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Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the vesicular rash is a hallmark sign, it is absent in approximately 5% of cases. Visceral involvement may precede cutaneous lesions, complicate early recognition, and increase the risk of severe complications. This scoping review screened 594 articles of which 153 met the inclusion criteria, yielding 156 individual cases. Patients were predominantly male (53.8%), with a mean age of 42.3 years. The overall mortality rate was 25.0%. Multiple organs were involved in 46.1% of cases. The most frequently affected were the lungs (56%), liver (44%), heart (16%), kidneys (11%), pancreas (11%), stomach (10%), and esophagus (6%). Antivirals were administered in 89.1% of cases, while corticosteroids were used in 22.4%, with no significant impact on outcomes. Early diagnosis, achieved in 65.4% of patients, was significantly associated with survival (p = 0.043). Mortality was significantly associated with underlying comorbidities (p = 0.004), especially autoimmune diseases requiring immunosuppression (p = 0.048). Septic shock or multi-organ dysfunction (MODS), hepatitis, acute kidney injury, and acute liver failure were linked to higher mortality in univariate analysis. Multivariate analysis identified comorbidities (p < 0.001), septic shock/MODS (p = 0.008), and acute liver failure (p = 0.039) as independent predictors of mortality. Patients with septic shock/MODS had over twice the risk of death (OR = 2.24; p = 0.008). This review underscores the diagnostic challenges and high mortality of VD-VZV. Early recognition and timely administration of antiviral treatment appear critical for survival. Greater clinical awareness and further research are needed to guide management.

The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus ( VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus ( n  = 9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.

Vasculopathies caused by varicella zoster virus (VZV) are indicative of a productive virus infection in cerebral arteries after either reactivation of VZV (shingles) or primary infection (chickenpox). VZV vasculopathy can cause ischaemic infarction of the brain and spinal cord, as well as aneurysm, subarachnoid and cerebral haemorrhage, carotid dissection, and, rarely, peripheral arterial disease. VZV vasculopathy in immunocompetent or immunocompromised individuals can be unifocal or multifocal with deep-seated and superficial infarctions. Lesions at the grey–white matter junction on brain imaging are a clue to diagnosis. Involvement of both large and small arteries is more common than that of either alone. Most patients have a mononuclear cerebrospinal fluid pleocytosis, often with red blood cells. Cerebrospinal fluid pleocytosis and rash are absent in about a third of cases. Anti-VZV IgG antibody in the cerebrospinal fluid is found more frequently than VZV DNA. In recent years, the number of recognised VZV vasculopathies has grown, and accurate diagnosis is important for the effective treatment of these disorders.

Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA. Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters. Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination. This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine. ClinicalTrials.gov NCT02514018. Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.

•Real-world evidence of MMRV clinical protection against varicella is essential.•Data showed effectiveness of two doses MMRV against varicella of any severity of 93%.•Two-dose schedule should be recommended to optimise immunisation programmes worldwide. Priorix-Tetra™ (MMRV GlaxoSmithKline Biologicals’ vaccine) was developed based on the existing measles-mumps-rubella and varicella vaccines. In this study, we aimed to estimate the effectiveness of the combined measles-mumps-rubella-varicella Priorix-Tetra™ vaccine against varicella in real-world conditions. We conducted a post-marketing retrospective case-control study in the Apulia region of Italy in children aged 1–9 years born between January 1, 2008 and December 31, 2016. We assessed the effectiveness against varicella of all grades of severity (including hospitalisation) and against hospitalisation for varicella of a single and two doses of Priorix-Tetra™. Moreover, we also assessed effectiveness of monovalent varicella (monovalent-V) vaccine and any varicella vaccines. Vaccine effectiveness was calculated as (1–OR) x 100. We introduced demographic variables in the model to adjust Vaccine effectiveness (aVE) by potential confounders (sex and year of birth). We recorded 625 varicella cases and matched them with 1,875 controls. Among 625 cases, 198 had received a single MMRV dose, 10 two MMRV doses, 46 a single monovalent-V dose, none two monovalent-V doses; four a monovalent-V as first dose and MMRV as second dose, and one a MMRV as first dose and monovalent-V as second dose; 366 cases were not vaccinated. The aVE against varicella of all grades of severity was 77.0% and 93.0% after a single dose and after two doses of MMRV, respectively. The aVE against varicella of all grades was 72.0% after a single dose of monovalent-V vaccine. The aVE against varicella of all grades of severity was 76.0% after a single dose and 94.0% after two doses of any varicella vaccine. The aVE against varicella hospitalisation was 96% after a single dose of any varicella vaccine. Priorix-Tetra™ showed to be an effective vaccine and the two-dose schedule should be recommended to optimise immunisation programmes. A single dose was able to provide protection against varicella hospitalisation.

