Varicella-zoster Virus Antibody Research Articles

Study on Varicella-Zoster Virus Antibody Levels among Children Aged 1-7 Years in Changzhou, China.

We aim to understand the varicella-zoster virus (VZV) antibody levels in children after vaccination and to construct VZV-IgG centile curves and reference values for children aged 1-7 years. From September to October 2023, a total of 806 children were recruited according to the time intervals of 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination, as well as age groups. A generalized additive model for location, shape, and scale (GAMLSS) was applied to estimate P3, P10, P25, P50, P75, P90, and P97 centile reference values of VZV-IgG, and 95% reference intervals were calculated. A total of 785 children were included in the analysis, with an overall positivity rate of 70.3%, a median antibody concentration of 192.05 (82.89-571.14) mIU/mL, and a positivity rate of 57.7% for one dose of vaccine and 84.2% for two doses. Antibody positivity rates at 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination were 65.1%, 74.4%, 80.4%, 67.7%, and 63.0%, respectively. The GAMLSS results showed that VZV-IgG had a tendency to increase and then decrease after vaccination, and the second dose of vaccination could significantly increase VZV-IgG. Two doses of varicella vaccine should be administered to children in a timely manner and included in the routine vaccination programs.

Is the level of varicella-zoster virus IgG associated with symptomatic status of genital herpes simplex virus infection? A case-control study.

Herpes simplex virus (HSV) is a common infection, affecting the majority of the population by age of 50. Recurrent symptomatic outbreaks, experienced by a minority, have significant psychological and psychosexual effects. The varicella zoster virus (VZV), resembling HSV, shows potential for a functional cure via vaccination. This study seeks to investigate if there is an association between low VZV antibody levels and recurrent HSV outbreaks. A total of 110 patients with symptomatic and asymptomatic HSV were recruited during their sexual health screen. Serum samples were collected between Aug 2019 - July 2022; breaks in the study occurred due to COVID. The primary outcome measure was the serological status of HSV and VZV IgG titre level. The average age was 37.3years (range 21-65years). For people with asymptomatic genital HSV2 the average VZV IgG titre was 2373.9IU/mL (n = 17); and 1219.0IU/mL for the symptomatic group (n = 67); p ≤ 0.00001), with similar results for HSV1. There is a strong association between average higher varicella-zoster virus (VZV) IgG level and being an asymptomatic carrier of herpes simplex sirus (HSV)1&2. A feasibility study to assess the use of the VZV vaccine as a treatment of HSV is planned.

Immunogenicity and safety of a live-attenuated varicella vaccine in a healthy population aged 13 years and older: A randomized, double-blind, controlled study

ObjectivesVaccines for prevention against varicella are important for adolescents and adults, who have an increased risk of severe varicella. This study aimed to evaluate the immunogenicity and safety of a two-dose immunization schedule of a live-attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) in healthy adolescents and adults. MethodsA randomized, double-blind, controlled clinical trial was conducted in healthy population aged ≥ 13 years old in China. Participants in block 1 were randomly assigned (1:1) to receive two doses of either the test vaccine or an active control vaccine, administered 4, 6 or 8 weeks apart. Participants in block 2 were randomly assigned (2:1) to receive two doses of test vaccine or placebo, administered 10 weeks apart. The primary immunogenicity endpoint was the seroconversion rates and GMTs of varicella zoster virus (VZV) antibodies measured by fluorescent-antibody-to-membrane-antigen (FAMA) 4 weeks post-immunization. The primary safety endpoint was the incidence of adverse reactions within 4 weeks after each dose. ResultsA total of 2398 participants were enrolled. The seroconversion rates of VZV antibodies were 79.55 % in the test group and 76.41 % in the active control group respectively 4 weeks after two doses of pooled schedule, with the difference of 3.14 % (95 %CI: −0.69 %, 6.97 %). The GMTs were 1:162.07 and 1:160.04 respectively, with the ratio of 1.013 (95 %CI: 0.910, 1.127). Both the seroconversion rates and GMTs reached the prespecified non-inferiority criteria. Two-dose schedule with an interval of 10 weeks could also induce high immune responses, with a seroconversion rate of 83.22 % and a GMT of 1:160.38 in the test group. Safety profiles were similar among the test group, active control group and placebo group. ConclusionVarV, manufactured by Sinovac (Dalian), demonstrated higher immune response and better flexibility in the immunization schedule among heathy population aged 13 years and older, without increased safety risk.

