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Background: The rubella virus is a major contributor to birth defects globally and is preventable by vaccination. In 2020, the world was supposed to be free of both rubella and Congenital Rubella Syndrome (CRS) however this goal has yet to be realized with only 93 out of 194 WHO member states confirmed rubella-free in 2020. Methods: A retrospective measles and rubella case-based surveillance data record review was conducted from 2018 to 2022 to document rubella epidemiology after the introduction of rubella vaccination in Lesotho and progress toward elimination. All samples submitted for surveillance purposes and tested for rubella were considered but only filtered according to inclusion and exclusion criteria. Descriptive statistics were used to analyse the data. Results: Of the 1041 samples that were tested for rubella between 2018 and 2022, 10 (1%) were confirmed measles positive and were excluded from further analysis. The median age of the respondents was 6.0 (IQR 4.0–8.0.) years. About 643 (62.4%) of respondents were in the age category of 5 - <13 years. Rubella prevalence was 1% (95% CI; 0.5 -1.8%). The non-measles, non-rubella rash illness rate of 2 per 100 000 population was obtained at the national level each year of the study period but by only 2 of the country's 10 districts in 2021. Conclusions: The study showed low rubella prevalence. Rubella infection was predominant in those aged 5 - < 13 years. Failure to meet surveillance targets at certain time points during the study period may have led to an underestimation of rubella cases. There is a need to improve the quality of measles and rubella surveillance in Lesotho. Supplementary immunization activities would also be useful in closing immunity gaps, limiting outbreaks, and advancing rubella and CRS elimination in Lesotho. [ABSTRACT FROM AUTHOR]

The association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immunodeficiencies has raised concerns about the ability of immunoglobulin preparations to neutralize VDRVs. We investigated the capacity of immunoglobulin to neutralize rubella vaccine virus and 4 VDRV strains. As expected, the rubella vaccine virus itself was potently neutralized by immunoglobulin preparations, but the VDRV isolates from patients after intrahost evolution, 2–6 times less so. Diagnosis of immune deficiencies before possible live-virus vaccination is thus of critical importance, while immunoglobulin replacement therapy can be expected to provide protection from rubella virus infection. [ABSTRACT FROM AUTHOR]

Purpose: To identify the types of viral infection in aqueous humor (AqH) among patients diagnosed as Fuchs uveitis syndrome (FUS) or Posner-Schlossman syndrome (PSS) and investigate their relevance to clinical manifestations and visual outcome. Methods: A total of 375 patients and 171 patients were diagnosed as FUS or PSS in our department. AqH and serum samples from 68 FUS patients and 16 PSS patients were obtained during eye surgery. The viral etiologies, clinical features, auxiliary tests and visual prognosis of patients with FUS or PSS who underwent AqH analysis were analysed and compared. Results: Among 68 FUS patients, rubella virus (RV), cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella-zoster virus were identified in 17, 11, 1 and 1 patients, respectively. Seven patients with CMV and 1 with HSV were identified in 16 PSS patients. In both FUS and PSS groups, virus-associated eyes had higher proportion of secondary glaucoma and worse visual prognosis as compared with non-virus-associated eyes (all P < 0.05). In FUS group, specifically, CMV infection manifested as more obvious anterior segment inflammation and lower corneal endothelial cell density (CECD). RV infection showed a higher percentage of vitritis. In PSS group, CMV-associated PSS had a lower retinal nerve fiber layer thickness and CECD, worse visual prognosis as compared with non-virus-associated PSS (all P < 0.05). Conclusion: Our study identified 4 types of viral infection in FUS and 2 types of viral infection in PSS. Virus-associated patients are usually associated with more obvious clinical signs and poor visual prognosis. [ABSTRACT FROM AUTHOR]

