Varicella-zoster Virus Antibody Research Articles

Use and Limitations of Varicella‐Zoster Virus–Specific Serological Testing to Evaluate Breakthrough Disease in Vaccinees and to Screen for Susceptibility to Varicella

A plethora of tests for determining the presence of antibodies to varicella-zoster virus (VZV) have been developed over the years, with a wide range of performance standards. There is general agreement that the presence of VZV antibodies in serum indicates immunity to varicella and protection from chickenpox, although the role of specific antibody in mediating protection remains unclear. Both antibodies and cellular immunity probably interact to mediate immunity to the virus. In any case, VZV-specific serum antibody is a useful indicator of protection against chickenpox in patients and persons at high risk of exposure, whether they have been immunized or naturally infected. Serological tests are also a useful implement for evaluating the length of time that immunity to varicella persists after vaccination and whether waning of vaccine-induced immunity occurs. The purpose of this review is to contrast the strengths and weaknesses of currently available VZV antibody assays. Although several of these methods are useful for various specific applications, simpler and more accurate tests to measure antibodies to VZV are a high priority for future research and development.

Serology and serum DNA detection in shingles.

To investigate the sensitivity of various laboratory approaches in the diagnosis of herpes zoster from patient serum. Paired sera from 53 consecutive adult patients with acute herpes zoster were tested for the presence of varicella-zoster virus (VZV) antibodies. All acute sera were tested subsequently by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. In addition, convalescent sera of patients who tested initially positive for VZV DNA underwent PCR analysis. VZV IgM antibodies were found by enzyme immunoassay (EIA) in 5 acute (9%) and 20 convalescent (38%) zoster sera. VZV DNA was detected by PCR in 21 (40%) acute zoster sera and was no longer detectable in the convalescent samples. A seroconversion or a fourfold or greater titre increase was found by complement fixation (CF) test in 41 (77%), by IgG indirect fluorescent antibody assay (IgG IFA) in 43 (81%) and by CF and IgG IFA combined in 45 of 53 (85%) paired zoster sera. The combination of all serological methods detected 51 (96%) and PCR combined with serology identified 52 (98%) of 53 patients. Optimal laboratory sensitivity in the diagnosis of herpes zoster from serum can be achieved by the combination of PCR and serology of paired serum samples. Serological methods alone are of limited value for early diagnosis of zoster when therapy can be initiated, because CF and IgG IFA need convalescent serum and IgM test sensitivity is insufficient. Early diagnosis of VZV reactivation is possible from serum by PCR in the first days of illness and test sensitivity needs further improvement. The findings highlight the need for future studies into the usefulness of PCR and serology in atypical cases of VZV reactivation.

Serology and serum DNA detection in shingles.

To investigate the sensitivity of various laboratory approaches in the diagnosis of herpes zoster from patient serum. Paired sera from 53 consecutive adult patients with acute herpes zoster were tested for the presence of varicella-zoster virus (VZV) antibodies. All acute sera were tested subsequently by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. In addition, convalescent sera of patients who tested initially positive for VZV DNA underwent PCR analysis. VZV IgM antibodies were found by enzyme immunoassay (EIA) in 5 acute (9%) and 20 convalescent (38%) zoster sera. VZV DNA was detected by PCR in 21 (40%) acute zoster sera and was no longer detectable in the convalescent samples. A seroconversion or a fourfold or greater titre increase was found by complement fixation (CF) test in 41 (77%), by IgG indirect fluorescent antibody assay (IgG IFA) in 43 (81%) and by CF and IgG IFA combined in 45 of 53 (85%) paired zoster sera. The combination of all serological methods detected 51 (96%) and PCR combined with serology identified 52 (98%) of 53 patients. Optimal laboratory sensitivity in the diagnosis of herpes zoster from serum can be achieved by the combination of PCR and serology of paired serum samples. Serological methods alone are of limited value for early diagnosis of zoster when therapy can be initiated, because CF and IgG IFA need convalescent serum and IgM test sensitivity is insufficient. Early diagnosis of VZV reactivation is possible from serum by PCR in the first days of illness and test sensitivity needs further improvement. The findings highlight the need for future studies into the usefulness of PCR and serology in atypical cases of VZV reactivation.

