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Background/Objectives: We aimed to determine in multiple sclerosis (MS) whether intrathecal immunoglobulin G (IgG) production against measles- (M), rubella- (R), and varicella zoster (Z) viruses, which is called MRZ reaction (MRZR) and considered the most specific soluble biomarker for MS, is associated with demographic and basic cerebrospinal fluid (CSF) parameters reflecting inflammation. Methods: We analyzed the presence of positive MRZR and associations with demographic and clinical routine CSF parameters in 513 patients with MS and 182 non-MS patients. Results: Comparing MS patients versus non-MS patients, positive MRZR (38.8% versus 2.2%; specificity 97.8%; positive likelihood ratio, PLR 17.7) had a better specificity and PLR for MS than CSF-specific OCB (89.5% versus 22.0%; specificity 78.0%; PLR 4.1). A positive MRZR in MS patients was associated with female sex (p = 0.0001), pleocytosis (p < 0.0001), higher frequency of presence of plasma cells in CSF (p = 0.0248), normal CSF/serum albumin ratio (p = 0.0005), and intrathecal production of total IgG or CSF-specific OCB (both p < 0.0001), but not with intrathecal production of total IgA or IgM. Conclusions: This study confirms the MRZR as a highly specific marker of MS and shows that MRZR-positive MS patients more frequently are female and show inflammatory changes of basic CSF parameters than MRZR-negative MS patients. [ABSTRACT FROM AUTHOR]

Recombinant zoster vaccine (RZV) is recommended for individuals ≥ 50 years of age for protection against herpes zoster (HZ). This study quantifies RZV coverage and assesses predictors for RZV vaccination using a U.S. claims database. Univariate linear regression provided annual prevalence of RZV vaccination and multivariable logistic regression provided ORs and 95% CIs for associations between predictors and RZV vaccination. A total of 4,124,315 individuals (19,080,914 person-years) were included in this study. Since receiving FDA approval for the prevention of HZ, RZV coverage (of at least one dose) has reached approximately 17% within the eligible U.S. population by January 2021, although significant disparities between demographic groups were noted. Our findings suggest that HZ vaccine coverage may be reduced below goal in the U.S. and highlights the importance of continuing to monitor RZV vaccination. Additionally, as our study found disparities in vaccine coverage, attention towards marginalized and medically underserved populations is needed.

The first manifestation of a viral infection may be conjunctivitis. There are limited data on the etiology of viral conjunctivitis in Vanuatu, a country in the South Pacific Ocean. Patients presenting to one of two Vanuatu health centers with presumed infectious conjunctivitis were eligible if symptom onset was within 14 days of screening. Conjunctival and anterior nasal swabs were obtained and subjected to unbiased RNA deep sequencing (RNA-seq) to identify DNA and RNA viruses. For samples collected from May to November 2021, RNA-seq identified a viral etiology in 12/48 patients. Human adenovirus species were the most common viruses (58%) detected, followed by human herpes viruses (cytomegalovirus, varicella zoster virus, and human herpes 7 virus). Rhinovirus C, Epstein-Barr virus, and bocavirus were also detected. In summary, the etiology for viral conjunctivitis in Vanuatu appears broad. Unbiased testing may be useful for disease surveillance.

Objective: This study aimed to evaluate the association between obstructive sleep apnea (OSA) and humoral immunity to varicella zoster virus (VZV). Methods: This retrospective cohort study included patients who underwent polysomnography and concurrently agreed for blood collection between January 2018 and February 2021. Habitual snorers and patients with severe obstructive sleep apnea were evaluated to compare the VZV immunoglobulin G (IgG) antibody titer between habitual snorer group and OSA group. Correlation between VZV IgG antibody titer and various sleep related respiratory parameters were also evaluated. Results: We found that the VZV IgG antibody titer of the habitual snorer group (n = 60) was significantly higher than that of the severe OSA group (n = 54) (244.1 ± 80.9 and 163.09 ± 48.39, respectively. Data are presented as mean ± standard deviation, P < 0.001). According to Spearman's correlation analysis, the VZV IgG antibody titer was moderately negatively correlated with apnea hypopnea index (r = -0.477, P < 0.001), apnea index (r = -0.496, P < 0.001), hypopnea index (r = -0.398, P < 0.001), respiratory disturbance index (r = -0.467, P < 0.001), arousal index (r = -0.467, P < 0.001) and oxygen desaturation index (r = -0.475, P < 0.001). Minimal oxygen saturation was moderately positively correlated with VZV IgG antibody titer (r = 0.474, P < 0.001). Conclusion: Humoral immunity to VZV is significantly reduced in patients with severe OSA, and VZV IgG antibody titer was inversely correlated with respiratory events during sleep. [ABSTRACT FROM AUTHOR]

BackgroundStaphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections.ObjectivesTo determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD.MethodsWe conducted a population-based cohort study using UK-based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections.ResultsAmong 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50-52% greater risk of HSV and 18-33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38-4·54] and adults with severe AD (HR 4·45, 95% CI 1·76-11·25). Patients with AD had a 26-40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20-1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD.ConclusionsAD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose-dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications.

BackgroundThe incidence of herpes zoster (HZ) has been increasing in recent decades. Although 2 vaccines for HZ are available, there have been few studies on the incidence rates of HZ and postherpetic neuralgia (PHN) since their introduction. This study examined the incidence rates of HZ and PHN from 1994 to 2018 in the United States to determine if they have continued to increase since introduction of the HZ vaccines.MethodsA de-identified longitudinal administrative claims database, the OptumLabs Data Warehouse, was used to assess incidence rates among individuals continuously enrolled in the database for ≥365 days with no prior history of HZ or PHN. Unstandardized and standardized incidence rates were calculated by year, 10-year age groups, sex, and race/ethnicity.ResultsThere were 610 766 individuals with HZ (median age, 56.3; interquartile range, 43.0-68.7 years; 59.8% women; 70.6% white). From 1994 to 2018, the incidence of HZ increased from 286.0 (95% confidence interval [CI], 259.1-312.8) to 579.6 (95% CI, 554.2-605.0) cases per 100 000 person-years, an annual increase of 3.1% (95% CI, 2.5-3.6%). Since 2007, annual HZ incidence rates have decreased in individuals ≤20 and >60 years old. The overall incidence rate of PHN was 57.5 (95% CI, 56.0-59.0) cases per 100 000 person-years. The proportion of individuals with HZ who developed PHN was higher from 2007 to 2018 than from 1994 to 2006.ConclusionsHZ incidence rates have continued to increase in age groups for which HZ vaccines are not currently recommended, warranting a review of current vaccine recommendations.

Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.

BackgroundThe recombinant zoster vaccine had over 90% efficacy in preventing herpes zoster in clinical trials. However, its effectiveness outside of a clinical trial setting has not been investigated. This study aimed to assess the effectiveness of the recombinant zoster vaccine in general practice.MethodsA de-identified administrative claims database, the OptumLabs Data Warehouse, was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against herpes zoster in nonimmunocompromised, vaccine age-eligible individuals enrolled in the database for ≥365 days.ResultsA total of 4 769 819 adults were included in this study, with 173 745 (3.6%) adults receiving 2 valid doses of the recombinant zoster vaccine. The incidence rate of herpes zoster was 258.8 (95% confidence interval [CI], 230.0-289.4) cases per 100 000 person-years in vaccinated persons compared with 893.1 (95% CI, 886.2-900.0) in unvaccinated persons. Recombinant zoster vaccine effectiveness was 85.5% (95% CI, 83.5-87.3%) overall, with an effectiveness of 86.8% (95% CI, 84.6-88.7%) in individuals 50 to 79 years old compared with 80.3% (95% CI, 75.1-84.3%) in individuals aged 80 and older. In patients with a history of live zoster vaccine within 5 years of study inclusion, vaccine effectiveness was 84.8% (95% CI, 75.3-90.7%).ConclusionsRecombinant zoster vaccine effectiveness against herpes zoster was high in a real-world setting. Given the low vaccine coverage and high effectiveness, a major public health effort is needed to identify and address barriers to vaccination and increase immunization rates.