Anterior uveitis is the most common type of uveitis worldwide. The etiologies of anterior uveitis can be divided into infectious and non-infectious (idiopathic, autoimmune, autoinflammatory, trauma, and others). The viral pathogens most commonly associated with infectious anterior uveitis include Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, and Rubella Virus. Other emerging causes of viral anterior uveitis are West Nile Virus, Human-Immunodeficiency Virus, Epstein-Barr Virus, Parechovirus, Dengue Virus, Chikungunya Virus, and Human Herpesvirus type 6,7, and 8. Early recognition allows prompt management and mitigates its potential ocular complications. This article provides an updated literature review of the epidemiology, clinical manifestations, diagnostic tools, and treatment options for viral anterior uveitis. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a demyelinating disease affecting millions of people worldwide. Hereditary susceptibility and environmental factors contribute to disease risk. Infection with Epstein–Barr virus (EBV) and human herpesvirus 6A (HHV‐6A) have previously been associated with MS risk. Other neurotropic viruses, such as rubella virus (RV), are possible candidates in MS aetiopathogenesis, but previous results are limited and conflicting. Methods: In this nested case–control study of biobank samples in a Swedish cohort, we analysed the serological response towards RV before the clinical onset of MS with a bead‐based multiplex assay in subjects vaccinated and unvaccinated towards RV. The association between RV seropositivity and MS risk was analysed with conditional logistic regression. Results: Seropositivity towards RV was associated with an increased risk of MS for unvaccinated subjects, even when adjusting for plausible confounders including EBV, HHV‐6A, cytomegalovirus and vitamin D (adjusted odds ratio [AOR] = 4.0, 95% confidence interval [CI] 1.8–8.8). Cases also had stronger antibody reactivity towards rubella than controls, which was not seen for other neurotropic viruses such as herpes simplex or varicella zoster. Furthermore, we observed an association between RV seropositivity and MS in vaccinated subjects. However, this association was not significant when adjusting for the aforementioned confounders (AOR = 1.7, 95% CI 1.0–2.9). Conclusions: To our knowledge, these are the first reported associations between early RV seropositivity and later MS development. This suggests a broadening of the virus hypothesis in MS aetiology, where molecular mimicry between rubella epitopes and human central nervous system molecules could be an attractive possible mechanism. [ABSTRACT FROM AUTHOR]

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. 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. 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). Absence of male evidence and control of socioeconomic status and environmental exposure. Differential antibody seropositive rates of T gondii , rubella, and cytomegalovirus in BD were observed. • Serum pathogen antibody positive rates varied across age groups. • T gondii IgG was associated with family history of BD. • Rubella IgG was associated with type-II BD, BD with early onset and BD without psychotic symptom history. • CMV IgG was associated with type-I BD and BD without early onset. [ABSTRACT FROM AUTHOR]

Serological screening for TORCH(Toxoplasma gondii [TOX], Rubella virus [RV], Cytomegalovirus [CMV], and Herpes simplex virus [HSV]) infections is an effective method for preventing congenital infections caused by TORCH pathogens.In this study, we retrospectively analyzed the characteristics of TORCH infections in 17,807 infertile women of childbearing age in northwest China.We conducted serological detection of TORCH-pathogen-specific IgM and IgG antibodies. The seroprevalence of TORCH infections was statistically analyzed by applying χ2 and Fisher exact-probability tests to evaluate the differences among ages and across quarters of the year. The overall IgM/IgG seroprevalences of TOX, RV, CMV, HSV-1, and HSV-2 were 0.46/3.4%, 0.77/84.93%, 0.68/97.54%, 1.2/82.83%, and 0.62/10.04%, respectively. The positive rates for RV-IgM in women ≥ 40 years old were significantly higher than those for women 25–39 (P < 0.05) years of age. The seroprevalence of HSV1-IgM was higher in the third and fourth quarters of the year (seasons) (P < 0.001), and the seroprevalence of CMV-IgG was statistically significant between differences quarters (P = 0.017), and the seroprevalence of CMV-IgG in the first quarter was lower than that in the third and fourth quarters (Bonferroni correction, P = 0.009 > 0.0083), suggesting no statistically significant difference between the latter two groups. This study showed that in northwestern China the risk of acquiring primary infection by a TORCH pathogen among infertile women of childbearing age were still high, especially Toxoplasma gondii and Herpesvirus type 2 infection. Therefore, effective prevention strategies that include serological screening for TORCH should be implemented. [ABSTRACT FROM AUTHOR]

