Serum signature of antibodies to Toxoplasma gondii, rubella virus, and cytomegalovirus in females with bipolar disorder: A cross-sectional study.

BACKGROUND AND AIM: Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and cytomegalovirus (CMV) shared clinical relevance with BD, remains controversial. This study aimed to investigate this association. METHODS: Antibody seropositivity of IgM and IgG to T gondii, rubella virus, and CMV of females with BD and controls was extracted based on medical records from January 2018 to January 2023. Family history, type of BD, onset age, and psychotic symptom history were also collected. RESULTS: 585 individuals with BD and 800 healthy controls were involved. Individuals with BD revealed a lower positive rate of T gondii IgG in the 10-20 aged group (OR = 0.10), and a higher positive rate of rubella IgG in the 10-20 (OR = 5.44) and 20-30 aged group (OR = 3.15). BD with family history preferred a higher positive rate of T gondii IgG (OR = 24.00). Type-I BD owned a decreased positive rate of rubella IgG (OR = 0.37) and an elevated positive rate of CMV IgG (OR = 2.12) compared to type-II BD, while BD with early onset showed contrast results compared to BD without early onset (Rubella IgG, OR = 2.54; CMV IgG, OR = 0.26). BD with psychotic symptom history displayed a lower positive rate of rubella IgG (OR = 0.50). LIMITATIONS: Absence of male evidence and control of socioeconomic status and environmental exposure. CONCLUSIONS: Differential antibody seropositive rates of T gondii, rubella, and cytomegalovirus in BD were observed.

Multiplex Bead Assay for the Serological Surveillance of Measles and Rubella.

There is increasing interest in evaluating antibody responses to multiple antigen targets in a single assay. Immunity to measles and rubella are often evaluated together because immunity is provided through combined vaccines and because routine immunization efforts and surveillance for measles and rubella pathogens are combined in many countries. The multiplex bead assay (MBA) also known as the multiplex immunoassay (MIA) described here combines the measurement of measles- and rubella-specific IgG antibodies in serum quantitatively according to international serum standards and has been successfully utilized in integrated serological surveillance.

Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Frequency of an intrathecal IgM synthesis and MRZ reaction in children with MS.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. An intrathecal IgM synthesis is associated with a more rapid progression of MS and the intrathecal immune response to measles -, rubella -and varicella zoster virus (MRZR) which, if present, increases the likelihood of a diagnosis of MS in adults. OBJECTIVE: To evaluate the frequency of an intrathecal IgM synthesis and MRZR in children with MS. MethodsChildren with MS and a data set including clinical and treatment history, MRI at onset, in addition to a CSF analysis, and determination of antibody index (AI) of measles, rubella, and zoster antibodies, were eligible. The presence of an intrathecal IgM synthesis and/or a positive MRZ reaction were compared to biomarkers of a more progressive disease course. RESULTS: In 75 children with MS, OCBs were present in 93.3 %). 49,2 % experienced their first relapse within 6 months. 50.7 % had a total lesion load of more than 10 lesions in the first brain MRI. Spinal lesions were identified in 64 %. 23.5 % had a positive MRZR and 40.3 % an intrathecal IgM synthesis. No significant associations were detected between the presence of an intrathecal IgM synthesis and MRZR and parameters including the relapse rate in the first two years. CONCLUSION: An intrathecal IgM synthesis and a positive MRZR are found in a subset of MS children but are not associated with markers associated with a poor prognosis.

HLA Associations of Intrathecal IgG Production against Specific Viruses in Multiple Sclerosis.

OBJECTIVE: Specific human leucocyte antigen (HLA) alleles are not only associated with higher risk to develop multiple sclerosis (MS) and other autoimmune diseases, but also with the severity of various viral and bacterial infections. Here, we analyzed the most specific biomarker for MS, that is, the polyspecific intrathecal IgG antibody production against measles, rubella, and varicella zoster virus (MRZ reaction), for possible HLA associations in MS. METHODS: We assessed MRZ reaction from 184 Swiss patients with MS and clinically isolated syndrome (CIS) and 89 Swiss non-MS/non-CIS control patients, and performed HLA sequence-based typing, to check for associations of positive MRZ reaction with the most prevalent HLA alleles. We used a cohort of 176 Swedish MS/CIS patients to replicate significant findings. RESULTS: Whereas positive MRZ reaction showed a prevalence of 38.0% in MS/CIS patients, it was highly specific (97.7%) for MS/CIS. We identified HLA-DRB1*15:01 and other tightly linked alleles of the HLA-DR15 haplotype as the strongest HLA-encoded risk factors for a positive MRZ reaction in Swiss MS/CIS (odds ratio [OR], 3.90, 95% confidence interval [CI] 2.05-7.46, padjusted = 0.0004) and replicated these findings in Swedish MS/CIS patients (OR 2.18, 95%-CI 1.16-4.02, padjusted = 0.028). In addition, female MS/CIS patients had a significantly higher probability for a positive MRZ reaction than male patients in both cohorts combined (padjusted <0.005). INTERPRETATION: HLA-DRB1*15:01, the strongest genetic risk factor for MS, and female sex, 1 of the most prominent demographic risk factors for developing MS, predispose in MS/CIS patients for a positive MRZ reaction, the most specific CSF biomarker for MS. ANN NEUROL 2024;95:1112-1126.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