BackgroundThe incidence of herpes zoster (HZ) has been on the rise for decades in the United States. Clinical trials for the recombinant zoster vaccine (RZV) demonstrated vaccine efficacy of over 90% in preventing herpes zoster. However, there is limited information on its effectiveness outside of a clinical trial setting, as well as its effectiveness against herpes zoster ophthalmicus (HZO).MethodsA de-identified electronic health records database from Kaiser Permanente Hawaii (KPH) was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against HZ and HZO in immunocompetent, vaccine age-eligible individuals without a prior history of HZ, who were continuously enrolled in KPH for ≥365 days prior to becoming age-eligible for RZV between January 1, 2018, through December 31, 2019.ResultsA total of 78 356 adults were included in this study, with 11 864 (15.1%) adults receiving two valid doses of the recombinant zoster vaccine. The incidence rate of HZ was 325.6 (95% CI: 217.7 to 464.4) cases per 100 000 person-years in vaccinated persons compared to 1063.3 cases per 100 000 person-years (95% CI: 1006.0 to 1122.8) in the unvaccinated group. The incidence rate of HZO was 11.9 (95% CI: 0.7 to 52.3) cases per 100 000 person-years in the vaccinated group compared to 72.1 (95% CI: 58.0 to 88.3) in the unvaccinated group. RZV was 83.5% (95% CI: 74.9% to 89.2%) effective against HZ and 93.3% (95% CI: 48.7% to 99.1%) effective against HZO.ConclusionsRZV has demonstrated high effectiveness against both HZ and HZO outside of a clinical trial setting in the United States. Vaccine coverage is low, emphasizing the need for public health efforts to increase vaccination to reduce morbidity from HZ and HZO.

Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP-the largest among human herpesviruses-uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.

PURPOSE: Iridocorneal endothelial (ICE) syndrome is a group of rare ocular conditions that result from abnormal corneal endothelial cells, leading to secondary glaucoma, iris distortions, and corneal edema. The etiology of ICE is unknown, although it has been associated with viral infections, such as herpes simplex virus. In this study, we sought to identify an infectious etiology for ICE using advanced molecular techniques. METHODS: Metagenomic RNA sequencing (MDS) is a high-throughput sequencing approach that can identify all pathogens in any clinical sample, including RNA viruses. Descemet membrane and aqueous fluid from patients with ICE syndrome were subjected to MDS testing. RESULTS: Samples from 3 patients with ICE were analyzed. MDS was performed on the aqueous fluid of 3 patients and Descemet membrane and endothelial cell tissue from 1 patient. Viral pathogens were not identified in any of the samples. CONCLUSIONS: We were unable to identify a viral etiology in the tissues of patients with the Chandler variant of ICE syndrome, although this study was limited by sample size.

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P =

BackgroundVaricella zoster virus (VZV) causes both varicella (chickenpox) and herpes zoster (shingles) and is associated with significant global morbidity. Most epidemiological data on VZV come from high-income countries, and to date there are limited data on the burden of VZV in Africa.MethodsWe assessed the seroprevalence of VZV antibodies among children in the Democratic Republic of Congo in collaboration with the 2013-2014 Demographic and Health Survey. Dried blood spot samples collected from children 6-59 months of age were run on Dynex™ Technologies Multiplier FLEX® chemiluminescent immunoassay platform to assess serologic response. Multivariate logistic regression was then used to determine risk factors for VZV seropositivity.ResultsSerologic and survey data were matched for 7,195 children 6-59 months of age, among whom 8% were positive and 2% indeterminate for VZV antibodies in weighted analyses. In multivariate analyses, the odds of seropositivity increased with increasing age, increasing socioeconomic status, mother's education level, rural residence, and province (South Kivu, North Kivu, Bandundu, Bas Congo had the highest odds of a positive test result compared with Kinshasa).ConclusionOur data suggest that VZV is circulating in DRC, and seropositivity is low among children 6-59 months. Seropositivity increased with age and varied by other sociodemographic factors, such as geographic location. This study provides the first nationally representative estimates of VZV infection among children in the DRC.