EPID-17. ANTIBODY REACTIVITY TO VARICELLA ZOSTER VIRUS IS ASSOCIATED WITH IMPROVED GLIOMA SURVIVAL AND IS MODIFIED BY GERMLINE HLA POLYMORPHISMS

Abstract Antigenic reactivity towards varicella zoster virus (VZV) has shown a consistent reduction in glioma risk across multiple studies on multiple continents. To our knowledge this is the virus to be robustly associated with reduced risk of any cancer. Our recent work has shown that high VZV reactivity is also assumed with improved glioma prognosis. Using the UKBioBank we have previously shown that germline HLA polymorphism, rs9273325, significantly effects reactivity to VZV. In this study we investigate the VZV glioma survival association in the context of germline HLA polymorphisms. METHODS: We measured quantitative IgG reactivity towards VZV gE, and conducted genome wide array based genotyping in 891 adults with glioma. Associations of patient IgG levels (1st quartile vs. quartiles 2,3,4) with overall survival were estimated using Cox models adjusted for age, sex, self-reported race, surgery type, dexamethasone usage at blood draw. RESULTS: VZV seroreactivity was significantly associated with reduced mortality (HR=0.83, 95% CI: 0.70-0.99; p=0.034), as expected from our previous study. Among patients with rs9273325-GG, higher levels of VZV antibodies were associated better prognosis (HR=0.75, 0.62-0.92; p=0.005), but in the rs9273325-GA/AA strata this relationship with VZV antibodies was not observed (HR=0.94, 0.66-1.35; p=0.75). Similar results were observed in grade IV gliomas, IDHwt GBMs. CONCLUSIONS: Strong antibody response to VZV is associated with improved glioma prognosis and the effect of VZV reactivity on glioma survival is modified by a specific HLA polymorphism, a Gene x Virus interaction, that is unlikely due to chance. This study highlights the importance of accounting for HLA variation in immune related studies, including oncolytic viral therapies. Our findings also point towards a potentially MHC mediated mechanism by which VZV could be priming an immune response targeting glioma cells. Further investigations into this mechanism and VZV/shingles vaccination as a potential glioma therapeutic are warranted.

Seroprevalence of VZV and HSV-2 Antibodies among Women of Childbearing Age Referring to Health Centres of Mashhad, Iran: The Need for Consideration of VZV Vaccination Program.

Infections with herpes simplex virus type 2 (HSV-2) and varicella-zoster virus (VZV) are associated with serious maternal and neonatal health consequences. The literature review reveals a research gap regarding the seroprevalence of HSV-2 and VZV among women of reproductive age in Mashhad, Northeast of Iran. The present study aims to evaluate the seroprevalence of these viruses among a group of women in Mashhad, Iran. Sera were collected by health center personnel using a cluster sampling method from healthy women with specific age characteristics residing in three distinct socioeconomic regions of the city. The participants, aged 20-35, were divided into three groups (20-25, 26-30, and 31-35 years). The levels of VZV and HSV-2 IgG antibodies were evaluated using commercial ELISA kits. Subsequently, the results were analyzed using SPSS software. A total of 93 women were included in the study. Anti-HSV-2 IgG antibody was detected in 3 out of 93 participants (7.5%), while anti-VZV IgG antibody was found positive in 80 out of 93 individuals (83.3%). The HSV-2 positive cases were concurrently positive for the VZV antibody. There was no significant difference in the positivity of anti-HSV-2 and anti-VZV antibody positivity within age groups or socioeconomic status (P > 0.05). The high seroprevalence of VZV among nonvaccinated participants indicates a widespread presence of the virus and underscores its potentially serious impact on community health. Therefore, it is recommended that a VZV vaccination program be considered by the health system. Furthermore, the reactivation of latent HSV-2, whether symptomatic or asymptomatic, during pregnancy should not be disregarded as a life-threatening threat.