Introduction. Rubella virus is an RNA-containing virus capable of infecting human cells and causing infectious disease. Infection of pregnant women with rubella virus can lead to abortion or congenital rubella syndrome (CRS), a set of long-term birth defects including incomplete fetal organ development and mental retardation. There is no specific treatment for rubella and CRS. The regulation of antiviral immune response and viral reproduction by long non-coding RNAs is currently under active investigation. In this study, we evaluated the changes in the expression profile of long non-coding RNAs in rubella virus-infected A549 epithelial by RNA sequencing. Materials and Methods. A549 cells were infected with a wild-type variant of laboratory strain C-77 of rubella virus with a multiplicity of infection of 1.0 infectious units per cell and incubated for 72 hours. Virus titres were determined by the CCID method in the sensitive RK-13 cell culture. 48 h after infection, the cell monolayer was lysed, RNA was isolated, and libraries were prepared for sequencing. Sequencing was performed on the NextSeq500 platform (Illumina, USA) in paired-end reading mode. Validation of the obtained RNA sequencing data was performed using quantitative real-time PCR. Results. Rubella virus replication affects the production of some long non-coding RNAs by altering their expression profile. Thus, upon infection of A549 epithelial cells with rubella virus, there was a significant increase in the expression of such long non-coding RNAs as GAS5, NEAT1, LUCAT1, MIR210HG, MEG3, EPB41L4A-AS1, ZFAS1, and SNHG 1, 7, 12, 29, 32. DANCR, IGFL2-AS1, IGFL2-AS1, MIR1915HG, and SNHG14 were most significantly decreased in expression. Gene ontology (GO)-analysis revealed that long non-coding RNAs are involved at different levels in the mechanisms of immune response, in particular, RNA processing and nucleic acid metabolism; therefore, up- and down-regulation of these molecules leads to modulation of human antiviral immune response in response to rubella virus infection. Conclusion. Thus, the regulation of long non-coding RNA production by rubella virus has been shown for the first time. Differentially expressed long non-coding RNAs can be used as prognostic and diagnostic biomarkers of viral diseases.

Background: Measles and rubella are vaccine-preventable diseases targeted for elimination in most World Health Organization regions, and China is considered to have momentum towards measles elimination. Therefore, this study aimed to assess the population immunity levels against measles and rubella in Zhejiang Province in China in order to provide valuable insights for informing future public health measures and contributing to the ongoing global campaign against these diseases. Materials and methods: A cross-sectional serological survey was conducted in 2022. A total of 2740 blood samples were collected from healthy individuals spanning the age range of 0–59 years, representing diverse demographic strata across 11 prefectures in Zhejiang Province in China. The sera were tested for measles and rubella IgG antibodies to determine positivity rates and geometric mean concentrations (GMCs). Results: The overall positivity rate for the measles IgG antibody was 85.3%, with a GMC of 588.30 mIU/mL. The positivity rate for the rubella IgG antibody was 70.9%, and the GMC was 35.30 IU/mL. Measles IgG antibody positivity rates across the 0–11 months, 12–23 months, 24–35 months, 3–5 years, 6–9 years, 10–14 years, 15–19 years, 20–29 years, and 30–59 years age groups were 63.1%, 92.5%, 97.0%, 94.0%, 85.8%, 77.3%, 86.9%, 84.9%, and 88.7%, respectively (trend χ2 = 118.34, p < 0.001). Correspondingly, rubella antibody positivity rates for these same age brackets were 55.9%, 87.9%, 94.7%, 88.2%, 69.9%, 54.2%, 72.6%, 67.5%, and 74.3% (trend χ2 = 199.18, p < 0.001). Both univariate and multivariate analyses consistently demonstrated that age, immunization history, and differing economic levels were significant factors contributing to variations in antibody levels. Conclusions: The seroprevalence of measles and rubella was lower than that required for herd immunity. Periodic vaccination campaigns should be launched to increase immunity. [ABSTRACT FROM AUTHOR]

