Detection of varicella-zoster virus-specific IgA antibodies in varicella and zoster patients and in healthy adults of various ages by solid-phase radioimmunoassay

The varicella-zoster virus(VZV)-specific serum immunoglobulin A(IgA) response was studied in varicella and zoster patients and in healthy adults of various ages by a sensitive solid-phase radioimmunoassay technique. Significant rises in VZV-specific IgA titer were found for both varicella and zoster patients, while VZV-specific IgA was also detected in greater than 90% of healthy adults but at lower titers. No significant decrease in VZV-specific IgA titer with increasing age was found. The role of humoral versus cell-mediated immunity in VZV reactivation is discussed.     

Antibodies against herpes simplex virus in a group of healthy humans without reactions to herpes simplex virus antigens in blasttransformation assays

22 healthy individuals with different reactions in humoral and cell-mediated immunity to herpes simplex virus (HSV), as found in complement-fixation, neutralization, and blasttransformation assays have been further investigated using antibody-dependent cell-mediated immunity (ADCC) as a serological test. Sera from all individuals were absorbed on HSV-infected, varicella zoster virus (VZV)-infected or uninfected cell monolayers, before they were used in ADCC with HSV-infected cells, as target. The results with absorbed sera were compared with the results from unabsorbed sera. Fresh uninactivated sera have also been used in some of the investigations. By these experiments a group of individuals was found, who were HSV-positive in ADCC, but negative in all other, above-mentioned tests. Because of these reactions they are proposed to be HSV-positives without a latent infection.     

A varicella outbreak in B-cell lymphoma patients receiving rituximab-containing chemotherapy

Varicella, characterized by a vesicular rash, occurs primarily in young children. Although older individuals can also be affected or vaccinated, outbreaks among adults are rare. We investigated a small outbreak of varicella in B-cell lymphoma patients for elucidation of risk factor of the disease. We experienced four cases of varicella after an index herpes zoster case. All varicella cases were confirmed varicella zoster virus (VZV) infection by PCR. All varicella cases occurred in diffuse large B-cell lymphoma patients receiving rituximab-containing chemotherapy. On the other hand, only three of the 18 non-varicella patients in the same room were receiving rituximab-containing chemotherapy (P = 0.005). All varicella patients had detectable serum anti-varicella zoster virus IgG antibodies before chemotherapy. Even in the presence of neutralizing antibodies to the virus, lymphoma patients treated with rituximab-containing chemotherapy can possibly become re-infected with varicella. These findings suggest that zoster patients should be strictly isolated in hematology and oncology ward, and prophylactic acyclovir should be considered for such patients when exposed to zoster/varicella.     

The etiologic agents of varicella and herpes zoster; serologic studies with the viruses as propagated in vitro

The preparation of antigenic materials capable of specific fixation of complement in the presence of convalescent phase sera from patients with varicella and herpes zoster is described. Satisfactory antigens were obtained by the repetitive harvest and subsequent concentration of the pooled nutrient fluids from bottle cultures of human embryonic skin-muscle tissue or of monkey kidney tissue infected with varicella or herpes zoster viruses. Specific fixation of complement was also demonstrated with antigens prepared from extracts of the infected cell sheets harvested from bottle cultures. In individuals with varicella, complement-fixing antibody usually appeared in the serum 4 or 5 days after the development of the exanthem and further significant increases in titer were characteristically observed during the 2nd week of illness. The complement-fixing antibody response in herpes zoster tended to follow the same pattern as in varicella, with the exception that in sera from some individuals relatively high titers were present in the acute phase specimen. Complement-fixing antigens prepared from varicella strains or from a zoster strain reacted to essentially the same degree with convalescent sera from the homologous and the heterologous clinical entities. The varicella-zoster antigens did not fix complement in the presence of paired sera obtained from a limited number of individuals with primary infections due to herpes simplex virus or from individuals with generalized vaccinia infection. Specific inhibition in vitro of the focal cytopathic process produced by the varicella-zoster viruses was demonstrated. This was accomplished by the incorporation of the sera under test as constituents of nutrient media of the cultures, either prior to or at the time of their inoculation with virus. The neutralization of focal cytopathogenicity thus obtained was relative in degree and never absolute; it was therefore assayed by repetitive counts of the number of focal lesions per culture in the various test groups. Inhibition of varicella-zoster viral cytopathogenicity occurred in the presence of convalescent serum from either clinical entity. The results of the immunologic studies with the viruses of herpes zoster and varicella as propagated in vitro are considered as providing further evidence in support of the concept of the close relationship and probable identity of the two agents.     

