Calibration and Evaluation of Quantitative Antibody Titers for Varicella-Zoster Virus by Use of the BioPlex 2200.

Most commercially available enzyme immunoassay-based methods have limited sensitivity to detect antibody responses to varicella-zoster virus (VZV) in vaccinated individuals, who produce lower antibody levels than those with natural infection. However, more sensitive methods are either not commercially available or less amenable to high-throughput testing. The BioPlex 2200 measles, mumps, rubella, and varicella (MMRV) IgG assay (Bio-Rad Laboratories, Hercules, CA) is an automated high-throughput platform based on the microsphere Luminex technology that measures antibodies against measles, mumps, rubella, and varicella viruses simultaneously. Although it has U.S. Food and Drug Administration approval as a qualitative diagnostic test for measles, mumps, rubella, and varicella virus immunity, in this study, we have validated the assay to produce quantitative titers (off label) against the VaccZyme VZV glycoprotein (VZVgp) low-level IgG kit (The Binding Site Ltd., Birmingham, UK) using the World Health Organization international standard. Here, we show that the BioPlex 2200 MMRV IgG assay has sensitivity superior to that of the Zeus enzyme-linked immunosorbent assay (ELISA) VZV IgG assay (Zeus Diagnostics, Branchburg, NJ). Using receiver operating characteristic (ROC) analysis and adjusting the cutoff levels, we improved the sensitivity of the quantitative BioPlex 2200 MMRV IgG assay to 97.4%, while maintaining 100% specificity.

Varicella zoster virus transmission dynamics in Vojvodina, Serbia.

This study aimed at establishing baseline key epidemiological parameters for varicella zoster virus (VZV) infection in Vojvodina, Serbia, with the ultimate goal to quantify the VZV transmission potential in the population. Seroprevalence data generated during the first large cross-sectional VZV serosurvey were modelled, using a two-tiered modelling approach to calculate age-specific forces of infection (FOI), the basic reproduction number (R0) and herd immunity threshold (H). Seroprevalence and modelling data were compared with corresponding pre-vaccination epidemiological parameters from 11 countries participating in the European Sero-Epidemiology Network 2 (ESEN2) project. Serbia fits into the general dynamic VZV transmission patterns in Europe in the pre-vaccine era, with estimated R0 = 4.12, (95% CI: 2.69-7.07) and H = 0.76 (95% CI: 0.63-0.86). The highest VZV transmission occurs among preschool children, as evidenced by the estimation of the highest FOI (0.22, 95% CI: 0.11-0.34) in the 0.5-4 age group, with a peak FOI of 0.25 at 2.23 years. Seroprevalence was consistently lower in 5-14 year-olds, resulting in considerable shares of VZV-susceptible adolescents (7.3%), and young adults (6%), resembling the situation in a minority of European countries. The obtained key epidemiological parameters showed most intense VZV transmission in preschool children aged <4 years, justifying the consideration of universal childhood immunization in the future. National immunization strategy should consider programs for VZV serologic screening and immunization of susceptible groups, including adolescents and women of reproductive age. This work is an important milestone towards the evaluation of varicella immunization policy options in Serbia.

Seroprevalence of antibodies against varicella zoster virus and rubella virus among newly recruited expatriate healthcare workers: a cross-sectional study.

OBJECTIVES: To assess the state of immunity to varicella zoster virus (VZV) and rubella virus (RV) among newly recruited healthcare workers (HCWs) in Kuwait before they begin work, and to determine whether there are differences in the prevalence of seronegativity according to nationality, gender, age group and occupation group. SETTING: This cross-sectional study involved analysis of blood samples from workers newly recruited to the Kuwaiti healthcare system. PARTICIPANTS: All new non- national HCWs recruited during the study period (n=1540). INTERVENTION: Enzyme-linked immunoassays for VZV-specific and RV-specific IgG were performed. RESULTS: Among HCWs, 81.9% and 93.5% were immune to VZV and RV, respectively. Male seronegativity was higher than that of females for both viruses. Regarding VZV, the majority of seronegative individuals were Indians (23.5%), followed by Somalis (12.5), Filipinos (6.5) and Egyptians (5.4%); the between-group differences were significant for all groups. The age groups 20-30 and 30-40 years were most likely to be seronegative, with prevalences of 18.2% and 18.9%, respectively. VZV seronegativity was most common among nurses (21.1%) and least common among physicians (9.2%), and the difference was significant. In addition, RV seronegativity was most frequent among Somalis (12.5%) and lowest among Indians (5.3%); other nationalities (Egyptian, Filipino and others) ranged between 9.1% and 9.6%. Seronegative individuals were most frequently in the younger age group (<20 years old) (17.5%), followed by the >40 years old group (10.4%). RV seronegativity was highest among nurses (6.9%) and lowest among physicians (5.2%). CONCLUSION: The prevalence of seronegativity is highest among Indians for VZV and Somalis for RV, and HCWs aged 20-40 years for VZV and <20 years for RV. For both viruses, the seronegativity rate was highest for male HCWs, and for nurses compared with other HCWs, with physicians having the lowest prevalence of both viruses.

Association between false-positive TORCH and antiphospholipid antibodies in healthy pregnant women.

The present study investigated: (a) the presence of antiphospholipid antibodies and (b) the obstetric outcome in healthy pregnant women showing false-positive TORCH-Toxoplasmosis, Other: syphilis, varicella-zoster, Rubella, Cytomegalovirus (CMV), and Herpes infections-results. Data from 23 singleton healthy pregnancies with false-positive TORCH results were collected. Each woman was systematically screened for TORCH IgG and IgM during the pre-conception assessment and/or at the beginning of pregnancy. In the presence of IgM positivity, when indicated (CMV, toxoplasmosis, rubella, herpes simplex virus), IgG avidity was evaluated and, if possible, polymerase chain reaction was performed on an amniotic fluid sample in order to distinguish between primary infection or false positivity. The antiphospholipid antibodies tests were: lupus anticoagulant, anticardiolipin antibodies IgG, IgM, and anti-ß2glicoprotein I IgG, IgM. The antiphospholipid antibodies tests, if positive, were repeated after 12 weeks to confirm the results. In pregnant women with false-positive TORCH, the overall prevalence of positive antiphospholipid antibodies for one or more tests was 52.2%. To clarify the correlation of false-positive TORCH results with clinical practice, obstetric outcome was analyzed in terms of live births, week of delivery, neonatal birth weight, and neonatal birth weight percentile. A statistically significant lower neonatal birth weight and neonatal birth weight percentile were observed in women with false-positive TORCH associated with antiphospholipid antibodies positivity (Group A) in comparison with those in women with false-positive TORCH without antiphospholipid antibodies positivity (Group B). No statistically significant difference was found for the week of delivery between the two groups. It is hoped that future studies will verify the life-long persistence of antiphospholipid antibodies positivity by follow-up of these women and identify who will develop a classical antiphospholipid syndrome or other autoimmune disorders.