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Herpes zoster (HZ), commonly known as shingles, is a painful blistering rash in dermatomal distribution, caused by the reactivation of varicella-zoster virus (VZV) that was acquired during a primary varicella infection. While commonly afflicting adults, cases of HZ in paediatric patients are infrequently reported. Such cases are predominantly reported in children who have had prior exposure to VZV, either during pregnancy, early childhood or have been vaccinated with live attenuated VZV. This report presents the first known case to our knowledge of HZ as the initial manifestation of a VZV infection in an immunocompetent toddler in the UK. The report details the chronology of the infection event and discusses the clinical context behind HZ presentations in paediatrics globally. It provides a compelling illustration of the uncommon presentation of VZV infection in an immunocompetent child devoid of antecedent virus exposure, thus meriting acknowledgement and potentially further investigation as to the cause., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The patient, a 36-year-old female, had no previous history of shingles. She was admitted to the hospital due to nausea and lightheadedness. Upon admission, she was diagnosed with bilateral medial medullary infarcts. She received treatment with intravenous edaravone and argatroban, as well as antiplatelet therapy with aspirin and clopidogrel. However, her dysphagia, dysarthria, and paraplegia worsened. Due to changes in the lesion of the basilar artery on brain ‍MRA, we suspected the possibility of basilar artery dissection, and discontinued antiplatelet therapy. Subsequent imaging studies suggested vasculitis. After examining the cerebrospinal fluid, we diagnosed varicella-zoster virus (VZV) vasculopathy. Based on this diagnosis, we administered steroid pulse therapy for three days, started intravenous acyclovir, and resumed antithrombotic therapy with clopidogrel. Prednisone was administered for five days. Biochemical tests revealed an elevated D-dimer level. Due to the presence of lower extremity venous thrombus, clopidogrel was replaced with apixaban. The acyclovir infusion was discontinued due to observed acyclovir-induced neutropenia. These treatments improved neurological symptoms, circumflex thickening of the basilar artery, and contrast effects in the same area. On the 70th day, the patient was transferred to the hospital for rehabilitation. It is important to consider VZV angiopathy as a potential cause of juvenile cerebral infarction accompanying progressive basilar artery stenosis, regardless of the presence or absence of a skin rash.

The authors present a case of meningoencephalitis caused by Varicella zoster virus (VZV) infection, which initially manifested as orbital myositis followed by rapid progression to orbital apex syndrome, meningoencephalitis and death. There was no development of a cutaneous rash. An orbital biopsy demonstrated VZV infection, which was confirmed on a lumbar puncture. In this case, VZV meningoencephalitis was not responsive to steroid or antiviral therapy. This case highlights an atypical presentation of VZV with orbital myositis preceding intracranial involvement.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Visceral disseminated varicella zoster virus (VZV) infection is a rare but life-threatening complication in immunosuppressed patients. Herein, we report a survival case of visceral disseminated VZV infection in a patient with systemic lupus erythematosus (SLE)., Case Presentation: A 37-year-old woman was diagnosed as SLE and initial induction therapy was started. Two months after starting the immunosuppressive therapy consisting of 40 mg of prednisolone (PSL) and 1500 mg of mycophenolate mofetil (MMF) daily, she suddenly developed strong abdominal pain, which was required opioid analgesics, followed by systemic skin blisters, which were diagnosed as varicella. Laboratory findings showed rapid exacerbation of severe liver failure, coagulation abnormalities and increased numbers of blood VZV deoxyribonucleic acid (DNA). Therefore, she was diagnosed as visceral disseminated VZV infection. Multidisciplinary treatment with acyclovir, immunoglobulin and antibiotics was started, the dose of PSL was reduced, and MMF was withdrawn. By their treatment, her symptoms were resolved and she finally discharged., Conclusions: Our case highlights the importance of a clinical suspicion of visceral disseminated VZV infections, and the necessity of immediate administration of acyclovir and reduced doses of immunosuppressant to save patients with SLE., (© 2023. The Author(s).)

In this case report, we describe two unusual presentations of varicella-zoster virus (VZV) reactivation without rash, a condition known as Zoster Sine Herpete (ZSH). In Case 1, a 58-year-old woman presented with severe right-sided chest pain under her breast that radiated to the ipsilateral back. After the initial workup ruled out cardiac and musculoskeletal etiologies, the characteristic dermatomal distribution of pain made us suspect VZV reactivation. A diagnosis of ZSH was made with positive VZV IgG and IgM serologies and symptomatic relief after famciclovir treatment. In Case 2, a 43-year-old woman presented with a severe headache and resolved sharp right flank pain. She was diagnosed with varicella meningitis after cerebrospinal fluid showed positive VZV DNA. Intravenous acyclovir treatment resulted in symptom resolution. The most common presentation of VZV reactivation is Herpes Zoster, or shingles, making ZSH a frequently missed diagnosis. High clinical suspicion is warranted to prevent life-threatening complications of ZSH., (© 2023. The Author(s).)