More than 100 laboratories in the World Health Organization Global Measles and Rubella Laboratory Network (GMRLN) perform nucleic acid-based methods for case confirmation of measles or rubella infections and/or strain surveillance (genotyping). The quality of laboratory data is critical to ensure that diagnostic results and country reports to regional verification committees are based on accurate data. A molecular External Quality Assurance (mEQA) program was initiated by the US-CDC in 2014 to evaluate the performance of laboratories in the network. The inclusion of testing for measles and rubella viruses, with a focus on detection and genotyping, plus the diversity of assays and platforms employed required a flexible and comprehensive proficiency testing program. A stepwise introduction of new evaluation criteria gradually increased the stringency of the proficiency testing program, while giving laboratories time to implement the required changes. The mEQA program plays an important role in many processes in the GMRLN, including informing plans for the training of laboratory staff, access to reagents, and the submission of sequence data to global databases. The EQA program for Local Public Health Institutes in Japan is described as an example for national mEQA programs. As more laboratories initiate molecular testing, the mEQA will need to continue to expand and to adapt to the changing landscape for molecular testing. [ABSTRACT FROM AUTHOR]

To identify the clinical characteristics that may predict the diagnosis of Rubella virus (RV) or Cytomegalovirus (CMV) among cases of chronic treatment resistant or steroid dependent unilateral anterior uveitis (AU). Thirty-three consecutive patients with a diagnosis of CMV and 32 patients with RV chronic AU were enrolled. The respective frequency of certain demographic and clinical characteristics was compared between the two groups. The presence of abnormal vessels in the anterior chamber angle (75% and 6.1%, respectively, p <.001), vitritis (68.8%–12.1%, p <.001), iris heterochromia (40.6%–15.2%, p =.022) and iris nodules (21.9%–3%, p =.027) were more common among RV AU. Conversely, intraocular pressure greater than 26 mmHg was more commonly encountered in CMV associated AU (63.6%–15.6%, respectively, p <.001) and large keratic precipitates were detected only in CMV-associated AU. RV- and CMV-induced chronic AU differ significantly in the prevalence of specific clinical characteristics. [ABSTRACT FROM AUTHOR]

Rubella, or German measles, is a vaccine-preventable disease. Rubella infection is usually mild; however, infection in pregnancy is associated with severe outcomes for the baby, including pregnancy loss or a combination of developmental defects called congenital rubella syndrome. Within the last ten-year period, two cases of congenital rubella syndrome in Saskatchewan were reported to the provincial ministry and the Public Health Agency of Canada of the newborns of mothers who had recently arrived from Sub-Saharan Africa. Both infants had multiple health complications at birth consistent with congenital rubella and tested positive for the rubella virus. The article discusses the challenges encountered by the healthcare system in diagnosing, investigating, monitoring and managing cases of congenital rubella syndrome to prevent further sporadic transmission. The article emphasizes the need to provide additional support for cases and their households, especially new Canadians with less support to comply with public health advice and the importance of routine immunization to eliminate rubella globally. [ABSTRACT FROM AUTHOR]

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella-containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden if the absolute risk of infection during child-bearing age increases. The dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with persistently high transmission intensity. Low or declining rubella virus transmission intensity is associated with both greater burden without vaccination and greater burden reduction with vaccination. The risk of resurgent burden due to incomplete vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase versus a large, immediate burden decrease strongly favors RCV introduction. [ABSTRACT FROM AUTHOR]

