Varicella-zoster virus meningitis with hypoglycorrhachia: A case report

BACKGROUND Varicella-zoster virus(VZV)is a common viral infection,but meningitis is a rare complication of VZV infection.The cerebrospinal fluid glucose of viral meningitis is usually within the normal range,which is different from bacteria,fungi,and cancerous meningitis.This paper reports a case of VZV meningitis with hypoglycorrhachia and the relevant literature was reviewed.CASE SUMMARY We report a case of an immunocompetent 39-year-old male,presenting with severe headache and fevers,without meningeal signs or exanthem,found to have VZV meningitis by the metagenomic next-generation sequencing of cerebrospinal fluid.The cerebrospinal fluid analysis revealed hypoglycorrhachia(cerebrospinal fluid glucose of 2.16)and he was treated successfully with intravenous acyclovir.Our literature review identified only ten cases diagnosed with VZV meningitis with hypoglycorrhachia previously reported to date in the English literature whose cerebrospinal fluid glucose was from 1.6 to 2.7mmol/L,with a ratio of cerebrospinal fluid to serum glucose from 0.30 to 0.49.CONCLUSION Although rare,the cerebrospinal fluid of patients with VZV meningitis may have hypoglycorrhachia,which broadens the understanding of the disease.

Microbiology laboratory and the management of motherchild varicella-zoster virus infection

Varicella-zoster virus, which is responsible for varicella(chickenpox) and herpes zoster(shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella(particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times:(1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection;(2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear(atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation;(3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and(4) when the baby is born and it is necessary to confirm a diagnosis of varicella(and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn.

Varicella-zoster virus-associated meningitis,encephalitis,and myelitis with sporadic skin blisters:A case report

BACKGROUND Varicella-zoster virus(VZV)generally causes chickenpox at first infection in childhood and then establishes latent infection in the dorsal root ganglia of the spinal cord or other nerves.Virus reactivation owing to an impaired immune system causes inflammation along spinal nerves from the affected spinal segment,leading to skin manifestations(herpes zoster).Viremia and subsequent hematogenous transmission and nerve axonal transport of the virus may lead to meningitis,encephalitis,and myelitis.One such case is described in this study.CASE SUMMARY A 64-year-old man presented with dysuria,pyrexia,and progressive disturbance in consciousness.He had signs of meningeal irritation,and cerebrospinal fluid(CSF)analysis revealed marked pleocytosis with mononuclear predominance and a CSF/serum glucose ratio of 0.64.Head magnetic resonance imaging revealed hyperintense areas in the frontal lobes.He had four isolated blisters with papules and halos on his right chest,right lumbar region,and left scapular region.Infected giant cells were detected using the Tzanck test.Degenerated epidermal cells with intranuclear inclusion bodies and ballooning degeneration were present on skin biopsy.Serum VZV antibody titers suggested previous infection,and the CSF tested positive for VZV-DNA.He developed paraplegia,decreased temperature perception in the legs,urinary retention,and fecal incontinence.The patient was diagnosed with meningitis,encephalitis,and myelitis and was treated with acyclovir for 23 days and prednisolone for 14 days.Despite gradual improvement,the urinary retention and gait disturbances persisted as sequelae.CONCLUSION VZV reactivation should be considered in differential diagnoses of patients with sporadic blisters and unexplained central nervous system symptoms.

Review of varicella-zoster virus infections in pregnant women and neonates

Even though varicella is rare in pregnancy, the disease can lead occasionally to disastrous illnesses for both the mother and her neonate. By contrast, normal zoster is not associated with special problems during pregnancy and peri- natal period. Pregnant women, who contract varicella, are at risk of varicella pneumonia which must be regarded as medical emergency. At any stage during pregnancy, chickenpox may cause intrauterine infection. The consequences for the fetus depend on the time of maternal disease. During the first two trimesters, maternal varicella may result in congenital varicella syndrome which may occur in nearly 2%. Typical symptoms are skin lesions in dermatomal distribution, neurological defects, eye diseases, and skeletal anomalies. Maternal infection near term is associated with a substantial risk of intrauterine acquired neonatal chickenpox in the neonate. If the mother develops varicella rash between day 4 (5) ante partum and day 2 post partum, generalized neonatal varicella leading to death in about 20% of the cases has to be expected. The present paper reviews the clinical consequences and the currently available concepts of prevention, diagnosis, and therapy of varicella-zoster virus infections during pregnancy.