面神经炎与抗水痘-带状疱疹病毒抗体的相关性探讨

目的　通过比较面神经炎患者与正常对照之间的抗水痘 带状疱疹病毒抗体滴度的差异以及面神经炎患者在不同疾病阶段的抗水痘 带状疱疹病毒抗体滴度变化 ,探讨抗水痘 带状疱疹病毒抗体与面神经炎之间的关联。方法　用酶标记葡萄球菌A蛋白 (SPA)染色法对 11例面神经炎患者及 2 6例正常人血清中抗水痘 带状疱疹病毒 (VZV)抗体进行检测 ,还对其中 6名患者进行了发病早期及 2周后的血清抗VZV抗体检测。结果　面神经炎患者组的抗VZV抗体滴度显著高于对照组 (P <0 .0 5 ) ;在 6例患者的不同疾病阶段测得的抗体滴度中 ,3例患者在发病 2周后抗体滴度比发病初期增加 4倍以上 ,1例增加 2倍 ,2例无改变。结论　抗VZV抗体滴度与面神经炎的发病相关 ,提示VZV感染可能是面神经炎的致病因素之一。     

Myths and Misconceptions: Varicella-Zoster Virus Exposure,Infection Risks,Complications, and Treatments

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

The interaction between human monocytes and red cells. Specificity for IgG subclasses and IgG fragments

Studies were carried out in order to characterize the specificity of IgG sub-classes and IgG fragments for rosette formation using red cells and human mononuclear cells. Rosette formation of red cells coated with anti-D was inhibited by free IgG₁ and IgG₃; less inhibition occurred with IgG₂ and IgG₄. Red cells specifically coated with IgG₁ and IgG₃ by chromic chloride were bound to monocytes. Rosette inhibition of anti-D-coated red cells occurred with free Fc fragment of IgG globulin, and only partly with F(ab'')₂. Inhibitory capacity of Fc fragments of IgG and γ₁ heavy chain from heavy chain disease was reversed by the cleavage of disulfide bonds. No inhibition was noted with Fab, or with pepsin components II, III, or IV. These studies indicated that the mononuclear receptor was specific for IgG₁ and IgG₃. The peptide portion of IgG globulin which attached to the mononuclear cell appeared to reside in the N-terminal portion of the Fc fragment and also appeared to require the integrity of the inter-heavy chain disulfide bond. A specific receptor for C3 was not confirmed.     

SYNTHESIS,ASSEMBLY, AND SECRETION OF GAMMA GLOBULIN BY MOUSE MYELOMA CELLS : III. ASSEMBLY OF THE THREE SUBCLASSES OF IGG

The synthesis, assembly, and secretion of the three major subclasses of mouse IgG has been examined in 14 myeloma tumors and two cultured cell lines as well as in the cells from the popliteal lymph nodes of immunized mice. The total amount of IgG synthesized was between 15 and 43% of the cytoplasmic proteins made during a 15 min period. H₂ and H₂L were the major precursors of IgG_2a and IgG₁ but, in all of the tumors, HL was also an intermediate. In contrast, HL was a major precursor of IgG_2b. Most of the noncovalent and covalent assembly of IgG occurred after release of the newly synthesized H and L chains from the polyribosomes and assembly was not completed until 10 min or more after the synthesis of the polypeptide chains.     

2017年北京地区水痘病原学监测结果分析

目的了解北京地区水痘–带状疱疹病毒（VZV）毒株类型及优势流行亚型，为水痘暴发疫情的防治提供依据。方法收集2017年北京地区水痘暴发疫情病例的疱疹液标本。 采用实时荧光PCR方法，进行VZV及野毒株和疫苗株鉴定，根据VZV第22个开放阅读框基因片段序列，确定北京地区VZV进化关系。结果2017年共收集到水痘病例标本316份，VZV病毒核酸阳性271份，阳性率为85.76%，均为野毒株。 共获得240份VZV基因片段，其中234株毒株是clade2型，占97.50%，3株clade1型和3株clade4型，分别占1.25%。 其中clade2型分布在北京地区16个区（县），clade1型和clade4型分别分布在西城区和大兴区。结论2017年北京地区水痘病例主要由clade2型VZV引起，同时对新出现的clade1型和clade4型要加强监测。     

Disseminated fusariosis emerged from prolonged local genital infection after cord blood transplantation

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.     

