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Purpose: Varicella zoster virus-related encephalitis (VZV-RE) is a rare and often misdiagnosed condition caused by an infection with the VZV. It leads to meningitis or encephalitis, with patients frequently experiencing poor prognosis. In this study, we used metagenomic next-generation sequencing (mNGS) to rapidly and accurately detect and identify the VZV pathogen directly from cerebrospinal fluid (CSF) samples, aiming to achieve a definitive diagnosis for encephalitis patients. Methods: In this retrospective study, we analyzed the clinical characteristics and laboratory evaluations of 28 patients at the Harrison International Peace Hospital in Hebei, China, between 2018 and 2024. These patients were diagnosed with neurological disorders using mNGS techniques applied to CSF. Results: In this cohort of 28 patients, 11 were females and 17 males, with a median age of 65 (IQR: 42.3-70). VZV-RE presented with a range of clinical manifestations, the most common being headaches (81.2%), fever>38°C (42.9%), and vomiting (42.9%). Less frequent symptoms include personality changes (10.7%), speech impairments (21.4%), cranial nerve involvement (21.4%), altered consciousness (17.9%) and convulsions (3.6%). Herpes zoster rash was observed in 35.7% of the cases. Neurological examination revealed nuchal rigidity in only 5 patients. CSF analysis indicated mild pressure and protein levels increase, with all patients having negative bacterial cultures. Abnormal electroencephalogram (EEG) findings were noted in 10.7% (N=3), and encephalorrhagia on Magnetic Resonance Imaging (MRI) was observed in 3.6%. VZV-RE was confirmed through mNGS analysis of CSF within three days of admission. All patients received empiric treatment with acyclovir or valacyclovir, with 21.4% receiving hormonotherapy, and 7.14% receiving immunoglobulin therapy. At the three-month follow-up, 10.7% of the patients had persistent neurologic sequelae, and the mortality rate was 3.6%. Conclusions: Performing mNGS on CSF offers a rapidly and precisely diagnostic method for identifying causative pathogens in patients with VZV central nervous system (CNS) infections, especially when traditional CNS examination results are negative. Furthermore, the cases reported highlight the positive therapeutic effect of ganciclovir in treating VZV infections. [ABSTRACT FROM AUTHOR]

This report describes a challenging case of refractory acute retinal necrosis (ARN) with peripapillary choroiditis as the initial presenting sign. Imaging studies confirmed multifocal choroidal lesions and noted the novel sign of vertical hyper-reflective strips (VHRS) in the outer nuclear layer. Initial treatment with acyclovir and valacyclovir failed, and involvement of the other eye suggested a resistant variant of varicella zoster virus. High-dose oral famciclovir therapy resulted in rapid resolution of ARN in both eyes. This case highlights the rare occurrence of choroiditis, the novel finding of VHRS, and the potential utility of high-dose oral famciclovir in treating refractory ARN. [ABSTRACT FROM AUTHOR]

An increase in the number of herpes zoster patients has been reported since universal varicella immunization was introduced, perhaps because of reduced opportunities for varicella patients to experience the natural booster effect caused by reexposure. We investigated recent trends of varicella zoster virus (VZV)–related central nervous system (CNS) infections at a university hospital in Japan. We enrolled patients with suspected CNS infection during 2013–2022 and tested cerebrospinal fluid samples by real-time PCR for DNA from 7 human herpesviruses. VZV DNA was the most commonly detected in 62 (10.2%) of 615 patients. Kulldorff’s circular spatial scan statistics demonstrated a significant temporal cluster of patients with VZV-related CNS infections during 2019–2022 (p = 0.008). Among persons with such infections, the percentage with aseptic meningitis was significantly higher during 2019–2022 (86.8%), when the temporal cluster of cases occurred, than during 2013–2018 (50.0%) (p = 0.0029).

Abstract Varicella is endemic worldwide. In China, varicella has not yet been included in the list of legal infectious diseases, nor has a unified national surveillance program been established. And the live attenuated varicella vaccine has not been included in routine immunization. In this study, we analyzed for the first time the varicella epidemiology in Jilin Province in the past 20 years, and the nucleotide site, amino acid site and N-glycosylation site variation of glycoprotein in varicella-zoster virus (VZV) surface 9 in the past 15 years. The results showed that the reported incidence of varicella in Jilin Province in the last 20 years was fluctuating above and below 20/100,000, especially after the epidemic of the COVID-19, and fatal cases appeared in individual years. The genotypic branching of VZV was monitored as Clade 2 in the last 15 years. 9 glycogen nucleotide sites of VZV had different degrees of variability, and the variability had specificity. Therefore, it gives us the idea that in order to reduce the incidence of varicella and herpes zoster, a provincial or even national surveillance program should be introduced as early as possible, and the dynamic monitoring of the variability of the nucleotide sites of VZV should be strengthened at the same time as the vaccine immunization strategy is introduced.