Live Attenuated Measles, Mumps, Rubella, and Varicella Zoster Virus Vaccine (Priorix-Tetra™)

The live attenuated tetravalent vaccine against measles, mumps, rubella, and varicella zoster viruses (MMRV) is a combination of the measles, mumps, and rubella (MMR) vaccine and the varicella zoster virus vaccine. The immunogenicity after each dose of a two-dose vaccination course of MMRV vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster vaccines, or a single dose of separately administered MMR plus varicella zoster vaccines followed by a dose of MMR vaccine, in infants aged 9-24 months. In infants aged 9-24 months administered a two-dose course of MMRV vaccine, geometric mean titers for antibodies against all vaccine antigens increased after the second dose relative to the first dose, with the increase being most pronounced for varicella zoster virus antibodies (10- to 21-fold). MMRV as the second vaccination was immunogenic in children aged 5-6 years who had previously received either MMRV or MMR as the first vaccination at 12-24 months of age. The immunogenicity for measles, mumps, rubella, and varicella zoster viruses, in terms of seropositivity and antibody titers, was not altered when MMRV was coadministered with a booster dose of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b conjugate vaccine in infants aged 12-23 months. Nor was the immunogenicity of the latter vaccine altered by coadministration. The tolerability profile of MMRV vaccine was comparable to that of separately administered MMR plus varicella zoster vaccines or of MMR vaccine alone. Injection-site redness and fever (rectal temperature > or =38degreesC or axillary temperature > or =37.5degreesC) were the most frequent adverse events in both groups.

Unilateral associated laryngeal paralysis due to varicella-zoster virus: virus antibody testing and videofluoroscopic findings

The relationship between varicella-zoster virus and idiopathic associated laryngeal paralysis was examined in five patients, using complement fixation or enzyme immunoassay testing. In all cases, significant changes in serum levels of varicella-zoster virus antibody were observed. Videofluoroscopy was useful in assessing the severity of the dysphagia and in making an accurate diagnosis; both laryngeal elevation and weakness of pharyngeal wall contraction were also observed. In two cases in which antiviral therapy was delayed, the outcome was poor, with increased levels of varicella-zoster virus immunoglobulin M found on enzyme immunoassay. The outcome of the condition may thus depend both on the speed of antiviral therapy commencement following onset of symptoms, and on the levels of varicella-zoster virus immunoglobulin M antibody (measured by enzyme immunoassay). Our study suggests that varicella-zoster virus should be considered in the differential diagnosis of patients with idiopathic associated laryngeal paralysis, and rapid antiviral therapy should be initiated when necessary.

Safety and Immunogenicity Profile of the Concomitant Administration of ZOSTAVAX and Inactivated Influenza Vaccine in Adults Aged 50 and Older

To evaluate the safety and immunogenicity of ZOSTAVAX administered concomitantly with inactivated influenza vaccine or sequentially in adults aged 50 and older. Randomized, blinded, placebo-controlled study. Thirteen U.S. and seven European study sites. Three hundred eighty-two concomitantly, 380 sequentially vaccinated subjects. The concomitant vaccination group received influenza vaccine and ZOSTAVAX at separate injection sites on Day 1 and placebo at Week 4. The nonconcomitant vaccination group received influenza vaccine and placebo at separate injection sites on Day 1 and ZOSTAVAX at Week 4. Primary safety endpoints: vaccine-related serious adverse experiences (AEs) within 28 days postvaccination (PV); and diary card-prompted local and systemic AEs. Primary immunogenicity endpoints: geometric mean titer (GMT) and geometric mean fold rise (GMFR) from baseline of varicella-zoster virus (VZV) antibody (Ab) at 4 weeks PV according to glycoprotein enzyme-linked immunosorbent assay (gpELISA) and GMT of influenza Ab for the three vaccine strains (2005-2006 influenza season) at 4 weeks PV according to hemagglutination inhibition assay. Secondary immunogenicity endpoint: influenza seroconversion rates (SCRs). No serious AEs related to ZOSTAVAX were observed during the study. VZV Ab GMTs 4 weeks PV for the concomitant and sequential groups were 554 and 597 gpELISA U/mL, respectively. The estimated VZV Ab GMT ratio was 0.9 (95% confidence interval (CI)=0.8-1.0), indicating noninferior (P<.001 for the null hypothesis of GMT ratio <0.67) responses. Estimated VZV Ab GMFR from baseline in the concomitant group was 2.1 (95% CI=2.0-2.3), indicating acceptable fold rise. Estimated GMT ratios (concomitant/sequential) for influenza strains A(H1N1), A(H3N2), and B were 0.9 (95% CI=0.8-1.1), 1.1 (95% CI=0.9-1.3), and 0.9 (95% CI=0.8-1.1), respectively, and SCRs were comparable across both groups, with more than 85% achieving titers of 1:40 or greater, meeting regulatory criteria. ZOSTAVAX and influenza vaccine given concomitantly are generally well tolerated in adults aged 50 and older. Ab responses were similar whether ZOSTAVAX and influenza vaccine were given concomitantly or sequentially.