Varicella zoster virus antigens in the epidermis of patients with herpes zoster before and after treatment with acyclovir: an immunohistochemical study

Using a monoclonal antibody to varicella zoster virus (VZV), an immunohistochemical study was performed before and after treatment with acyclovir (750 mg/day intravenously for 5 - 7 days) to investigate the distribution of VZV antigens in the epidermis of four in-patients with herpes zoster, and to correlate their presence with clinical manifestations of the disease. Biopsy specimens were obtained from epidermal lesions on admission to hospital prior to acyclovir administration, and again following treatment. In all cases, VZV antigens were found extensively in the erythematous and vesicular lesions before treatment, but they were not detected 5 - 7 days later in the ulcerative, crusted or pigmented lesions after acyclovir therapy. Further controlled studies will be necessary to compare the distribution of epidermal VZV antigens in acyclovir-treated patients with that in a placebo group to determine whether the loss of VZV antigens was due to acyclovir or to a natural decrease over time.     

Immunology of Varicella Immunization in the elderly

OBJECTIVE: To review the varicella-zoster virus (VZV) and herpes zoster disease and to summarize published reports on the use of the live-attenuated varicella zoster vaccine to enhance cell-mediated immunity in elderly individuals. DATA SOURCE: A MEDLINE search (1966-August 1999) for English-language clinical studies and review articles pertaining to VZV and the live-attenuated varicella vaccine was conducted; references obtained from these publications were subsequently reviewed for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: Representative clinical trials were summarized and relevant information was selected to assist in the understanding of VZV, the subsequent immune response, and the live-attenuated varicella vaccine. DATA SYNTHESIS: The physiologic, age-related decline in VZV cell-mediated immunity has been shown to be restored on administration of live-attenuated varicella vaccine. Various studies report serum anti-VZV antibody concentrations, and production of interferon-gamma were increased following vaccination. Concentrations subsequently returned to baseline one year after vaccination. Increase in responder cell frequency, a measure of cell-mediated immunity, has been reported to last up to four years after vaccination, at concentrations similar or superior to those observed following herpes zoster. CONCLUSIONS: Enhancement of cell-mediated immune response in elderly individuals through vaccination with live-attenuated varicella vaccine is a possible measure to protect this population from herpes zoster and to attenuate its complications. A summary of immunogenicity studies to identify the immune response to live-attenuated varicella vaccine in the elderly is presented. The absolute clinical significance, as well as appropriate administration guidelines of this prophylactic intervention, will become evident following forthcoming large, masked, placebo-controlled trials.     

Human herpesvirus 6 (HHV-6): incidence in healthy blood donors and in patients with acute infections caused by other herpes viruses

Antibodies to HHV-6 were detected by immunofluorescence in 8.04% of 460 healthy blood donors in West Austria. Testing sera from patients with acute or reactivated infections with other herpesviruses, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and varicella zoster virus (VZV) we observed a remarkably higher prevalence of antibodies to HHV-6 in patients with CMV infections (75%) and also in patients with EBV infections (50%). Patients with HSV and VZV infections were positive for HHV 6 in 12.5% and 6.6% of cases, respectively. Many of the patients with CMV infection were transplant recipients. The high incidence of positive HH 6 serology in these patients could be due to new infection by HHV 6 or to the reactivation of a previous infection with HHV 6 by means of allogenic cell stimulation. Furthermore, preliminary results from our laboratory point to a serological cross-reaction between HHV 6 and CMV, which may also contribute to this result.     

Varicella zoster virus meningoencephalitis accompanied by sporadic skin lesions in an older immunocompetent adult

A previously healthy 75-year-old man complained of persistent fever, headache, nausea, mild gait disturbance, memory disorder, and sporadic vesicular skin lesions. Viral meningoencephalitis was diagnosed, based on cerebrospinal fluid (CSF) analysis. Intensive CSF analysis suggested that the patient's illness was caused by varicella zoster virus (VZV). The patient recovered completely after treatment with intravenous acyclovir. VZV infection should be considered as a possible cause of central nervous system disease, even in an immunocompetent patient. VZV reactivation was strongly suspected because of the results of anti-VZV antibody evaluations in serum and CSF, although the skin lesions were not similar to those of herpes zoster.     