PurposeMethodsResultsConclusionTo report a treatment approach of a rare presentation of herpes zoster ophthalmicus (HZO) with optic neuropathy and oculomotor nerve palsy.Report of one case.Multiple lesions involving the optic nerve and cavernous sinus were demonstrated on magnetic resonance imaging in a patient with a characteristic herpes zoster rash in the V1 dermatomal distribution. Following treatment with systemic ganciclovir and intravenous corticosteroids, the patient experienced dramatic improvement in visual acuity, from hand motion to 20/25.This report demonstrates a rare case of HZO optic neuropathy with cavernous sinus involvement that was successfully treated with an unconventional medication regimen. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionThis study aimed to investigate the clinical characteristics, diagnostic markers, and treatment outcomes of varicella-zoster virus-associated anterior uveitis (VZV-AU) with and without ophthalmic herpes zoster (herpes zoster ophthalmicus (HZO) and zoster sine herpete (ZSH), respectively).Clinical records of 47 VZV-AU patients (21 ZSH, 26 hZO) were retrospectively reviewed for clinical findings, medication use, and PCR using aqueous humor (AH) results.There was no significant difference in age, gender, visual acuity (VA), or intraocular pressure (IOP) between the two groups. At the initial visit, small-to-medium white keratic precipitates (KPs) were significantly more observed in ZSH group than in HZO group, although there was no significant difference in the frequencies of other ocular findings between the two groups. Early antiviral medication use was significantly higher in HZO group (96.2%) than in ZSH group (19.1%). PCR was performed in 85.7% of ZSH and 53.8% of HZO patients. VZV-DNA positivity and viral load were similar between groups. Multivariate analysis revealed a positive correlation between white KPs and VZV viral load in AH. Although the ultimate use of antiviral medication was still less in ZSH group (71.4%), there were no significant differences in VA and IOP at the last visit between the two groups.Patients with ZSH had more white KPs and received less early antiviral medication than those with HZO. However, visual outcomes were similar between the two groups. Small-to-medium white KPs were significantly associated with the viral load of VZV in AH, suggesting that they could be an active marker. [ABSTRACT FROM AUTHOR]

ABSTRACT Herpes zoster (HZ) is a cutaneous viral disease that typically presents with a dermatomal vesicular eruption. Immunosuppressed patients are more likely to have atypical HZ involving chronic ulceration and disseminated distribution, making diagnosis a challenge. The current report describes a unique case of HZ in a woman with systemic lupus on immunosuppressive therapy manifesting as persistent lower extremity ulceration with diffuse dermal and endothelial infection and secondary panniculitis without epidermal involvement. Other potential etiologies were thoroughly excluded. The ulceration successfully responded to several weeks of valacyclovir. Recognizing atypical clinicopathologic manifestations of HZ in the setting of immune compromise is critical to accurate diagnosis and prompt therapy. [ABSTRACT FROM AUTHOR]

Background: The presence of intrathecal total IgG production is a hallmark of cerebrospinal fluid (CSF) characteristics in multiple sclerosis (MS). Herein, we systematically analyze how the intensity (instead of mere presence) of intrathecal total IgG production relates to basic CSF parameters in MS. Methods: We retrospectively assessed clinical routine CSF findings from 390 therapy-naïve relapsing-remitting MS patients diagnosed according to 2017 revised McDonald criteria. The intensity of intrathecal total IgG synthesis according to Reiber's formula was stratified and correlated to demographics, CSF white cell count (WCC), and diversity of MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of the 3 viruses; measles (M), rubella (R), and varicella zoster (Z) virus. Results: The higher intensity of intrathecal total IgG production significantly correlated with higher CSF WCC (Spearman's ρ = 0.433, p < 0.001) and with the increasing presence and diversity of positive MRZ reaction (Spearman's ρ = 0.600, p < 0.001). Female patients showed higher intensity of intrathecal total IgG production and higher prevalence of positive MRZ reaction than males. Conclusions: The intensity of intrathecal total IgG production correlates with the degree of CSF WCC and diversity of MRZ reaction in MS. As yet unidentified female sex-related factors increase the intensity and diversity of intrathecal IgG production in MS. [ABSTRACT FROM AUTHOR]

Background: Varicella can lead to severe complications in immunocompromised children, including those undergoing hematopoietic stem cell transplantation (HSCT) or chemotherapy. Preventing primary varicella zoster virus (VZV) infection is crucial in these populations to mitigate morbidity and mortality. This study aimed to evaluate the immunogenicity and safety of the live attenuated MAV/06 varicella vaccine in pediatric patients post-HSCT and post-chemotherapy. Additionally, it sought to compare fluorescent-antibody-to-membrane-antigen (FAMA) and enzyme-linked immunosorbent assay (ELISA) titers to establish effective cut-off levels for protection against varicella. Methods: The FAMA assay was conducted at the Vaccine Bio Research Institute, and a VARICELLA-ZOSTER ELISA (Vircell, Granada, Spain) kit, which relies on lysate from whole cells infected with VZV, was used to determine VZV IgG. A prospective cohort study was conducted with 76 pediatric patients under 18 years old who tested negative for VZV IgG via ELISA. Patients post-HSCT and post-chemotherapy were included. Participants received the MAV/06 varicella vaccine, and serologic responses were evaluated using ELISA and FAMA. Results: The median age of participants was 9.8 years, with acute lymphoid leukemia and acute myeloid leukemia being the most common underlying disease. Post-dose 1, the seropositive rate was 56.1% by ELISA and 97.2% by FAMA. Based on the FAMA seropositive cut-off ≥1:4, post-dose 1 geometric mean titers (GMTs) of seropositive patients in the post-HSCT group were 14.7 (95% CI, 11.3–19.1) versus 20.2 (95% CI, 13.0–31.3) in the post-chemotherapy group (p = 0.690). Based on a FAMA seropositive cut-off ≥1:16, the post-dose 1 GMT of patients considered seropositive in the post-HSCT group was 19.3 (95% CI, 15.6–24.0) versus 34.1 (95% CI, 21.0–55.4) in the post-chemotherapy group (p = 0.116), and post-dose 2 FAMA titers of 76.1 (95% CI, 14.6–398.1) in the post-HSCT group and 64.0 (95% CI, 11.4–358.1) in the post-HSCT group (p = 0.853) were observed. In patients with lower baseline FAMA titers (1:4 to 1:8), 66.7% in the post-HSCT group and 71.5% in the post-chemotherapy group achieved a greater than four-fold increase in FAMA titers post-dose 1, while those with higher baseline titers (≥1:16) did not. There were no serious adverse events or vaccine-related rashes occurring in any of the patients. Conclusion: The MAV/06 varicella vaccine is immunogenic in pediatric patients post-HSCT and post-chemotherapy, particularly when administered in a two-dose schedule using a cut-off FAMA titer of <1:16. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions We evaluated whether a history of low‐dose rituximab treatment affected herpes zoster development after living kidney transplantation.We enrolled 103 living kidney transplant recipients. Patients were divided into two groups according to their history of rituximab treatment; rituximab was administered to 50 living kidney transplant recipients. We assessed the difference in herpes zoster events between the two groups and determined the risk factors for herpes zoster using multivariate regression analysis.The total dose of rituximab in each kidney transplant recipient who received rituximab therapy was 200–400 mg. The rate of herpes zoster events after transplantation in recipients who received rituximab therapy (4 of 50, 8%) was not higher than that in recipients who did not receive rituximab (9 of 53, 17%) (p = 0.238). Herpes zoster‐free survival did not significantly differ between the two groups (p = 0.409). In the multivariate regression analysis, the association between varicella zoster vaccination before transplantation and herpes zoster events after transplantation was confirmed, whereas rituximab therapy was not associated with herpes zoster events.Low‐dose rituximab therapy in kidney transplant recipients did not influence herpes zoster development after transplantation. Varicella zoster vaccination before transplantation may play an important role in preventing herpes zoster after transplantation. [ABSTRACT FROM AUTHOR]

