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We aimed to describe longitudinal functional outcome among survivors after an infectious encephalitis (IE) and to analyse risk factors for poor functional outcome. Patients included in the prospective ENCEIF cohort (France, 2016–2019) were followed-up at 6 months and 1 year after hospital discharge for assessment of (a) functional outcome using modified Rankin scale (mRS) and (b) cognitive function and abilities to perform activities of daily living. Risk factors for poor outcome on the full distribution of mRS were estimated using multivariable mixed ordinal regression analysis with time between hospital discharge and follow-up as a covariate. Our follow-up study included 322 patients with 896 mRS evaluations. Median age was 66 (50–74) years, 197/322 were male (61%) and 35/322 were immunocompromised (11%). Causative agents were herpes simplex virus 1 in 95/322 cases (30%), varicella zoster virus in 46/322 cases (14%), others documented IE in 90/322 cases (28%) and unknown in 91/322 cases (28%). Intensive care unit (ICU) admission was necessary for 117/322 patients (36%). Brain imaging was abnormal in 180/311 (58%) of patients. At 6 months, 95/287 (33%) had fully recovered and 181/287 (63%) had persisting symptoms. At 12 months, 124/253 (49%) had fully recovered and 108/253 (43%) had persisting symptoms. The proportion of patients who improved was 41% (117/287) during the first 6 months, and 24% (52/218) between 6 and 12 months. Factors significantly associated with poor functional outcome were age, immunosuppression, ICU admission, abnormal brain imaging and causative agents, notably herpes simplex virus 1. Follow-up visit during the first 120 days did not detect significant change in functional outcome, but was strongly associated with better outcome at the subsequent evaluation. : After IE, improvement may take several months. Functional outcome is associated with baseline health status (age and immunosuppression), abnormal brain imaging, ICU admission and causative agents. [ABSTRACT FROM AUTHOR]

Herpesviruses represent common and significant infectious complications after allogeneic haematopoietic cell transplantation (HCT). In the last decade, major advances in the prevention and treatment of these infections were accomplished. The aim of this paper is to review the recent advances in the prophylaxis and treatment of herpesvirus infections after allogeneic HCT, to assess the persisting challenges, and to offer future directions for the prevention and management of these infections. We searched PubMed for relevant literature regarding specific herpesviruses complicating allogeneic HCT through March 2024. The largest advances in this past decade were witnessed for cytomegalovirus (CMV) with the advent of letermovir for primary prophylaxis and the development of maribavir as an option for refractory and/or resistant CMV infections in transplant recipients. For varicella zoster virus, prevention of reactivation with the recombinant zoster vaccine offers an additional prophylactic intervention. Pritelivir is being explored for the treatment of drug-resistant or refractory Herpes simplex virus infections. Although rituximab is now an established option for preemptive therapy for Epstein-Barr virus, Human Herpesvirus-6 remains the most elusive virus of the herpesvirus family, with a lack of evidence supporting the benefit of any agent for prophylaxis or for optimal preemptive therapy. Although considerable advances have been achieved for the treatment and prevention of herpes virus infections, most notably with CMV, the coming years should hold additional opportunities to tame the beast in these herpesviruses postallogeneic HCT, with the advent of new antivirals, cell-mediated immunity testing, and cytotoxic T lymphocytes infusions. [ABSTRACT FROM AUTHOR]

• Number of hospitalizations and mortality in Poland due to herpes zoster was relatively small. • Mean annual first-time herpes zoster hospitalization rate was 5.8 per 100,000 person-years. • Over 70 % of hospitalized patients due to herpes zoster were over 60 years old. • Risk factors included female gender, older age and residence in urban areas. The varicella-zoster virus (VZV) is an infectious agent that causes both chickenpox and herpes zoster/shingles (HZ). This infection can take various clinical forms, result in permanent complications, and be a marker of immunosuppression, e.g. in the course of a neoplastic disease. The aim of this study is to analyze epidemiological trends in hospitalization and hospital mortality rate among HZ patients in Poland (2012–2021). Our study is a population-based, retrospective analysis of hospital discharge records of patients with HZ. Data were obtained from the National Institute of Public Health in Poland, and they covered the period from 2012 to 2021. All hospitalization records with primary or secondary ICD-10 B02 code diagnosis were included in the study. We analyzed the total number of 23,432 hospital discharge records of HZ patients in 2012–2021. The study group consisted of 22,169 (94.6 %) hospitalization records of first-time diagnosis of HZ in hospitalized patients: 9,309 males (42 %) and 12,860 females (58 %). In this group, 70.3 % were patients over 60 years old. The mean and median age was 64 and 69 years, respectively. The mean annual first-time hospitalization rate for HZ was estimated to be 5.8 per 100,000 person-years (95 % CI: 4.8–6.7 per 100,000 person-years). The hospitalization rate for HZ was similar during 2012–2019. There was a significant decrease in hospitalizations in 2020–2021 in comparison with the previous years (R2 = 0.42, p < 0.05). Women showed a higher hospitalization rate than men (p < 0.001). Urban residents had a higher hospitalization rate than rural residents (p < 0.001). In the analyzed period, 246 deaths were recorded (1.1 % of all hospitalized HZ patients) −119 males and 127 females. The HZ-related number of hospitalizations and mortality in Poland are relatively low, but HZ is still a significant health problem. Risk factors include female gender, older age and residence in urban areas. [ABSTRACT FROM AUTHOR]

Kidney transplant (KT) recipients have an increased risk of herpes zoster (HZ) and its complications. Although recombinant zoster vaccine is favoured over zoster vaccine live (ZVL), ZVL is also recommended to prevent HZ for KT candidates. We aimed to evaluate the clinical effectiveness of ZVL in KT recipients immunized before transplantation. Adult patients who received kidney transplantation from January 2014 to December 2018 were enrolled. Patients were observed until HZ occurrence, death, loss of allograft, loss to follow-up, or 5 years after transplantation. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare the incidence of HZ after transplantation between vaccinated and unvaccinated patients. A total of 84 vaccinated and 340 unvaccinated patients were included. The median age was higher in the vaccinated group (57 vs. 54 years, p 0.003). Grafts from deceased donors were more frequently transplanted in the unvaccinated group (16.7% vs. 51.8%, p < 0.001). Five-year cumulative HZ incidence was 11.9%, which translated to 26.27 (95% CI, 19.33–34.95) per 1000 person-years. The incidence in the vaccinated and unvaccinated groups was 3.9% and 13.7%, respectively. After adjustment, vaccination showed significant protective effectiveness against HZ (adjusted hazard ratio, 0.18, 95% CI, 0.05–0.60). In addition, all four cases of disseminated zoster occurred in the unvaccinated group. Our study, the first on the clinical effectiveness of zoster vaccines for KT recipients, suggests that ZVL before transplantation effectively prevents HZ. [ABSTRACT FROM AUTHOR]

