The Screening of Rubella Virus, Cytomegalovirus, Hepatitis B Virus, and Toxoplasma gondii Antibodies in Prepregnancy and Reproductive-Age Women in Tabriz, Iran

Objectives. The organisms of Toxoplasma gondii, Rubella virus, Cytomegalovirus, and Herpes simplex virus as an acronym of TORCH are major pathogens in prepregnancy and reproductive-age women. These microorganisms are considered a serious problem and cause 2-3% of all birth defects in the fetus. Our study was aimed at screening the seroprevalence of TORCH antibodies among prepregnancy and reproductive-age women in Tabriz, Iran. Design and Setting. This study was carried out in 2726 prepregnancy and reproductive-age women, who were referred to the laboratory for prenatal TORCH screening. To detect the presence of IgG, IgM antibodies and Hepatitis B surface antigen against these microorganisms were carried out using a chemiluminescence immunoassay analyzer (CLIA). Results. In the current study, the rates of anti-Toxoplasma gondii IgG, anti-Rubella virus IgG, and anti-Cytomegalovirus IgG were found in 722 cases (26.5%), 2579 cases (94.6%0), and 2718 cases (99.7%), respectively. Moreover, the rates of anti-Toxoplasma gondii IgM, anti-Rubella virus IgM, and anti-Cytomegalovirus IgM were discovered in 10 cases (0.4%), 13 cases (0.5%), and 16 cases (0.6%), respectively. The Hepatitis B surface antigen was found in 32 cases (1.2%). The dissemination of positive TORCH in various ages was different ( P < 0.05 ). Conclusions. In our study, the seroprevalence of acute TORCH infections was relatively low. Due to the probability of vertical transmission to the fetus during pregnancy and the unpleasant complication of these pathogens, it is essential to be screened for detection of specific IgG and IgM antibodies in reproductive ages.

Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

A Study of the Impact of Graphene Oxide on Viral Infection Related to A549 and TC28a2 Human Cell Lines

Graphene has been one of the most tested materials since its discovery in 2004. It is known for its special properties, such as electrical conductivity, elasticity and flexibility, antimicrobial effect, and high biocompatibility with many mammal cells. In medicine, the antibacterial, antiviral, and antitumor properties of graphene have been tested as intensively as its drug carrying ability. In this study, the protective effect of graphene oxide against Rubella virus infection of human lung epithelial carcinoma cells and human chondrocyte cells was examined. Cells were incubated with graphene oxide alone and in combination with the Rubella virus. The cytopathic effect in two incubation time periods was measured using DAPI dye as a percentage value of the changed cells. It was shown that the graphene oxide alone has no cytopathic effect on any of tested cell lines, while the Rubella virus alone is highly cytopathic to the cells. However, in combination with the graphene oxide percentage of the changed cells, its cytotopathicity is significantly lower. Moreover, it can be concluded that graphene oxide has protective properties against the Rubella virus infection to cells, lowering its cytopathic changes to the human cells.

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages

Macrophages (MΦ) are known to exhibit distinct responses to viral and bacterial infection, but how they react when exposed to the pathogens in succession is less well understood. Accordingly, we determined the effect of a rubella virus (RV)-induced infection followed by an LPS-induced challenge on cytokine production, signal transduction and metabolic pathways in human GM (M1-like)- and M (M2-like)-MΦ. We found that infection of both subsets with RV resulted in a low TNF-α and a high interferon (IFN, type I and type III) release whereby M-MΦ produced far more IFNs than GM-MΦ. Thus, TNF-α production in contrast to IFN production is not a dominant feature of RV infection in these cells. Upon addition of LPS to RV-infected MΦ compared to the addition of LPS to the uninfected cells the TNF-α response only slightly increased, whereas the IFN-response of both subtypes was greatly enhanced. The subset specific cytokine expression pattern remained unchanged under these assay conditions. The priming effect of RV was also observed when replacing RV by IFN-β one putative priming stimulus induced by RV. Small amounts of IFN-β were sufficient for phosphorylation of Stat1 and to induce IFN-production in response to LPS. Analysis of signal transduction pathways activated by successive exposure of MΦ to RV and LPS revealed an increased phosphorylation of NFκB (M-MΦ), but different to uninfected MΦ a reduced phosphorylation of ERK1/2 (both subtypes). Furthermore, metabolic pathways were affected; the LPS-induced increase in glycolysis was dampened in both subtypes after RV infection. In conclusion, we show that RV infection and exogenously added IFN-β can prime MΦ to produce high amounts of IFNs in response to LPS and that changes in glycolysis and signal transduction are associated with the priming effect. These findings will help to understand to what extent MΦ defense to viral infection is modulated by a following exposure to a bacterial infection.