Herpes Zoster (HZ) is an acute painful infection caused by reactivation of latent Varicella Zoster Virus (VZV) manifesting as a painful vesicular rash in a dermatomal distribution. Herpes Zoster Ophthalmicus (HZO) is implicated with high risk of ocular involvement which can even result in permanent vision loss. We report a case of an elderly female who presented with severe pain on right upper face followed by a papulovesicular rash, was found to have early ocular involvement and later developed the symptoms of encephalitis. Timely diagnosis and prompt treatment resulted in complete recovery in minimal duration. [ABSTRACT FROM AUTHOR]

The document discusses the importance of antiviral prophylaxis to prevent herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation in adult patients with newly diagnosed acute leukemia. It highlights the efficacy of antiviral medications like acyclovir in reducing the incidence of symptomatic HSV reactivation during intensive chemotherapy. The study conducted in Italian centers belonging to SEIFEM group revealed a heterogeneous scenario in antiviral prophylaxis policies, with some centers not adhering to current international guidelines. The authors suggest the need for harmonization in applying antiviral prevention approaches and further prospective studies to optimize the schedule and duration of antiviral prophylaxis in different acute leukemia subgroups. [Extracted from the article]

The mucosa of the oral cavity is exposed to a large number of different microorganisms such as archaea, bacteria, fungi, parasites, and viruses. Among those, viruses cause specific infections, which can easily be transmitted from one person to another. The infectious route may not only include patients and their relatives but also the dental professional team. Thus, a wide knowledge regarding specific viral infections is crucial for the daily routine. Signs and symptoms of oral viral infections can be completely absent or develop into a pronounced clinical picture, so that early detection and information determine the further course of the infection and its influence on other inflammatory diseases, such as periodontitis, as well as the safety of family members and the social environment. As the clinical manifestation of viral infections may be highly variable leading to heterogenous mucosal lesions it is, in most cases, mandatory to differentiate them by specific microbiological tests in addition to clinical examination procedures. This article will give an overview of the role of viruses infecting the oral mucosa, and in addition, describe their clinical manifestation and management. [ABSTRACT FROM AUTHOR]

Purpose: To report the coincidence of acute retinal necrosis (ARN) syndrome following acute meningoencephalitis and presumed coronavirus disease 2019 (COVID-19) in an immunocompetent patient. Case Report: A 58-year-old female presented to our emergency department with sudden unilateral visual loss following a recent hospitalization for viral meningoencephalitis. Magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, polymerase chain reaction (PCR) of the aqueous humor, reverse transcription polymerase chain reaction (RT- PCR) of the nasopharyngeal swab specimen, chest computed tomography (CT), and fundus photography were performed for the patient. Ophthalmic examination revealed severe ocular inflammation and yellowish patches of necrotizing retinitis in the right eye, compatible with the diagnosis of ARN. The result of aqueous humor PCR was positive for varicella zoster virus (VZV). The patient received a single intravitreal ganciclovir injection and 10 days of intravenous ganciclovir, followed by oral acyclovir. The patient underwent COVID-19 screening tests: while the chest CT scan showed features highly suggestive of COVID-19, the RT-PCR was negative on two occasions. Two months later, best-corrected visual acuity improved to 20/70 in the right eye, the anterior chamber reaction and keratic precipitates resolved, and the vitreous haze decreased significantly. Conclusion: A case of VZV-induced ARN following acutemeningoencephalitiswas observed in association with presumed COVID-19. This could be an incidental finding during the COVID-19 pandemic; however, it could also suggest that COVID-19 might trigger ARN in cases with latent herpes family viruses. [ABSTRACT FROM AUTHOR]