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.

Visceral disseminated varicella zoster virus infection (VD-VZV) is a rare complication in immunocompromised patients. Although systemic lupus erythematosus (SLE) patients have a higher risk of VZV infection, only a few reports describe VD-VZV in SLE. Here, we report a 48-year-old woman with SLE who had received maintenance therapy. She was transferred to the hospital because of severe epigastric pain. There were no significant abnormalities in abdominal computed tomography and upper gastrointestinal endoscopy. On hospital day 4, she developed vesicular eruption on her face and abdomen. VZV antigen was detected in specimens obtained from skin lesions, and treatment with acyclovir was started. VZV DNA in blood turned out to be positive, and the epigastric pain was thought to be caused by VD-VZV. There is a risk of VD-VZV in patients with SLE, even in those receiving non-intensive maintenance therapy., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: We present a case of a 55-year-old man with a rash on his right foot that was biopsied and diagnosed as a Varicella Zoster virus infection with an accompanying positive immunohistochemical study with antiviral antibodies. He concomitantly suffered from a Varicella Zoster virus meningitis. The skin biopsies not only showed clear histologic signs of viral cytopathic effects but also showed intercellular IgG and C3 intraepidermal staining by direct immunofluorescence study, findings which are typically consistent with pemphigus vulgaris. However, the patient did not have any history of pemphigus; there was no mucosal involvement, and serum antibodies to desmoglein 1 and 3 were negative. After discharge, the patient continued to have right-sided foot pain, and he continued the acyclovir treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We herein report the case of a 78-year-old woman who was diagnosed as having disseminated herpes zoster (DHZ) complicated with probable varicella-zoster pneumonia during maintenance therapy for microscopic polyangiitis. Because the patient had severe renal dysfunction, amenamevir administration was started to avoid any neurotoxicity of acyclovir, which is suggested to be optimal for treatment. It ameliorated her symptoms without any adverse events. This is the first report suggesting the efficacy of amenamevir in the treatment of severe herpes zoster infection with coexisting DHZ and probable varicella-zoster pneumonia. Amenamevir could thus be a treatment option for severe varicella zoster virus infections.

Varicella-zoster virus (VZV) can cause visceral disseminated VZV infection in immunocompromised patients. We experienced visceral disseminated VZV infection in an immunocompetent host. A 78-year-old woman visited our hospital complaining of abdominal pain that had persisted for 7 days. On day 3 after admission, a skin rash with blisters appeared mainly on her head and trunk that was diagnosed as generalized zoster via rapid skin VZV diagnostic kit. Esophagogastroduodenoscopy showed gastric erosions, and VZV was detected by real-time polymerase chain reaction testing of the gastric mucosal biopsy specimen. Computed tomography imaging also revealed pancreatitis and colitis, and she was diagnosed as having visceral disseminated VZV infection involving multiple organs. She was treated with acyclovir intravenously, after which her skin rash and abdominal pain disappeared. Because visceral disseminated VZV infection can occur in immunocompetent patients, this disease should be considered in patients with unexplained inflammatory lesions of the gastrointestinal tract or pancreas., (© 2022. Japanese Society of Gastroenterology.)

The triggering effect of herpes simplex virus infection on the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is now well established. However, there are very few reports that has linked a varicella zoster virus (VZV) reactivation with anti-NMDAR encephalitis. In this report, we describe a case of a 57-year-old man presented with atypical clinical presentation of anti-NMDAR encephalitis with gait ataxia, complete ophtalmoplegia, and abolished reflexes followed by drowsiness and confusion. Initial diagnosis of Bickerstaff's brainstem encephalitis was suspected. Few days later, the patient developed herpes zoster in a localized right T1-T2 dermatome. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for VZV was negative. CSF anti-NMDA antibodies were proved positive. A diagnosis of anti-NMDAR encephalitis with concomitant VZV skin reactivation was retained. Favorable outcome with combined antiviral treatment and immunomodulatory therapy was observed. Concomitant VZV reactivation with autoimmune encephalitis is possible. Prognosis and therapeutic options in this rare condition remain to be clarified., (© 2022. Journal of NeuroVirology, Inc.)

Ethnopharmacological Relevance: Elaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as "sanduyoung," has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES., Aim of the Study: In the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES., Methods: and methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells., Results: To evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1β, IL-6, and TNF-α., Conclusion: E. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection., (Copyright © 2021. Published by Elsevier B.V.)

Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes viruses can also infect stromal cells. While established in the ocular setting, cutaneous stromal herpes (deep herpes) is previously unreported and may evade clinical and microscopic detection. We searched for skin biopsies with herpes stromal disease. Clinical information was retrieved via electronic medical records and pathology records system. Hematoxylin and eosin slides, immunohistochemical staining, and polymerase chain reaction detection of viral DNA was performed. We identified 12 specimens from 10 patients with cutaneous stromal herpes simplex virus 1/2 (n=7) or varicella-zoster virus infection (n=5). The most common site involved was the buttocks/perianal region (n=6). Ulceration was a frequent dermatologic finding (n=8). Pyoderma gangrenosum was clinically suspected in 6 specimens (50%). Eight patients (80%) were immunosuppressed. Biopsies frequently demonstrated a dense dermal mixed inflammatory infiltrate with subcutaneous extension and enlarged cells with viral cytopathic changes confirmed by herpes simplex virus 1/2 or varicella-zoster virus immunohistochemistry (n=10) or polymerase chain reaction (n=2). Most specimens (67%) lacked evidence of characteristic epidermal keratinocyte infection. This study presents the first known report of the ability of herpes virus to infect deep stromal cells of the dermis. We raise awareness of cutaneous stromal herpes in patients presenting with atypical clinical lesions, particularly while immunocompromised. Establishing the correct diagnosis is critical for initiating therapy., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND Varicella zoster virus (VZV) infection causes 2 clinically distinct forms of the disease: varicella (chickenpox) and herpes zoster (shingles). Primary VZV infection results in the diffuse vesicular rash of varicella, or chickenpox. Endogenous reactivation of latent VZV typically results in a localized skin infection known as herpes zoster, or shingles. The infection usually manifests as a self-limited disease. However, it can be associated with various neurological complications such as encephalitis, meningitis, ventriculitis, cerebellar ataxia, ischemic or hemorrhagic, and, rarely, cerebral venous sinus thrombosis (CVST). This report presents a case of cerebral venous sinus thrombosis due to varicella zoster virus infection in a 20-year-old Nepalese man who presented to the Emergency Department with headache. CASE REPORT A 20-year-old Nepalese male patient presented to the Emergency Department with headache of 10 day's duration. Five days prior to that, he had a diffuse pruritic skin rash. Examination as well as serology confirmed the presence of primary varicella infection. Computed tomography (CT) and magnetic resonance venography (MRV) demonstrated CVST. Thrombophilia workup revealed a transient elevation of antiphospholipid serology. Shortly after admission, the patient had a transient seizure. He was treated with acyclovir, levetiracetam, and anticoagulation. A comprehensive literature review of similar cases was performed to establish a link between thrombotic complications and primary VZV infection and to formulate possible mechanistic pathways. CONCLUSIONS This report shows that primary VSV infection can be associated with vasculopathy and CVST. Physicians should recognize this serious complication, which should be diagnosed and treated without delay.

A novel methodology to access alkynyl nucleoside analogues is elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro. Regiochemistry of the functionalization was achieved with the aid of 5-endo-dig electrophilic halocyclization of acetyl 5-p-tolyl- or 5-p-pentylphenyl-2'-deoxyuridine. Structure of one of the resulting nucleosides, 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452-481 nm. High quantum yields of 0.53-0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, are potential tools for fluorescent tagging, studying nucleoside metabolism, 2'-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds posess antiviral activity (EC 50 1.3-13.2 μM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p-pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p-pentylphenyl potency as a pharmacophore., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: To provide an overview of the current knowledge on the Human Immunodeficiency Virus (HIV)-associated retinopathies., Methods: A PubMed search was performed, using the key terms "HIV Retinopathy OR Retinitis" and "HIV AND Retinitis" to find manuscripts published within the last ten years., Results: If left untreated, HIV infection causes a progressive immunodeficiency caused by depletion of CD4-positive T lymphocytes. Noninfectious HIV retinopathy, clinically manifested by cotton wool spots. Once the CD4 count drops below 200 c/μl, immunodeficiency creates a vulnerability for systemic opportunistic infections. Within the posterior segment of the eye, cytomegalovirus (CMV) retinitis has to be distinguished from infections with other members of the herpes virus family, as well as from toxoplasmosis, tuberculosis, and syphilis. Upon restoration of the immune system, immune recovery uveitis may manifest in one third of CMV affected eyes., Conclusion: Targeted antiviral treatment and secondary recurrence prophylaxis prevent vision loss of the retina prior to immune recovery.