TORCH infections usually result in mild maternal morbidity, but may cause severe congenital abnormalities. Therefore, it is important to detect maternal infections, monitor the fetus after the disease has been recognized, and define the seronegative women who are at risk of primary infection during pregnancy. From 2014 to 2023, serum samples from 1032 childbearing-aged and pregnant women (16–45 years) were tested for IgM/IgG antibodies to the most common TORCH pathogens: Toxoplasma gondii, rubella virus (RUBV), cytomegalovirus (CMV), and herpes simplex viruses (HSV-1 and HSV-2). The overall IgG seroprevalence rates were 20.1% for T. gondii, 91.3% for RUBV, 70.5% for CMV, 66.8% for HSV-1, and 3.5% for HSV-2. Only HSV-2 seroprevalence was age-related, with a significant progressive increase in seropositivity from 0% in those aged less than 26 years to 9.3% in those older than 40 years. The seroprevalence of T. gondii was higher in residents of suburban/rural areas than in residents of urban areas (27.4% vs. 17.1%). In addition, participants from continental regions were more often toxoplasma-seropositive than those from coastal regions (22.2% vs. 15.3%). HSV-1 seroprevalence was also higher in suburban/rural areas (71.7% vs. 64.7%). Obstetric history was not associated with TORCH seropositivity. Univariate and multivariate risk analysis showed that suburban/rural areas of residence and continental geographic regions were significant risk factors for T. gondii seroprevalence. Furthermore, suburban/rural area of residence was a significant risk factor for HSV-1 seroprevalence, while older age was a significant risk factor for HSV-2 seroprevalence. A declining trend in the seroprevalence of all TORCH pathogens was observed compared to previous Croatian studies (2005–2011). Similarly, the proportion of women simultaneously IgG-seropositive to two or three pathogens decreased over time. The maternal serology before pregnancy could potentially reduce the burden of congenital TORCH infections. [ABSTRACT FROM AUTHOR]

Rubella virus is an important human pathogen that can cause neurological deficits in a developing fetus when contracted during pregnancy. Despite successful vaccination programs in the Americas and many developed countries, rubella remains endemic in many regions worldwide and outbreaks occur wherever population immunity is insufficient. Intense interest since rubella virus was first isolated in 1962 has advanced our understanding of clinical outcomes after infection disrupts key processes of fetal neurodevelopment. Yet it is still largely unknown which cell types in the developing brain are targeted. We show that in human brain slices, rubella virus predominantly infects microglia. This infection occurs in a heterogeneous population but not in a highly microglia-enriched monoculture in the absence of other cell types. By using an organoid-microglia model, we further demonstrate that rubella virus infection leads to a profound interferon response in non-microglial cells, including neurons and neural progenitor cells, and this response is attenuated by the presence of microglia.

ABSTRACT Rubella virus (RuV) is an enveloped virus that usually causes mild disease in children, but can produce miscarriage or severe congenital birth defects. While in nature RuV only infects humans, the discovery of the related Ruhugu (RuhV) and Rustrela (RusV) viruses highlights the spillover potential of mammalian rubiviruses to humans. RuV buds into the Golgi, but its assembly and exit are not well understood. We identified a potential late domain motif 278PPAY281 at the C-terminus of the RuV E2 envelope protein. Such late domain motifs can promote virus budding by recruiting the cellular ESCRT machinery. An E2 Y281A mutation reduced infectious virus production by >3 logs and inhibited virus particle production. However, RuV was insensitive to inhibition by dominant-negative VPS4, and thus appeared ESCRT-independent. The E2 Y281A mutation did not significantly inhibit the production of the viral structural proteins capsid (Cp), E2, and E1, or dimerization, glycosylation, Golgi transport, and colocalization of E2 and E1. However, E2 Y281A significantly reduced glycoprotein-Cp colocalization and interaction, and inhibited Cp localization to the Golgi. Revertants of the E2 Y281A mutant contained an E2 281V substitution or the second site mutations [E2 N277I + Cp D215A]. These mutations promoted virus growth, particle production, E2/Cp colocalization and Cp-Golgi localization. Both the E2 substitutions 281V and 277I were found at the corresponding positions in the RuhV E2 protein. Taken together, our data identify a key interaction of the RuV E2 endodomain with the Cp during RuV biogenesis, and support the close evolutionary relationship between human and animal rubiviruses.IMPORTANCERubella virus (RuV) is an enveloped virus that only infects humans, where transplacental infection can cause miscarriage or congenital birth defects. We identified a potential late domain, 278PPAY281, at the C terminus of the E2 envelope protein. However, rather than this domain recruiting the cellular ESCRT machinery as predicted, our data indicate that E2 Y281 promotes a critical interaction of the E2 endodomain with the capsid protein, leading to capsid's localization to the Golgi where virus budding occurs. Revertant analysis demonstrated that two substitutions on the E2 protein could partially rescue virus growth and Cp-Golgi localization. Both residues were found at the corresponding positions in Ruhugu virus E2, supporting the close evolutionary relationship between RuV and Ruhugu virus, a recently discovered rubivirus from bats.