According to evidence-based guidelines, vaccines against measles and varicella are generally recommended to susceptible HIV-positive patients, as long as they are not severely immunocompromised. However, routine screening to determine serologic status is not recommended. We conducted a seroprevalence study of anti-measles and anti-Varicella-Zoster virus (VZV) antibodies in adults living with HIV (PLWHA) consulting at Avicenne University Hospital in a Parisian suburb. Sera were collected in years 2018–2020 and tested by commercial immunoassays in 268 patients. Most of the patients were born in Sub-Saharan Africa (55 %) and only 23 % in Europe. Measles and varicella seropositivity were present respectively in 91.4 % and 96.2 % of patients. One patient in ten was seronegative to at least one of tested diseases. In the univariate analysis, only younger age (p = 0.027) was associated with a higher risk of measles seronegativity, while shorter time since arrival in France (p < 0.001) and shorter time since HIV discovery (p = 0.007) were associated with a higher risk of VZV seronegativity. In multivariate analysis no association was found. This study highlights the absence of specific risk factors for VZV and measles seronegativity in PLWHA and supports the importance of routine screening, in order to increase immunization rates and reduce risk of complications. [ABSTRACT FROM AUTHOR]

Two distinct diseases are attributable to the varicella zoster virus, varicella (chickenpox) and zoster (shingles). This study assesses the impact and cost-effectiveness of a childhood varicella vaccination program in England. We use an age-structured dynamic transmission model and a health economic decision tree. The model incorporates recent data on varicella and zoster epidemiology, including the effects of exogenous boosting on zoster incidence. By simulating various vaccination strategies, including routine and catch-up programs, the study evaluates the potential reduction in varicella and zoster cases due to vaccination and the associated vaccine cost-effectiveness (from the NHS perspective). We find that a two-dose varicella vaccination program could significantly reduce varicella incidence, potentially achieving near-elimination if high coverage rates are maintained. However, the model also predicts a temporary increase in zoster incidence due to reduced natural boosting from varicella exposure; this is partly mitigated by the current zoster vaccination program and the effect is much less substantial than previously estimated. Cost-effectiveness analyses reveal that all vaccination strategies modelled are cost-effective at typical thresholds, with the routine vaccination scenario being the most economically advantageous. Sensitivity analyses demonstrate that vaccine price and varicella treatment costs are the primary drivers of cost-effectiveness. The study supports the introduction of a childhood varicella vaccination program in England, which offers substantial health benefits and is highly likely to be cost-effective. • The study models the impact and cost-effectiveness of universal varicella vaccination in England. • A two-dose program could significantly reduce varicella cases and achieve near elimination with high coverage. • The program may cause a temporary increase in zoster cases, but this to a lesser extent than previously believed. • All vaccination strategies examined were found to be cost-effective, with routine vaccination being the most beneficial. • Cost-effectiveness depends primarily on vaccine prices and varicella treatment costs. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster presents as clustered blisters on one side of the body, accompanied by nerve pain. This is caused by reactivation of the varicella zoster virus, and it occurs primarily in people with weakened immunity. Tumor and chemotherapy drugs can impair the patient's immune function, induce herpes zoster and prolong the course of disease.In these patients, skin changes can last for months and blisters can recur and cause serious complications such as postherpetic neuralgia.Acupuncture is a common alternative therapy for herpes zoster in East Asia.Case Presentation: We report a case of an elderly male patient with widespread herpes zoster in the trunk after non-Hodgkin's lymphoma chemotherapy. The patient had received conventional treatment with valaciclovir and mecobalamin within 24 hours of symptom onset. Because neither the clustered blisters nor the nerve pain were improved a week later, acupuncture and related techniques were applied. These included electro-acupuncture, surrounding acupuncture, fire acupuncture, and cupping. The patient recovered 20 days after the herpes zoster attack, and there were no adverse reactions during the treatment process.Conclusions: This case suggests that acupuncture and related techniques are effective interventions for this condition.This case report is innovative because it shows that acupuncture as an adjuvant treatment can improve the skin lesions in patients with HZ after tumour chemotherapy, relieve pain, and shorten the course of HZ. [ABSTRACT FROM AUTHOR]

• One or two doses of varicella vaccine provided long-term protection against varicella. • Vaccine efficacy tended to be higher after two doses of varicella vaccine versus one dose. • Immune responses persisted 10 years regardless of the schedule used. • One- or two-dose schedules of varicella vaccine had acceptable safety profile. We assessed the 10-year efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV) or one dose of a monovalent varicella vaccine (V) in children from Czech Republic, Lithuania, Poland, Romania and Slovakia. This was a phase IIIB follow-up of an observer-blind, randomized, controlled trial (NCT00226499). In phase A, healthy children aged 12–22 months from 10 European countries were randomized in a 3:3:1 ratio to receive two doses of MMRV (MMRV group), one dose of MMR followed by one dose of V (MMR + V group), or two doses of MMR (MMR; control group), 42 days apart. Vaccine efficacy (VE) against varicella (confirmed by viral DNA detection or epidemiological link and clinical assessment) was calculated with 95% confidence intervals using Cox proportional hazards regression model. Immunogenicity was assessed as seropositivity rates and geometric mean concentrations (GMCs). Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. A total of 3705 children were vaccinated (1590, MMRV group; 1586, MMR + V group; 529, MMR group). There were 663 confirmed varicella cases (47, MMRV group; 349, MMR + V group; 267, MMR group). VE ranged between 95.4% (Lithuania) and 97.4% (Slovakia) in the MMRV group and between 59.3% (Lithuania) and 74% (Slovakia) in the MMR + V group. At year 10, seropositivity rates were 99.5%–100% in the MMRV group, 98%–100% in the MMR + V group and 50%–100% in the MMR control group, and the anti-VZV antibody GMCs were comparable between MMRV and MMR + V groups. The occurrence of solicited and unsolicited AEs was similar across groups and no SAE was considered as vaccination-related. No new safety concerns were identified. Our results indicated that two doses of varicella zoster virus-containing vaccine provided better protection than one dose against varicella and induced antibody responses that persisted 10 years post-vaccination. [ABSTRACT FROM AUTHOR]

Objectives: The value of chickenpox vaccination is still debated in the literature and by jurisdictions worldwide. This uncertainty is reflected in the inconsistent uptake of the vaccine, where some countries offer routine childhood immunization programs, others have targeted programs, and in many the vaccine is only privately available. Even across the countries that have universal funding for the vaccine, there is a diversity of schedules and dosing intervals. Using an agent-based model of chickenpox and shingles, we conducted an economic evaluation of chickenpox vaccination in Alberta, Canada.Methods: We compared the cost-effectiveness of 2 common chickenpox vaccination schedules, specifically a long dosing interval (first dose: 12 months; second dose: 4-6 years) and a short dosing interval (first dose: 12 months; second dose: 18 months).Results: The economic evaluation demonstrated a shorter dosing interval may be marginally preferred, although it consistently led to higher costs from both the societal and healthcare perspectives. We found that chickenpox vaccination would be cost-saving and highly cost-effective from the societal and healthcare perspective, assuming there was no impact on shingles.Conclusion: Chickenpox vaccine was cost-effective when not considering shingles and remained so even if there was a minor increase in shingles following vaccination. However, if chickenpox vaccination did lead to a substantial increase in shingles, then chickenpox vaccination was not cost-effective from the healthcare perspective. [ABSTRACT FROM AUTHOR]

• Data on safety and immunogenicity of live vaccination in immunosuppressed patients are scarce. • Physicians need a simple risk assessment to decide on vaccination of immunosuppressed children. • Varicella zoster vaccination was well tolerated and immunogenic in patients with IBD or AIH. • A clinical- and laboratory-based approach may ensure safety and immunity of the VZV vaccine strain. Children with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS). This prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response. A total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3–16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination. All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn's disease the day after vaccination. The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078). VZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357). [ABSTRACT FROM AUTHOR]