Severe Thrombocytopenia in Aged Rhesus Macaques (Macaca mulatta) Infected with Simian Varicella Virus

Simian varicella virus was diagnosed in 2 geriatric rhesus macaques (Macaca mulatta). The macaques presented with typical skin lesions as well as severe thrombocytopenia as a result of infection. Idiopathic thrombocytopenic purpura is a known complication of varicella zoster virus infection in humans; however, this condition has not been reported previously as a complication of SVV infection. This case report discusses the clinical presentation, pathology, and thrombocytopenia of the affected macaques.Abbreviation: DIC, disseminated intravascular coagulation; ITP,idiopathic thrombocytopenic purpura; McHV1,Macacine herpesvirus 1; MV, measles virus; SVV, simian varicella virus; VZV, varicella zoster virusSimian varicella virus (SVV; Cercopithecine herpesvirus 9) is an alphaherpesvirus that causes vesicular dermatitis with occasional disseminated infection in susceptible species of nonhuman primates. SVV shares 70% to 75% homology with the varicella zoster virus (VZV), the causative agent of chickenpox in humans.⁷ The 2 diseases share many comparable features, including clinical presentation, pathogenesis, and pathologic lesions. Despite these similarities, the viruses are species specific with SVV affecting Old World monkeys and VZV affecting humans and, occasionally, great apes.² Both viruses result in latent infection of the neural ganglia with the potential for reactivation at a later date.⁶ Secondary reactivated varicella disease in humans is termed shingles, which is characterized by a unilateral vesicular rash limited to the area of skin innervated by one to 3 dermatomes, while reactivated disease in nonhuman primates appears as a generalized rash similar to initial disease presentation.¹³Idiopathic thrombocytopenic purpura is a complication of viral disease in humans, commonly following infection with VZV, rubella, Epstein–Barr virus, influenza, and HIV.¹¹ Idiopathic thrombocytopenic purpura is characterized clinically by bruising and petechial hemorrhage of the skin with a significant reduction in platelet number. However, a similar syndrome after infection of macaques with SVV has not been described previously.In July 2009, 2 cases of simian varicella presented at a nonhuman primate research facility housing on average 300 nonhuman primates comprised of approximately 80 olive baboons and 100 rhesus, 100 cynomolgus, and 20 stumptail macaques. The following report describes the clinical presentation and thrombocytopenia that developed as a consequence of SVV infection.     

Specific humoral response to cows’ milk proteins and ovalbumin in children with atopic dermatitis

Summary Serum antibodies to four common food antigens, three cows’ milk proteins (casein, α-lactalbumin and β-lactoglobulin) and ovalbumin, were investigated in 21 children with atopic dermatitis (aged 3 months to 3 years) and in 15 age-matched healthy controls. Specific IgE was measured by radioallergosorbent test; an ELISA was developed to detect specific IgG, IgG subclasses and IgA. Specific IgE was found in 76% of patients, while antigen-directed IgG and IgA were present both in patients and healthy controls; IgG to ovalbumin and IgA to α-lactalbumin were significantly higher in children with atopic dermatitis. The analysis of the IgG subclass distribution showed different patterns of response, IgG1 and IgG4 being higher in patients (even though statistically significant only for ovalbumin), and IgG2 and IgG3 being lower in this group. The presence of food-specific IgE in the majority of atopic children and the different specific IgG subclass patterns observed in patients and controls may reflect an alteration in the immune response to dietary proteins in atopic dermatitis.     

Enzyme-linked immunosorbent assay for detection of virus-specific IgM antibodies to varicella-zoster virus

A sensitive enzyme-linked immunosorbent assay (ELISA) is described for detection of varicella-zoster virus (VZV) IgM antibodies. The antigen consisted of a sonically disrupted extract of VZV-infected human embryo cells. The tested sera were absorbed with Staphylococcus aureus (strain Cowan I) before analysis. Rabbit anti-human IgM peroxidase conjugate was used to detect human IgM bound to viral antigen. The results were compared with those obtained by the indirect fluorescent antibody to membrane antigen (IFAMA) technique. Comparison of titers obtained by ELISA with those obtained by IFAMA for sera of chickenpox patients showed agreement between the results in 8 of 9 patients. In 1 chickenpox patient, no VZV IgM antibodies could be detected by IFAMA, while a titer of 3,200 was obtained by ELISA. The ELISA technique described gave titers more than 100 times higher than those obtained by IFAMA. VZV IgM antibody was detected by ELISA and IFAMA in only 1 of 5 zoster patients. No VZV IgM antibodies were found by ELISA in 45 control sera (healthy adults and hospitalized patients with various other diseases). Neither were they found in paired sera of 6 patients with acute herpes simplex infections, 2 patients with Epstein-Barr virus infections, and 3 patients with human cytomegalovirus infections.     