Nodding syndrome (NS) is a mostly East African pediatric epileptiform encephalopathy of unknown etiology that shares some clinical features with measles-associated subacute sclerosing panencephalitis (SSPE) and progressive rubella panencephalitis. Two independent studies in northern Uganda identified an association between NS and prior measles infection, while an earlier study in South Sudan found an inverse association. We report preliminary serologic analyses of antibodies to measles (MV), rubella (RV), HSV-1, and CMV viruses in northern Ugandan children with NS and Household (HC) and Community (CC) Controls. Only MV-positive titers were significantly different (3-fold and > 2-fold) in NS relative to HC and HC + CC, respectively. While these results are consistent with greater prior measles infection in Ugandan persons with NS, further studies are needed to determine whether Measles virus (MV) plays any role in the etiology and pathogenesis of NS. Resolving this issue will be invaluable for the thousands of children at risk for this devastating yet often neglected condition.

Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders. [ABSTRACT FROM AUTHOR]

The Immunization Agenda 2030 (IA2030) Impact Goal 1.1. aims to reduce the number of future deaths averted through immunization in the next decade. To estimate the potential impact of the aspirational coverage targets for IA2030, we developed an analytical framework and estimated the number of deaths averted due to an ambitious vaccination coverage scenario from 2021 to 2030 in 194 countries. A demographic model was used to determine annual age-specific mortality estimates associated with vaccine coverage rates. For ten pathogens (Hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, yellow fever), we derived single measures of country-, age-, and pathogen-specific relative risk of deaths conditional upon coverage rates, leveraging the data from 18 modeling groups as part of the Vaccine Impact Model Consortium (VIMC) for 110 countries. We used a logistic regression model to extrapolate the relative risk estimates to countries that were not modeled by VIMC. For four pathogens (diphtheria, tetanus, pertussis and tuberculosis), we used estimates from the Global Burden of Disease 2019 study and existing literature on vaccine efficacy. A future scenario defining years of vaccine introduction and scale-up needed to reach aspirational targets was developed as an input to estimate the long-term impact of vaccination taking place from 2021 to 2030. Overall, an estimated 51.5 million (95 % CI: 44.0–63.2) deaths are expected to be averted due to vaccinations administered between the years 2021 and 2030. With immunization coverage projected to increase over 2021–2030 an average of 5.2 million per year (4.4–6.3) deaths will be averted annually, with 4.4 million (3.9–5.1) deaths be averted for the year 2021, gradually rising to 5.8 million (4.9–7.5) deaths averted in 2030. The largest proportion of deaths is attributed to Measles and Hepatitis B accounting for 18.8 million (17.8–20.0) and 14.0 million (11.5–16.9) of total deaths averted respectively. The results from this global analysis demonstrate the substantial potential mortality reductions achievable if the IA2030 targets are met by 2030. Deaths caused by vaccine preventable diseases disproportionately affect LMICs in the African region. [ABSTRACT FROM AUTHOR]

Summary: Infectious susceptibility is a component of many inborn errors of immunity. Nevertheless, antibiotic use is often used as a surrogate in history taking for infectious susceptibility, thereby disadvantaging patients who present with viral infections as their phenotype. Further complicating clinical evaluations are unusual manifestations of viral infections which may be less familiar that the typical respiratory viral infections. This review covers several unusual viral phenotypes arising in patients with inborn errors of immunity and other settings of immune compromise. In some cases, chronic infections lead to oncogenesis or tumor‐like growths and the conditions and mechanisms of viral‐induced oncogenesis will be described. This review covers enterovirus, rubella, measles, papillomavirus, and parvovirus B19. It does not cover EBV and hemophagocytic lymphohistiocytosis nor lymphomagenesis related to EBV. EBV susceptibility has been recently reviewed. Our goal is to increase awareness of the unusual manifestations of viral infections in patients with IEI and to describe treatment modalities utilized in this setting. Coincidentally, each of the discussed viral infections can have a cutaneous component and figures will serve as a reminder of the physical features of these viruses. Given the high morbidity and mortality, early recognition can only improve outcomes. [ABSTRACT FROM AUTHOR]