Background: Neurologic complications of varicella zoster virus (VZV) reactivation can be associated with considerable mortality and morbidity. Aseptic meningitis associated with VZV infection is rare, occurring in 0.5% of immunocompetent individuals. One third of VZV-related neurologic disease occurs without the classic herpes zoster exanthema, making early recognition more difficult.Case Report: A 60-year-old man presented to the emergency department with chest pain and impaired memory that he attributed to a transient ischemic attack as suggested by an urgent care facility 1 day earlier. He suffered a seizure while in the emergency department and was admitted to the intensive care unit. A computed tomography scan of his head and a magnetic resonance imaging scan were both negative for acute findings. An abnormal electroencephalogram consistent with an encephalopathy together with his new-onset seizure triggered a lumbar puncture that was positive for VZV. He was placed on acyclovir and was discharged from the hospital 5 days after admission. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The typical presentation of a VZV central nervous system infection occurs with a sudden onset of fever, headache, nuchal rigidity, and focal neurologic signs. Our patient's recent impaired memory and subsequent seizure were likely manifestations of the developing VZV meningoencephalitis, while his chest pain may have correlated with subsequent development of a vesicular rash. Seizures are encountered in 11% of patients with VZV central nervous system infection, and VZV has recently been associated with cerebral vasculopathy. Awareness of alternative presentations for herpes zoster and meningitis is important in cases without classic symptoms to enable diagnosis and prevent delays in treatment. [ABSTRACT FROM AUTHOR]

Children may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration. In six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003–2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR. Among 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups. HZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses. [ABSTRACT FROM AUTHOR]

• No effect of HIV exposure on immunogenicity of hepatitis-A and varicella vaccines. • Most children were seropositive after single dose hepatitis-A vaccine. • Less than half seroconverted after one dose of varicella vaccine. HIV-exposed uninfected (HEU) children have increased risk of infectious morbidity during early childhood. We evaluated the short-term immunogenicity and safety of single dose inactivated hepatitis-A virus (HAV) vaccine and live attenuated varicella zoster virus (VZV) vaccine in South African children. 195 HIV-unexposed and 64 HEU children received either one dose of HAV or VZV vaccine at 18 months of age. Blood samples were tested for hepatitis-A or VZV antibodies before and one month after vaccination by chemiluminescent microparticle immunoassay and enzyme-linked immunosorbent assay, respectively. All children were evaluated for solicited adverse events (AEs). One-month post-vaccination, a similar percentage of HIV-unexposed (91.8%) and HEU (82.9%) children were seropositive for hepatitis-A (p = 0.144). VZV antibody geometric mean fold-rise was also similar in HIV-unexposed (5.6; 95%CI: 4.6–6.7) and HEU children (5.1; 95%CI: 3.7–7.2); however, only 44% HIV-unexposed and HEU seroconverted (titers > 50 mIU/ml). AEs occurred with similar frequency and severity between groups, except for more systemic AEs after VZV vaccination in HEU than HIV-unexposed children. Single dose HAV and VZV vaccine was similarly immunogenic in HIV-unexposed and HEU children. We did not identify differences in short-term humoral immunity after administration of either a live attenuated or inactivated vaccine. Seroconversion rates after a single dose of VZV vaccine were, however, lower compared to reports from previous studies (85–89%). Clinical trials registration: NCT03330171. [ABSTRACT FROM AUTHOR]

• Even long-term antiviral prophylaxis in hematopoietic cell transplantation (HCT) recipients was recommend as standard preventive stratagem for varicella zoster virus (VZV) infection, epidemiology of VZV infection in pediatric autologous HCT recipients is uncertain. • The incidence of VZV infection differs by age. • Difference of VZV infection was evaluated between single and tandem autologous HCTs. • We explored the risk factors for severe VZV infection in the pediatric autologous HCT population. 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. [ABSTRACT FROM AUTHOR]

• Varicella zoster virus (VZV) infections of the central nervous system (CNS) can develop in immunocompetent subjects and young individuals aged ˂ 50 years. • Skin rash and systemic inflammatory signs may be absent from a large proportion of patients. • Old age may be associated with more severe presentations of VZV CNS infection. • No clinical trial assessing the efficacy of antiviral therapy in VZV CNS infections have been performed. • Intravenous acyclovir is the preferred antiviral therapy. • Oral valacyclovir is a potentially effective antiviral agent, although not extensively studied. To describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon. Retrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR. 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. 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. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) infection is reported regularly among adolescents and adults in Caribbean island populations. The disease more often runs a severe course among these populations, causing a substantial burden. The aim of this sero-epidemiological study was to obtain an insight into VZV susceptibility and its determinants in island populations of the Caribbean Netherlands (CN). Participants from Bonaire, St. Eustatius, and Saba (n = 1829, aged 0–90 years) donated a blood sample and completed a questionnaire. VZV-specific IgG antibodies were determined using a bead-based multiplex immunoassay. Risk factors were analysed using a logistic regression model. Overall seroprevalence in CN was 78%, being lowest on St. Eustatius (73%) and highest on Bonaire and Saba (79%). Seropositivity increased gradually with age, with 60% and 80% at ages 10 years and 30 years, respectively, and ranging between 80% and 90% thereafter. Higher odds for VZV seronegativity were seen among persons who were born in CN or had resided there since early childhood, and among single-person households. VZV susceptibility is relatively high among adolescents and adults in CN. In order to reduce the burden of VZV-related disease in these populations, routine varicella vaccination is recommended. As data are scarce, the study findings can serve as a blueprint for the epidemiology in tropical regions. [ABSTRACT FROM AUTHOR]

• CSF-VZV renders VZV either the pathogenic culprit or a stress-related epiphenomenon. • We studied the significance of CSF-VZV coupled with neurological manifestations. • Of 125 CSF-VZV-positive patients, only 9(7 %) had alternative attributable diagnoses. • High VZV viral load and rash correlated with a greater risk of stroke. • Empiric antiviral treatment was not associated with superior prognosis. Varicella zoster virus (VZV) is among the leading pathogens causing meningitis and encephalitis. While VZV-PCR-positive CSF is considered a gold-standard for diagnosis, it is not-uncommon to detect VZV-DNA in CSF of patients with other acute or chronic illness. Our goal was to determine the clinical relevance of VZV-PCR-positive CSF when investigating patients with neurological symptoms. In this retrospective cohort from the largest hospital in Israel, we collected demographic, clinical and laboratory data of patients with VZV-PCR-positive CSF, analyzing the significance of various parameters. During a 5-years study, 125 patient-unique VZV-PCR-positive CSFs were recorded, in which only 9 alternative diagnoses were noted. The commonest symptoms were headache (N = 104, 83 %) and rash (N = 96, 76 %). PCR-cycle-threshold (Ct), a surrogate of viral burden, did not significantly vary across the clinical manifestations; however, patients with rash and Ct<35 were prone to develop stroke in the following year (N = 6, 7 %). Empiric nucleoside-analogue treatment was not associated with a better outcome compared to treatment administered upon a positive-PCR result. Our findings suggest that in patients with neurological symptoms, detection of VZV-DNA in CSF renders VZV the probable culprit. Nevertheless, a systematic evaluation of treatment and follow-up algorithms of patients with suspected or proved VZV meningitis and encephalitis is needed. The benefits of a prompt treatment should be weighed against the potential complications of nucleoside-analogue. Conversely, the propensity for stroke in patients with higher viral-burden, necessitates further studies assessing VZV causal role, directing additional workup, treatment and monitoring policy. [ABSTRACT FROM AUTHOR]