Varicella zoster virus (VZV) causes varicella during acute infection and establishes latency in the sensory ganglia. Reactivation of VZV results in herpes zoster, a debilitating and painful disease. It is believed that VZV reactivates due to a decline in cell-mediated immunity; however, the roles that CD4 versus CD8 T cells play in the prevention of herpes zoster remain poorly understood. To address this question, we used a well-characterized model of VZV infection where rhesus macaques are intrabronchially infected with the homologous simian varicella virus (SVV). Latently infected rhesus macaques were thymectomized and depleted of either CD4 or CD8 T cells to induce selective senescence of each T cell subset. After T cell depletion, the animals were transferred to a new housing room to induce stress. SVV reactivation (viremia in the absence of rash) was detected in three out of six CD8-depleted and two out of six CD4-depleted animals suggesting that both CD4 and CD8 T cells play a critical role in preventing SVV reactivation. Viral loads in multiple ganglia were higher in reactivated animals compared to non-reactivated animals. In addition, reactivation results in sustained transcriptional changes in the ganglia that enriched to gene ontology and diseases terms associated with neuronal function and inflammation indicative of potential damage as a result of viral reactivation. These studies support the critical role of cellular immunity in preventing varicella virus reactivation and indicate that reactivation results in long-lasting remodeling of the ganglia transcriptome.

UNLABELLED: Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression. IMPORTANCE: Many aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection.

ObjectivesTo determine the role of equine herpesvirus (EHV) in idiopathic keratoconjunctivitis in horses and to determine whether sample collection method affects detection of EHV DNA by quantitative polymerase chain reaction (qPCR).Animals studiedTwelve horses with idiopathic keratoconjunctivitis and six horses without signs of ophthalmic disease.ProceduresConjunctival swabs, corneal scrapings, and conjunctival biopsies were collected from 18 horses: 12 clinical cases with idiopathic keratoconjunctivitis and six euthanized controls. In horses with both eyes involved, the samples were taken from the eye judged to be more severely affected. Samples were tested with qPCR for EHV-1, EHV-2, EHV-4, and EHV-5 DNA. Quantity of EHV DNA and viral replicative activity were compared between the two populations and among the different sampling techniques; relative sensitivities of the sampling techniques were determined.ResultsPrevalence of EHV DNA as assessed by qPCR did not differ significantly between control horses and those with idiopathic keratoconjunctivitis. Sampling by conjunctival swab was more likely to yield viral DNA as assessed by qPCR than was conjunctival biopsy. EHV-1 and EHV-4 DNA were not detected in either normal or IKC-affected horses; EHV-2 DNA was detected in two of 12 affected horses but not in normal horses. EHV-5 DNA was commonly found in ophthalmically normal horses and horses with idiopathic keratoconjunctivitis.ConclusionsBecause EHV-5 DNA was commonly found in control horses and in horses with idiopathic keratoconjunctivitis, qPCR was not useful for the etiological diagnosis of equine keratoconjunctivitis. Conjunctival swabs were significantly better at obtaining viral DNA samples than conjunctival biopsy in horses in which EHV-5 DNA was found.

Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death - a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14xVI1.

BackgroundArsenic is an immunotoxicant. Clinical reports observe the reactivation of varicella zoster virus (VZV) in people who have recovered from arsenic poisoning and in patients with acute promyelocytic leukemia that have been treated with arsenic trioxide.ObjectiveWe evaluated the association between arsenic and the seroprevalence of VZV IgG antibody in a representative sample of the U.S.MethodsWe analyzed data from 3,348 participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2009-2010 pooled survey cycles. Participants were eligible if they were 6-49 years of age with information on both VZV IgG and urinary arsenic concentrations. We used two measures of total urinary arsenic (TUA): TUA1 was defined as the sum of arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, and TUA2 was defined as total urinary arsenic minus arsenobetaine and arsenocholine.ResultsThe overall weighted seronegative prevalence of VZV was 2.2% for the pooled NHANES sample. The geometric means of TUA1 and TUA2 were 6.57 μg/L and 5.64 μg/L, respectively. After adjusting for age, sex, race, income, creatinine, and survey cycle, odds ratios for a negative VZV IgG result in association with 1-unit increases in natural log-transformed (ln)-TUA1 and ln-TUA2 were 1.87 (95% CI: 1.03, 3.44) and 1.40 (95% CI: 1.0, 1.97), respectively.ConclusionsIn this cross-sectional analysis, urinary arsenic was inversely associated with VZV IgG seroprevalence in the U.S.PopulationThis finding is in accordance with clinical observations of zoster virus reactivation from high doses of arsenic. Additional studies are needed to confirm the association and evaluate causal mechanisms.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.