Cytokine changes in the aqueous humor in rubella-related Fuchs heterochromic iridocyclitis

This retrospective study aimed to determine the correlation between cytokine levels and virus status in the aqueous humor of 38 patients with Fuchs heterochromic iridocyclitis (FHI) with/without viral presence between May 2017 and January 2020. The levels of cytokines were analyzed in the groups with and without virus-related FHI. Among the patients, 50% had rubella virus, 5.26% had cytomegalovirus, and 2.63% had herpes simplex virus infections. The expression of interleukin-6 (IL-6) and IL-8 was significantly higher and that of basic fibroblast growth factor (bFGF) was significantly lower in the virus-positive group than in the virus-negative group (P = 0.015, P = 0.001, and P = 0.001, respectively). Although there was no significant difference in the mean expression of vascular cell adhesion protein 1 (VCAM-1), IL-10, and vascular endothelial growth factor (VEGF), those of VCAM-1 and IL-10 were higher (M = 1338, M = 1390, respectively; M = 6.225 and 10.600, respectively) and that of VEGF was lower (M = 134.5, M = 38.70, respectively) in the virus-positive group than in the virus-negative group. Similar findings were observed for the expressions of IL-6, IL-8, and bFGF in the rubella-positive and -negative groups. Viral presence was highly related to FHI, especially that of the rubella virus. High levels of inflammatory cytokines and low levels of neovascularization-related factors are involved in rubella-related FHI. These study findings could be helpful in the diagnosis and treatment of FHI.

Evaluation of diagnostic accuracy of eight commercial assays for the detection of rubella virus specific IgM antibodies

Rubella and congenital rubella syndrome are caused by the rubella virus and are preventable through vaccination, making disease eradication possible. Monitoring of progress towards global eradication and local elimination requires high quality, sensitive disease surveillance that includes laboratory confirmation of cases. Previous evaluations of anti-rubella IgM detection methods resulted in the broad adoption of Enzygnost (most recently manufactured by Siemens) enzyme-linked immunosorbent assay (ELISA or EIA) kits within WHO’s global measles and rubella laboratory network but they have been discontinued. This study evaluates seven comparable ELISA methods from six manufacturers (Trinity Biotech, Euroimmun, Clin-Tech, NovaTec and Virion\Serion) as well as one automated chemiluminescent assay (CLIA) from Diasorin. These methods consisted of three IgM capture methods and five indirect ELISA methods. A panel of 238 sera was used for the evaluation that included 38 archival rubella IgM positive sera and 200 sera collected from symptomatically similar cases, such as measles, dengue, parvovirus B19 and roseola. With this panel of sera, the sensitivity of the methods ranged from 63.2% to 100% and the specificity from 80.0% to 99.5%. No single method had both sensitivity and specificity >90%, unless sera with equivocal results were considered to be presumptive positive. Some methods, particularly the Serion ELISA, had a large number of false positives with parvovirus B19 IgM positive sera as well as sera from confirmed measles cases. The performance characteristics identified in this evaluation serve as a reminder to not rely solely on rubella IgM results for case confirmation in elimination settings.

Simultaneous Seroprevalence to Toxoplasma gondii, Cytomegalovirus and Rubella Virus in Childbearing Women from Western Romania

Background and Objectives: Toxoplasma gondii, cytomegalovirus (CMV) and rubella virus, besides other agents, belong to a group named the TORCH complex. Research on the epidemiology of these agents in women is of particular interest, as primary infection during pregnancy could cause severe damage to the fetus. Women who had contracted infection before pregnancy develop IgG antibodies, so the fetus is protected in case of contact with the same agent. Our scope was to identify the childbearing women simultaneously protected or susceptible to a primary infection to two or three agents mentioned above. Materials and Methods: A cross-sectional study was performed on 6961 fertile Caucasian women from Western Romania, to analyze the simultaneous seroprevalence to two or three of the pathogens from the TORCH complex: Toxoplasma gondii, CMV, and rubella virus. Sampling was conducted at two time points: 2008–2010 (group 1; 1461 participants) and 2015–2018 (group 2; 5500 participants). Results: The percentage of women simultaneously seropositive to IgG-anti-Toxoplasma gondii/IgG-anti-CMV, IgG-anti-Toxoplasma gondii/IgG-anti-rubella, IgG-anti-CMV/IgG-anti-rubella or IgG-anti-Toxoplasma gondii and IgG-anti-CMV/IgG-anti-rubella antibodies decreased between the two groups (2008–2010 vs. 2015–2018): 41.4% vs. 36.1%, OR = 0.79, p = 0.0002; 41.8% vs. 35.7%, OR = 0.77, p < 0.0001; 88.9% vs. 83.6%, OR = 0.63, p < 0.0001; 39.6% vs. 33.2%, OR = 0.75, p < 0.0001. When comparing women from urban and rural areas, the simultaneous seroprevalence was higher in rural areas. In women tested 2008–2010 (group 1) the simultaneous seroprevalence (urban vs. rural) was: 38.4% vs. 49.1%, OR = 1.54, p = 0.0002; 38.4% vs. 50.6%, OR = 1.64, p < 0.0001; 88.8% vs. 89.2%, OR = 1.04, NS; 36.4% vs. 47.7%, OR = 1.58, p = 0.0001. A similar trend was found in women tested in group 2. Conclusions: The rate of simultaneous seropositivity to Toxoplasma gondii, CMV and rubella virus among Romanian women of reproductive age decreased significantly between 2008–2010 and 2015–2018 and the susceptibility to infections increased. It is necessary to apply increased prevention measures among susceptible pregnant women.