• Varicella zoster virus meningitis post first dose of BNT162b2 mRNA COVID-19 vaccine • A 71-year-old immunocompetent woman developed fever, headache and stiff neck • Varicella zoster virus confirmed by polymerase chain reaction of cerebrospinal fluid • This is the fourth such report worldwide suggesting a possible link to the vaccine We report a case of varicella zoster virus (VZV) meningitis following BNT162b2 mRNA COVID-19 vaccination in an immunocompetent patient. A final diagnosis was made based on identification of VZV via positive polymerase chain reaction of cerebrospinal fluid along with characteristic symptoms such as fever, headache, and stiff neck. This phenomenon has been reported elsewhere; this is the 13th such case reported worldwide and the 7th case in immunocompetent patients, indicating the need for careful monitoring after COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

• Neither vaccination certificate nor history of chicken pox predicts VZV immunity. • Insufficient VZV vaccination catch-up in birth cohorts born prior 2005. • Better realization of vaccination catch-up by paediatrician than general practitioner. • Serologic investigations demonstrate occult immunization of non-immunized patients. Immunosuppressed patients are at risk of severe infections with vaccination preventable diseases. We evaluated vaccination rate and immunity of children and adolescents with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). Immunization rate of 329 children with IBD (n = 300) and AIH (n = 29) was assessed in seven German centres using vaccination certificates, history of chicken pox and by determining anti-varicella zoster virus (VZV) and anti-measles IgG antibodies. Of the total cohort 86% received long-term immunosuppression. Four doses of a hexavalent vaccine were documented in 89%, at least one dose of measles, mumps, and rubella (MMR) vaccination was documented in 325 (99%), with 300 (92%) receiving two doses. Anti-measles IgG concentrations were insufficient in 11% of the immunized patients. VZV vaccination was officially recommended in Germany since 2004, and implemented in 88% born from 2005 onwards. In patients born earlier VZV catch up vaccination only reached 25% (n = 67). Of 118 patients with documented VZV vaccination 25 (21%) did not display sufficient anti-VZV IgG. Of 198 patients with a history of chicken pox, six had undetectable anti-VZV IgG. Of 29 patients having neither had chicken pox nor VZV vaccination, 20 were found to have sufficient anti-VZV IgG. In our cohort vaccination coverage for hexavalent and MMR vaccinations was good, but insufficient for VZV vaccination in patients born before 2005. Neither the vaccination certificate nor the history of chicken pox is reliable to predict VZV immunity indicating a need for serologic investigations and if needed vaccination before initiating immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

• A universal vaccination has resulted in a reduction of varicella cases. • The number of breakthrough varicella (BV) patients has increased gradually. • Although breakthrough varicella has mild symptoms, clinical diagnosis is difficult. • LAMP methods without DNA extraction is useful for rapid diagnosis BV. Since patients with breakthrough varicella (BV) have mild symptoms, clinical diagnosis is difficult. In high vaccine coverage area, as BV occurs sporadically, point of care test is required for controlling varicella outbreak. In this study, the reliability of varicella zoster virus (VZV)-loop mediated isothermal amplification (LAMP) was evaluated for the rapid diagnosis of BV. A total of 328 swab samples collected from patients with suspected varicella were analyzed. For the laboratory diagnosis of varicella, VZV real-time PCR was carried out using DNA extracted from swab samples. Swab samples without DNA extraction were used for VZV-LAMP(direct-LAMP). VZV infection was diagnosed by real-time PCR in 285 cases, including 105 natural varicella cases and 180 BV cases. VZV DNA was detected in 250 (87.8%) of the 285 cases by direct-LAMP. The presence and duration of fever, number of skin eruptions, and VZV DNA load were significantly lower in BV than natural varicella. The sensitivity of direct-LAMP for the diagnosis of varicella and BV was 93.3% and 84.4%, respectively. Direct LAMP was considered to be useful for rapid diagnosis of BV as it has several advantages such as low cost, ease and rapidity, as compared to real time PCR. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out of 2163 patients who underwent allogeneic HCT, 22 (1.0%) developed severe HZ at a rate of 1 per 228 person-years, including dermatomal/multidermatomal disease (n = 5), disseminated skin disease (n = 5), HZ ophthalmicus (n = 4), meningitis/encephalitis (n = 4), pneumonia (n = 2), viremia (n = 1), and erythema multiforme (n = 1). Severe HZ infection occurred in a bimodal distribution during the early peri-HCT period and at 12 to 24 months post-HCT (median, 12.7 months). Twelve patients (54.5%) were compliant with ACV prophylaxis at the time of HZ diagnosis. Eleven patients (50%) died during the study period, only 2 of whom (9.1%) with active VZV infection. Mortality was higher in patients on immunosuppressive therapy (62.5% versus 16.7%; P =.045) and with concurrent graft-versus-host disease (75.0% versus 35.7%; P =.044). These data suggest that severe HZ remains an important consideration despite ACV prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (zoster) also commonly known as "shingles," occurs following re-activation of the varicella zoster virus. It contributes a large cost burden to the U.S. health care system, with an estimated 1 million cases costing $1 billion annually. The current gold standard treatment is acyclovir, which limits viral replication. However, acyclovir has been reported to cause neurotoxicity in patients with acute or chronic kidney disease.Case Report: This case presents an occurrence of acyclovir-induced toxic encephalopathy in a patient with normal renal function. A 63-year-old male presented to the emergency department with ataxia, tremors, fluctuating aphasia, confusion, agitation, and fatigue. Results of imaging, lumbar puncture, and laboratory studies directed clinicians toward acyclovir toxicity, despite a normal creatinine level. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians will likely be the first point of contact in the health care system following the onset of acyclovir toxicity. With an increasing incidence of zoster disease, such atypical toxic manifestations may increase. Early recognition is important to avoid permanent neurologic compromise. [ABSTRACT FROM AUTHOR]

• Pneumonia is a major complication of varicella zoster virus (VZV) infection in adults, especially in immunocompromised patients. • We describe an immunocompromised adult with VZV pneumonia treated successfully with intravenous VZV-specific IgG in addition to acyclovir. • Hospitals and national health agencies should increase their efforts in providing easier access to this treatment for at-risk patients. 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. [ABSTRACT FROM AUTHOR]