Glioma is the most common cancer of the central nervous system but with few confirmed risk factors. It has been inversely associated with chicken pox, shingles and seroreactivity to varicella virus (VZV), as well as to allergies and allergy-associated IgE. The role of antibody reactivity against individual VZV antigens has not been assessed. Ten VZV-related proteins, selected for high immunogenicity or known function, were synthesized and used as targets for antibody measurements in the sera of 143 glioma cases and 131 healthy controls selected from the San Francisco Bay Area Adult Glioma Study. Glioma cases exhibited significantly reduced seroreactivity compared to controls for six antigens, including proteins IE63 [odds ratio (OR) = 0.26, 95% confidence interval (CI): 0.12-0.58, comparing lowest quartile to highest) and the VZV-unique protein ORF2p (OR = 0.44, 95% CI: 0.21-0.96, lowest quartile to highest). When stratifying the study population into those with low and high self-reported allergy history, VZV protein seroreactivity was only associated inversely with glioma among individuals self-reporting more than two allergies. The data provide insight into both allergy and VZV effects on glioma: strong anti-VZV reactions in highly allergic individuals are associated with reduced occurrence of glioma. This result suggests a role for specificity in the anti-VZV immunity in brain tumor suppression for both individual VZV antigens and in the fine-tuning of the immune response by allergy. Anti-VZV reactions may also be a biomarker of effective CNS immunosurveillance owing to the tropism of the virus.

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine's duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y.

Objectives There is uncertainty if varicella zoster virus (VZV) triggers GCA. This is based on discordant reports of VZV detection in GCA temporal artery biopsies. We conducted a multimodal evaluation for VZV in the inception Giant Cell Arteritis and PET Scan (GAPS) cohort. Methods Consecutive patients who underwent temporal artery biopsy for suspected GCA were clinically reviewed for active and past VZV infection and followed for 6 months. Serum was tested for VZV IgM and IgG. Temporal artery biopsy (TAB) sections were stained for VZV antigen using the VZV Mouse Cocktail Antibody (Cell Marque, Rocklin, CA, USA). A selection of GCA and control tissues were stained with the VZV gE antibody (Santa Cruz Biotechnology, Dallas, TX, USA), which was used in previous studies. Results A total of 58 patients met inclusion criteria, 12 (21%) had biopsy-positive GCA and 20 had clinically positive GCA. None had herpes zoster at enrolment and only one patient developed a VZV clinical syndrome (zoster ophthalmicus) on follow-up. There was no difference in VZV exposure between GCA and non-GCA patients. None of the 53 patients who had VZV serology collected had positive VZV IgM antibodies. VZV antigen was not convincingly demonstrated in any of the TAB specimens; 57 TABs stained negative and 1 stained equivocally positive. The Santa Cruz Biotechnology VZV antibody exhibited positive staining in a range of negative control tissues, questioning its specificity for VZV antigen. Conclusion The absence of active infection markers argues against VZV reactivation being the trigger for GCA. Non-specific immunohistochemistry staining may account for positive findings in previous studies. [ABSTRACT FROM AUTHOR]