Backgrounds: A contemporary public health challenge is the increase in the prevalence rates of herpes zoster (HZ) worldwide. Methods: In this work, the gE gene structure was analyzed using bioinformatics techniques, and three plasmids of varying lengths, tgE537, tgE200, and tgE350, were expressed in Chinese hamster ovary (CHO) cells. These proteins were used to immunize BALB/c mice with Al/CpG adjuvant; ELISPOT and FCM were used to evaluate cellular immunity; and ELISA, VZV microneutralization, and FAMA assays were performed to detect antibody titers. Results: Target protein concentrations of 1.8 mg/mL for tgE537, 0.15 mg/mL for tgE200 and 0.65 mg/mL for tgE350 were effectively produced. The ability of the three protein segments to stimulate CD4+ and CD8+ T cells, as well as to cause lymphocytes to secrete IFN-γ and IL-4, did not significantly differ from one another. Both tgE537 and tgE350 were capable of generating VZV-specific antibodies and neutralizing antibodies, while tgE350 had the highest neutralizing antibody titer (4388). There was no equivalent humoral immune response induced by tgE200. Conclusions: The results of this investigation provide the groundwork for the creation of HZ recombinant vaccines using truncated proteins as antigens. [ABSTRACT FROM AUTHOR]

Jugular foramen syndrome (JFS) is a lower cranial neuropathy syndrome characterized by dysphonia and dysphagia. The syndrome is caused by dysfunction of the glossopharyngeal, vagus, and spinal accessory nerves at the level of the pars nervosa and pars vascularis within the jugular foramen. There are numerous etiologies for JFS, including malignancy, trauma, vascular, and infection. Here, we present the case of a healthy adult man who developed JFS secondary to an atypical presentation of Varicella Zoster meningitis, and was promptly diagnosed and treated with rapid symptom resolution. We diagnosed the patient using specialized skull-based imaging which detailed the jugular foramen, as well as CSF analysis. This case highlights the clinical value of detailed structural evaluation, consideration for infection in the absence of systemic symptoms, and favorable outcomes following early identification and treatment.

To investigate epidemiology of and risk factors for laboratory-confirmed mpox during the 2022 outbreak in Nigeria, we enrolled 265 persons with suspected mpox. A total of 163 (61.5%) were confirmed to have mpox; 137 (84.0%) were adults, 112 (68.7%) male, 143 (87.7%) urban/semi-urban dwellers, 12 (7.4%) self-reported gay men, and 3 (1.8%) female sex workers. Significant risk factors for adults were sexual and nonsexual contact with persons who had mpox, as well as risky sexual behavior. For children, risk factors were close contact with an mpox-positive person and prior animal exposure. Odds of being mpox positive were higher for adults with HIV and lower for those co-infected with varicella zoster virus (VZV). No children were HIV-seropositive; odds of being mpox positive were higher for children with VZV infection. Our findings indicate mpox affects primarily adults in Nigeria, partially driven by sexual activity; childhood cases were driven by close contact, animal exposure, and VZV co-infection.

We describe a case of an immunocompetent adult male patient originally from the Democratic Republic of Congo (DRC), who was referred to our unit for a several-day history of fever and a pruritic, vesicular rash. There was initial concern in the Emergency Department for Mpox (formerly known as “monkeypox”) given the current epidemiology versus other viral etiologies. Primary varicella zoster virus (pVZV) infection was ultimately diagnosed by PCR from a swabbed, unroofed lesion, and he recovered completely with supportive management and without antiviral therapy. We herein describe how common viral exanthems may best be differentiated in an emergency or outpatient setting.

PurposeMethodsResultsConclusionTo report the clinical course of two cases of acute retinal necrosis (ARN) caused by varicella zoster virus (VZV) and cytomegalovirus (CMV) co-infection detected by polymerase chain reaction (PCR) on aqueous tap.Observational case reports.Two patients presented to our services with unilateral panuveitis suggestive of ARN complicated by hemorrhagic vasculitis and started empirical therapy. Aqueous PCR was performed on the same day and showed double positivity for VZV and CMV, which guided treatment. At follow-up, wide-field color fundus imaging and high-resolution optical coherence tomography showed resolution of active retinitis.Our cases suggest that ARN complicated by hemorrhagic vasculitis may be secondary to CMV and VZV co-infection, both in patients with an unremarkable clinical history and in those with immunodeficiency. In our cases, aqueous PCR testing was of paramount importance to determine the aetiology of ARN and to adjust the antiviral therapy accordingly. [ABSTRACT FROM AUTHOR]

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice—responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines. [ABSTRACT FROM AUTHOR]

Introduction Central nervous system (CNS) infection due to the varicella zoster virus (VZV) can complicate the primary infection or the reactivation, leading to significant mortality and morbidity. This study aimed to describe the clinical, laboratory, and radiological characteristics of patients with confirmed VZV CNS infection in a tertiary hospital in Greece. Methods Data about patients hospitalized from January 2018 to September 2023 with CNS infection by VZV, confirmed by a syndromic polymerase chain reaction in the cerebrospinal fluid (CSF), were retrospectively collected and evaluated. Results In total, 14 patients were recorded. The median age was 49 years, and 35.7% were male. Headache was present in 71.4%, a rash in 57.1%, and fevers, nausea or vomiting, and disorientation in 35.7%. The CSF showed lymphocytic pleocytosis in all patients. Brain magnetic resonance imaging was performed in 53.8%. Empirical antivirals were given in 69.2%, and intravenous acyclovir was given to all patients after identification of VZV in the CSF. Only 7.1% (1 patient) required intensive care unit admission, and 7.1% (1 patient) died. Patients presenting without a rash may be slightly younger, have a slightly lower Charlson comorbidity index, be more likely to present with photophobia or phonophobia, and have lower serum CRP. Conclusions Patients presenting with VZV CNS infection have lymphocytic pleocytosis in the CSF and usually have a favorable outcome with antiviral treatment. Those presenting without a rash may have a different overall clinical phenotype from those with a rash; however, this must be evaluated in larger studies in the future. [ABSTRACT FROM AUTHOR]

The article focuses on homeopathic management of Herpes Zoster, particularly through a concise materia medica that explores remedies for both acute outbreaks and post-herpetic neuralgia (PHN). It emphasizes the importance of recognizing symptom patterns and characteristics in the use of specific homeopathic treatments for shingles, including remedies like Mezereum, Ranunculus bulbosus, and Rhus toxicodendron.