• First comprehensive work on in vitro antiviral assay using HHV-3 from Chickenpox and Herpes Zoster patients. • In vitro cytotoxicity assay of Aqueous, Ethanolic & aqueous ethanolic leaf extracts of chosen plant leaves in HEp-2 cells. • First of its kind in reporting the in vitro antiviral activity in the leaves of chosen plants in comparison with Acyclovir against the HHV-3. • First of its kind in in silico analysis of the phytochemicals from Punica granatum L. against the HHV-3 protease through discovery studio. • Interpretation of ADMETSAR properties of the screened active phytochemicals. Human Herpes Virus-3 (Varicella Zoster Virus) causes Chickenpox in childhood and reactivates after decades of being latent to cause Herpes Zoster in adults. The aim of this study was to evaluate the in vitro antiviral potency on the leaves of Punica granatum L., Momordica charantia L., Andrographis paniculata Nees. and Melia azedarach L., against the Human Herpes Virus-3 isolated from Chickenpox and Zoster in comparison with acyclovir. Aqueous, ethanolic and aqueous ethanolic extracts were prepared from the chosen plant leaves by lyophilization process and subjected to in vitro cytotoxicity assay in HEp-2 cells followed by the in vitro antiviral evaluation against the clinical isolates of HHV-3 using post incubation assay. The structure of leaf chemicals were retrieved from protein data bank and in silico drug analysis was carried out through discovery studio targeting the protease of HHV-3.The drug likeliness and the ADMETSAR properties of the screened active phytochemicals were calculated. Aqueous extract from the leaves of Punica granatum L., exhibited potential antiviral activity against the HHV-3. The in silico docking results found that the phytochemicals of Punica granatum L., interacted on the active site of the HHV-3 protease. Aqueous extract from the leaves of Punica granatum L. was superior in exhibiting its antiviral efficacy to HHV-3 whose in vitro activity was comparable with acyclovir. As the leaf phytochemicals interacted with the HHV-3 protease, the antiviral activity of the Punica granatum L., leaves may interfere with the capsid assembly of the HHV-3. [ABSTRACT FROM AUTHOR]

Highlights • Three commercial molecular methods, one using isothermal helicase dependent amplification and the other two using PCR, were compared to each other and to viral culture for the detection of herpes simplex virus (HSV) type 1 and type 2. • Two assays used direct sample testing while the 3rd required a brief nucleic acid extraction step. One assay also included varicella zoster virus (VZV) detection. • All three commercial assays showed high sensitivity and specificity and were significantly more sensitive than viral culture. • Choice of assays will depend on factors other than sensitivity and specificity, such as procedural complexity, turnaround time, throughput, and the need for dual HSV and VZV detection. Abstract Background Molecular methods enable more rapid and sensitive detection of herpes simplex virus (HSV) than viral culture. Objective Three commercial molecular methods, all of which detect both HSV-1 and HSV-2, were compared to viral culture for the detection of HSV from swab specimens. Study design Pediatric and adult patient viral swab specimens were cultured for HSV. Residual swab fluid was frozen at −80 °C until tested with the 3 molecular methods: the Quidel Solana HSV 1 + 2/VZV Assay, the Focus Diagnostics Simplexa HSV 1 & 2 Direct Assay and the Luminex Aries HSV 1&2 Assay. A true positive was defined as positive by culture or positive by ≥ 2/3 molecular methods. Results 177 specimens were studied. The sensitivity of culture was 81.3% (61/75, 95% CI 70.7–89.4%) and specificity was 100% (102/102, 95% CI 96.4–100%). The sensitivities of both the Solana and Simplexa were 100% (75/75, 95% CI 95.2–100%) and specificities were also both 100% (102/102, 95% CI 96.4–100%). The Aries had a sensitivity of 98.7% (74/75, 95% CI 92.8–99.97%) and specificity 99.0% (101/102, 95% CI 94.7–99.98%). All three molecular methods were significantly more sensitive than culture (p ≤ 0.0005 for Solana and Simplexa and p ≤ 0.0012 for Aries). Conclusion All the molecular methods studied provided a significantly higher sensitivity than culture. In addition, the molecular methods took 1–2 hours to perform compared to a mean of 2.1 days for culture results. Use of any of the three molecular methods could lead to improved patient care. [ABSTRACT FROM AUTHOR]

Objectives: To assess the value of bee products with respect to antiviral efficacy against herpes viruses.Design: A systematic review was done using the JUSTfind System of the Justus-Liebig-University Gießen and Scopus.Results: Three trials on honey and 6 trials on propolis were conducted. Each trial provided evidence that these two bee products are interesting alternatives to acyclovir, especially propolis, which was found to be superior to acyclovir in 4 trials.Conclusions: The evidence from these trials suggests that propolis is the best of all natural possibilities in the treatment of herpetic skin lesions, especially those related to HSV-1. Future studies should analyse if propolis could be an adjunct to treatment with acyclovir. For lesions in the oral cavity, honey could be an interesting alternative. [ABSTRACT FROM AUTHOR]

• BNT162b2 might be associated with increased incidence of Bell's palsy, herpes simplex and zoster. • Oropharyngeal samples before and 1 week after vaccination were tested for 7 herpesviruses. • No increase in herpesviruses shedding was seen after BNT162b2 vaccination. Concerns were raised over an increase in Bell's palsy, herpes simplex and herpes zoster after BNT162b2 vaccination, all are manifestations of herpesviruses reactivation. As herpesviruses commonly reactivate in the oropharynx, we have hypothesized that oropharyngeal shedding of herpesviruses will increase after vaccination. Immune-competent Adults, excluding those using topical steroids or manifesting symptomatic herpesvirus infection, were sampled before BNT162b2 vaccination and one week after. Herpesviruses 1–7 shedding was tested with a multiplexed PCR. In 103 paired samples the prevalence of herpesviruses was similar before and after vaccination: HSV1, 3.9% vs. 5.8% (p = 0.75); HSV2, 0% vs. 1% (p = not applicable, NA); VZV, 0% vs. 0% (p = NA); EBV, 14.6% vs. 17.5% (p = 0.63); CMV, 0% vs. 0% (p = NA); HHV6, 4.9% vs. 7.8% (p = 0.55); HHV7, 71.8% vs. 72.8% (p = 1); any herpesvirus, 73.8% vs. 74.8% (p = 1). We did not find evidence for increased oropharyngeal reactivation of herpesviruses one week after BNT162b2. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) is associated with herpes zoster (HZ) or herpes zoster ophthalmicus (HZO). All antiviral agents currently licensed for the management of VZV replication via modulating different mechanisms, and the resistance is on the rise. There is a need to develop new antiviral agents with distinct mechanisms of action and adequate safety profiles. Pralatrexate (PDX) is a fourth-generation anti-folate agent with an inhibitory activity on folate (FA) metabolism and has been used as an anti-tumor drug. We observed that PDX possessed potent inhibitory activity against VZV infection. In this study, we reported the antiviral effects and the underlying mechanism of PDX against VZV infection. The results showed that PDX not only inhibited VZV replication in vitro and in mice corneal tissues but also reduced the inflammatory response and apoptosis induced by viral infection. Furthermore, PDX treatment showed a similar anti-VSV inhibitory effect in both in vitro and in vivo models. Mechanistically, PDX inhibited viral replication by interrupting the substrate supply for de novo purine and thymidine synthesis. In conclusion, this study discovered the potent antiviral activity of PDX with a novel mechanism and presented a new strategy for VZV treatment that targets a cellular metabolic mechanism essential for viral replication. The present study provided a new insight into the development of broad-spectrum antiviral agents. [Display omitted] • Antifolates have potential antiviral effects. • PDX, an antitumor agent, inhibits the replication of VSV and VZV in vitro and in vivo. • PDX exhibits broad-spectrum antiviral effect via temporarily interrupting folate metabolism. [ABSTRACT FROM AUTHOR]