Zoster sine herpete (ZSH) is one of the atypical clinical manifestations of herpes zoster (HZ), which stems from infection and reactivation of the varicella-zoster virus (VZV) in the cranial nerve, spinal nerve, viscera, or autonomic nerve. Patients with ZSH display variable symptoms, such as neuralgia, however, different from HZ, ZSH show no zoster, which makes clinical diagnosis difficult. ZSH not only causes initial symptoms, such as neuropathic pain in the affected nerve, Bell palsy, and Ramsay Hunt syndrome, but also postherpetic neuralgia and fatal complications such as VZV encephalitis and stroke. The misdiagnosis of ZSH and tardy antiviral treatment may lead to severe ZSH sequelae. We review the publications related to ZSH, especially its diagnosis with VZV DNA and/or anti-VZV immunoglobulin (IgG and IgM). More work about ZSH, especially ZSH epidemiological survey and guidelines for its diagnosis and treatment, are needed because most of the present studies are case reports. [ABSTRACT FROM AUTHOR]

Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.

By analyzing vesicle fluids and crusted scabs from 136 persons with suspected monkeypox, we identified 51 cases of monkeypox by PCR, sequenced the hemagglutinin gene, and confirmed 94% of cases by virus culture. PCR demonstrated chickenpox in 61 patients. Coinfection with both viruses was found in 1 additional patient.

Abstract A 77‐year‐old woman presented with ophthalmic zoster and nasal tip involvement, consistent with Hutchinson's sign. Ocular examination disclosed a swollen upper eyelid, chemosis, conjunctival injection, pus, and mild corneal endothelial decompensation. The presence of Hutchinson's sign requires urgent consultation with an ophthalmologist due to the high risk of ocular complications.

Abstract Background Chorioretinitis is an unusual form of varicella zoster virus (VZV)-associated uveitis, and no report has described VZV-associated chorioretinitis using serial optical coherence tomography (OCT) images obtained during the course of resolution. Case presentation A 61-year-old woman presented with acute, unilateral vision loss in her right eye. Her visual acuity was count fingers in the right eye and 16/20 in the left eye, and she exhibited skin vesicles on her right forehead. Slit lamp biomicroscopy, funduscopy, OCT, and intraocular fluid analysis were performed. The right eye exhibited multiple inflammatory lesions at the posterior pole, macular edema, and disc swelling on the fundus examination. OCT revealed predominant involvement of the choroid and the retinal pigment epithelium (RPE). Intraocular fluid analysis showed positivity for VZV. The patient was admitted and treated with intravenous acyclovir. Additional oral prednisolone was used to reduce the inflammatory reaction. After 2 weeks of treatment with acyclovir, the lesion resolved, with undulation of the RPE. Her final visual acuity was 20/20. Conclusions VZV-associated posterior uveitis may present as multifocal chorioretinitis. Intraocular fluid analysis is important to detect an infectious origin.

Varicella is a highly contagious viral infection with self-limiting presentation, yet, it can be more severe in adults. There is a major risk of transmission between health care workers and patients who are susceptible. This study was done to investigate anti-VZV (varicella zoster virus) antibody among nursing students. The anti-VZV IgG was measured in all nursing students in Nursing and Midwifery School of Langeroud who participated in this cross-sectional study. That is, the antibody was measured in 101 students by ELISA method. Seventy-three (72.3%) students had anti-VZV IgG, 27 students (26.7%) were seronegative and one student had borderline IgG. There are a noticeable proportion of seronegative nursing students who were susceptible to VZV infection. They can develop the infection from other staff and patients in hospital and also transmit it to others, especially immunocompromised patients. Therefore, it is recommended that we screen anti-VZV antibody in nursing students and vaccinate seronegative ones. [ABSTRACT FROM AUTHOR]

Background: Infections in pregnant women or women planning pregnancy caused by the protozoan Toxoplasma gondii and the viruses varicella zoster virus (VZV) and human parvovirus B19 can be a danger to the fetus. Aim of the study: The aim of the study was to determine the serological status of women of childbearing age in relation to T. gondii, VZV and human parvovirus B19 in a region of Eastern Poland (Biała Podlaska District). Material and methods: The study group consisted of 174 women aged 19 to 35 (average 23, SD 3.68) from the Biała Podlaska District. Anti-T. gondii IgM/IgG antibodies, anti-VZV IgG and anti-human parvovirus B19 IgG were detected by ELISA. Results: Serological screening revealed that the most common antibodies were anti-VZV and anti-parvovirus B19 (in 96% and 60.9% of women, respectively). Anti-T. gondii antibodies were found in 28.6%. No correlation was found between the presence of anti-T. gondii, human parvovirus B19, and VZV antibodies and the age of the examined women, their place of residence, and their education. Conclusions: About 4%, 39% and 71.2% of women participating in this study were still susceptible to infection with VZV, human parvovirus B19, and T. gondii, respectively. It is therefore important to address health education primarily in women of childbearing age in order to help them undertake relevant measures for prevention of T. gondii, human parvovirus B19 and VZV infection. [ABSTRACT FROM AUTHOR]