Background The nonclassical antigen presentation molecule CD1d presents lipid antigens to invariant natural killer T (iNKT) cells. Activation of these cells triggers a rapid cytokine response providing an interface between innate and adaptive immune responses. The importance of CD1d and iNKT cells in varicella zoster virus (VZV) infection has been emphasized by clinical reports of individuals with CD1d or iNKT cell deficiencies experiencing severe, disseminated varicella postvaccination. Methods Three strains of VZV (VZV-S, rOka, and VZV rOka-66S) were used to infect Jurkat cells. Flow cytometry of VZV- and mock-infected cells assessed the modulatory impact of VZV on CD1d protein. Infected cell supernatant and transwell co-culture experiments explored the role of soluble factors in VZV-mediated immunomodulation. CD1d transcripts were assessed by reverse-transcription polymerase chain reaction. Results Surface and intracellular flow cytometry demonstrated that CD1d was strikingly downregulated by VZV-S and rOka in both infected and VZV antigen-negative cells compared to mock. CD1d downregulation is cell-contact dependent and CD1d transcripts are targeted by VZV. Mechanistic investigations using rOka-66S (unable to express the viral kinase ORF66) implicate this protein in CD1d modulation in infected cells. Conclusions VZV implements multiple mechanisms targeting both CD1d transcript and protein. This provides evidence of VZV interaction with and manipulation of the CD1d–iNKT cell axis. [ABSTRACT FROM AUTHOR]

Background: Evidence from previous observational studies suggest that infection by herpes simplex virus (HSV) and varicella zoster virus (VZV) increase the risk of dementia. Objective: To investigate if older adults exposed to HSV treatment have lower risk of dementia than the rest of the population. Methods: We used the 10% Australian Pharmaceutical Benefits Scheme (PBS) database from 2013 to 2022 to ascertain the cross-sectional, time-series and longitudinal association between exposure to HSV treatment and the dispensing of antidementia medicines. Participants were men and women aged 60 years or older. We used Anatomical Therapeutic Chemical (ATC) codes to identify medicines dispensed for the treatment of HSV and dementia. Results: During the year 2022 6,868 (1.2%) of 559,561 of participants aged 60 years or over were dispensed antidementia agent. The odds ratio (OR) of being dispensed an antidementia agent among individuals dispensed treatment for HSV was 0.73 (99% CI = 0.56–0.95). Multilevel logistic regression for the 2013–2022 period for those dispensed HSV treatment was 0.87 (99% CI = 0.75–1.00). Split-time span series from 2013 was associated with hazard ratio of 0.98 (99% CI = 0.89–1.07) for individuals dispensed relative to those not dispensed HSV treatment. All analyses were adjusted for age, sex, and the dispensing of medicines for the treatment of diabetes, hyperlipidemia, hypertension, and ischemic heart disease. Conclusions: The dispensing of antiviral medicines for the treatment of HSV and VZV is consistently, but not conclusively, associated with decreased dispensing of antidementia medicines. This suggests that treatment of HSV and VZV infections may contribute to reduce the risk of dementia. [ABSTRACT FROM AUTHOR]

Background and Objectives: Herpes zoster, or shingles, is caused by the varicella-zoster virus (VZV), which initially presents as chickenpox in children. VZV is a global health concern, especially in winter and spring, affecting 10-20% of adults over 50 and posing a 30% risk for the general population. This study used PCR to detect VZV, confirming results with duplicated DNA samples and identifying 234 bp fragments by targeting the gpB gene. Materials and Methods: This study examined 50 herpes zoster cases from October 2020 to April 2021, involving 30 males and 20 females aged 10 to 90, diagnosed by dermatologists. Data were collected via a questionnaire. PCR detected VZV by amplifying the gpB and MCP genes from skin lesion samples. Six positive 234-bp PCR products were sequenced at Macrogen Inc. in Seoul, South Korea. Results: Six DNA samples with 234 bp amplicons were sequenced, showing 99-100% similarity to human alpha herpesvirus sequences in the gpB gene. NCBI BLAST matched these sequences to a reference (GenBank acc. MT370830.1), assigning accession numbers LC642111, LC642112, and LC642113. Eight nucleic acid substitutions caused amino acid changes in the gpB protein: isoleucine to threonine, serine to isoleucine, and threonine to Proline. These variants were deposited in NCBI GenBank as gpB3 samples. Conclusion: The study found high sequence similarity to known VZV sequences, identifying six nucleic acid variations and eight SNPs. Notable amino acid changes in the gpB protein were deposited in NCBI GenBank as the gpB3 sample. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) reactivates from ganglionic sensory neurons to produce herpes zoster (shingles) in a unilateral dermatomal distribution, typically in the thoracic region. Reactivation not only heightens the risk of stroke and other neurological complications but also increases susceptibility to co-infections with various viral and bacterial pathogens at sites distant from the original infection. The mechanism by which VZV results in complications remote from the initial foci remains unclear. Small extracellular vesicles (sEVs) are membranous signaling structures that can deliver proteins and nucleic acids to modify the function of distal cells and tissues during normal physiological conditions. Although viruses have been documented to exploit the sEV machinery to propagate infection, the role of non-infectious sEVs released from VZV-infected neurons in viral spread and disease has not been studied. Using multi-omic approaches, we characterized the content of sEVs released from VZV-infected human sensory neurons (VZV sEVs). One viral protein was detected (immediate-early 62), as well as numerous immunosuppressive and vascular disease-associated host proteins and miRNAs that were absent in sEVs from uninfected neurons. Notably, VZV sEVs are non-infectious yet transcriptionally altered primary human cells, suppressing the antiviral type 1 interferon response and promoting neuroinvasion of a secondary pathogen in vivo. These results challenge our understanding of VZV infection, proposing that the virus may contribute to distant pathologies through non-infectious sEVs beyond the primary infection site. Furthermore, this study provides a previously undescribed immune-evasion mechanism induced by VZV that highlights the significance of non-infectious sEVs in early VZV pathogenesis. IMPORTANCE Varicella zoster virus (VZV) is a ubiquitous human virus that predominantly spreads by direct cell-cell contact and requires efficient and immediate host immune evasion strategies to spread. The mechanisms of immune evasion prior to virion entry have not been fully elucidated and represent a critical gap in our complete understanding of VZV pathogenesis. This study describes a previously unreported antiviral evasion strategy employed by VZV through the exploitation of the infected host cell’s small extracellular vesicle (sEV) machinery. These findings suggest that non-infectious VZV sEVs could travel throughout the body, affecting cells remote from the site of infection and challenging the current understanding of VZV clinical disease, which has focused on local effects and direct infection. The significance of these sEVs in early VZV pathogenesis highlights the importance of further investigating their role in viral spread and secondary disease development to reduce systemic complications following VZV infections. [ABSTRACT FROM AUTHOR]