The comparative sero-epidemiology of varicella zoster virus in 11 countries in the European region

The European sero-epidemiology network (ESEN2) aims to standardise serological surveillance of varicella zoster virus (VZV) in 11 participant countries. In each country, serum banks were collected between 1996 and 2003 and tested for VZV antibodies. Assay results were standardised so that international comparisons could be made. Age-specific forces of infection were calculated for three age groups (<5, 5–9 and ≥10 years of age) and used to estimate the base reproduction number ( R 0) and the herd immunity threshold ( H). Most VZV infection occurred in childhood, but there was a wide variation in transmissibility, with R 0 ranging from 16.9 in the Netherlands to 3.3 in Italy. Herd immunity thresholds varied from 70% in Italy to 94% in the Netherlands. There are substantial differences in VZV sero-epidemiology within the European region, which will need to be taken into account in designing national policies regarding VZV vaccination.

Immunogenicity of Oka/Merck Varicella Vaccine in Children Vaccinated at 12–14 Months of Age Versus 15–23 Months of Age

Recent reports suggest that breakthrough varicella may be more common in children when the Oka/Merck varicella vaccine is given at 12-14 months of age than when it is given at older ages. An analysis of 5 postlicensure clinical trials with this vaccine was conducted to evaluate immune response relative to the age of the vaccine recipient. In 5 clinical trials, 3771 children, 12 through 23 months of age with no history of varicella, received an injection of varicella vaccine. Varicella-zoster virus (VZV) antibody was measured 6 weeks postvaccination by glycoprotein enzyme-linked immunosorbent assay (gpELISA), an assay that correlates with neutralizing antibody. Endpoints evaluated were the response rate (percent of subjects with VZV antibody > or =5 gpELISA units/mL, a titer shown to correlate with protection) and geometric mean titer (GMT) of VZV antibody. Each endpoint was compared across 3 age groups (12-14, 15-17, and 18-23 months of age). Response rates by initial VZV serostatus were evaluated for children vaccinated at 12-14 months of age to assess whether maternal antibody had an impact on the immune response. The response rates were similar among 12-14, 15-17, and 18-23 month olds (93.8, 90.8, and 93.1%, respectively); GMTs were significantly higher among the 12-14 month olds (15.1, 13.5, and 13.7 gpELISA units/mL, respectively). Among children 12-14 months of age, response rates and GMTs were similar regardless of their prevaccination VZV serostatus. Oka/Merck varicella vaccine is highly immunogenic when given to children 12-14 months of age. The immunogenicity profile is similar to that of children 15-17 and 18-23 months of age. The presence of low titers of VZV antibody before vaccination did not influence vaccine response in 12-14 month olds. These results support current recommendations for universal varicella vaccination beginning at 12 months of age.

Clinical Diagnosis of Herpes Zoster in Family Practice

Family physicians usually diagnose herpes zoster on clinical grounds only, possibly resulting in false-positive diagnoses and unnecessary treatment. We wanted to determine the positive predictive value of the physicians' judgment in diagnosing herpes zoster and to assess the applicability of dried blood spot analysis for diagnosis of herpes zoster in family practice. Our study population consisted of 272 patients older than 50 years with herpes zoster (rash for less than 7 days). Dried blood spot samples were collected from all patients and sent by mail to the laboratory. Baseline measurements included clinical signs (localization, severity, and duration of rash) and symptoms (duration and severity of pain). Varicella-zoster virus antibodies were determined at baseline and 5 to 10 days later. Multivariate logistic regression was used to assess independent associations between clinical variables and serological confirmation of herpes zoster. Dried blood spot analysis was possible in 260 patients (96%). In 236 the diagnosis of herpes zoster was confirmed serologically (positive predictive value of clinical judgment 90.8%; 95% confidence interval, 87.3%-94.3%). Independent clinical variables for serologically confirmed herpes zoster were severity and duration of rash at first examination. Family physicians have good clinical judgment when diagnosing herpes zoster in older patients. Dried blood spot analysis is a logistically convenient method for serological investigation of patients in family practice, but it is rarely needed for diagnosing herpes zoster.