Analysis of Morphological Changes in the CNS and Internal Organs of Macaca mulatta Monkeys after Intracerebral Injection of a Low-Attenuated Rubella Virus Strain.

We studied the localization and severity of morphological changes in CNS and internal organs of animals intacerebrally infected with a low-attenuated rubella virus strain "Orlov-14". The data obtained can be used as morphological criteria reflecting low level of attenuation of rubella virus strains to improve the control of the safety of attenuated strains of live rubella vaccines.

Rubella Eradication: Not Yet Accomplished, but Entirely Feasible.

Rubella virus is the most teratogenic virus known to science and is capable of causing large epidemics. The RA 27/3 rubella vaccine, usually combined with measles vaccine, has eliminated rubella and congenital rubella syndrome from much of the world, notably from the Western Hemisphere. Except in immunosuppressed individuals, it is remarkably safe. Together with rubella vaccine strains used in China and Japan, eradication of the rubella virus is possible, indeed more feasible than eradication of measles or mumps.

Transcriptional signatures associated with rubella virus-specific humoral immunity after a third dose of MMR vaccine in women of childbearing age.

Multiple factors linked to host genetics/inherent biology play a role in interindividual variability in immune response outcomes after rubella vaccination. In order to identify these factors, we conducted a study of rubella-specific humoral immunity before (Baseline) and after (Day 28) a third dose of MMR-II vaccine in a cohort of 109 women of childbearing age. We performed mRNA-Seq profiling of PBMCs after rubella virus in vitro stimulation to delineate genes associated with post-vaccination rubella humoral immunity and to define genes mediating the association between prior immune response status (high or low antibody) and subsequent immune response outcome. Our study identified novel genes that mediated the association between prior immune response and neutralizing antibody titer after a third MMR vaccine dose. These genes included the following: CDC34; CSNK1D; APOBEC3F; RAD18; AAAS; SLC37A1; FAS; and JAK2. The encoded proteins are involved in innate antiviral response, IFN/cytokine signaling, B cell repertoire generation, the clonal selection of B lymphocytes in germinal centers, and somatic hypermutation/antibody affinity maturation to promote optimal antigen-specific B cell immune function. These data advance our understanding of how subjects' prior immune status and/or genetic propensity to respond to rubella/MMR vaccination ultimately affects innate immunity and humoral immune outcomes after vaccination.

Persistence of Anti-Rubella Immunoglobulin G Antibody Titers in Young Adults Involved in a Short-Term Periodic Immunization in Japan.

In Japan, several rubella outbreaks in adults have erupted due to insufficient immunity against rubella virus (RUBV). Although selective immunization is being promoted along with routine rubella vaccination as its eradication strategy, serosurveillance against RUBV needs to be implemented in the generations corresponding to the vaccination transition period. In this study, a survey of anti-rubella immunoglobulin G (IgG) antibody titers was conducted among young adults involved in the transitional periods of the routine rubella vaccination program. Specifically, serosurveillance was performed in 370 healthy young adults aged 18-20 years, wherein their serum samples were analyzed using an enzyme immunoassay to determine rubella-specific IgG antibody titers. Although multiple regression analysis revealed significant differences only in medical history, more than 90% of participants exhibited seropositivity, excluding those who received a single-dose vaccine alone. Based on elapsed periods after the last vaccination, rubella-specific IgG antibody titers in less than a 6-year period were higher than those in more than a 10-year period. Although almost all study participants in the transitional period had seropositivity, the results may indicate that this persistence is related to past rubella outbreaks.

