Specific immunoglobulin responses after varicella and herpes zoster.

The indirect immunofluorescence technique has been used to titrate the specific immunoglobulins in 200 sera from 64 patients with varicella, and 195 sera from 67 patients with herpes zoster. IgG and IgM antibodies were detected in all patients with varicella, and IgA in 59 (92%). All three classes of antibody appeared 2--5 days after the onset of the rash, increased virtually simultaneously and reached maximum titres during the second and third weeks. IgG then declined slowly, but never became undetectable and was still present in five subjects who were retested after 2--4 years; it was present in 88 out of 100 healthy young adults and probably persists indefinitely after varicella. IgA and IgM antibodies declined more rapidly and were not detected in specimens taken more than a year after the illness. IgA, however, may possibly persist in some cases since low titres were found in 8 out of 88 young adults who possessed IgG antibody and had presumably had varicella in the past. IgA responses were significantly weaker in children under the age of 6 years than in older children and adults. Six out of 67 patients with zoster were tested at various times before the onset of the rash: IgG antibody was detected in all. IgG was present in all sera taken after the onset of the rash, increased rapidly after 2--5 days, reached maximum titres during the second and third weeks and then declined slowly. IgA antibody was detected in 66 patients (99%) and IgM in 52 (78%); both types of antibody followed transient courses, as in varicella. Maximum titres of IgG and complement-fixing antibodies were greater after zoster than after varicella, but the differences were not significant. IgA and IgM titres in young adults with zoster were significantly lower than in older patients, and also lower than in young adults with varicella. Increases in varicella-zoster antibody in patients with herpes simplex virus infections consisted mainly of IgG, sometimes IgA, but never IgM.     

国产和进口水痘疫苗免疫效果对比研究

[目的 ]　比较国产和进口水痘疫苗免疫效果 ,了解宝山区儿童水痘—带状疱疹病毒 (VZV)自然感染情况。　[方法 ]　随机选择 2 6 5名无水痘病史的 0～ 7岁儿童调查血清抗VZV -IgG阳性率 ;选择 84名 1～ 2岁VZV易感儿童随机分成两组 ,分别接种国产和进口水痘疫苗 ,免疫后 6周采血 ,用酶联免疫吸附试验检测抗VZV -IgG。　 [结果 ]　 1～ 7岁儿童抗VZV -IgG阳性率分别为 2 .0 0 %、11.11%、2 0 .0 0 %、17.6 5 %、30 .77%、40 .0 0 %、32 .14 % ;免前抗VZV -IgG阴性儿童 ,分别接种国产和进口水痘疫苗后 ,抗体阳转率分别为 90 .70 % ( 39/43)和 95 .12 % ( 39/41) ,两者差别无显著性 ;两种疫苗的抗VZV-IgG几何平均滴度倒数 (GMRT)分别为 2 0 4.848( 95 %CI190 .73～ 2 6 0 4.79)和 482 .6 9( 95 %CI93.30～ 2 497.5 ) ,进口疫苗GMRT略高于国产疫苗。　 [结论 ]　宝山区婴幼儿 6个月内部分存在VZV -IgG母体免疫 ,7个月后母体免疫消失 ;国产水痘疫苗免疫效果良好 ,本区 1～ 7岁儿童是易感人群 ,尤其是 1～ 4岁易感儿童适宜接种     

Humoral and cellular response after varicella vaccination in VZV IgG seronegative kidney transplant candidates