Primary infection with varicella-zoster virus (VZV) causes chickenpox, a benign and self-limited disease in healthy children. In patients with primary or acquired immunodeficiencies, primary infection can be life-threatening, due to rapid dissemination of the virus to various organs [lung, gastrointestinal tract, liver, eye, central nervous system (CNS)]. We retrospectively described and compared the clinical presentations and outcomes of disseminated varicella infection (DV) in patients with acquired (AID) ( n = 7) and primary (PID) ( n = 12) immunodeficiencies. Patients with AID were on immunosuppression (mostly steroids) for nephrotic syndrome, solid organ transplantation or the treatment of hemopathies, whereas those with PID had combined immunodeficiency (CID) or severe CID (SCID). The course of the disease was severe and fulminant in patients with AID, with multiple organ failure, no rash or a delayed rash, whereas patients with CID and SICD presented typical signs of chickenpox, including a rash, with dissemination to other organs, including the lungs and CNS. In the PID group, antiviral treatment was prolonged until immune reconstitution after bone marrow transplantation, which was performed in 10/12 patients. Four patients died, and three experienced neurological sequelae. SCID patients had the worst outcome. Our findings highlight substantial differences in the clinical presentation and course of DV between children with AID and PID, suggesting differences in pathophysiology. Prevention, early diagnosis and treatment are required to improve outcome., (Copyright © 2020 Bastard, Galerne, Lefevre-Utile, Briand, Baruchel, Durand, Landman-Parker, Gouache, Boddaert, Moshous, Gaudelus, Cohen, Deschenes, Fischer, Blanche, de Pontual and Neven.)

Purpose: To describe the reactivation of Varicella-Zoster Virus Anterior Uveitis after YAG laser peripheral iridotomy., Case Report: A 69-year-old woman referred with unilateral, anterior uveitis associated with decreased corneal sensation and increased intraocular pressure 5 days after YAG laser peripheral iridotomy. The impression of herpetic anterior uveitis reactivation followed by YAG PI confirmed by polymerase chain reaction of aqueous humor by detecting varicella zoster virus. Treatment with oral acyclovir and topical corticosteroid and cycloplegic resulted control of both the intraocular inflammation and pressure., Conclusion: YAG PI may be a risk factor for reactivation of herpetic anterior uveitis. Prophylaxis with acyclovir may be necessary after YAG PI to prevent reactivation of herpetic anterior uveitis.

Background: The aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS)., Case Presentation: Four patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22-52 years). The median symptoms onset to clinic time was 3.5 days (range 3-6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3-7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H 2 O; range 165-400 mm H 2 O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147-478 × 10^6/L; median 1.41 g/L, range 0.57-1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10-14 days. All patients recovered completely., Conclusions: VZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.