Genetic and antigenic characterization of wild type rubella viruses isolated from India.

Rubella, is a contagious disease caused by Rubella virus (RuV) that manifests as fever with skin-rashes in children and adults along with complications in pregnant women. WHO-SEAR has set a target for Rubella elimination by 2023. This is the first report of antigenic characterization and genome sequencing of nine RuVs sampled during 1992, 2007-9, and 2015-17 from four Indian states. Comparative analysis of Indian RuVs (2B) with that of global isolates and vaccine strain RA 27/3 (1a) revealed that the observed mutations in structural proteins have no major impact on the 3D structure, function and antigenicity. Indian RuVs formed three major clusters (Pune-1992, Kannur-2009 and Chitradurg-2007) in genome-based phylogeny of global isolates. Neutralizing antibody titers in a panel of serum samples from measles negative cases were significantly higher to the vaccine strain compared to a wild-type 2B isolate (Kannur) with concordance of 91.9%, thereby substantiating the use of current vaccines.

Rubella Immunity among Italian Female Healthcare Workers: A Serological Study.

Rubella, also known as German measles or three-day measles, is an infectious disease caused by virus of the genus Rubivirus, which may be prevented by vaccination. The infection is potentially dangerous for non immune subjects, although 20-50% of infected subjects are asymptomatic. Healthcare workers (HCWs) have an increased potential exposure to rubella in comparison to the general population, putting them and their patients at risk of infection and its complications. In 2019, 20 cases of rubella have been reported in Italy. According to the Italian National Immunization and Prevention Plan, HCWs should provide a written certification of vaccination for rubella or serological evidence of protective antibodies. The aim of the study was to evaluate the rubella immunization status in female HCWs of the teaching hospital Policlinic Rome Tor Vergata (PTV) of childbearing age. For this purpose, we retrospectively checked the serologic values of rubella-specific IgG antibodies analyzing the clinical records of the HCWs of undergoing the occupational health surveillance program from January 1st to June1st 2020. Five hundred fourteen HCWs with a mean age of 23.19 (range 19-37, DS: 2.80) were included: 90.3% (464) showed a protective antibody titre. The mean value of the anti-rubella IgG was 49.59 IU/mL. Our study shows a non-protective anti rubella IgG titre in a substantial percentage of HCWs (9.7%). As vaccine protection decreases over the years and the risk of congenital rubella syndrome (CRS) in vaccinated subjects should not be underestimated, we suggest routine screening of the immunological status followed by the administration of a third dose of vaccine if the antibody titre becomes non-protective.

Prevalence of herpes -, measles morbillivirus-, parvovirus B19 - and rubella viruses immunoglobulin G among women with chronic hepatitis B of reproductive age in Denmark: A cross-sectional study.

OBJECTIVES: The aim of this study was to investigate whether the seroprevalence of IgG antibodies against seven viruses (cytomegalovirus, herpes simplex virus 1&2, measles morbillivirus, parvovirus B19, rubella, and varicella-zoster virus), which can potentially compromise maternal and fetal wellbeing, differs based on country of origin among women with chronic hepatitis B (CHB). METHOD: This study was a single-center, hospital-based cross-sectional study. The study included women with CHB 15-45 years of age, included in the Danish Database for Hepatitis B and C. Seroprevalence estimates were calculated with a 95% confidence interval and were compared between age groups, regions of origin, and to the general population. RESULTS: 177 women were included in the study. Overall, the seroprevalences of antibodies were similar among women with CHB with origin outside Denmark and compared to the general population in Denmark, but there was a notable difference in the seroprevalence of antibodies against herpes simplex 2 between women from Africa (37.1% CI 95% 22.0;55.1) and women from the Middle East (2.5% CI 95% 0.1;14.7). CONCLUSION: Women with CHB whose origin is outside Denmark do not appear to differ, based on origin, or be at greater risk of acquiring these viruses during pregnancy than their Danish counterparts.

Relatives of rubella virus in diverse mammals.