Case report: Relapsed disseminated cutaneous herpes zoster successfully treated with brivudine

A 64-year-old man presented with painful rash on the trunk and extremities for more than half a month. Nephrotic syndrome had been diagnosed 2 years ago and had been regularly treated with glucocorticoids and immunosuppressants. He developed herpes zoster 1 year ago. Laboratory investigation demonstrated varicella-zoster virus DNA (VZV-DNA), varicella-zoster virus IgM (VZV-IgM), and varicella-zoster virus antibody IgG (VZV-IgG) were all positive. After the clinical diagnosis of relapsed disseminated cutaneous herpes zoster had been confirmed, systemic therapy with brivudine 125 mg everyday was started.

Inherited polymorphisms in the Human Leukocyte Antigen Region modify the association between varicella-zoster virus antibody reactivity and glioma prognosis.

Inherited polymorphisms in the Human Leukocyte Antigen Region modify the association between varicella-zoster virus antibody reactivity and glioma prognosis.

Seroprevalence of varicella-zoster virus antibody and immunogenicity of live attenuated varicella vaccine in healthcare workers in Taiwan.

Healthcare workers (HCWs) without evidence of immunity to varicella-zoster virus (VZV) are recommended to undergo varicella vaccination. Immunogenicity of live attenuated varicella vaccine has rarely been investigated among HCWs in Taiwan. Anti-VZV immunoglobulin G (IgG) titer was checked for all HCWs at Changhua Christian Hospital from 2011 to 2017. One-dose and two-dose (separated by 4-8 weeks) vaccines were administered to HCWs with equivocal and negative anti-varicella IgG results, respectively. Follow-up anti-VZV IgG was determined at least 4 weeks after completion of vaccination. Factors associated with seroconversion to varicella vaccination were analyzed. Among 2406 included HCWs, the anti-VZV IgG serostatus was tested positive, equivocal and negative in 1924 (79.9%), 117 (4.9%) and 365 (15.2%), respectively. The seroprevalence had decreased from 88.0% (235/267) in 2011 to 72.2% (270/374) in 2017 (p for trend <0.05). A total of 67.8% (327/482) HCWs completed scheduled vaccination and serological follow-up. The seroconversion rates for HCWs with baseline equivocal and negative anti-VZV IgG results were 100% (80/80) and 79.4% (196/247) after one- and two-dose vaccination, respectively. In multivariate analysis, obesity (adjusted odds ratio, 0.308; 95% confidence interval [CI], 0.11-0.94, p=0.039) was the only factor statistically significantly associated with seroconversion to vaccination. Decreasing trends of seroprevalence of VZV were observed among HCWs from 2011 to 2017. HCWs who were obese were less likely to respond to varicella vaccination.

Current Methods for the Detection of Antibodies of Varicella-Zoster Virus: A Review

Infection with the varicella-zoster virus (VZV) causes chickenpox and shingles, which lead to significant morbidity and mortality globally. The detection of serum VZV-specific antibodies is important for the clinical diagnosis and sero-epidemiological research of VZV infection, and for assessing the effect of VZV vaccine immunization. Over recent decades, a variety of methods for VZV antibody detection have been developed. This review summarizes and compares the current methods for detecting VZV antibodies, and discussed future directions for this field.

Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies.

Studying antibody dynamics following re-exposure to infection and/or vaccination is crucial for a better understanding of fundamental immunological processes, vaccine development, and health policy research. We adopted a nonlinear mixed modeling approach based on ordinary differential equations (ODE) to characterize varicella-zoster virus specific antibody dynamics during and after clinical herpes zoster. Our ODEs models convert underlying immunological processes into mathematical formulations, allowing for testable data analysis. In order to cope with inter- and intra-individual variability, mixed models include population-averaged parameters (fixed effects) and individual-specific parameters (random effects). We explored the use of various ODE-based nonlinear mixed models to describe longitudinally collected markers of immunological response in 61 herpes zoster patients. Starting from a general formulation of such models, we study different plausible processes underlying observed antibody titer concentrations over time, including various individual-specific parameters. Among the converged models, the best fitting and most parsimonious model implies that once Varicella-zoster virus (VZV) reactivation is clinically apparent (i.e., Herpes-zoster (HZ) can be diagnosed), short-living and long-living antibody secreting cells (SASC and LASC, respectively) will not expand anymore. Additionally, we investigated the relationship between age and viral load on SASC using a covariate model to gain a deeper understanding of the population's characteristics. The results of this study provide crucial and unique insights that can aid in improving our understanding of VZV antibody dynamics and in making more accurate projections regarding the potential impact of vaccines.