We describe a case of an immunocompetent adult male patient originally from the Democratic Republic of Congo (DRC), who was referred to our unit for a several-day history of fever and a pruritic, vesicular rash. There was initial concern in the Emergency Department for Mpox (formerly known as "monkeypox") given the current epidemiology versus other viral etiologies. Primary varicella zoster virus (pVZV) infection was ultimately diagnosed by PCR from a swabbed, unroofed lesion, and he recovered completely with supportive management and without antiviral therapy. We herein describe how common viral exanthems may best be differentiated in an emergency or outpatient setting. [ABSTRACT FROM AUTHOR]

Herpes zoster (HZ) is a frequent dermatitis caused by reactivation of the varicella-zoster virus (VZV), previously silent in the dorsal root ganglia of the spinal cord after primary infection. It is more common in adults and the elderly and occasional in children. HZ affecting two dermatomes or HZ duplex (HZD), has a clinical incidence of less than 0.5% and is typically related to an impaired immune response. In particular, it is frequently observed in individuals with malignancies, diabetes, prolonged chemotherapy or radiation therapy, high-dose corticosteroid use, and prolonged immunosuppressive therapy. In the current report, 4 cases of HZD are presented in patients immunosuppressed due to other diseases, its pathogenesis is discussed and its risk factors are analyzed, in order to stimulate greater vigilance among dermatologists who manage immunocompromised patients. [ABSTRACT FROM AUTHOR]

Background Varicella zoster virus (VZV) can reactivate and cause meningitis, but few studies have distinguished it from meningoencephalitis regarding treatment recommendations. The objective of this study was to assess the outcomes of a large series of patients with VZV meningitis according to their therapeutic management. Methods We conducted a bicentric retrospective cohort study, in Paris, France, including all adult patients with a cerebrospinal fluid sample positive for VZV by polymerase chain reaction between April 2014 and June 2022. We distinguished meningitis from encephalitis according to the International Encephalitis Consortium criteria. Unfavorable outcome was defined as mortality or functional sequelae defined by a loss of 2 points on the modified Rankin Scale. Results We included 123 patients with meningitis. Among them, 14% received no antivirals, while 20% were treated with oral valacyclovir alone, 41% with a short course of intravenous (IV) acyclovir before switch to valacyclovir, and 25% with a long course of IV acyclovir. Outcomes were favorable regardless of antiviral regimen. In multivariate analysis, only age, underlying immunosuppression, and cranial radiculitis appear to be predictive factors for longer IV therapy, based on the Akaike information criterion. Conclusions In this study, patients with VZV meningitis had a good outcome, with no evidence of any impact of the treatment strategy. However, further studies are needed to support the possibility of milder treatment in immunocompetent patients, avoiding cost and side effects of IV acyclovir. [ABSTRACT FROM AUTHOR]

We describe a case with natural killer cell deficiency of late-onset Oka vaccine varicella zoster virus (VZV) strain and Herpes simplex virus-1 (HSV-1) dual infection resulting in fatal clinical course. An 18-month-old boy presented with a papulovesicular rash, mucocutaneous candidiasis, encephalopathy, and severe respiratory distress 6 months after receiving varicella vaccine. VZV and HSV-1 were analysed by real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) and Oka vaccine strain of VZV by gene sequencing. HSV-1 and VZV dual infection was detected in the blood and skin samples by RT-qPCR. Gene sequencing of VZV isolated from vesicular lesions was compatible with the Oka vaccine strain. Flow cytometry revealed a natural killer deficiency, but whole exome analysis failed to identify an associated genetic defect. Vesicular rashes in immunocompromised patients who were inadvertently vaccinated should be taken seriously, and antiviral therapy should be prompt and aggressive. [ABSTRACT FROM AUTHOR]