Although long-term antiviral prophylaxis is recommended to prevent varicella zoster virus (VZV) infection in seropositive recipients of allogeneic and autologous (auto-) hematopoietic cell transplantation (HCT), studies of VZV infections in pediatric auto-HCT recipients are rare. This study aimed to investigate the incidence and characteristics of VZV infection in pediatric auto-HCT recipients and explore the risk factors of VZV infection and its effect on survival outcomes. This study included all pediatric patients who underwent auto-HCT at Samsung Medical Center, Seoul, Korea, between January 1998 and December 2013. Before 2006, short-term acyclovir prophylaxis was provided until neutrophil engraftment; thereafter, routine prophylaxis was not provided. Patients who developed either herpes zoster or chickenpox within 2 years from transplantation were identified, and a chart review was performed. A total of 413 recipients and 698 auto-HCTs were included. Sixty-one episodes of VZV infections were identified in 54 patients. Fourteen cases of VZV infection (23%; 14 of 61) occurred within 30 days after auto-HCT. The cumulative incidence of the first episode of VZV infection at 2 years after transplantation was 14% (95% confidence interval [CI], 7.9% to 22.8%) in all recipients and 9% (95% CI, 1.0 to 26.6) in VZV-seronegative patients. Notably, the VZV infection rate increased with age and the VZV infection rate in patients age 15 to 19 years was almost three times higher than in patients age 0 to 4 years (28% versus 10%; P = .003). However, there was no difference in the VZV infection rate between recipients of single auto-HCT and recipients of tandem auto-HCT. Two patients died of disseminated VZV infection. VZV infection is a considerable risk in auto-HCT recipients with or without short-term prophylaxis. Universal antiviral prophylaxis might be considered, particularly in older children, regardless of VZV serologic results. To our knowledge, this is the largest study of VZV infection in pediatric auto-HCT recipients reported to date., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon., Methods: Retrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR., Results: Twenty patients were identified (13 males). The average age was 49.7±22.2 years. The most common complaint was headache (n=17/20). Common comorbidities included hypertension (n=7/20) and diabetes mellitus (n=5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5±6.6 vs. 12.2±5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae., Conclusion: VZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Varicella zoster virus, the worldwide infectious human virus responsible for acute varicella and chickenpox, commonly spreads from exposure through contact with a skin lesion or airborne respiratory droplets. Keratinocytes, major targets and source of transmission of the virus present in the skin, represent an ideal choice of cell to stop early virus progression. In their recent study, Tommasi et al. show regulatory mechanisms of cytokeratin 10 through the protease kallikrein-6 as a suitable and druggable pathway to reduce varicella zoster virus dissemination., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The most common infection in patients positive for anti-interferon-gamma autoantibodies (anti-IFN-γ AAbs) is disseminated nontuberculous mycobacterial (dNTM) infection. Here, we report a rare case of triple infection caused by Cryptococcus, varicella-zoster virus (VZV), and nontuberculous mycobacterium in a patient with anti-IFN-γ AAbs., Case Presentation: A 53-year-old Thai man presented with a progressively enlarging right cervical mass with low-grade fever and significant weight loss for 4 months. He also developed a lesion at his left index finger. A biopsy of that lesion showed granulomatous inflammation with yeast-like organisms morphologically consistent with cryptococcosis. Serum cryptococcal antigen was positive. Histopathology of a right cervical lymph node revealed chronic granulomatous lymphadenitis, and the lymph node culture grew Mycobacterium abscessus. One month later, he complained of vision loss in his left eye and subsequently developed a group of painful vesicles at the right popliteal area of S1 dermatome. Lumbar puncture was performed and his cerebrospinal fluid was positive for VZV DNA. His blood test for anti-HIV antibody was negative. Anti-IFN-γ AAbs was positive, but test for anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF AAbs) was negative. He was treated with amphotericin B plus fluconazole for cryptococcosis; a combination of amikacin, imipenem, azithromycin, and levofloxacin for dNTM infection; and, intravenous acyclovir for disseminated VZV infection. After treatment, our patient's fever and cervical lymphadenopathy were subsided, and his vision and visual acuity were both improved., Conclusions: This is the first case of triple infection with cryptococcosis, VZV, and dNTM in a patient who tested positive for anti-IFN-γ AAbs and negative for anti-GM-CSF AAbs. This case will increase awareness and heighten suspicion of these infections in patients with the described presentations and clinical characteristics, and this will accelerate diagnosis and treatment.

Background: Varicella-zoster virus (VZV) infection can be diagnosed clinically once classical rash occurs but the diagnosis is challenging when typical rash is absent. We reported a case of fulminant central nervous system (CNS) VZV infection in a human immunodeficiency virus (HIV)-infected patient without typical VZV-related rash. CNS VZV infection was unexpected identified by metagenomic next-generation sequencing (mNGS)., Case Presentation: A 28-year-old HIV-infected patient presented with neurological symptoms for 3 days. The patient, who was not suspected of VZV infection at admission, quickly progressed to deep coma during the first 24 h of hospitalization. An unbiased mNGS was performed on DNA extract from 300 μL cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 97,248 (out of 38,561,967) sequence reads uniquely aligned to the VZV genome, and these reads covered a high percentage (99.91%) of the VZV. Presence of VZV DNA in CSF was further verified by VZV-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed CNS VZV infection., Conclusions: This study suggests that mNGS may be a useful diagnostic tool for CNS VZV infection. As mNGS could identify all pathogens directly from CSF sample in a single run, it has the promise of strengthening our ability to diagnose CNS infections in HIV-infected patients.

Although several effective treatments exist against Varicella zoster virus (VZV), resistant strains have emerged and the treatment is usually not definite and may have various undesired side effects. Thus, alternative treatment options are necessary. Here we studied the inhibitory effects of natural polysaccharides (PSs) obtained from renewable sources, varied by their structure and charge, on VZV infection in vitro , using a plaque assay. In terms of selectivity indices, almost all the tested PSs were very active; in the order of λ  >  ἰ  >  G >  κ  >  P against VZV compared to Acyclovir as a reference drug and exhibited dose-dependent behavior. Our results, which showed a strong inhibition of VZV infection when the cells were treated with ἰ only at the time of infection or only post infection may indicate a multistep inhibitory effect. It seems that ἰ may block different stages of the virus replication cycle including early steps such as absorption and penetration to the host cells and also late steps after the penetration into the host cells. These results are part of an on-going research that highlights the PSs as potential novel nontoxic candidates that can be used against VZV, and contributes to the elucidation of their mode of action.

Competing Interests: Competing interests: None declared.