Objective: To determine the utility of ophthalmologic examination as part of evaluation for infection in infants with intrauterine growth restriction (IUGR).Study Design: This is a single-institution retrospective chart review of neonates diagnosed with symmetric IUGR or small for gestational age (SGA) who underwent complete ophthalmologic consultation to assess for intraocular findings suggestive of congenital infection. Data collected included other factors that may cause IUGR, findings of general and ophthalmologic examinations, and results of investigation for intrauterine infection. Cost minimization analysis was also performed.Results: One hundred neonates met the study's inclusion criteria (IUGR, n = 24; SGA, n = 45; IUGR and SGA, n = 31). The mean gestational age at birth was 34.6 ± 3.0 weeks, and the mean birth weight was 1691 ± 530 g; 74% had an identifiable risk factor for IUGR and 84 patients underwent investigation for intrauterine infection. Two of the 73 patients who had urine culture for cytomegalovirus (CMV) were positive (1 of whom had systemic signs of severe congenital infection without eye involvement, the other who had no clinical signs of congenital CMV); evaluations for infection were negative otherwise. No patients had any ophthalmologic signs of congenital infection.Conclusions: Current literature suggests that routine evaluation of neonates with isolated IUGR for congenital infection may be low-yield and not cost-effective. Our study found that routine ophthalmologic evaluation in newborns with symmetric IUGR who have no systemic signs of intrauterine infection is of little value. [ABSTRACT FROM AUTHOR]

Le virus varicelle-zona (VZV) appartient à la famille des herpès virus. La varicelle est la manifestation clinique de la primo-infection au VZV et le zona celle de sa réactivation. L'infection au VZV est très contagieuse. Elle doit conduire à une grande vigilance en période périnatale. La prise en charge de la varicelle de l'enfant se révèle en général simple. L'immunité acquise après la primo-infection est quasi définitive. The varicella zoster virus (VZV) belongs to the family of herpesviruses. Varicella (chickenpox) is the clinical manifestation of the primary infection with VZV and zoster (shingles) that of its reactivation. VZV infection is highly contagious. It requires a high level of vigilance during the perinatal period. Treatment of chickenpox in children is generally straightforward. The immunity acquired after the primary infection is virtually definitive. [ABSTRACT FROM AUTHOR]

Abstract A 53-year-old immunocompetent male visited our hospital complaining of chest pain which persisted for 6 h. After detailed examination, the patient was diagnosed with viral pericarditis and treated with aspirin. On day 3 after admission, rash with blisters appeared on the right side of chest. Paired serum evaluation on the day of admission and 3 weeks later revealed that varicella zoster virus(VZV)titer had significantly increased, and the patient was diagnosed with pericarditis caused by herpes zoster. Although VZV is known to cause various complications, there are few reports of pericarditis associated with VZV. We should consider the possibility of concomitant pericarditis with herpes zoster. < Learning objective: Although varicella zoster virus may cause various complications, the occurrence of myopericarditis is rare. Based on this case, it is suggested that pericarditis may develop concurrently with herpes zoster. Therefore, we should consider this possibility in patients exhibiting herpes zoster on the chest.> [ABSTRACT FROM AUTHOR]

Objectives: To examine the impact of Australia's single dose infant varicella vaccination program, we assessed single dose varicella vaccine effectiveness (VE) in preventing hospitalised disease using two methods.Methods: Clinically confirmed varicella cases from the Paediatric Active Enhanced Disease Surveillance (PAEDS) sentinel network were age-matched to 20 controls obtained from the Australian Immunisation Register. Conditional logistic regression models were used to estimate VE and compared with estimates obtained using our second approach.Results: There were 78 hospitalised varicella cases during the post vaccine introduction period from January 2008 to December 2015, who were eligible for funded varicella vaccination. Median age at onset was 4.5 years and more than half (59%) were vaccinated. The majority of children received one vaccine brand (Varilrix, GSK). The estimated case-control VE for one dose of vaccine against hospitalised varicella was 64.7% (95% CI: 43.3-78.0%); estimates using the screening method were not significantly different. Exclusion of children who were immunocompromised did not significantly alter VE estimates.Conclusions: Although Australia's program has impacted on the burden of varicella disease, single dose VE against varicella hospitalisation is only moderate. Greater reductions in varicella disease could potentially be achieved by incorporation of a second vaccine dose into the program to minimise breakthrough disease and interrupt virus circulation. [ABSTRACT FROM AUTHOR]

Highlights • This is the first molecular epidemiological study on VZV clades in Spain. • First evidence of VZV clade recombination in Spain: clade 1 and clade 3 recombinants were found in six cases. • VZV clade 2 vaccine strains were found in three patients with herpes zoster and one with neurological disease. Abstract Background Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain. Objectives To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016. Study Design In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs. Results Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001). Conclusions Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population. [ABSTRACT FROM AUTHOR]

In most individuals, varicella zoster virus (VZV) causes varicella upon primary infection and zoster during reactivation. However, in a subset of individuals, VZV may cause severe disease, including encephalitis. Host genetics is believed to be the main determinant of exacerbated disease manifestations. Recent studies have demonstrated that defects in the DNA sensor RNA polymerase III (POL III) confer selective increased susceptibility to VZV infection, thus providing fundamental new insight into VZV immunity. Here we describe the roles of POL III in housekeeping and immune surveillance during VZV infection. We present the latest knowledge on the role of POL III in VZV infection and discuss outstanding questions related to the role of POL III in VZV immunity, and how this insight can be translated into clinical medicine. Highlights Accumulation of DNA in the cytoplasm is detected by sensor proteins to induce antimicrobial defences, including antiviral cytokines called interferons. Heterozygous mutations in the cytosolic DNA sensor RNA POL III are associated with elevated risk of developing severe disease during VZV infection. Nuclear POL III transcribes 5S RNA, while cytoplasmic POL III transcribes AT-rich DNA into an RNA form that activates the immune receptor RIG-I. Heterozygous mutations in POL III impair immune sensing, but retain nuclear transcription. Immune control of VZV infection involves a number of immune receptors, including POL III, which work in a cell-type-dependent manner to orchestrate antiviral defences. The development of whole-exome/genome sequencing techniques has led to identification of novel primary immunodeficiencies with increased susceptibility to a narrow set of infections. [ABSTRACT FROM AUTHOR]

Highlights • Survivors of HCT are at increased risk of VZV reactivation. • Prolonged antiviral prophylaxis with acyclovir or valacyclovir remains the standard preventive measure against VZV reactivation although it remains unclear when it can be stopped. • New vaccines for VZV are in development and under evaluation for prevention of herpes zoster in the HCT population. Abstract Reactivation of varicella zoster virus (VZV) remains a significant public health burden for long-term survivors of hematopoietic cell transplantation. Delayed immune reconstitution after transplantation due to immunosuppression, post-transplant therapies, poor engraftment, and graft-versus-host disease leave a large number of patients at risk for herpes zoster (shingles) and its highly morbid complications. Although prophylaxis with acyclovir or valacyclovir has reduced the incidence of VZV reactivation as long as prophylaxis is continued, the incidence of disease in the late post-transplant period or after stopping prophylaxis is greater in the hematopoietic cell transplantation population than the general public. Therefore, additional interventions beyond long-term use of prophylactic antivirals are required to suppress VZV. Vaccines to elicit VZV-specific immunity represent one method to enhance prevention of VZV reactivation, but care must be taken with live vaccines. Inactivated vaccines have been developed and require well-designed studies to determine their safety and efficacy in this high-risk population. Here, we report the available evidence for established and newly developed vaccines for VZV and discuss our view on their role in protecting our transplant survivors against VZV reactivation. [ABSTRACT FROM AUTHOR]