Dynamical study of varicella-zoster virus model in sense of Mittag-Leffler kernel

The primary varicella-zoster virus(VzV)infection that causes chickenpox(also known as varicella),spreads quickly among people and,in severe circumstances,can cause to fever and encephalitis.In this paper,the Mittag-Leffler fractional operator is used to examine the mathematical representation of the vzV.Five fractional-order differential equations are created in terms of the disease's dynamical analysis such as S:Susceptible,V:Vaccinated,E:Exposed,I:Infectious and R:Recovered.We derive the existence criterion,positive solution,Hyers-Ulam stability,and boundedness of results in order to examine the suggested fractional-order model's wellposedness.Finally,some numerical examples for the VzV model of various fractional orders are shown with the aid of the generalized Adams-Bashforth-Moulton approach to show the viability of the obtained results.

Insights into varicella-zoster virus assembly from the B-and C-capsid at near-atomic resolution structures

Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.

Ambispective epidemiological observational study of varicella-zoster virus infection: An 18 year-single-center Bulgarian experience

BACKGROUND Varicella(chickenpox)and herpes zoster(shingles)are outcomes of varicella-zoster virus(VZV)infection,and understanding their incidence trends is vital for public health planning.AIM To conduct an ambispective epidemiological study by analyzing the main epidemiological characteristics of VZV infection during an 18 year-period(2000-2018).METHODS We used descriptive and epidemiological methods to characterize chickenpox in Bulgaria,the city of Plovdiv and the region for a period of 18 years(2000-2018).RESULTS The average incidence of varicella-zoster infection for the period 2000–2018 in the Plovdiv region was estimated at 449.58‰.The highest relative share of the infection was assessed in the month of January at 13.6%,and the lowest in the months of August and September at 2.9%(both months).The age group most affected by the infection was 1-4 years,followed by 5-9 years.This corresponds to the so-called"pro-epidemic population"-a phenomenon typical for airborne infections,confirming their mass impact on the perpetuation of VZV infection.CONCLUSION Our findings reveal significant insights into VZV epidemiology,including age-specific incidence rates,clinical manifestations,and vaccination impact.This comprehensive analysis contributes to the broader understanding of VZV infec-tion dynamics and may inform evidence-based preventive measures.

Varicella-Zoster Virus Encephalitis with Hyponatremia in an Immunocompetent Elderly Patient:A Case Report

As a common cause of viral encephalitis,varicella-zoster virus(VZV)may invade the central nervous system of immunosuppressed patients during reactivation.Herein,we report a rare case of an immunocompetent patient with VZV encephalitis who developed severe hyponatremia and was considered to have a suspected primary infection.The patient was diagnosed with the support of second-generation sequencing and had persistent hyponatremia after being cured.Although rare,this case suggests that VZV encephalitis may occur in unexpected patients and present with unusual clinical manifestations,requiring advanced detection methods and clinical expertise for resolution.

Truncated glycoprotein E of varicella-zoster virus is an ideal immunogen for Escherichia coli-based vaccine design

Varicella-zoster virus(VZV)is a highly infectious agent responsible for both varicella and herpes zoster disease.Despite high efficacy,there remain safety and accessibility concerns with the licensed vaccines.Here,we sought to produce a VZV g E immunogen using an E.coli expression system.We found that the soluble expression and yield of g E protein could be enhanced via C-terminal truncations to the protein,thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing.The lead truncated g E(aa 31–358),hereafter referred to as tg E,was a homogenous monomer in solution and showed excellent antigenicity.Finally,we assessed and compared the immunogenicity of tg E with commercial v Oka LAV and Shingrix vaccine.We found that aluminum-adjuvanted tg E was immunogenic as compared with v Oka LAV.When adjuvanted with AS01B,a two-dose immunization of tg E showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage,especially in terms of the proportion of IFN-γ-expressing CD4^(+)T cells.In conclusion,this method of E.coli-mediate tg E expression offers a cost-effective and scalable strategy to generate an ideal VZV g E immunogen for the development of both varicella and zoster vaccines.

LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with Shingrix^(TM) in VZV-primed mice

Latent varicella-zoster virus(VZV)may be reactivated to cause herpes zoster,which affects one in three people during their lifetime.The currently available subunit vaccine Shingrix^(TM) is superior to the attenuated vaccine Zostavax®in terms of both safety and efficacy,but the supply of its key adjuvant component QS21 is limited.With ionizable lipid nanoparticles(LNPs)that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers,and oligodeoxynucleotides containing CpG motifs(CpG ODNs)approved by the FDA for a subunit hepatitis B vaccine as immunostimulators,we developed a LNP vaccine encapsulating VZV-glycoprotein E(gE)and CpG ODN,and compared its immunogenicity with Shingrix^(TM) in C57BL/6J mice.The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to Shingrix^(TM) as determined by enzymelinked immunosorbent assay(ELISA).Most importantly,the LNP vaccine induced comparable levels of cellmediated immunity(CMI)that plays decisive roles in the efficacy of zoster vaccines to Shingrix^(TM) in a VZVprimed mouse model that was adopted for preclinical studies of Shingrix^(TM) .Number of IL-2 and IFN-γsecreting splenocytes and proportion of T helper 1(Th1)cytokine-expressing CD4^(+)T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of Shingrix^(TM) boosted mice.All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities,indicating the potential of LNP-CpGadjuvanted VZV-gE as a more cost-effective zoster vaccine.