Stroke is a common worldwide cause of death and disability, resulting from an obstruction or reduction in blood flow to the brain. Research has demonstrated that systemic infection such as herpes zoster (HZ) / ophthalmicus herpes zoster (HZO) can potentially trigger stroke. This study includes an updated systematic review and meta‐analysis of the epidemiologic data on the connection between HZ/HZO infection and the risk of stroke. A meticulous search of different database yielded 905 studies. Furthermore, an additional 14 studies from a previous meta‐analysis were incorporated. Eligible studies underwent rigorous screening, resulting in 18 papers. Statistical analyses, including random/fixed effects models and subgroup analyses, were conducted to assess pooled relative risk (RR) and heterogeneity. The meta‐analysis consisted of 5,505,885 participants and found a statistically significant association between HZ infection and the risk of stroke (pooled RR = 1.22, 95% confidence interval [CI] 1.12–1.34). The HZO infection showed a significantly higher overall pooled RR of 1.71 (95% CI 1.06–2.75), indicating a strong connection with the risk of stroke. Subgroup analysis revealed that the odds ratio might play a significant role in causing heterogeneity. Time since infection emerged as a crucial factor, with heightened stroke risk in the initial year post‐HZ/HZO exposure, followed by a decline after the first year. Asian/Non‐Asian studies demonstrated varied results in HZ/HZO patients. Meta‐analysis reveals a significant HZ/HZO‐stroke link. Subgroups highlight varied risks and warrant extended Asian/non‐Asian patient investigation. [ABSTRACT FROM AUTHOR]

Purpose: To report the coincidence of acute retinal necrosis (ARN) syndrome following acute meningoencephalitis and presumed coronavirus disease 2019 (COVID-19) in an immunocompetent patient. Case Report: A 58-year-old female presented to our emergency department with sudden unilateral visual loss following a recent hospitalization for viral meningoencephalitis. Magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, polymerase chain reaction (PCR) of the aqueous humor, reverse transcription polymerase chain reaction (RTPCR) of the nasopharyngeal swab specimen, chest computed tomography (CT), and fundus photography were performed for the patient. Ophthalmic examination revealed severe ocular inflammation and yellowish patches of necrotizing retinitis in the right eye, compatible with the diagnosis of ARN. The result of aqueous humor PCR was positive for varicella zoster virus (VZV). The patient received a single intravitreal ganciclovir injection and 10 days of intravenous ganciclovir, followed by oral acyclovir. The patient underwent COVID-19 screening tests: while the chest CT scan showed features highly suggestive of COVID-19, the RT-PCR was negative on two occasions. Two months later, best-corrected visual acuity improved to 20/70 in the right eye, the anterior chamber reaction and keratic precipitates resolved, and the vitreous haze decreased significantly. Conclusion: A case of VZV-induced ARN following acute meningoencephalitis was observed in association with presumed COVID-19. This could be an incidental finding during the COVID-19 pandemic; however, it could also suggest that COVID-19 might trigger ARN in cases with latent herpes family viruses.

PurposeVaricella zoster virus-related encephalitis (VZV-RE) is a rare and often misdiagnosed condition caused by an infection with the VZV. It leads to meningitis or encephalitis, with patients frequently experiencing poor prognosis. In this study, we used metagenomic next-generation sequencing (mNGS) to rapidly and accurately detect and identify the VZV pathogen directly from cerebrospinal fluid (CSF) samples, aiming to achieve a definitive diagnosis for encephalitis patients.MethodsIn this retrospective study, we analyzed the clinical characteristics and laboratory evaluations of 28 patients at the Harrison International Peace Hospital in Hebei, China, between 2018 and 2024. These patients were diagnosed with neurological disorders using mNGS techniques applied to CSF.ResultsIn this cohort of 28 patients, 11 were females and 17 males, with a median age of 65 (IQR: 42.3-70). VZV-RE presented with a range of clinical manifestations, the most common being headaches (81.2%), fever>38°C (42.9%), and vomiting (42.9%). Less frequent symptoms include personality changes (10.7%), speech impairments (21.4%), cranial nerve involvement (21.4%), altered consciousness (17.9%) and convulsions (3.6%). Herpes zoster rash was observed in 35.7% of the cases. Neurological examination revealed nuchal rigidity in only 5 patients. CSF analysis indicated mild pressure and protein levels increase, with all patients having negative bacterial cultures. Abnormal electroencephalogram (EEG) findings were noted in 10.7% (N=3), and encephalorrhagia on Magnetic Resonance Imaging (MRI) was observed in 3.6%. VZV-RE was confirmed through mNGS analysis of CSF within three days of admission. All patients received empiric treatment with acyclovir or valacyclovir, with 21.4% receiving hormonotherapy, and 7.14% receiving immunoglobulin therapy. At the three-month follow-up, 10.7% of the patients had persistent neurologic sequelae, and the mortality rate was 3.6%.ConclusionsPerforming mNGS on CSF offers a rapidly and precisely diagnostic method for identifying causative pathogens in patients with VZV central nervous system (CNS) infections, especially when traditional CNS examination results are negative. Furthermore, the cases reported highlight the positive therapeutic effect of ganciclovir in treating VZV infections.

Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.

ABSTRACTThis qualitative, cross-sectional study aimed to understand the barriers and facilitators related to the adherence and completion of the recombinant zoster vaccine (RZV) two-dose series in Canada, as perceived by healthcare providers (HCPs) and patients. Data collection occurred via 60-minute concept elicitation interviews with 12 HCPs (4 physicians, 2 nurse practitioners, 6 pharmacists) who had prescribed and/or administered RZV in Canada, and 21 patients aged ≥50 years who had received ≥1 dose of RZV. Patients were categorized as adherent (received both doses within the recommended 2-to-6-month timeframe; n = 11) or non-adherent (received only one dose or second dose outside the recommended timeframe; n = 10). Interview transcripts were coded and analyzed using a two-part thematic analysis approach. HCP-identified barriers to RZV adherence included high out-of-pocket cost, inconsistent/lack of health plan coverage, inconvenient processes for accessing RZV, and patient forgetfulness. HCP-identified facilitators included desire for shingles protection, HCP encouragement, and reminders. Barriers to RZV adherence identified by patients included lack of HCP knowledge/experience with RZV, receiving unreliable/confusing information, having unpleasant/severe side effects following the first dose, high out-of-pocket cost, lack of insurance coverage, and forgetfulness. Patient-identified facilitators included self-motivation, financial support, convenient processes for obtaining RZV, and reminders. In conclusion, many factors can influence RZV series completion and adherence among adults in Canada, including cost, insurance coverage, HCP knowledge and encouragement, and reminders. Awareness of these factors may inform HCPs in helping patients overcome barriers and identify opportunities for future consideration, facilitating protection against herpes zoster.