Background Immunity decreases with age, which leads to reactivation of varicella zoster virus (VZV). In human subjects age-associated immune changes are usually measured in blood leukocytes; however, this might not reflect alterations in tissue-specific immunity. Objectives We used a VZV antigen challenge system in the skin to investigate changes in tissue-specific mechanisms involved in the decreased response to this virus during aging. Methods We assessed cutaneous immunity based on the extent of erythema and induration after intradermal VZV antigen injection. We also performed immune histology and transcriptomic analyses on skin biopsy specimens taken from the challenge site in young (<40 years) and old (>65 years) subjects. Results Old human subjects exhibited decreased erythema and induration, CD4 + and CD8 + T-cell infiltration, and attenuated global gene activation at the site of cutaneous VZV antigen challenge compared with young subjects. This was associated with increased sterile inflammation in the skin in the same subjects related to p38 mitogen-activated protein kinase–related proinflammatory cytokine production ( P < .0007). We inhibited systemic inflammation in old subjects by means of pretreatment with an oral small-molecule p38 mitogen-activated protein kinase inhibitor (Losmapimod; GlaxoSmithKline, Brentford, United Kingdom), which reduced both serum C-reactive protein levels and peripheral blood monocyte secretion of IL-6 and TNF-α. In contrast, cutaneous responses to VZV antigen challenge were increased significantly in the same subjects ( P < .0003). Conclusion Excessive inflammation in the skin early after antigen challenge retards antigen-specific immunity. However, this can be reversed by inhibition of inflammatory cytokine production that can be used to promote vaccine efficacy and the treatment of infections and malignancy during aging. [ABSTRACT FROM AUTHOR]

The clinical relevance of herpes zoster (HZ) and its increased incidence in recent years has prompted a search for more effective measures of prevention and therapy. A number of vaccines has been developed. For two of them, the live attenuated HZ vaccine (LAHZV) and the adjuvanted recombinant subunit HZ vaccine (SUHZV), data regarding immunogenicity, efficacy, safety and reactogenicity have been collected. This information allows us to draw some conclusions about what can be expected from their use and what is still required to definitively solve the problem of HZ prevention. The currently licensed vaccine LAHZV is only partially satisfactory in terms of efficacy, but it is safe and exhibits acceptable reactogenicity. Because LAHZV is also highly cost effective, it should be used as widely as possible until new, more effective preparations are developed. In this regard, preliminary data regarding SUHZV are very promising, although more studies are needed before it can be licensed for routine use. Other vaccines, such as the inactivated VZV vaccine, are in development. It seems likely that in the near future, more effective HZ prevention for older adults can be achieved. [ABSTRACT FROM AUTHOR]

Objective To describe the clinical presentation and long-term disease outcomes of varicella zoster virus (VZV) infection–related myelitis (VZVM) in immunocompetent patients. Method A series of 10 immunocompetent patients with VZVM were retrospectively observed and followed (3–96 months). Results The onset of myelitis was timed in relation to the appearance of VZV-associated rash (−3 to 50 days). Rash locations included the cervical (5), thoracic (2), and lumbar (3) dermatomes, whereas myelitis localized to the cervical (6) and thoracic (9) spinal cord and the medulla (1). Spinal MRI revealed extensive longitudinal transverse myelitis in nine patients, with multiple segmental lesions (≥2 segments) evident in five patients. Aquaporin-4, myelin oligodendrocyte glycoprotein, ganglioside Q1b, and ganglioside T1b antibodies were detected in some patients. Three patients fulfilled the 2015 diagnostic criteria for neuromyelitis optica spectrum disease, of whom two relapsed. Seven patients were treated with intravenous antivirals and methylprednisolone, with the remaining three patients receiving methylprednisolone only. Ongoing immunosuppressive therapy was provided for two patients who experienced relapses. To date, no patients have reported VZV reactivation. Over the course of follow-up, the Expanded Disability Status Scale (EDSS) score deceased from 4.9 to 2.6 on average. Conclusions VZVM runs a relatively benign course in immunocompetent patients, although relapses can occur depending on patient immune status. A comprehensive evaluation of patient's autoimmune condition is recommended. [ABSTRACT FROM AUTHOR]

We tested the performance of MRZ-reaction, an intrathecal humoral immune response against-Measles (M), Rubella (R) and Varicella Zoster (Z) viruses, in multiple sclerosis (MS) diagnosis. The MRZ-reaction was significantly more positive in MS than in non-MS group with a specificity of 91.9%. In MS group, the RZ-profile was the most prevalent and the R-specific antibody-index was correlated to the number of oligoclonal bands (OCB) in CSF. Interestingly, the MRZ-reaction was detected in 53% of OCB-negative-MS patients. The MRZ-reaction seems to be a relevant CSF diagnostic marker of MS disease. The likely relation between its positivity and the vaccination status deserves to be investigated. [ABSTRACT FROM AUTHOR]

Abstract Purpose The objective of this review was to summarize the recent literature describing the current burden of disease due to herpesviruses in the antiviral and transplant era; describe mechanisms of action of antiviral agents and the development of resistance; summarize the literature of recent antiviral agents brought to market as well as agents under development; and to present literature on future strategies for herpesvirus therapeutics. Methods An extensive search of the medical literature related to antiherpesviral therapy was conducted to compose this narrative review. Literature searches were performed via PubMed and ultimately 137 articles were included as most relevant to the scope of this article. Findings Herpesviruses are a family of DNA viruses that are ubiquitous throughout human populations and share the feature of establishing lifelong infections in a latent phase with the potential of periodic reactivation. With the exception of herpes simplex virus, varicella zoster virus, and Epstein-Barr virus, which have a significant disease burden in individuals with normal immune function, the morbidity and mortality of the remaining viruses are primarily associated with the immunocompromised host. Over the last half-century, several agents have been tested in large randomized, placebo-controlled trials that have resulted in safe and effective antiviral agents for the treatment of many of these infections. Implications With increasing use of antiherpesviral agents for extended periods, particularly in immunocompromised hosts, the emergence of resistant viruses has necessitated the development of newer agents with novel targets and better side-effect profiles. [ABSTRACT FROM AUTHOR]

Disseminated fusariosis (DF) is a rare life threatening fungal infection in immunocompromised hosts. We herein report a case of a fatal DF mimicking varicella zoster virus (VZV) infection that was emerged from a localized genital infection during cord blood transplantation (CBT) in a patient with severe aplastic anemia (SAA). The patient developed an ulcer following small painful vesicles mimics herpes simplex virus infection (HSV) on the glans penis before CBT, but a Fusarium species was identified. Despite administration of voriconazole, liposomal amphotericin B and granulocyte transfusion, the lesion was extended to extensive skin looked like VZV infection and the patients died after CBT. Massive fusarium infiltration was detected in multiple organs at autopsy. A genetic analysis of the mold identified Fusarium solani after his death. It should be noted that in patients with fusarium infection, localized and disseminated lesions of fusarium infection sometimes mimic HSV and VZV infections, which hampers an early diagnosis. [ABSTRACT FROM AUTHOR]