Susceptibility to varicella in childbearing age women, Central Italy: Is there a need for vaccinating this population group?

We conducted a cross-sectional seroprevalence study of varicella-zoster virus (VZV) antibodies in childbearing age women aged 17-42 years. Sera were collected in Central Italy in years 2001-2002 and were tested by a commercial VZV IgG enzyme immunoassay. Overall VZV seroprevalence was 80.9% and it showed a significant increase by age, confirming a considerable circulation of VZV also in the older age groups not commonly considered at high risk. This study further supports the importance of vaccinating susceptible adolescents and women of childbearing age in order to reduce both maternal and foetal complications associated with varicella in pregnancy.

Comparison of the Safety and Immunogenicity of a Refrigerator-Stable Versus a Frozen Formulation of ProQuad (Measles, Mumps, Rubella, and Varicella Virus Vaccine Live)

A refrigerator-stable formulation of ProQuad has been developed to expand the utility of ProQuad to areas in which maintenance of a frozen cold chain (-15 degrees C or colder) during storage and transport may not be feasible. The objective of this study was to demonstrate that the immunogenicity and safety profiles of a refrigerator-stable formulation of ProQuad are similar to the recently licensed frozen formulation. In this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either the refrigerator-stable formulation of ProQuad (N = 1006) or the frozen formulation of ProQuad (N = 513). Patients were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination. The refrigerator-stable formulation of ProQuad was generally well tolerated. The incidence of adverse experiences was similar between groups. No vaccine-related serious adverse experiences were reported. For both groups, the response rate was > or = 97.7% for measles, mumps, and rubella, and the percentage of patients with a varicella zoster virus antibody titer of > or = 5 U/mL glycoprotein antigen-based enzyme-linked immunosorbent assay after vaccination was > or = 88.8%. The geometric mean titers for all antigens were numerically slightly higher in patients who received the refrigerator-stable formulation. The refrigerator-stable formulation of ProQuad is generally well tolerated, highly immunogenic, and noninferior in terms of postvaccination antibody responses. This refrigerator-stable formulation may improve ease of vaccine administration, increase use of the vaccine throughout the world because of its improved storage conditions, and replace the frozen formulation of ProQuad or any dose of M-M-RII and Varivax in routine practice.

Seroprevalence of varicella antibodies among pregnant women in Lyon-France

The purpose of the study was to calculate the seroprevalence of immunity to the varicella-zoster virus (VZV) infection and to evaluate the positive predictive value (PPV) and the negative predictive value (NPV) of the self-reported history of VZV infection in pregnant women. A cross sectional study was conducted in 18 private medical analysis laboratories. Information on socio-demographic characteristics and past history of varicella or zoster were collected using a questionnaire. Blood samples were obtained to determine the serological levels of past exposure to VZV. Overall, 486 pregnant women were recruited. The seroprevalence of VZV antibodies was 98.8%. Six women were seronegative, of whom four were primiparous. The PPV was high (99.5%) while the NPV was only 10.3%. The PPV is a reliable marker of prior VZV infection. In contrast, a negative history does not predict lack of immunity and should be completed by serological analysis which might be introduced to routine antenatal blood tests.

The seroepidemiology of varicella zoster virus among pregnant Bangladeshi and white British women in the London Borough of Tower Hamlets, UK

We investigated the comparative seroepidemiology of varicella zoster virus (VZV) in pregnant women of two ethnic groups, white British and Bangladeshi, living in an inner city area of London, United Kingdom. Women aged 16-45 years were recruited from antenatal clinics of the Royal London Hospital in the Borough of Tower Hamlets. Complete data were obtained from 275 white British and 765 Bangladeshi women. VZV antibody prevalence was 93.1% (95% CI 89.4-95.8) and 86.0% (95% CI 83.3-88.4) respectively. Women who were born in Bangladesh and lived there at least until the age of 15 years had the lowest odds of being immune (OR 0.37, 95% CI 0.22-0.63). This implies they will have an increased risk of varicella during pregnancy. Women arriving in the United Kingdom in adulthood should be screened routinely during pregnancy and vaccination offered postpartum if they are susceptible.