As of 2024, Thailand has not incorporated the varicella-zoster virus (VZV) vaccine into the Expanded Program on Immunization (EPI). This study aimed to evaluate VZV seroprevalence across all age groups in Chonburi Province, Thailand, during the post-COVID-19 era, and to support the development of a vaccination plan against VZV. A total of 950 participants were enrolled from October 2022 to January 2023. VZV antibody levels were measured using ELISA kits (EUROIMMUN, Lübeck, Germany), with seropositivity set at ≥110 IU/L. The overall VZV seropositivity rate was 64.8%, similar to rates in 1994 and 2014. However, seropositivity rates for the 5–9, 10–14, and 15–19 age groups were significantly higher in the 1994 study, and for the 10–14 and 15–19 age groups in the 2014 study, indicating a declining trend among young Thai individuals. The seropositivity rate increased with age, with a seroprevalence exceeding 80% in individuals aged 30 years and older. Our study found a significant association between the history of varicella and seropositivity. Thus, a positive history may indicate immunity. In conclusion, a significant portion of Thai adolescents are still vulnerable to varicella, highlighting the crucial role of vaccination in averting serious illness.

Summary: Background: To evaluate the immunogenicity of the inactivated herpes-zoster vaccine HZ/su in patients at increased risk for VZV-reactivation, we analysed the quantity and quality of the vaccine-induced cellular and humoral immunity in patients on dialysis with uremic immunodeficiency. Methods: In this observational study, 29 patients and 39 immunocompetent controls underwent standard dual-dose vaccination. Blood samples were analysed before and two weeks after each vaccination, and after one year. Specific T-cells were characterized after stimulation with VZV-gE-peptides based on induction of cytokines and CTLA-4-expression using flow-cytometry. Antibodies were analysed using ELISA. Findings: Both groups showed an increase in VZV-gE-specific CD4 T-cell levels over time (p

Visual disturbances are common in patients who received renal transplant. Visual acuity is reduced in 60% of renal transplant patients after 10-year posttransplant. The most common causes are cataracts, diabetic retinopathy, and hypertensive retinopathy. However, infectious causes of visual loss are rare and most commonly associated with cytomegalovirus and toxoplasmosis infections. Here, we report a 32-year-old male who developed visual loss 6 months after receiving a live-related kidney transplant. The patient had a history of varicella infection in the immediate posttransplant period. The visual loss was secondary to acute retinal necrosis probably secondary to a Varicella infection. This rare manifestation is even more unique in a posttransplant scenario which is usually associated with progressive outer retinal necrosis. The patient had developed irreversible visual loss secondary to the retinal necrosis. Here, we report this rare association as well as 2-year ophthalmological follow-up of this patient.

Introduction: Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in the sensory ganglia and disseminates to these sites remain unclear. Methods: We combined a single-cell sequencing approach and a wellestablished rhesus macaque experimental model using Simian varicella virus (SVV), which recapitulates the VZV infection in humans, to define the acute immune response to SVV in the lung as well as compare the transcriptome of infected and bystander lung-resident T cells and macrophages. Results and discussion: Our analysis showed a decrease in the frequency of alveolar macrophages concomitant with an increase in that of infiltrating macrophages expressing antiviral genes as well as proliferating T cells, effector CD8 T cells, and T cells expressing granzyme A (GZMA) shortly after infection. Moreover, infected T cells harbored higher numbers of viral transcripts compared to infected macrophages. Furthermore, genes associated with cellular metabolism (glycolysis and oxidative phosphorylation) showed differential expression in infected cells, suggesting adaptations to support viral replication. Overall, these data suggest that SVV infection remodels the transcriptome of bystander and infected lung-resident T cells and macrophages. [ABSTRACT FROM AUTHOR]

Background Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus–induced neurologic disease (VZV-ND). Methods This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid. Results We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non–VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25–128) and 82 days (IQR, 36–132) for VZV-ND and non–VZV-ND, respectively, not reaching statistical significance (P =.056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P =.2). Conclusions We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The immunomodulatory effect of CMV makes coinfection with other microbes, like VZV possible and potentially deadlier in the post kidney transplant period. Treatment should be started promptly. Both infections can be treated with Valganciclovir. Infections are common complications in kidney transplant recipients owing to the lifelong immunosuppression. Cytomegalovirus (CMV) and Varicella Zoster Virus (VZV) infections are quite common in the posttransplant period. Coinfection with both however has been reported only once. The immunomodulatory effect of CMV makes their interaction with other organisms like VZV potentially sinister. This is a case of a young woman who developed coinfection with HZV and CMV in the first month following a live related kidney transplantation from her mother. Transplant surgery went well with good urine output, but serum creatinine did not fall below 1.7 mg/dL. Immunosuppression consisted of intravenous (IV), followed by oral prednisolone, Mycophenolate Sodium (MPS) and Tacrolimus. 25 days after an uneventful surgery, she developed fever, followed by pain and vesicular eruption on the forehead, typical of VZV infection, along with rising creatinine. CMV PCR yielded 300 copies/mL of DNA, which was undetectable in both donor and recipient pre‐transplant. Total white blood cell count fell to 2 × 109/L. MPS was temporarily stopped. Treatment with Valgancyclovir led to resolution of fever, skin lesions and brought serum creatinine down to baseline over 2 weeks. [ABSTRACT FROM AUTHOR]