Varicella zoster and herpes zoster are infections caused by the highly contagious varicella-zoster virus (VZV). Despite widespread availability of vaccines against VZV, as well as varicella vaccination rates >95%, VZV remains a public health concern because of several common myths and misconceptions. Because of the success of routine varicella vaccination programs, some people mistakenly believe that varicella and herpes zoster are now no longer a threat to public health. Another common misconception is that shingles is less infectious than varicella; however, clinical evidence indicates otherwise. Several knowledge gaps exist around VZV transmission and the availability and use of varicella zoster immune globulin (human) for postexposure prophylaxis against VZV. To help reduce the incidence of severe disease in high-risk individuals (eg, elderly people, pregnant women, unvaccinated persons, infants, and immunocompromised children and adults), this article addresses misbeliefs and broadens awareness of VZV exposure, infection risks, complications, and treatments., (Copyright © 2019. Published by Elsevier Inc.)

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, prevention, and management of varicella zoster virus (VZV) in the pre- and post-transplant period. Primary varicella is an uncommon complication post-solid-organ transplant (SOT), except among pediatric transplant patients and those seronegative for VZV. As the majority of SOT recipients are seropositive for VZV, herpes zoster (HZ) occurs frequently following SOT, particularly among recipients who are older (≥65 years of age) and those receiving more intensive immunosuppression. Transplant providers should aware of the increased risk for HZ-related complications such as dissemination, organ-specific involvement, and post-herpetic neuralgia. Treatment for localized zoster is primarily given as oral regimens, but those with more complicated presentations or those at risk for dissemination should be treated initially with IV therapy. Available antiviral prophylaxis regimens and vaccination strategies for varicella and HZ among these immunosuppressed patients remain a mainstay for prevention in the pre-and post-transplant periods. Finally, we discuss important approaches to addressing post-exposure prophylaxis and infection control practices for those SOT patients with documented VZV infections., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disorder of the central nervous system (CNS). Early treatment is the key for neurological recovery., Methods: A case of ADEM associated with varicella-zoster virus infection was presented, in which magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) examinations were included., Results: Magnetic resonance imaging of the brain revealed multiple hyperintense lesions at the subcortical level on fluid-attenuated inversion recovery (FLAIR), and MRI of the spinal cord revealed longitudinally segmented hyperintense lesions at the spinal cord on T2-weighted images. The patient was treated with methylprednisolone and gancyclovir, and had a favorable recovery. Subsequent MRI of the brain and cervical cord showed the previous abnormal hyperintensities had markedly disappeared., Conclusion: A rare case of ADEM with longitudinal segmented hyperintense lesions at the spinal cord on T2-weighted images was presented. Excellent response to ADEM treatment with high-dose steroids was reported resulting in a remarkable neurological recovery. A long-term follow-up is needed for prognosis., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

This case describes an uncommon presentation of herpes zoster in an adolescent with viral meningitis and concomitant genital shingles. A 15-year-old immunocompetent girl with background of well-controlled Graves' disease presented with 3 days of fever, frontal headache, terminal neck stiffness and photophobia. This was preceded by 4 days of pain and itch over vaginal and anal region. She had one dose of varicella vaccination at 18 months old and developed mild primary varicella infection around 5 years of age. Varicella zoster virus DNA was detected both in cerebrospinal fluid and in vesicles over her right labial majora. While there is no international consensus on the recommended duration of treatment for zoster with neurological complications, she was treated with intravenous acyclovir for 10 days with good clinical response. Her fever, headache and neck stiffness resolved after 2 days and genital lesions resolved after 9 days of antiviral therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Varicella-zoster virus (VZV) is an alphaherpesvirus that lacks the herpesviral neurovirulence protein ICP34.5. The underlying hypothesis of this project was that inhibitors of autophagy reduce VZV infectivity. We selected the vacuolar proton ATPase inhibitor bafilomycin A1 for analysis because of its well-known antiautophagy property of impeding acidification during the late stage of autophagic flux. We documented that bafilomycin treatment from 48 to 72 h postinfection lowered VZV titers substantially ( P ≤ 0.008). Because we were unable to define the site of the block in the infectious cycle by confocal microscopy, we turned to electron microscopy. Capsids were observed in the nucleus, in the perinuclear space, and in the cytoplasm adjacent to Golgi apparatus vesicles. Many of the capsids had an aberrant appearance, as has been observed previously in infections not treated with bafilomycin. In contrast to prior untreated infections, however, secondary envelopment of capsids was not seen in the trans -Golgi network, nor were prototypical enveloped particles with capsids (virions) seen in cytoplasmic vesicles after bafilomycin treatment. Instead, multiple particles with varying diameters without capsids (light particles) were seen in large virus assembly compartments near the disorganized Golgi apparatus. Bafilomycin treatment also led to increased numbers of multivesicular bodies in the cytoplasm, some of which contained remnants of the Golgi apparatus. In summary, we have defined a previously unrecognized property of bafilomycin whereby it disrupted the site of secondary envelopment of VZV capsids by altering the pH of the trans -Golgi network and thereby preventing the correct formation of virus assembly compartments. IMPORTANCE This study of VZV assembly in the presence of bafilomycin A1 emphasizes the importance of the Golgi apparatus/ trans -Golgi network as a platform in the alphaherpesvirus life cycle. We have previously shown that VZV induces levels of autophagy far above the basal levels of autophagy in human skin, a major site of VZV assembly. The current study documented that bafilomycin treatment led to impaired assembly of VZV capsids after primary envelopment/de-envelopment but before secondary reenvelopment. This VZV study also complemented prior herpes simplex virus 1 and pseudorabies virus studies investigating two other inhibitors of endoplasmic reticulum (ER)/Golgi apparatus function: brefeldin A and monensin. Studies with porcine herpesvirus demonstrated that primary enveloped particles accumulated in the perinuclear space in the presence of brefeldin A, while studies with herpes simplex virus 1 documented an impaired secondary assembly of enveloped viral particles in the presence of monensin., (Copyright © 2019 Girsch et al.)