BackgroundIn immunocompromised patients, primary infection with VZV may have a disastrous clinical course. Vaccination of VZV-seronegative patients on the waiting list for renal transplantation may prevent severe disease. However, the immunologic response of end-stage renal disease patients to peptide vaccines is far from optimal. Our question was whether end-stage renal disease patients with undetectable VZV-IgG levels were able to mount an adequate humoral and cellular response to a live attenuated varicella vaccine.MethodsKidney transplant candidates with undetectable VZV levels were vaccinated twice with a live attenuated varicella vaccine at an interval of 6 weeks. VZV IgG levels were analysed till 2 years after vaccination. The VZV-specific T-cell reactivity was determined prior to vaccination and after transplantation.ResultsSeventy-seven percent (40/52) of the vaccinees reached positive VZV-IgG levels after vaccination (responders). Eighty-two percent (9/11) showed an increase in VZV-specific CD4⁺ memory T-cells (both central and effector memory cells). The percentage VZV-specific CD8⁺ memory T-cells did not increase. None of the non-responders suffered from primary VZV after transplantation. No severe vaccine-related adverse events were reported, only spontaneously resolving local skin irritation.ConclusionThe live attenuated varicella vaccine evokes positive VZV IgG-levels and VZV-specific memory T-cells in VZV-seronegative potential kidney transplant candidates.     

Case report: occupationally related recurrent varicella (chickenpox) in a hospital nurse

Commonly accepted outcomes of varicella-zoster virus (VZV) infections include chickenpox (primary) and shingles (recurrence or latency), as well lifetime immunity against chickenpox. We report the case of a registered nurse who worked in a neurologic surgery ward in a general hospital in Taipei, Taiwan. While working there for approximately 1 year, she developed recurrent chickenpox after caring for a paraparesis patient, who had herpes zoster during hospitalization in August 2002. The varicella incubation period was 10 days, which matched the range (10-21 days). Recently negative specific serum IgM and positive specific serum IgG indicated a past VZV infection. The nurse did not get herpes zoster from the second episode of varicella on 9 August 2002 to 4 April 2005 and is now convalescing. We conclude that occupational VZV hazards exist in the health care environment and suggest testing for VZV antibody and a VZV vaccination program for susceptible health care workers. Key words: chickenpox, indirect fluroscent antibody, occupational exposure, polymerase chain reaction, shingles, Taiwan, varicella-zoster virus.     

Detection of specific IgM in varicella and herpes zoster by antibody-capture radioimmunoassay

A simple and sensitive M antibody-capture radioimmunoassay (MACRIA) is described which utilizes crude commercial VZV antigen and a single monoclonal anti-VZV antibody. This was compared to the immunofluorescence (IF) test for IgM antibody and was used to study IgM responses in sera from 261 patients with varicella and 220 patients with herpes zoster. With MACRIA, IgM antibodies were detected in all patients with varicella. The IgM antibodies appeared shortly after onset of rash, reached peak levels between 1 and 4 weeks after onset and then declined to low or undetectable levels in most, though not all, patients after 3 months. IgM antibodies were also detected in 98.2% of patients with herpes zoster, but the levels of IgM were significantly lower than after varicella and there was wider individual variation both in magnitude and duration of the IgM responses, in some cases only lasting 2-3 weeks. Comparison between MACRIA and IF showed good agreement in the detection of IgM antibodies following varicella. Discordant results were obtained with 13% of sera, of which 81% were taken either early or late after onset of rash and contained very low IgM levels. In contrast, 62 (28%) of the 220 sera from patients with zoster gave discordant results in the two tests, all except five being MACRIA-positive but IF-negative. The largest proportion of discordant results were obtained with sera taken more than 3 months after onset of rash, but 18 (29%) contained high IgM levels and were taken during the period of peak IgM responses. The diagnostic applications of the VZV MACRIA are discussed.     

The postmarketing safety profile of varicella vaccine

The postmarketing safety profile of varicella vaccine was evaluated by analyzing selected adverse experience reports temporally associated with the administration of the vaccine. There were 7963 reports voluntarily submitted to Merck for an overall reporting rate of 5.0 per 10000 doses of vaccine distributed. A varicella zoster virus (VZV) identification program detected the presence of the Oka vaccine strain in three individuals with an immune deficiency - two with pneumonia and one with hepatitis - and in three instances of secondary transmission from vaccinees with vesicular lesions to susceptible household contacts. The Oka vaccine strain was present in 23 patients and wild-type VZV was present in 15 patients with herpes zoster. Vesicular rashes that occurred within 2 weeks of vaccination were more likely to contain the presence of wild-type VZV, while vesicular rashes that occurred more than 2 weeks post-vaccination were more likely to contain the Oka vaccine strain. Eleven patients were hospitalized with complications of breakthrough varicella infection.     

