varicella is a common disease in young children, while herpes zoster is more frequent in older individuals. A common complication of herpes zoster is postherpetic neuralgia, a persistent and debilitating pain that can remain months up to years after the resolution of the rash. In this study, we show that the relative affinity of HLA variants associated with higher postherpetic neuralgia risk for varicella-zoster virus peptides is lower than that of variants with a lower risk. These results provide new insight into the development of postherpetic neuralgia and strongly support the hypothesis that one of its possible underlying causes is a suboptimal anti-VZV immune response due to weak HLA binding peptide affinity.

Cost-effectiveness of vaccination against herpes zoster.

Herpes zoster (HZ) is a common disease among elderly, which may develop into a severe pain syndrome labeled postherpetic neuralgia (PHN). A live-attenuated varicella zoster virus vaccine has been shown to be effective in reducing the incidence and burden of illness of HZ and PHN, providing the opportunity to prevent significant health-related and financial consequences of HZ. In this review, we summarize the available literature on cost-effectiveness of HZ vaccination and discuss critical parameters for cost-effectiveness results. A search in PubMed and EMBASE was performed to identify full cost-effectiveness studies published before April 2013. Fourteen cost-effectiveness studies were included, all performed in western countries. All studies evaluated cost-effectiveness among elderly above 50 years and used costs per quality-adjusted life year (QALY) gained as primary outcome. The vast majority of studies showed vaccination of 60- to 75-year-old individuals to be cost-effective, when duration of vaccine efficacy was longer than 10 years. Duration of vaccine efficacy, vaccine price, HZ incidence, HZ incidence and discount rates were influential to the incremental cost-effectiveness ratio (ICER). HZ vaccination may be a worthwhile intervention from a cost-effectiveness point of view. More extensive reporting on methodology and more detailed results of sensitivity analyses would be desirable to address uncertainty and to guarantee optimal comparability between studies, for example regarding model structure, discounting, vaccine characteristics and loss of quality of life due to HZ and PHN.

Local and systemic cytokine expression in patients with postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN. METHODS: Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1ß, IL-2, and IL-8). RESULTS: IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar. CONCLUSION: While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered.

The global epidemiology of herpes zoster.

Varicella-zoster virus (VZV) is a ubiquitous, highly neurotropic, exclusively human α-herpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in neurons of cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia along the entire neuraxis. As humans undergo a natural decline in cell-mediated immunity (CMI) to VZV with age, VZV frequently reactivates to produce zoster, characterized by maculopapular or vesicular rash and dermatomal-distribution pain. Pain and rash usually occur within days of each other. Pain is severe and often burning. Colorful descriptions of zoster exist worldwide. In Arabic, Hezam innar ( ) means belt of fire; in Hindi, Baoisayaa daga ( ) means big rash; in Norwegian, Helvetesild means Hell's fire (also described as a bell of roses from Hell); and in Spanish, Culebrilla means small snake.(1) The most common complication of zoster is postherpetic neuralgia (PHN), operationally defined as pain lasting for more than 90 days after rash. Zoster may be followed by multiple neurologic disorders (meningoencephalitis, myelitis, and vasculopathy, including VZV temporal arteritis) as well as ocular disease (acute or progressive outer retinal necrosis).