Analysis of factors associated with varicella-zoster virus susceptibility among children 0–12 years old in Taiwan

Objectives Varicella is a highly infectious disease caused by varicella-zoster virus (VZV). The aim of this study was to explore the geographical difference of VZV antibody seroprevalence among children in private vaccination areas in Taiwan, controlling for potential factors relating to varicella susceptibility. Patients and method A cross-sectional survey of the seroprevalence of VZV antibodies among children 0–12 years of age was conducted in Taiwan between August and December 2003. Sera of children visiting the outpatient unit of the participating hospitals around the island were collected. Six hundred and fifty-six parents among those of the 931 children studied agreed to answer the self-administered questionnaire regarding the possible factors associated with varicella susceptibility. IgG antibodies to VZV were measured using an enzyme-linked immunosorbent assay kit, Enzygnost anti VZV/IgG. Results The susceptibility was the highest at age 1 year, and then decreased as the age increased. Children living in southern and eastern Taiwan showed higher susceptibility to varicella than those living in northern area (odds ratio (OR) = 2.71 and 2.10, respectively). Prior history of varicella infection, varicella vaccination, and contact with cases remained to be associated with the susceptibility after multivariate analysis. Conclusions Children who lived in tropical and rural regions and those who had no history of varicella infection, varicella vaccination, and contact with cases, might be more susceptible to varicella. Island-wide VZV seroprevalence surveillance is required to examine whether the geographical difference of susceptibility in Taiwan will become less significant or disappear after the mass varicella vaccination program initiated in 2004.

Safety and immunogenicity of a zoster vaccine in varicella-zoster virus seronegative and low-seropositive healthy adults

Objective To evaluate immunogenicity and tolerability of a live attenuated zoster vaccine in varicella-zoster virus (VZV) seronegative or low-seropositive adults ≥30 years of age. Study design Double-blind, placebo-controlled, randomized, multicenter study. Subjects were enrolled in two stages by prescreened serostatus. Subjects with a low VZV antibody titer (≤5 gpELISA units/mL) were enrolled in Stage 1. Subjects with undetecable VZV antibodies and no safety issues identified during Stage 1 were enrolled in Stage 2. All enrolled subjects were randomized 4:1 to receive one dose (∼50,000 PFU) of zoster vaccine or placebo and were followed for safety for 42 days postvaccination. Primary objectives/hypotheses: (1) no vaccine-related serious adverse experiences (AE); (2) ≤1 laboratory-confirmed varicella-like rash with >50 lesions within 42 days postvaccination. Secondary objective: summarize the VZV antibody response postvaccination. Results Twenty-one subjects (age 27 to 69 years; median 34) enrolled (1148 prescreened); 18 (including 4 seronegative subjects) received vaccine and 3 (including 1 seronegative subject) received placebo. Twenty subjects completed the study; one subject withdrew for reasons unrelated to safety. No serious vaccine-related AE or laboratory-confirmed varicella-like rashes with >50 lesions were reported. In the zoster vaccine group, all 4 of the initially seronegative subjects (age 32 to 36 years; median 33.5) seroconverted and 6 of the 13 (46.2%) initially seropositive subjects had a ≥4-fold rise in VZV-specific antibody titer at 6 weeks postvaccination. Conclusions The zoster vaccine appears to be immunogenic and generally well tolerated in healthy adults ≥30 years of age, regardless of initial VZV antibody serostatus.

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 > or = 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 > or = 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 (> or = 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.

Loss of Varicella Zoster Virus Antibodies Despite Detectable Cell Mediated Immunity after Vaccination

Vaccination of children against VZV has been included in the recommendations of the "permanent committee of vaccination" (STIKO; Ständige Impfkommission of the Robert Koch Institute, Berlin, Germany) in July 2004. Due to this recommendation the medical practitioner and the laboratories will be confronted with the problem of serologic non-responders or loss of humoral immunity more frequently. Here we report the case of a Varicella Zoster Virus (VZV) vaccinee, who lost detectable VZV antibodies although she had a persisting VZV specific CD4 cellular immune response. We compare these parameters to the VZV specific CD4 T cell responses of VZV seronegative and seropositive healthy persons, as well as patients with VZV disease. VZV specific CD4 frequencies of VZV antibody seronegative persons remained on the average below 0.1% (median 0.04%, +/- SD 0.03, range 0.01-0.08%) and were significantly lower than VZV specific frequencies of seropositive healthy persons (median 0.3%, +/- SD 0.24, range 0.06-0.81%; Mann-Whitney U-test p = 0.001). The samples of patients with VZV associated disease showed an even higher median level of VZV specific CD4 cell response than the VZV seropositive healthy persons (median 1.04%, +/- SD 1.06, range 0.51-2.92%, Mann-Whitney U-test p = 0.008). The VZV specific immune response of the health care worker directly after vaccination was comparable to the VZV specific immunity in VZV seropositive healthy adults. Despite serological reconversion 1.5 years later the VZV specific CD4 response still remained measurable and positive. The new general VZV vaccination recommendation for children in Germany will probably increase the number of persons that will be seronegative after vaccination. To gain more information concerning the absence of seroconversion or the loss of immunity, it will be necessary to focus future post-VZV vaccination immunity studies not only on serologic testing but also on the measuring of the cell mediated immunity.