水痘疫苗及其免疫策略

水痘是由水痘-带状疱疹病毒(VZV)引起的儿童期高度传染性疾病。世界各地都有发生。VZV初次感染后可在体内建立潜伏感染,以后可被激活引起带状疱疹。1974年研制成功的水痘减毒活疫苗对预防和控制水痘有着重要作用。该文介绍了水痘疫苗的由来、安全性、免疫效果和免疫策略等。     

Responses of varicella zoster virus (VZV)-specific immunity in seropositive adults after inhalation of inactivated or live attenuated varicella vaccine

To examine boostering of varicella zoster virus (VZV)-specific immunity in seropositive adults after nasal inhalation of heat-inactivated or live attenuated varicella vaccine, we determined specific cellular immunity, IgG antibody in sera and secretory IgA antibody in saliva before and after the inhalation. The mean titers in specific IgG antibody and skin test findings significantly increased following inhalation of both vaccines. However, the ratio of a two-fold or more increase in the levels of IgG antibody or skin test did not show significant difference after inhalation of the inactivated vaccine in comparison with those in the control. After inhalation of the live vaccine, the ratio showed significant difference but transmission of the live vaccine virus to others was suspected. No significant increase in VZV-secretory IgA antibody levels in saliva was noted following inhalation. The results of this study suggested that nasal inhalation of the live vaccine could increase specific immunity in adults. This method would be similar to the natural infection and simpler than subcutaneous injection.     

An analysis of infection control of varicella-zoster virus infections in Addenbrooke's Hospital Cambridge over a 5-year period, 1987-92.

This prospective study analyses infections with varicella-zoster virus (VZV) in Addenbrooke''s Hospital, Cambridge during 1987-92 and examines the spread of infection. In total, 93 patients and staff experienced VZV infection. Twenty-one patients had varicella and 49 experienced zoster. None of 101 patients and 1 of 625 staff members in contact with varicella cases acquired infection. By contrast, 2 of 227 patients, and 5 of 1039 staff in contact with zoster cases acquired varicella. One out of 28 (3.6%) VZV antibody-negative patients and staff in contact with varicella acquired infection, compared with 5 out of 29 (17.2%) VZV antibody-negative patients and staff in contact with zoster. Thus, zoster was found to be a more frequent cause of nosocomial infection than varicella. Fourteen members of staff had VZV infection during the study period. One of 99 patients and none of 389 staff members in contact with these cases developed varicella. The cost of dealing with infection control for VZV infections in our hospital is estimated to be Pounds 714 per patient case and a total of Pounds 13,204 per year.     

Clinicopathologic understanding and control of varicella-zoster virus infection

As reflections by the recipient for the Japanese society for vaccinology Takahashi award, clinicopathologic understanding and control of varicella-zoster virus (VZV) infection was briefly reviewed. In 1974, a live varicella vaccine was developed by attenuating the Oka strain of VZV after the passages in non-human cells at a low temperature. The vaccine was immunogenic, well tolerated, and effective, and distributed worldwide so far. For post-exposure prophylaxis of varicella, the vaccine and acyclovir is effectively used in the incubation period of varicella. The delayed type hypersensitivity to VZV skin test antigen was applied for evaluation of cell-mediated immunity to VZV which is commercially available in Japan. The biphasic viremia during incubation period of varicella and airborne spread of VZV from varicella patients and from herpes zoster patients with localized lesions were shown by the virus isolation or by detection of the virus DNA.     