Antibodies to varicella-zoster virus and three other herpesviruses and survival in adults with glioma.

Lifetime exposure to the varicella-zoster virus (VZV) has been consistently inversely associated with glioma risk, however, the relationship of VZV with survival in adults with glioma has not been investigated. In this study, we analyzed the survival of adults with glioma in relation to their antibody measurements to 4 common herpes viral infections, including VZV, measured post-diagnosis. We analyzed IgG antibody measurements to VZV, cytomegalovirus (CMV), herpes simplex virus 1/2 (HSV), and Epstein-Barr virus (EBV) collected from 1378 adults with glioma diagnosed between 1991 and 2010. Blood was obtained a median of 3 months after surgery. Associations of patient IgG levels with overall survival were estimated using Cox models adjusted for age, sex, self-reported race, surgery type, dexamethasone usage at blood draw, and tumor grade. Models were stratified by recruitment series and meta-analyzed to account for time-dependent treatment effects. VZV antibody seropositivity was associated with improved survival outcomes in adults with glioma (Hazard ratio, HR = 0.70, 95% Confidence Interval 0.54-0.90, P = .006). Amongst cases who were seropositive for VZV antibodies, survival was significantly improved for those above the 25th percentile of continuous reactivity measurements versus those below (HR = 0.76, 0.66-0.88, P = .0003). Antibody seropositivity to EBV was separately associated with improved survival (HR = 0.71, 0.53-0.96, P = .028). Antibody positivity to 2 other common viruses (CMV, HSV) was not associated with altered survival. Low levels of VZV or EBV antibodies are associated with poorer survival outcomes for adults with glioma. Differential immune response rather than viral exposure may explain these findings.

Diagnostic Usefulness of Varicella Zoster Virus-Specific Immunoglobulin (Ig) A and IgG in Patients With Herpes Zoster.

Whether varicella zoster virus (VZV) antibody titer could discriminate patients with herpes zoster (HZ) from healthy controls (HCs) is unclear. We evaluated the diagnostic usefulness of VZV-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies in patients with confirmed HZ. Study subjects comprised patients with confirmed HZ by salivary VZV DNA positivity and control age- and sex-matched HCs. Saliva was collected and concurrent blood samples were obtained on the first visit day (acute phase) and after 4 weeks (convalescent phase) from 44 HZ patients. All 44 healthy volunteers provided blood and saliva samples once. The median VZV IgA titers in acute-phase (5.2 mIU/mL, P < 0.001) and convalescent-phase (15.8 mIU/mL, P < 0.001) serum samples from HZ patients were significantly higher than those in HCs (1.35 mIU/mL). VZV IgA positivity was detected in about 20% of acute phase serum and convalescent-phase serum of HZ patients. The median VZV IgG antibody titers of HZ patients during acute (1,471.0 mIU/mL, P < 0.001) and convalescent (4,934.7 mIU/mL, P < 0.001) phases were significantly higher than the median titer reported for HCs (591.6 mIU/mL). A four-fold or higher increase in VZV IgG antibody titer was observed in 36.4% of HZ patients. VZV IgA positivity or four-fold or higher increase in VZV IgG antibody titers were not detected in a satisfactory proportion of HZ-infected patients. However, the titer of VZV IgA or IgG antibody particularly in convalescent-phase sera may discriminate HZ patients from HCs.