Varicella zoster virus is a common viral infection with over 50% of patients over the age of 80 years infected with the virus. Following reactivation, some patients succumb to complications of VZV reactivation with neurologic and optic pathway pathology such as VZV vasculopathy resulting in transient ischemic attacks, strokes, aneurysms, as well as optic neuritis. We show that high resolution vessel wall magnetic resonance imaging can aid in the diagnosis of this condition with circumferential wall thickening and enhancement of the infected vessels. Prompt diagnosis is critical as this is a treatable condition that could result in substantial morbidity or mortality if not recognized early. [ABSTRACT FROM AUTHOR]

Background Acute varicella zoster virus (VZV) replication in shingles is accompanied by VZV antibody boosting. It is unclear whether persisting virus shedding affects antibody levels. Objectives To investigate the relationship between VZV viral load and antibody titres in shingles patients during six months following diagnosis and assess whether VZV antibody titre could discriminate patients with recent shingles from healthy population controls. Study design A prospective study of 63 patients with active zoster. Blood samples were collected at baseline, one, three and six months to measure VZV DNA and IgG antibody titre. We compared VZV antibody titres of zoster patients and 441 controls. Results In acute zoster, viral load was highest at baseline and declined gradually over the following six months. Mean antibody titres rose fourfold, peaking at one month and remaining above baseline levels throughout the study. Antibody levels at one, three and six months after zoster were moderately correlated with baseline but not subsequent viral load. Regarding use of antibody titres to identify recent shingles, to achieve 80% sensitivity, specificity would be 23.4%, 67.7%, 64.8% and 52.6%, at baseline, visit 2, 3 and 4 respectively, whilst to achieve 80% specificity, sensitivity would be 28.3%, 66.1%, 52.6%, 38.6%, at baseline, visit 2, 3 and 4 respectively. Conclusions Clinical VZV reactivation boosted VZV antibody levels and the level of boosting was dependent upon baseline viral replication. While antibody titres could discriminate patients with shingles 1–6 months earlier from blood donor controls, there was a large trade-off between sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background Varicella is a common and usually mild disease but it has great importance in regard to general infectious morbidity. The current study aimed to characterize possible risk factors of varicella epidemiology in Bulgaria, a country where infection follows its natural epidemiological pattern as no mandatory or recommended vaccine is currently applied. Methods Administrative regions of Bulgaria were used as units of observation and a set of sociodemographic and economic determinants, as well as geographic location (south or north) were tested for associations with the mean 3-year varicella incidence rates (2013–2015). Results The proportion of urban population, proportion of females, number of health care units and proportion of urban population aged <10 years were the four sociodemographic variables most strongly and significantly correlated (p < 0.05) with varicella frequency (Spearman’s rank correlation coefficients of 0.62, 0.47, 0.43, and 0.38, respectively). After reducing the number of intercorrelated factors to a few principal components and accounting for confounders, the demographic component and geographic location remained most robustly associated with varicella incidence in Bulgaria (adjusted R 2 of 0.51, p < 0.001). Conclusions The results obtained identify important determinants in the local epidemiology of varicella and show that community characteristics should be considered, to improve our understanding of varicella distribution. [ABSTRACT FROM AUTHOR]

Background Varicella, most often a benign disease of childhood, is associated with an increased risk of arterial ischemic stroke in children. The aim of the present study was to estimate the incidence of post-varicella arterial ischemic stroke in the Danish child population and describe clinical characteristics of children admitted with post-varicella arterial ischemic stroke. Methods In the Danish National Patient Register, we identified inpatients 28 days to 16 years of age with a discharge diagnosis of stroke or cerebrovascular disease from 2010 to 2016. Medical files were reviewed, and children with arterial ischemic stroke and varicella infection less than 12 months before onset of symptoms were included. Results We identified 15 children with arterial ischemic stroke and varicella less than 12 months before. In nine children, the diagnosis was confirmed by detection of varicella zoster virus DNA or varicella zoster virus immunoglobulin G in the cerebrospinal fluid. All children were previously healthy, the mean age was four years, and 67% were male. The median time from varicella rash to arterial ischemic stroke was 4.6 months. The most common location of arterial ischemic stroke was the basal ganglia, and affected vessels were most often in the anterior circulation. Fifty-three percent experienced neurological sequelae of varying degree. Conclusions In Denmark, where varicella vaccination is not part of the childhood vaccination program, the estimated risk of post-varicella arterial ischemic stroke was one case (including possible cases) per 26,000 children with varicella. [ABSTRACT FROM AUTHOR]

Purpose Infection by Human Herpes Viruses (HHV) types 1–3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection. Our secondary aim is to emphasize the need for further research to elucidate the potential adverse effects of active HHV infection in irradiated tumor tissue and to design optimal management strategies to incorporate into cancer management guidelines. Materials and methods The literature regarding herpetic infection, herpetic reactivation, and recurrence occurring during radiotherapy and that regarding treatment guidelines for herpetic infections are reviewed. We aim to provide the oncologist with a reference for the infectious dangers of herpetic reactivation in patients under their care and well established methods for prevention, diagnosis, and treatment of such infections. Pain management is also considered. Conclusions In the radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and can alert the clinician to patients at risk for viral reactivation. RT-PCR is specific in identifying the exact viral culprit and is the preferred diagnostic method to measure interventional efficacy. It can also differentiate between herpetic infection and radionecrosis. The MicroTrak ® HSV1/HSV2/VZV staining kit has high sensitivity and specificity in acute lesions, is also the most rapid means to confirm diagnosis. Herpetic reactivation and recurrences during radiotherapy can cause interruptions, cessations, or prolongations of the radiotherapeutic course, thus decreasing the biologically effective dose, to sub-therapeutic levels. Active HHV infection within the treatment volume results in increased tumor radio-resistance and potentially sub-therapeutic care if left untreated. Visceral reactivations may result in fatality and therefore, a high index of suspicion is important to identify these active infections. The fact that such infections may be mistaken for acute and/or late radiation effects, leading to less than optimal treatment decisions, makes knowledge of this problem even more relevant. To minimize the risk of these sequelae, prompt anti-viral therapy is recommended, lasting the course of radiotherapy. [ABSTRACT FROM AUTHOR]

Background Studies have investigated a possible association between family history of HZ and the occurrence of HZ. However, the results were inconclusive and susceptible to bias. We evaluated this association in an elderly population. Methods The matched case-control study conducted at Kaiser Permanente Southern California in 2012-2015 included 656 incident HZ patients ≥60 whose skin lesion tested positive for varicella zoster virus by polymerase chain reaction. Half of the HZ patients were vaccinated with zoster vaccine as achieved by stratified sampling. The controls were randomly selected and 1:1 matched to the cases on sex, age (±1 year), and zoster vaccination (±3 months of the case’s vaccination date). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Results Having any blood relative with a history of HZ was associated with a slightly increased risk of HZ (adjusted OR = 1.37, 95% CI 1.05–1.79). The adjusted OR associated with having one and two categories of first-degree blood relatives with a history of HZ was 1.30 (95% CI: 0.97–1.73) and 2.53 (95% CI: 1.17–5.44), respectively. Conclusions Our results suggested a weak association between the development of HZ and a positive family history of HZ among the elderly population. [ABSTRACT FROM AUTHOR]