Varicella zoster virus (VZV) pneumonia is associated with significant mortality, especially in the immunocompromised host. VZV-specific immunoglobulins (VZIG) are currently used as post-exposure prophylaxis for at-risk patients, but not as adjunctive therapy. A novel case of VZV pneumonia in an immunocompromised patient, treated successfully with intravenous VZIG in combination with acyclovir, is reported here., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 43-year-old man with malignant lymphoma who had been treated with the cyclosphamide, vincrstine, procarbazine, and prednisolone (C-MOPP) regimen was admitted to our hospital with skin eruption. He was diagnosed to have varicella, and treatment with acyclovir and immune globulin was started. Chest computed tomography revealed multiple nodules in the both lung fields. Diagnostic thoracoscopic lung biopsy specimens revealed granuloma formation, and polymerase chain reaction testing revealed the presence of varicella-zoster virus DNA in the granulomatous tissue. It was unusual for the lung nodule in varicella pneumonia to increase in size over time in a patient who had undergone antiviral therapy, while also demonstrating multiple granulomas.

Background: Visceral disseminated varicella zoster virus (VDVZV) infection is a rare disease with a high mortality rate (55%) in immunocompromised patients, but it is not yet widely recognized in the field of nephrology. We report a case of VDVZV contracted during immunosuppressive therapy for membranous nephropathy., Case Presentation: A 36-year-old woman was diagnosed with membranous nephropathy and was being treated with immunosuppressive therapy consisting of 60 mg/day prednisolone, 150 mg/day mizoribine, and 150 mg/day cyclosporine. Nephrosis eased; therefore, the prednisolone dosage was reduced. However, 50 days after starting immunosuppressive therapy, the patient suddenly developed strong and spontaneous abdominal pain, predominantly in the epigastric area, without muscular guarding or rebound tenderness. Blood data indicated neutrophil-dominant elevated white blood cell count, reduced platelet count, elevated transaminase and lactate dehydrogenase, slightly increased C-reactive protein, and enhanced coagulability. Abdominal computed tomography revealed a mildly increased enhancement around the root of the superior mesenteric artery with no perforation, intestinal obstruction, or thrombosis. The cause of the abdominal pain was unknown, so the patient was carefully monitored and antibiotic agents and opioid analgesics administered. The following day, blisters appeared on the patient's skin, which were diagnosed as varicella. There was a marked increase in the blood concentration of VZV-DNA; therefore, the cause of the abdominal pain was diagnosed as VDVZV. Treatment with acyclovir and immunoglobulin was immediately started, and the immunosuppressive therapy dose reduced. The abdominal pain resolved rapidly, and the patient was discharged 1 week after symptom onset., Discussions and Conclusions: This patient was VZV-IgG positive, but developed VDVZV due to reinfection. Abdominal pain due to VDVZV precedes the skin rash, which makes it difficult to diagnose before the appearance of the rash, but measuring the VZV-DNA concentration in the blood may be effective. Saving the patient's life requires urgent administration of sufficient doses of acyclovir and reduced immunosuppressive therapy.