Since 1814, when rubella was first described, the origins of the disease and its causative agent, rubella virus (Matonaviridae: Rubivirus), have remained unclear1. Here we describe ruhugu virus and rustrela virus in Africa and Europe, respectively, which are, to our knowledge, the first known relatives of rubella virus. Ruhugu virus, which is the closest relative of rubella virus, was found in apparently healthy cyclops leaf-nosed bats (Hipposideros cyclops) in Uganda. Rustrela virus, which is an outgroup to the clade that comprises rubella and ruhugu viruses, was found in acutely encephalitic placental and marsupial animals at a zoo in Germany and in wild yellow-necked field mice (Apodemus flavicollis) at and near the zoo. Ruhugu and rustrela viruses share an identical genomic architecture with rubella virus2,3. The amino acid sequences of four putative B cell epitopes in the fusion (E1) protein of the rubella, ruhugu and rustrela viruses and two putative T cell epitopes in the capsid protein of the rubella and ruhugu viruses are moderately to highly conserved4-6. Modelling of E1 homotrimers in the post-fusion state predicts that ruhugu and rubella viruses have a similar capacity for fusion with the host-cell membrane5. Together, these findings show that some members of the family Matonaviridae can cross substantial barriers between host species and that rubella virus probably has a zoonotic origin. Our findings raise concerns about future zoonotic transmission of rubella-like viruses, but will facilitate comparative studies and animal models of rubella and congenital rubella syndrome.

Impact of vaccination on measles, mumps, and rubella antibody titers in Japanese healthcare workers: An observational study.

Given the complicated history of Japan's National Immunization Program, a significant proportion of Japanese people including healthcare workers (HCWs) still lack adequate immunity against measles, mumps, and rubella (MMR), resulting in occasional outbreaks. In 2014, the Japanese Society of Infection Prevention and Control (JSIPC) published vaccination guidelines for HCWs. We evaluated antibody titers before and after MMR vaccination in HCWs at the Nara Medical University Hospital, the attainment rate of the target antibody titers defined by the JSIPC guidelines, and the safety of vaccines. We measured MMR antibody titers in HCWs, followed by inoculation with the respective monovalent vaccines and/or trivalent MMR (tMMR) vaccine according to the JSIPC guidelines. Among 467 HCWs evaluated, antibody titers against measles and mumps measured using the IgG-enzyme immunoassay increased from 11.0 [interquartile range (IQR): 8.0-13.6] to 13.7 (IQR: 11.3-16.9; P < 0.001) and from 2.8 (IQR: 2.1-3.5) to 4.8 (IQR: 3.7-5.7; P < 0.001), respectively. By evaluating a logarithmic value of log2(X + 1) converted from an antibody titer X, antibody titers against rubella measured using the hemagglutination assay increased from 3.2 (IQR: 0-4.1) to 6.0 (IQR: 4.6-8.0; P < 0.001). Antibody titer elevated following tMMR vaccination was lower than that following monovalent vaccination in a single dose of the measles-containing, a single dose of the mumps-containing, and two doses of rubella-containing vaccine groups (P = 0.01, 0.01, and <0.001, respectively). After vaccination, 20.0%, 61.5%, and 46.2% of HCWs attained target antibody titers specified by the JSIPC guidelines for measles, rubella, and mumps, respectively. The systemic response in female HCWs who underwent monovalent mumps vaccination was statistically higher than that in others. Although the vaccination program for HCWs according to the JSIPC guidelines caused increased MMR antibody titers, the rates of attaining the target criteria were low.

Comparative studies of rubella virus immunity of immunized and non-immunized pregnant women visiting Kogi State University Teaching Hospital, Anyigba, North Central Nigeria.

Rubella is endemic worldwide and poses a serious threat to infants and pregnant women. Although the disease has been widely reported in parts of the country, there is currently no documented evidence of the disease in Anyigba. A comparative study of rubella immunity was conducted among immunized and non-immunized pregnant women visiting the Kogi State University Teaching Hospital, Anyigba. In a cross-sectional study, blood samples collected from 300 pregnant women (immunized = 127; non-immunized = 173) were tested for rubella antibodies using ELISA kit. Overall, anti-rubella-IgM and IgG seroprevalence rates of 38 (12.7%) and 83 (27.7%) were detected. Seventy (55.1%) of the immunized against 13 (7.5%) of non-immunized women had detectable IgG. The non-immunized women were significantly more seropositive for IgM than the immunized who recorded higher prevalence of IgG. Immunized and non-immunized women aged 23-32 years had higher IgG and IgM positivity rates. The difference in IgM and IgG seropositivity rates in relation to vaccination was statistically significant (P < 0.05) between the immunized (0.8%, 55.1%) and vaccine-naïve subjects (21.4%, 7.5%). Low level of awareness and high susceptibility to rubella virus infection especially among the non-immunized women was confirmed in study area, thus the need for government to strengthen education of masses and to make rubella vaccination freely available for women of childbearing age.