Theoretically, the subunit herpes zoster vaccine ShingrixTM could be used as a varicella vaccine that avoids the risk of developing shingles from vaccination, but bedside mixing strategies and the limited supply of the adjuvant component QS21 have made its application economically impracticable. With lipid nanoparticles (LNPs) that were approved by the FDA as vectors for severe acute respiratory syndrome coronavirus 2 vaccines, we designed a series of vaccines efficiently encapsulated with varicella-zoster virus glycoprotein E (VZV-gE) and nucleic acids including polyinosinic-polycytidylic acid (Poly I:C) and the natural phosphodiester CpG oligodeoxynucleotide (CpG ODN), which was approved by the FDA as an immunostimulator in a hepatitis B vaccine. Preclinical trial in mice showed that these LNP vaccines could induce VZV-gE IgG titers more than 16 times those induced by an alum adjuvant, and immunized serum could block in vitro infection completely at a dilution of 1:80, which indicated potential as a varicella vaccine. The magnitude of the cell-mediated immunity induced was generally more than 10 times that induced by the alum adjuvant, indicating potential as a zoster vaccine. These results showed that immunostimulatory nucleic acids together with LNPs have promise as safe and economical varicella and zoster vaccine candidates.

Introduction Varicella zoster virus (VZV) and subsequent herpes zoster (HZ) infection have been proposed as a causative agent of periapical pathoses and root resorption. This review aimed to identify, synthesize, and present a critical analysis of the available data on the association among VZV, subsequent HZ infection, and the development of periapical pathoses and root resorption and to analyze the level of evidence of available studies. Methods The literature search covered MEDLINE, Science Citation Index Expanded, and Scopus. A qualitative critical appraisal of the included articles was performed. Results The electronic database search yielded 66 hits from PubMed, 73 hits from Web of Science, and 107 from Scopus. Seven case reports and 3 cross-sectional studies were included in the final review. When summarized, in 7 patients with a history of a previous HZ attack and with no other apparent cause, 23 teeth were diagnosed with apical periodontitis, 8 teeth with internal and 1 tooth with external root resorption. The cross-sectional studies investigated the presence of VZV DNA in samples of acute apical abscess. The VZV DNA was found only in 2 of 65 samples. Conclusions All studies included in this systematic review had a low level of evidence (4 and 5). Still, the potential role of VZV in the etiopathogenesis of periapical pathoses and root resorption cannot be ruled out. Future investigations should be directed toward the analysis of VZV pathologic effects on pulp blood vessels, which might cause local ischemia and tissue necrosis. [ABSTRACT FROM AUTHOR]

Background Varicella-zoster virus (VZV) is one of the most common etiologies of aseptic meningitis. The severest manifestation of VZV meningitis is occasionally confused with tuberculous meningitis (TBM). Thus, we investigated the clinical manifestations of VZV meningitis as compared with those of TBM. Materials and Methods All adult patients who were diagnosed with VZV meningitis or TBM were enrolled at a tertiary hospital in Seoul, South Korea, during an 8-year period. The clinical characteristics and cerebrospinal fluid (CSF) profile of patients were analyzed. Results Seventy-nine patients with VZV meningitis and 24 patients with TBM were enrolled in this study. Of the 79 patients with VZV meningitis, 63 (80%) did not received empirical anti-tuberculous therapy (Group 1) and the remaining 16 (20%) received empirical anti-tuberculous therapy (Group 2), compared with 24 patients with TBM (Group 3). Altered mental status, intensive care unit (ICU) admission, neurologic sequelae, CSF protein levels, and CSF adenosine deaminase levels revealed a trend of being higher in Group 3 than Group 2, which was higher than Group 1. However, the CSF/serum glucose ratio was significantly lower in Group 3 than in Group 1 or Group 2. Conclusion About one fifth of VZV meningitis cases presented as severe manifestations, mimicking TBM. The CSF/serum glucose ratio might be useful to differentiate VZV meningitis from TBM until definite diagnostic tests are available. Physicians should keep in mind that a differential diagnosis between severe VZV meningitis and TBM is needed. [ABSTRACT FROM AUTHOR]