EPID-02. ANTIBODY REACTIVITY TO VARICELLA-ZOSTER VIRUS AND THREE OTHER HERPESVIRUSES AND SURVIVAL IN ADULTS WITH GLIOMA

Abstract Measures of Varicella-Zoster virus (VZV) have been consistently inversely associated with glioma risk, but the association with glioma survival has not been investigated. In this study we analyzed overall survival of individuals with glioma in relation to measured levels of antibodies to 4 common viral infections, measured post-diagnosis. METHODS We utilized immunoglobulin G (IgG) antibody measurements to VZV, Epstein-Barr virus (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV), collected from 1378 patients newly enrolled in the UCSF Adult Glioma Study between 1991-2010. Blood was obtained a median of 3 months post diagnostic surgery. Subject follow-up for survival is ongoing. The associations of IgG levels with overall survival were estimated using Cox models adjusted for age, sex, race, type of surgery, dexamethasone usage, and stratified by tumor grade. RESULTS The 1378 glioma patients studied had median survival of 2.1 years. VZV antibody seropositivity was associated with improved survival outcomes (Hazard ratio, HR = 0.70, 95% Confidence Interval 0.54-0.90, p = 0.0061), with a grade-IV specific association (HR=0.65, 0.48-0.87, p=0.0046). Amongst VZV seropositive cases, those in the bottom quartile of measured seroreactivity had significantly worse survival outcomes as compared to the upper three quartiles (HR = 1.31, 1.13-1.52, p = 0.0003). Antibody seropositivity to EBV was also associated with improved survival times (HR = 0.71, 0.53-0.96, p = 0.028). Antibody response to two other common viruses (CMV, HSV) were not associated with glioma survival (p = 0.213, p = 0.215, respectively). CONCLUSION This is the first study, to our knowledge, to associate virus-specific antibody levels with survival amongst glioma patients. These associations do not appear to be due to general tumor-induce immune suppression. Our results controlled for dexamethasone usage, a known immunosuppressor. IgG measurements were taken post-glioma diagnosis, therefore further study is needed to determine the direction of causation, and if anti-herpesvirus treatment, such as VZV vaccination, might be beneficial for glioma prognosis.

Zoster Polyneuritis Cranialis and Intracranial Vasculopathy.

A case report of varicella zoster virus (VZV) producing cranial polyneuropathy with intracranial vasculopathy afflicting the internal carotid artery, in a 45-year lady is presented. The clinical features included appearance of zosteriform rash in the left external auditory canal and concha, affliction of ophthalmic and maxillary divisions of V, VI, VII, VIII, IX and X cranial nerves. Contrast MRI brain demonstrated attenuated flow void in the left internal carotid artery. The diagnosis was confirmed with raised level of IgG VZV antibody in serum and detection of VZV IgG antibody in CSF, although PCR for VZV DNA in CSF was negative. The significance lies in atypical presentation, the diagnostic dilemma it poses, poor prognosis of cranial nerve function and the need for multidisciplinary approach to patient management and rehabilitation.

Overlapping Signs and Symptoms Between Recurrent Varicella and Pityriasis rosea Gibert.

Pityriasis rosea Gibert (PRG) has features similar to those of common infectious childhood diseases, suggesting a viral cause, but no agent has been identified to date. We describe 4 children with PRG and 2 with recurrent varicella who were studied using photochronography, virology and immunology. The 6 patients with skin rashes visited our pediatric clinic from April 2012 to May 2016. Photographs of their skin lesions were taken; blood, skin lesions, and/or nasal lavage samples were collected to detect varicella-zoster virus (VZV) DNA and antibodies; and skin tests were carried out to measure cell-mediated immunity to VZV. Herald patches were confirmed in 2 of 4 PRG patients. No specimen cultures were positive for infectious VZV. However, VZV-DNA was detected in skin lesions of 3 PRG patients. During the acute phase, 5 patients had IgG antibodies to VZV, and skin-test reactions were positive in 5 patients. IgG antibody titers to VZV at rash onset were high, suggesting that they were already rising at the appearance of the rash and that reinfection with VZV must have occurred during the prodromal stage or several weeks before rash appearance in PRG patients whose immunity had declined below the threshold. Our study suggests a new pathogenesis of PRG that might help to address incongruities of past theories on PRG sites of viral entry and replication, incubation period and variations in the clinical course of PRG from prodrome to healing.