Antibody response after varicella vaccination in children treated with budesonide inhalation suspension or non-steroidal conventional asthma therapy

We evaluated if budesonide inhalation suspension (BIS) reduces the immunogenicity of the varicella vaccine in paediatric patients with asthma. This open‐label, parallel‐group, cohort study included varicella‐naïve (disease and vaccine) children aged 12 months to 8 years with asthma requiring therapy. Patients who received ≥ 4 weeks of asthma treatment with BIS 0.25–1 mg daily or non‐steroidal conventional asthma therapy (NSCAT) daily or as needed and met eligibility requirements received the varicella vaccine (Varivax^®) and continued the same asthma treatment for ≥ 8 weeks postvaccination. Varicella‐zoster virus (VZV) antibody levels were assessed before and 6 weeks after vaccination using a glycoprotein enzyme‐linked immunosorbent assay (gpELISA). Adverse events (AEs) were assessed throughout the study. Antibody levels were analysed in 243 of 274 patients who were vaccinated and received treatment. After immunisation, the percentage of patients in each group achieving a ‘protective’ level of VZV antibody (≥ 5 gpELISA units/ml) was similar: 85% (129/151) in the BIS group and 90% (83/92) in the NSCAT group (relative risk = 0.95; 95% confidence interval 0.86–1.04). Eight patients in each group reported AEs related to varicella vaccination (primarily pyrexia, agitation and injection‐site reactions). There were no cases of severe varicella in either group; one case of mild varicella‐like rash was reported in a 12‐month‐old child in the NSCAT group 11 days after vaccination. VZV antibody responses and tolerability to the live varicella vaccine in paediatric asthma patients treated with BIS vs. NSCAT were comparable, demonstrating that young children with asthma receiving nebulised BIS can be immunised effectively with Varivax.     

Analysis of repeat units in the R2 region among different Oka varicella-zoster virus vaccine strains and wild-type strains in Germany

OBJECTIVE: The present study compared the number of R2 repeat units in six different Oka strains and in 54 varicella-zoster virus (VZV) wild-type strains isolated from patients with varicella or zoster in Germany. METHODS: The R2 genomic region was characterized by polymerase chain reaction and sequencing methods. RESULTS: Five VZV Oka vaccine strains showed a number of seven 42-bp units and, in one, eight repeats were found. In 11 VZV wild-type strains isolated from patients with varicella, the copy number ranged between four and eight, and in 43 strains from zoster a similar range between four and nine copies was observed. About 80% of all strains showed between five and seven repeated units. More than one third of strains revealed seven repeats like Oka. CONCLUSIONS: The size of the R2 repeat region can also be different in single Oka vaccine strains. In German VZV wild-type strains, the R2 fragment seems to be not as variable as in Japanese wild-type strains.     

Serodiagnosis of herpes encephalitis by indirect enzyme-linked immunosorbent assay,experience from a Swedish antiviral trial

Analysis of IgM/IgG/IgA antibody class activity to herpes simplex (HSV), measles and varicella zoster (VZV) antigen by indirect enzyme-linked immunosorbent assays has been applied to the cerebrospinal fluid and serum from 127 cases of focal encephalitis—39 patients with and 88 patietns without biopsy/necropsy.Results indicative of herpes etiology were found in 53 cases. Intrathecal antibody production was found in all CSF samples taken beyound the tenth day after the onset of neurological illness with one exception—a boy treated with acyclovir for a primary infection within 20 hours after the onset of illness. Intrathecal HSV antibody response was of IgG class in 94%, IgM class in 70% and IgA in 94%.In primary infections, the HSV IgM CSF response was high and contributed to an early diagnosis; in recurrent infections it was often at a low level and late. HSV IgM persisted from 60 to 328 days, IgG and IgA during observation times to 678 days. Cross-reactivity with varicellae zoster was found to be restricted to IgG only.