Herpes zoster is an infectious disease caused by the reactivation of the varicella zoster virus in the cranial or dorsal sensorial ganglia, characterized by a vesicular skin rash affecting one or more dermatomes. It is more common in the elderly, in association with the decline of the cell-mediated immunity in advanced age. In young adults, herpes zoster infection correlates more frequently with clinical conditions of low immunity. This paper reports a clinical case of herpes zoster with an atypical presentation, both with regard to the location and the high number of recurrences in a young immunocompetent female patient. The author discusses the case, based on the current scientific evidence, emphasizing the symptoms, clinical presentation, differential diagnosis, impact on quality of life and management. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to determine the hospital burden of varicella-zoster virus infection (VZV) in England during 2004-2013 to support a future cost-effectiveness analysis of a childhood varicella vaccination programme.Methods: We analysed the incidence, duration, outcome and costs of hospitalisations for VZV using the Hospital Episode Statistics (HES) database for the general and immunocompetent population. Mortality in HES was validated using data from the Office for National Statistics (ONS).Results: The average annual incidences of admissions due to varicella and herpes zoster were 7.6 (7.3-7.9) and 8.8 (8.6-9.0) per 100,000, respectively. The immunocompetent population accounted for 93% and 82% of the admissions due to varicella and herpes zoster, respectively. The average yearly number of hospital days was 10,748 (10,227-11,234) for varicella and 41,780 (40,257-43,287) for herpes zoster. The average yearly hospital costs (£2013/14) were £6.8 million (6.4-7.2) for varicella and £13.0 million (12.8-13.4) for herpes zoster. The average annual numbers of deaths identified in HES due to varicella and herpes zoster were 18.5 (14.3-22.8) and 160 (147-172), respectively. Comparison with ONS mortality data indicated a high level of uncertainty.Conclusions: Most of the hospital burden due to VZV-virus in England occurs in the immunocompetent population and is potentially vaccine-preventable. [ABSTRACT FROM AUTHOR]

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Herpes zoster (HZ) is a common disease in the aging population and immunocompromised individuals, with a lifetime risk of 20%-30% that increases with age. HZ is caused by reactivation of the varicella-zoster virus (VZV), which remains latent in the spinal dorsal root ganglia and cranial sensory ganglia after resolution of the primary VZV infection. The main focus of HZ management is rapid recovery from VZV infection as well as the reduction and prevention of zoster-associated pain (ZAP) and postherpetic neuralgia (PHN). The use of antivirals against VZV is essential in the treatment of HZ. However, limited antivirals are only licensed clinically for the treatment of HZ, including acyclovir, valacyclovir, famciclovir, brivudine, and amenamevir. Fortunately, some new antivirals against different types of Herpesviridae have been investigated and suggested as novel drugs against VZV. Therefore, this review focuses on discussing the difference in efficacy and safety in the currently licensed antivirals for the treatment of HZ, the applicability of future novel antivirals against VZV, and the preventive or therapeutic effects of these antivirals on ZAP or PHN.

Herpes zoster is a common disease caused by reactivation of latent varicella zoster virus in dorsal root ganglia. Unilateral, clustered vesicles with erythematous base within a dermatomal distribution is its typical clinical manifestation. Involvement of two noncontagious dermatomes is seen very rarely. A case of herpes zoster duplex bilateralis in 36-year-old immunosuppressed patient due to treatment of systemic lupus erythematosus were reported. [ABSTRACT FROM AUTHOR]