Use of hospitalization and pharmaceutical prescribing data to compare the prevaccination burden of varicella and herpes zoster in Australia

The aims of the study were to compare the burden of varicella and herpes zoster in Australia. No national surveillance exists for varicella or herpes zoster. We used hospital morbidity data from 1993-9 and pharmaceutical prescribing data from 1995-9. In the financial year 1998/99, there were 4718 hospitalizations for zoster compared to 1991 for varicella. For varicella the mean age of patients was 15 years compared to 69 years for zoster. The mean length of stay in hospital was 4.2 days for varicella and 12.7 days for zoster. Varicella accounted for 8396 (3726 with principal diagnosis varicella) bed days compared to 26 266 (5382 with principal diagnosis of zoster) for zoster. The in-hospital case-fatality rate was 0.4% for varicella and 1% for zoster. In 1999, 59 200 community-based cases of zoster were treated with antivirals. We estimate that 157 266 cases of zoster occurred in the community in 1999, a rate of 830 per 100 000 population. Herpes zoster has a higher burden of disease than varicella, and must be a component of disease surveillance in order to determine the full impact of vaccination on the epidemiology of varicella zoster virus (VZV).     

The burden and cost of hospitalised varicella and zoster in Australian children

BACKGROUND: Economic analyses of varicella-zoster virus (VZV) immunisation are sensitive to the costs of hospitalised cases, so there is a need to validate VZV hospitalisation data. AIMS: To assess the accuracy of hospital VZV coding data and to apply these parameters to a population-based sample to estimate incidence and costs. METHODS: A 3-year retrospective chart review from one hospital to document clinical features and validate coding data. A separate 9-year analysis of discharge data from two hospitals draining a defined region of suburban Melbourne, with adjustment for miscoding and estimates of direct hospital costs. RESULTS: After correction for miscoding, 224 patients were admitted to one hospital over 3 years, 79% with varicella and 21% with zoster. Miscoding resulted in a 15% underestimate of zoster cases and a 4% overestimate of varicella cases. Thirty-six percent of varicella admissions compared to 80% of zoster admissions were immunocompromised and/or had chronic disease. Compared to otherwise-healthy patients, immunocompromised patients were admitted earlier in their illness and had lower complication rates. Forty-two percent of immunocompromised/chronic disease patients with varicella had a known exposure, usually from a family member. The incidence of hospitalised varicella and zoster in under 15-year olds was 15.7 and 1.8 per 100,000 per year, respectively. This suggests that there are 615 varicella hospitalisations and 72 zoster hospitalisations in this age group each year in Australia, at a total direct cost of over 2.2 million AU dollars. CONCLUSION: These results highlight the considerable burden of hospitalised zoster and the importance of immunising non-immune contacts of immunocompromised individuals. They also support previous estimates of the incidence of hospitalised varicella in Australian children and adolescents, although direct medical costs may be higher than those previously estimated.     

Summary of the multidisciplinary guideline 'Varicella'

The multidisciplinary guideline 'Varicella' provides guidelines for diagnosis, therapy, and prevention of chickenpox. At the first pregnancy check, patients should be questioned about previous chickenpox; in case of a negative or doubtful history varicella zoster virus (VZV) serology is indicated. VZV antibody determination is also indicated in patients considered for immunosuppressive therapy and for healthcare workers with a negative VZV history who are in contact with immunocompromised patients. Administration of VZV immunoglobulin within 96 hours following VZV contact can mitigate the infection in pregnant women and patients with T-cell deficiency. VZV immunoglobulin treatment should be considered for newborn infants of mothers who developed chickenpox in the period from five days before to two days after delivery. Antivirals can reduce the severity of infection and are safe during pregnancy. Varicella vaccine protects against chickenpox, but is contraindicated in immunocompromised patients and pregnant women.     

Impact and costs of varicella prevention in a university hospital.