Recovery of intracranial stenoses in varicella zoster virus vasculitis after long-term treatment with valacyclovir and prednisolone

Background and purposeOptimal treatment of intracranial stenoses in varicella zoster virus (VZV)-associated vasculitis is unknown. This study aims to evaluate the merits and potential pitfalls of a specific therapeutic strategy, initially proposed by Don Gilden in 2015.MethodsWe describe three patients with intracranial stenoses caused by VZV vasculitis successfully treated by a long-term combination of valacyclovir and prednisolone.ResultsAll three patients were young men suffering from stroke. Only one reported a first contact to VZV in adulthood. All three presented stenoses in the intracranial part of the internal carotid artery or the proximal segments of the middle cerebral artery as well as an elevated cell count and positive VZV antibody index in cerebrospinal fluid. They received a combination therapy regimen with prednisone and valacyclovir about a minimum of one year. Intracranial stenoses improved markedly in one and almost resolved completely in the other two patients. Side effects of corticosteroid treatment occurred in two patients.ConclusionsLong-term combination treatment with prednisone and valacyclovir proved to be effective in three young men suffering from intracranial stenosis due to VZV vasculitis.

Development of an Indirect ELISA Kit for Rapid Detection of Varicella-Zoster Virus Antibody by Glycoprotein E.

Varicella-zoster virus (VZV), a highly infectious agent that causes varicella (chickenpox), can also cause zoster (shingles), a disorder that is frequently associated with severe neuralgia. A reliable serological VZV diagnostic assay would be useful for identifying unprotected individuals and for surveilling post-vaccination immunoprotection status. Toward this goal, VZV membrane glycoprotein E (gE), the immunodominant VZV protein, served as target antigen in an indirect ELISA kit developed here to detect anti-VZV antibodies in clinical samples. For target antigen preparation, Chinese hamster ovary (CHO) cells were modified to express and secrete the VZV gE ectodomain, which was subsequently purified and used as coating antigen in an indirect ELISA. Ultimately, the optimal purified gE coating antigen concentration was determined to be 2 μg.ml−1 and the OD450nm detection cutoff value was 0.286. The coefficient of variation (CV) of intra-assay and inter-assay were <10 and 15%, respectively. A comparative test of 66 clinical samples showed that the coincidence rate was 93.9% between the indirect ELISA and a commercial varicella-zoster virus IgG ELISA kit. Thus, the indirect ELISA kit developed here may be useful for achieving rapid, sensitive, and specific detection of anti-VZV antibodies.

An investigation on serum antibody level of varicella-zoster virus in healthy population in Beijing

Objective: To assess the level and trend of varicella-zoster virus (VZV) antibody among healthy population in Beijing in 2017, after the five-year implementation of the two doses varicella vaccination strategy in 2012, and to provide evidence for scientific evaluation of immunization strategy. Methods: A total of 2 144 subjects in ten age groups from 8 districts of Beijing city were recruited in this study using cross-sectional survey based on multi-stage cluster random sampling method. Serum samples were collected and VZV antibody was detected by ELISA. The influencing factors of antibody concentration and positive rate were analyzed and compared with the study in 2012. The antibody concentration and antibody positive rate were analyzed by nonparametric test and χ² test respectively. Results: The ratio of subjects with registered residence in Beijing city to other provinces was 1∶1. The ratio of male to female was 1∶1.08. The median concentration of VZV antibody was 341.4 (78.6, 1 497.8) mIU/ml, and the total antibody positive rate was 71.1% (1 524/2 144). There were significant differences in antibody positive rate (χ²=736.39, P<0.01) and antibody concentration (χ²=740.34, P<0.01) among different age groups. The antibody positive rate generally increased with age (χ²trend=7.32, Ptrend<0.01). Among 862 children under 14 years old, the antibody positive rate of two doses vaccination 72.8% (182/250) was significantly higher than that of one dose vaccination 51.9% (154/297) (χ²=25.14, P<0.01). There was significant difference between 1-4 years old group (χ²=11.71, P<0.01) and 10-14 years old group (χ²=5.95, P=0.02), but not in 5-9 years old group (χ²=3.00, P=0.07). Compared with the study in 2012, the antibody positive rate increased in 5-9 years old group (χ²=14.35, P<0.01) and decreased in 1-4 years old group (χ²=11.51, P=0.01) in 2017. Conclusion: The recommended varicella booster vaccination has significantly improved the VZV antibody level of children in Beijing city. In the future, it is necessary to explore a more optimized two doses varicella vaccination schedule for children in combination with epidemiological evidence.