Background: Limited data are available regarding the characteristics and prognosis of patients with stroke due to varicella zoster virus (VZV) vasculopathy., Methods: We studied 4 patients (2 men and 2 women; age, 38-63 years) from a single center who developed acute ischemic stroke due to VZV vasculopathy. The virological diagnosis was confirmed by detecting VZV DNA and/or the IgG antibody to VZV in the cerebrospinal fluid., Results: Three patients were taking immunosuppressive agents, including prednisolone and/or methotrexate, at baseline. Each patient had a characteristic skin rash prior to stroke, with the interval from rash to stroke onset ranging from 13 to 122 days. Two patients experienced antecedent cranial nerve palsies; one had the third, seventh, ninth, and 10th nerve palsies and the other had the fourth nerve palsy before stroke. Cerebral infarctions were located in the anterior circulation lesion (n = 1), in the posterior circulation lesion (n = 2), and in both lesions (n = 1). Intracranial arterial stenosis was only identified in one patient on magnetic resonance angiography. A high plasma d-dimer level was detected in 1 patient, whereas high β-thromboglobulin and platelet factor 4 levels were detected in 2 patients. As a result of combined therapies with acyclovir, steroid, and antithrombotic agents, neurological symptoms markedly improved in 3 patients, whereas 1 patient was left with moderate hemiplegia., Conclusions: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective : To explore the clinical characteristics and in vivo confocal microscopic (IVCM) findings of varicella zoster virus (VZV)-related corneal endotheliitis. Methods : Retrospectively reviewed 20 eyes with corneal edema which were diagnosed by real-time polymerase chain reaction. Results : one had VZV infection. Three had epithelial lesions. Six had mydriasis. Four had loss of iris pigment. Keratic precipitates (KPs) were mixed. Subbasal nerves had disappeared in 12 eyes. Langerhans cells were observed in seven eyes. The deviations in endothelial cell layers consisted of guttate ( n  = 1), enlarged intercellular gaps ( n  = 11), infiltration of inflammatory cells ( n  = 8), loss of defined cell boundaries ( n  = 1) and anomalous nucleus ( n  = 9). The shape of KPs in IVCM included type I ( n  = 6), type III ( n  = 3) and type IV ( n  = 4).Conclusion: VZV-related corneal endotheliitis is remarkably difficult to detect clinically. Most cases have no typical skin lesions. The typical clinical feature is that of segmental iris atrophy and mixed KPs.

Propolis is a generic name for a biological substance produced by bees used for multiple purposes in folk medicine. Propolis special extract GH 2002 is crude propolis highly purified by a special procedure and freed from the accompanying substances like pollen, wax, resins. The cytotoxic and antiherpetic effect of propolis extracts against Varicella zoster virus (VZV) was analysed in cell culture, and revealed a moderate cytotoxicity on lung fibroblasts with a CC 50 of 380 μg/ml. The 50 % inhibitory concentration (IC 50 ) of GH 2002 propolis extract for VZV plaque formation was determined at 64 μg/ml. The propolis extract exhibited high levels of antiviral activity against VZV in viral suspension tests, infectivity was significantly reduced by 93.9 % and a direct concentration-dependent antiviral activity could be demonstrated. In order to determine the mode of virus suppression by propolis, the extract was added at different times during the viral infection cycle. Addition of propolis to uninfected cells (pretreatment cells) prior to infection or to infected cells (replication) during intracellular replication had no or only minor effect on virus multiplication. However, propolis exhibited high anti-VZV activity when viruses were pretreated with propolis prior to infection thus indicating an unspecific interaction between the virus and propolis. The antiviral activity is comparable to acyclovir.

Existing treatments have limited efficacy against severe infection associated with herpes simplex virus (HSV) and herpes zoster virus (VZV), particularly in immunocompromized patients and those with multidermatomal infection. This issue, along with issues regarding drug resistance, support the need for improved therapeutic options. To investigate the antiviral effect of amenamevir, a VZV and HSV helicase-primase inhibitor, in severe infection conditions, mouse models of severe HSV-1 infection were developed by immunosuppression or multidermatomal infection. Mice with cyclosporin-induced immunosuppression and HSV-1 infection via inoculation of a dorsolateral area of skin were orally treated with amenamevir (10-100 mg/kg/day) for different durations (2-5 days). Immunosuppressed mice maintained high skin HSV-1 titers in the absence of treatment. Amenamevir successfully reduced HSV-1 titers at all tested doses in immunosuppressed mice, but required a longer treatment period to avoid a rebound in viral titers due to immunosuppression. To compare the efficacy of amenamevir and valacyclovir, a murine model of multidermatomal HSV-1 infection was generated by scarifying the dorsolateral area of skin in a line and inoculating broadly with HSV-1. The mice were treated with amenamevir or valacyclovir starting on Day 3, 4, or 5 post-infection for 5 days. Although both drugs similarly reduced disease scores when treatment was started on Day 3, amenamevir also reduced disease severity when treatment was initiated on Day 4, whereas valacyclovir did not. Amenamevir was not affected by the host's immune status in terms of effective oral doses and was more efficacious in treating severe cutaneous infection even when treatment initiation was delayed., (Copyright © 2018 Elsevier Inc. All rights reserved.)