Information regarding all patient and staff exposures to varicella-zoster virus (VZV) was prospectively accumulated from 1/1/86 to 12/31/86 at North Carolina Memorial Hospital. During this period of time 37 sources of exposure to VZV were reported: 10 outside and 27 within the hospital. Index cases for nosocomial exposure included: 12 patients with zoster, 9 patients with varicella, two staff with varicella, three visitors with varicella, and one staff with zoster. One hundred and twenty patients received nosocomial exposures; 28 had no history of VZV infection (23 per cent), of whom 11 were serosusceptible (39 per cent). Sources of nosocomial patient exposure included: other patients (85 per cent), staff (14 per cent), and a single visitor (1 per cent). More than 300 employees received nosocomial exposure; 158 had no history of VZV infection, of whom 49 were serosusceptible (31 per cent). Only a single employee and no patients developed clinical varicella as a result of nosocomial exposure. Costs associated with VZV control during 1986 totaled $55,934: $39,658 for work furloughs, $9,800 for serologies, $4,293 for patient isolation, $155 for varicella-zoster immune globulin, and $2,028 for infection control personnel time. These costs should be considered as part of any benefit-cost analysis of varicella immunization of health care personnel.     

Production of IgM antibody to HHV6 in reactivation and primary infection

The cross-reaction of HHV6 antibody with that to the other herpesviruses was studied in 96 blood donors whose sera were tested for IgG antibody to human herpesvirus type 6 (HHV6), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zostervirus (VZV) and herpes simplex virus (HSV). No correlation was found between IgG antibody to HHV6 and that to any of the other herpesviruses in these individuals. Antibodies to HHV6 and CMV were measured in patients undergoing documented serological responses to HHV6. Eleven cases of primary HHV6 infection associated with roseola infantum in babies, 1 of whom suffered from gastroenteritis as well as pyrexia and rash, are reported. Three cases of HHV6 reactivation, 1 in a 3-year-old child and 2 in adults, 1 of whom simultaneously underwent a primary CMV infection are also reported. Our results suggest that indirect immunofluorescence is a specific way of measuring HHV6 antibody, that HHV6 IgG and IgM can be detected in the absence of antibody to CMV and that HHV6 IgM is present both in primary HHV6 infections and in reactivations.     

A cluster of primary varicella cases among healthcare workers with false-positive varicella zoster virus titers.

BACKGROUND: Five cases of primary varicella zoster virus (VZV) we re diagnosed among hospital healthcare workers (HCWs). All had complied with a pre-employment VZV screening program and had been considered immune. OBJECTIVES: To summarize the investigation of VZV among un-immunized HCWs and to provide recommendations for avoiding false-positive serologic tests. DESIGN: Risk of transmission of VZV to susceptible HCWs is minimized through serologic screening. Varicella vaccine is recommended for susceptible HCWs. A commercially available latex bead agglutination assay (LA) is widely used because it is rapid and easy to perform. LA was compared with the whole-cell varicella ELISA standardized in the Centers for Disease Control and Prevention (CDC) National Herpes Laboratory. SETTING/POPULATION: Large inner-city, tertiary-employee population. RESULTS: In a year, 5 HCWs presented with laboratory-confirmed primary varicella infection. Four had VZV exposures 2 weeks prior to presentation. All had documented positive VZV titers by LA performed at hire. None were offered VZV vaccination. The original LAs were judged false-positives. INTERVENTION/FOLLOW-UP INVESTIGATION: Fifty-three consecutive VZV LA samples from the hospital laboratory were retested at the CDC. Forty-four samples concurred. Of the remaining 9, 4 were positive by hospital LA but negative by CDC IgG ELISA. Four were equivocal by hospital LA but negative by CDC IgG ELISA and LA. One was positive by hospital LA but negative by LA and equivocal by ELISA at the CDC. CONCLUSION: LA may be prone to false-positive results and inappropriate for screening hospital HCWs.     