P402 Incidence and outcomes of herpes zoster in the ozanimod phase, 3 ulcerative colitis and relapsing multiple sclerosis clinical program

Abstract Background Patients with ulcerative colitis (UC) and patients with multiple sclerosis (MS) have an elevated risk of developing herpes zoster (HZ), caused by reactivation of latent varicella zoster virus (VZV). Increased incidence of HZ has been reported with sphingosine, 1-phosphatase (S1P) receptor modulators. This analysis examined the number of patients who failed screening due to a lack of demonstrated VZV immunity and the incidence of HZ from completed phase, 3 ozanimod clinical trials. Methods Safety results were included from True North (52-week trial) in patients with UC, and SUNBEAM (12-month trial), and RADIANCE (24-month trial) in patients with MS. All patients were required to have had a positive VZV IgG antibody status or completed VZV vaccination ≥30 days prior to randomization based on known effects of S1P modulators. Patients with a negative VZV antibody titer could choose to receive the VZV vaccination to qualify for the trial. Number of pre-screen failures because of lack of demonstrated immunity, occurrence of HZ, and association between HZ cases and lymphopenia were analyzed. Results Of, 1831 patients with UC screened for VZV immunity, 104 (5.7%) failed screening due to lack of documentation of VZV antibody or VZV vaccination ≥30 days before randomization;, 22% (23/104) subsequently received varicella vaccination and were rescreened and enrolled. Of, 3332 MS patients tested for VZV immunity, 309 (9.3%) tested negative and, 32% (98/309) of these patients were vaccinated prior to randomization. In the UC and MS trials, the incidence of HZ cases was low in ozanimod-treated patients (8 cases [1.0%] and, 5 cases [0.6%], respectively; Table, 1). All cases were distributed across a single dermatome, did not result in a complication of HZ, and were treated with oral antivirals while patients remained on ozanimod. None of the patients discontinued ozanimod because of HZ and none of the HZ cases were associated with grade, 4 lymphopenia (defined as an absolute lymphocyte count &amp;lt;0.2 x, 109/L). Conclusion In the ozanimod phase, 3 UC and MS trials, 5%–10% of patients screened did not have demonstrated VZV immunity;, 22%–32% of these patients received varicella vaccination, were rescreened and enrolled. The overall HZ incidence in clinical trials was low (≤1% of patients), all cases were distributed across a single dermatome, and no serious or complicated cases occurred in ozanimod-treated patients with VZV immunity. Additional studies are warranted to evaluate the incidence of HZ in clinical practice.

Metagenomic Next-Generation Sequencing vs. Traditional Microbiological Tests for Diagnosing Varicella-Zoster Virus Central Nervous System Infection.

BackgroundUnbiased metagenomic next-generation sequencing (mNGS) detects pathogens in a target-independent manner. It is not well-understood whether mNGS has comparable sensitivity to target-dependent nucleic acid test for pathogen identification.MethodsThis study included 31 patients with chickenpox and neurological symptoms for screening of possible varicella-zoster virus (VZV) central nervous system (CNS) infection. Microbiological diagnosing of VZV cerebrospinal fluid (CSF) infection was performed on stored CSF samples using mNGS, quantitative and qualitative VZV-specific PCR assays, and VZV IgM antibodies test.ResultsThe median age was 30.0 [interquartile range (IQR), 24.3–33.3] years. 51.6% of the patients were men. About 80.6% of the patients had normal CSF white blood cell counts (≤ 5 × 106/L). VZV IgM antibodies presented in 16.1% of the CSF samples, and nucleic acids were detectable in 16.1 and 9.7% using two different VZV-specific real-time PCR protocols. Intriguingly, maximal identification of VZV elements was achieved by CSF mNGS (p = 0.001 and p = 007; compared with qualitative PCR and VZV IgM antibody test, respectively), with sequence reads of VZV being reported in 51.6% (16/31) of the CSF samples. All VZV PCR positive samples were positive when analyzed by mNGS. Of note, human betaherpesvirus 6A with clinical significance was unexpectedly detected in one CSF sample.ConclusionsOur study suggests that CSF mNGS may have higher sensitivity for VZV detection than CSF VZV PCR and antibody tests, and has the advantage of identifying unexpected pathogens.