成人中枢神经系统水痘-带状疱疹病毒感染七例并文献复习

目的探讨成人中枢神经系统水痘-带状疱疹病毒(varicella-zoster virus,VZV)感染的临床特点及预后。方法选取2013年7月至2024年4月首都医科大学附属北京友谊医院的中枢神经系统VZV患者,收集患者的一般资料和临床资料,分析患者的临床特点及预后,并复习既往文献。结果共纳入7例患者,其中男6例、女1例;发病年龄35~94岁,平均65.1岁。7例均为急性或亚急性起病、伴发热,4例伴意识障碍,5例脑膜刺激征(+),4例伴肢体瘫痪、头痛、头晕,3例伴周围性面瘫,5例伴皮肤疱疹。脑脊液压力80~190 mmH2O(1 mmH2O=0.0098 kPa)、WBC 14~1039×106/L、蛋白40.38~444.43 mg/dl、葡萄糖2.34~6.01 mmol/L、氯化物108.90~125.00 mmol/L。脑脊液宏基因二代测序(metage⁃nomic next-generation sequencing,mNGS)检测的VZV病毒DNA序列数7~8869。影像学结果示脑干及小脑受累3例,颈髓受累1例,硬脑膜或脊膜强化3例,伴硬膜下积液或出血1例、伴急性脑梗死2例。治疗后,住院期间死亡1例(发病后4个月),好转出院6例;死亡2例(发病后1.5~10个月),好转4例(发病后6~63个月)。既往文献报道,成人中枢神经系统VZV感染患者有病情重、预后差,脑脊液葡萄糖降低、合并颅神经或周围神经或脑血管受累等表现,但未见合并硬脑膜强化的病例报道。结论成人中枢神经系统VZV感染患者年龄分布较广、青年至高龄老年均可见,脑脊液蛋白和WBC可明显升高,部分患者葡萄糖和氯化物降低,类似结核杆菌感染。脑膜脑实质多同时受累时病情危重,高龄者预后差。怀疑中枢神经系统VZV感染者应尽早完善腰穿、脑脊液mNGS等辅助检查,在早期诊断和治疗后规范应用抗病毒感染药物,以改善预后。

经脑脊液宏基因组二代测序确诊的水痘-带状疱疹病毒脑膜脑炎临床分析

目的 探讨水痘-带状疱疹病毒(VZV)脑膜脑炎患者的诊断方法及脑脊液检查特点。方法回顾性分析开封市中心医院收治的15例应用脑脊液二代测序诊断的VZV脑膜脑炎的临床特点及实验室检查结果并行临床分析。结果 15例VZV脑膜脑炎患者中,11例表现为头痛,发热7例,合并皮肤带状疱疹8例,面神经麻痹1例,认知功能障碍4例,癫痫发作2例。脑脊液结果:白细胞数轻-中度升高,以淋巴细胞为主,其中6例氯化物降低,5例乳酸增高。结论 VZV脑膜脑炎患者临床上多表现为头痛,合并发热、皮肤带状疱疹者较多。脑脊液宏基因组二代测序是诊断VZV脑膜脑炎的一种新的有效方法。中枢神经系统VZV主要表现为脑膜炎与脑膜脑炎,抗病毒治疗预后良好。

Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization

Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.

IFN-a production by human mononuclear cells infected with varicella-zoster virus through TLR9-dependent and-independent pathways

Understanding the defense mechanisms of the host of an organism is important for infection control.In previous studies,we demonstrated that interferon-a(IFN-a),but not IL-12,was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus(VZV).Here,we investigated what kind of cell(s)and which signal molecule(s)are involved in IFN-a production.Using cell isolation and ELISA,we found that plasmacytoid dendritic cells(pDCs)were responsible for IFN-a production during VZV infection.We also found that Toll-like receptor 9(TLR9)was involved in VZV-induced IFN-a production because inhibitory CpG oligodeoxynucleotide inhibited IFN-a production.UV-inactivated VZV-induced IFN-a production was lower than that of active VZV,indicating another TLR9-independent pathway.Further studies demonstrated that double-stranded RNA-dependent protein kinase,but not DNA-dependent protein kinase was involved in VZV-induced IFN-a production.Together,these results suggest that pDCs play an important role in IFN-a production during VZV infection through TLR9-dependent and-independent pathways.