Varicella zoster virus (VZV) is a human-specific herpesvirus that establishes latency in peripheral neurons. The only transcripts detected in infected human trigeminal ganglia (TG) obtained shortly after death correspond to the VZV latency-associated transcript (VLT) and associated VLT-ORF63 splice variants. In vitro studies showed that VLT-ORF63 is translated into a protein (pVLT-ORF63) that induces VZV transcription. The mechanisms that lead to this restricted gene expression and the transition to lytic replication remain unknown, partly due to the difficulty of working with human neurons. In this study, we addressed whether the neuroblastoma-derived cell line SH-SY5Y could serve as a model to investigate the mechanisms that lead to repression of VZV gene expression followed by reactivation. VZV productively infected differentiated SH-SY5Y (dSH-SY5Y) whereas incubation with acyclovir (ACV) inhibited virus replication and induced a progressive repression of the virus. Upon removal of ACV there was production of viral particles in a subset of cells, while others contained non-replicating VZV genomes and VLT-containing transcripts for at least 20 days post-infection (dpi). Exogenous expression of VLT-ORF63 induced productive infection, suggesting that the non-replicating and repressed genomes remained functional. Interestingly, histone deposition was undetectable at VZV genomes in quiescently infected dSH-SY5Y cells, pointing to a potential novel mechanism leading to VZV repression in this neuronal setting.

Background The diagnosis of Varicella‐zoster virus related neurological disease (VZD) and Lyme neuroborreliosis (LNB) is based on clinical presentation as well as cerebrospinal fluid (CSF) results. Objectives To evaluate and compare the diagnostic utility of oligoclonal bands (OCB) and the κ‐free light chain (FLC) index in patients with VZD and LNB. Methods Patients with the diagnosis of VZD or LNB at the Department of Neurology of the Medical University of Innsbruck between 2008 to 2020 were included. OCB were determined by isoelectric focusing followed by immunoblotting, κ‐FLC were measured by immunonephelometry. Results A total of 82 patients were included in the study comprising 48 patients with VZD and 34 with LNB. LNB patients exhibited higher κ‐FLC indices (29 [14–45] vs. 4 [2–12], p < 0.001) and were more frequently OCB positive (65% vs. 8%, p < 0.001) than VZD patients. The disease duration was longer in OCB‐positive patients (VZD: 21 [18–28] days; LNB: 15 [7–22] days) compared to OCB‐negative patients (VZD: 10 [5–17] days, p = 0.030; LNB: 5 [4–7] days, p = 0.006). No differences in disease duration were observed between patients with positive or negative κ‐FLC index. In multivariable analysis, OCB positivity was associated with disease duration (Odds Ratio [OR]: 1.11, 95% confidence interval: 1.01–1.23, p = 0.028), while κ‐FLC index was not. Conclusions In both VZD and LNB, the κ‐FLC index was more frequently positive than OCB, particularly in cases with shorter disease duration. This suggests that the κ‐FLC index may be a more sensitive marker of (sub)acute intrathecal inflammation. In Varicella‐zoster virus related neurological disease (VZD) and Lyme neuroborreliosis (LNB), the κ‐free light chain (FLC) index was more frequently positive than oligoclonal bands (OCB), particularly in cases with shorter disease duration. This suggests that the κ‐FLC index may be a more sensitive marker of (sub)acute intrathecal inflammation.

Varicella-zoster virus (VZV) causes clinically significant illness during acute and recurrent infection accompanied by robust innate and acquired immune responses. Innate immune cells in skin and ganglion secrete type I interferon (IFN-I) and proinflammatory cytokines to control VZV. Varicella-zoster virus subverts pattern recognition receptor sensing to modulate antigen presentation and IFN-I production. During primary infection, VZV hijacks T cells to disseminate to the skin and establishes latency in ganglia. Durable T- and B-cell memory formed within a few weeks of infection is boosted by reactivation or re-exposure. Antigen-specific T cells are recruited and potentially retained in VZV-infected skin to counteract reactivation. In latently VZV-infected ganglia, however, virus-specific T cells have not been recovered, suggesting that local innate immune responses control VZV latency. Antibodies prevent primary VZV infection, whereas T cells are fundamental to resolving disease, limiting severity, and preventing reactivation. In this study, we review current knowledge on the interactions between VZV and the human immune system.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients’ quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunity. While diagnosis of more common HSV and/or VZV infections is frequently clinically based, immunocompromised hosts may have atypical skin presentation or visceral involvement. Thus, diagnostic confirmation using virus-specific tests such as polymerase chain reaction or immunohistochemical staining is crucial in some cases. Oral acyclovir, valacyclovir and famciclovir are usually used for mild to moderate infections and intravenous acyclovir is the drug of choice for severe or disseminated infections. Foscarnet can be used when acyclovir-resistance is confirmed or suspected. Pharmaceutical prophylaxis against HSV and/or VZV should be considered in high-risk cancers patients. Currently, there is no commercially available vaccine against HSV, but VZV vaccines are available to prevent varicella and zoster.