Seroepidemiology of Varicella zoster in Israel Prior to Large-scale Use of Varicella Vaccines

This large-scale study provides up-to-date estimates of Varicella zoster virus (VZV) age-specific seroprevalence and characteristics of VZV transmission in a representative sample of the Israeli population. In 2000-2001, 1,642 sera collected from an agestratified general population sample were tested for VZV antibodies using an indirect IgG ELISA system. The age-weighted VZV overall estimate was 90.2%. Seropositivity increased rapidly with age, from 68.9% at age 4 to 94.4% at age 7 and 96.6% at age 12 years. The highest force of infection was in the 4-5 years age group (0.548 per susceptible year) followed by the 6-9 years age group. Multivariate analysis revealed that VZV seroprevalence estimates were significantly associated with age and place of origin. The highest seroprevalence estimate was found among subjects of Eastern origin. The seroepidemiology of VZV in Israel shows a pattern corresponding to that described for developed European countries. This study indicates that the highest force of infection is in pre-school children. Knowledge of pre-vaccination seroepidemiology is important to evaluate the effect of vaccination programs on the epidemiology of the disease.

Increased Susceptibility to Varicella‐Zoster Virus among Israeli Physicians and Nurses Born in the Middle‐East Region

Nosocomial transmission of varicella-zoster virus (VZV) is recognized as a significant cause of morbidity in health care workers as well as in high-risk patients. The current study aimed to investigate the presence of VZV antibodies among physicians and nurses, to assess the variables affecting it, and to compare it with previous international studies. Data were obtained by a questionnaire regarding sociodemographic and occupational characteristics and by determination of serum antibodies to varicella-zoster. The seroprevalence of varicella-zoster among the 335 study participants was 94.8% (95%CI: 91.9%-96.9%), with no significant difference between nurses (94%) and physicians (97%). Decreased risk for the virus was observed in workers who immigrated to Israel from the Asia or Africa (OR=0.15; 95% CI: 0.04-0.51). Reduced immunity among these workers remained significant in a multivariate model, which also included age, gender, years of education, number of siblings, and crowding at childhood. Our data suggest that in spite of the high immunity among Israeli physicians and nurses in general, the implementation of small-scale vaccination programs aimed at workers from warmer and tropical areas, should be seriously considered.

Administration of Live Varicella Vaccine to HIV‐Infected Children with Current or Past Significant Depression of CD4+T Cells

Varicella can be a severe illness in human immunodeficiency virus (HIV)-infected children. The licensed, live attenuated varicella vaccine is safe and immunogenic in HIV-infected children with minimal symptoms and good preservation of CD4(+) T cells (Centers for Disease Control and Prevention immunologic category 1). To study the safety and immunogenicity of this vaccine in varicella-zoster virus (VZV)-naive, HIV-infected children with moderate symptoms and/or more pronounced past or current decreases in CD4(+) T cell counts, such children (age, 1-8 years) received 2 doses of vaccine 3 months apart. The children were observed in a structured fashion for adverse events. Blood was tested for VZV antibody and VZV-specific cell-mediated immunity (CMI) at baseline, 8 weeks after each dose, and annually for 3 years. Subjects who had no evidence of immunity 1 year after vaccination received a third dose and were retested. The vaccine was well tolerated; there were no vaccine-related, serious adverse events. Regardless of immunologic category, at least 79% of HIV-infected vaccine recipients developed VZV-specific antibody and/or CMI 2 months after 2 doses of vaccine, and 83% were responders 1 year after vaccination. HIV-infected children with a CD4(+) T cell percentage of > or =15% and a CD4(+) T cell count of > or =200 cells/ microL are likely to benefit from receiving varicella vaccine.