Immune Responses to Varicella-Zoster Virus Glycoprotein E Formulated with Poly(Lactic-co-Glycolic Acid) Nanoparticles and Nucleic Acid Adjuvants in Mice

The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved.Based on poly(lactic-co-glycolic acid)(PLGA)delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion(w/o/w)solvent evaporation method,we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E(VZV-g E)as an antigen and nucleic acids including polyinosinic-polycytidylic acid(Poly I:C)and phosphodiester Cp G oligodeoxynucleotide(Cp G ODN),encapsulated as immune stimulators.While cationic lipids(DOTAP)have more potential than neutral lipids(DOPC)for activating g E-specific cell-mediated immunity(CMI)in immunized mice,especially when g E is encapsulated in and presented on the surface of nanoparticles,PLGA particles without lipids have the greatest potential to induce not only the highest g Especific Ig G titers but also the strongest g E-specific CMI responses,including the highest proportions of interferon-c(IFNc)-and interleukin-2(IL-2)-producing CD4?/CD8?T cells according to a flow cytometry assay and the greatest numbers of IFN-c-and IL-2-producing splenocytes according to an enzyme-linked immunospot(ELISPOT)assay.These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.

Complicated multiple organ infection of Purpureocillium lilacinum and varicella-zoster virus infection in a patient with Evans’ syndrome

Purpureocillium lilacinum(P lilacinum)is a rare pathogenic fungus,which mainly involves immunocompromised individuals.Here,we report a case of complicated multiple-organ infections involving skin,lungs,and spleen in a 63-year-old female with Evans’syndrome after 9 months of glucocorticoid treatment.Microbial examinations of skin biopsy and blood samples revealed Plilacinum infections.Posaconazole was effectivein this patient.During anti-fungitreatment,she developedvaricella-zoster virus infection and was diagnosed through next-generation sequencing examination.In conclusion,Plilacinum may affect different organ systems and is susceptible to posaconazole treatment.The molecular-based methods like microbial cell-free DNA sequencing could provide accurate and timely identification of a wide range of infections.

北京株水痘活疫苗的研制

选择处于对数生长期的人胎肺二倍体细胞（2BS），接种北京-7株水痘-带状疱疹病毒．待受染病毒的细胞出现CPE时，将维持液换为不含牛血清的MEM。接种后的2M细胞，培育36～38小时即可收获较高满度的病毒。采用pH7．2～7．4含25％山梨醇作保护剂、以6000r／min离心30分钟除去病毒液中的细胞碎片，制成减毒活疫苗。

香菊流浸膏对水痘─带状疱疹病毒抑制作用的实验研究

采用细胞培养技术，通过五种不同的给药途径，观察香菊流浸膏对分离的水痘－带状疱疹病毒的实验室抑制作用。结果证实香菊流浸膏对水痘－带状疱疹病毒复制的每一环节均有不同程度的抑制作用。

江西省水痘-带状疱疹病毒基因特征研究

目的了解江西省2010至2013年流行的水痘-带状疱疹病毒的基因型别。方法选取2010年至2013年南昌市的水痘-带状疱疹临床诊断病例,采集疱疹液和(或)咽拭子标本,提取水痘病毒DNA,对病毒基因组的ORF22区及ORF68区进行扩增、测序和分析,将测序结果与Gene Bank的VZV参考株的基因序列进行比较。结果采集到的84份标本中共有55份检测到水痘-带状疱疹病毒核酸;ORF22区的测序结果经与水痘带状疱疹病毒J基因型的代表株p-Oka株及水痘疫苗代表株v-Oka株的基因序列进行对比,发现6个关键位点完全相同;对ORF68区的测序结果进行比对并未发现任何突变。结论江西省2010-2013年流行性的水痘-带状疱疹病毒均为J基因型。

北京市通州区健康人群水痘带状疱疹病毒抗体水平分析

目的了解北京市通州区健康人群水痘带状疱疹病毒(varicella-zoster virus,VZV)抗体水平,为传染病的预防控制提供科学依据。方法采用随机抽样的原则抽取通州区10个居委会,选择在当地连续居住6个月以上的健康人群为调查对象,通过问卷调查、查阅预防接种证和北京市免疫规划信息管理系统收集研究对象基本信息和疫苗免疫史,采用酶联免疫吸附试验检测水痘IgG抗体。率的比较用χ^(2)检验,不同组间抗体浓度的比较采用非参数秩和检验结果共调查894人,总VZV-IgG阳性率为66.78%(597/894),VZV-IgG浓度中位数为328.46 mIU/mL,各年龄组健康人群VZV-IgG阳性率为3.53%~98.81%,随着年龄增长,抗体阳性率越高。各年龄组抗体浓度中位数在42.27~1961.09 mIU/mL之间,随着年龄的增长,浓度先增高后降低,不同年龄组抗体水平差异有统计学意义(χ^(2)=181.542,P<0.001;Z=273.911,P<0.001)。15岁以下儿童阳性率和浓度中位数较低,分别为3.53%~61.90%和9.67~187.45 mIU/mL。结论通州区水痘的主要易感人群为15岁以下儿童,为水痘防控的重点人群。