Live zoster vaccination in an immunocompromised patient leading to death secondary to disseminated varicella zoster virus infection

In 2016, the live attenuated zoster vaccine (Zostavax, Merck and Co, USA) was introduced into the Australian National Immunisation Program for people aged 70 years who are not significantly immunocompromised. We report the administration of Zostavax in an immunocompromised patient with chronic lymphocytic leukaemia and no evidence of primary varicella zoster virus (VZV) infection. The patient presented with a bilateral vesicular facial rash 22 days after receiving Zostavax and was initially managed as an outpatient with oral acyclovir. He re-presented three days later and was diagnosed with disseminated VZV infection complicated by meningoencephalitis. The patient died following cardiac arrest on day 10 of hospitalisation. This unfortunate case highlights the challenge of safely implementing a high titre live vaccine in a population where contraindications are prevalent. The non-live recombinant herpes zoster subunit vaccine (Shingrix, GSK) may provide a safe and effective option to protect immunocompromised patients from shingles and post-herpetic neuralgia.     

Varicella-zoster virus seroprevalence in nursery and day-care workers in Lyon (France)

OBJECTIVE: Varicella is a potential occupational hazard for susceptible individuals working in pediatric institutions because infected adults run a greater risk of severe or even fatal varicella and because the disease is so common in children and so contagious. The seroprevalence of varicella-zoster virus (VZV) was examined in a sample of day-care workers in Lyon (France) to determine whether a targeted vaccination policy was needed. METHODS: Two hundred forty-one sera were sampled and analysed with an Elisa test between March and May 2001. Histories of past VZV infection were collected via questionnaires documented either before or after consultation of medical records or other sources of information. RESULTS: The overall VZV seroprevalence was 99.6%. The positive predictive values of past varicella histories (documented or not) were>99% showing that a history of previous varicella in day-care workers was reliable. However, only 68 to 71% of these with serologically confirmed varicella reported a prior history of varicella. All subjects reporting a non-positive history of varicella were seropositive. CONCLUSIONS: Virtually all day-care workers enrolled in this study presented serological evidence of VZV so that sub-populations at risk for varicella infection for which VZV vaccination may be effective could not be identified. However, the VZV seroprevalence of the workers in pediatric institutions being presumably higher than that of the general adult population (94-96.3%), vaccination of susceptible young recruits before any exposure to the VZV, or even vaccination of students willing to work in a pediatric institution, may be positive.     

酶联免疫吸附试验间接法检测水痘带状疱疹病毒IgG抗体方法的建立及应用

以１号水痘带状疱疹病毒（ＶＺＶ１）为毒种,制备酶联免疫吸附试验特异抗原,并以Ｖｅｒｏ－Ｅ６基质细胞抗原作对照,用ＥＬＩＳＡ间接法测定ＶＺＶ ＩｇＧ抗体。方法特异性经中和试验、封闭性阻断试验,检测事实状疱疹病人双份血清抗体滴度比较证实;其敏感性比间接免疫荧光法（ＩＦＡ）高数十倍;重现性经４８份血清３次重复测定平均ＯＤ值无显著差异。与Ｂｉｏｓｅｅｄ抗ＶＺＶ抗体ＩｇＧ ＥＬＩＳＡ试剂盒测定结果比较阳性符     

一起护理带状疱疹患者所致医务人员水痘暴发的调查与处理

目的 明确一起护理带状疱疹患者所致医务人员水痘暴发事件的流行病学特征，为水痘和带状疱疹的医院感染防控提供依据。方法 对山东省烟台市某三级医院2018年12月重症监护病房（ICU）内临床诊断为水痘的医务人员进行流行病学调查，分析流行病学特征及发病原因。结果 2018年12月17-19日，该院ICU共报告4名医务人员罹患水痘，其中有3名护士、1名护工，潜伏期内均看护过2床的带状疱疹患者，且距发病最长潜伏期内未接触过其他水痘和（或）发热出疹病例，判断为一起护理带状疱疹引起的医务人员医院感染暴发事件，通过积极采取隔离、接种疫苗、培训等措施，处置及时，未出现后续病例。结论 带状疱疹患者作为水痘的传染源不容忽视，治疗护理时严格执行空气隔离、接触隔离、标准预防等措施，可有效防控水痘-带状疱疹病毒医院感染的发生。