Rubella virus encodes a nonstructural polyprotein with RNA polymerase, methyltransferase, and papain-like cysteine protease activities, along with a putative macrodomain of unknown function. Macrodomains bind ADP-ribose adducts, a post-translational modification that plays a key role in host-virus conflicts. Some macrodomains can also remove the mono-ADP-ribose adduct or degrade poly-ADP-ribose chains. Here, we report high-resolution crystal structures of the macrodomain from rubella virus nonstructural protein p150, with and without ADP-ribose binding. The overall fold is most similar to macroD-type macrodomains from various nonviral species. The specific composition and structure of the residues that coordinate ADP-ribose in the rubella virus macrodomain are most similar to those of macrodomains from alphaviruses. Isothermal calorimetry shows that the rubella virus macrodomain binds ADP–ribose in solution. Enzyme assays show that the rubella virus macrodomain can hydrolyze both mono- and poly-ADP-ribose adducts. Site-directed mutagenesis identifies Asn39 and Cys49 required for mono-ADP-ribosylhydrolase (de-MARylation) activity. IMPORTANCE Rubella virus remains a global health threat. Rubella infections during pregnancy can cause serious congenital pathology, for which no antiviral treatments are available. Our work demonstrates that, like alpha- and coronaviruses, rubiviruses encode a mono-ADP-ribosylhydrolase with a structurally conserved macrodomain fold to counteract MARylation by poly (ADP–ribose) polymerases (PARPs) in the host innate immune response. Our structural data will guide future efforts to develop novel antiviral therapeutics against rubella or infections with related viruses. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV), in addition to other agents, is part of the TORCH complex (Toxoplasma gondii, Rubella virus, Cytomegalovirus, Herpes simplex viruses, and other agents). CMV infection is the most frequent cause of congenital malformations. This study aimed to establish the variation of prevalence of anti-CMV antibodies in pregnant women from the South-West region of Romania, according to demographic factors, such as age and area of residence, in two separate time periods (2013–2016 and 2019–2022). We collected from the hospital records the age, place of residence, and anti-CMV antibody test results using immune electrochemiluminescence and chemiluminescence. This study found that the seroprevalence of anti-CMV IgM antibodies increased slightly from 2013–2016 to 2019–2022, from 1.92% to 2.26%, and for IgG antibodies from 93.68% to 94.96%. In both groups was observed a descending trend of anti-CMV IgM seroprevalence with an increase in age, showing a decrease in seroprevalence from 3.57% to 1.09% in pregnant women from rural areas in the 31–35 years age group, while in urban areas, we observed a decrease in seroprevalence from 11.11% to 3.06% in the <20 years age group. The IgG seroprevalence showed an increase both in rural areas (from 93.97% to 95.52%) and urban areas (from 93.52% to 94.27%). In both groups, seroprevalence was higher in rural areas compared to urban regions. These results show a high rate of immunization against CMV in pregnant women in South-West Romania, which led to a low risk of acquiring the primary infection during pregnancy. However, the increase in the rate of primary CMV infections in pregnancy suggests the need for prioritizing screening programs and improving the existing protocols to enhance maternal and child healthcare. [ABSTRACT FROM AUTHOR]

Covid‐19 in West Africa masked outbreaks of vaccine‐preventable diseases such as the measles epidemic in children in Guinea in 2021–2022 characterized by a lack of confirmation of suspected clinical cases. During weeks 13–22 of 2022, saliva samples were collected from 213 children (3–60 months old) with measles‐like symptoms within the St Gabriel dispensary in Conakry. Samples were processed in Virus Transport Medium (VTM) and tested on the same day by triplex reverse transcriptase ‐real‐time polymerase chain reaction for Measles, Rubella and RNaseP. Samples were also tested for HHV6 and Parvovirus B19, viruses causing clinical signs similar to measles. We confirmed 146 (68.5%) measles cases, 27 (12.7%) rubella, 5 (2.3%) double‐positive measles‐rubella, 35 (16.4%) HHV‐6 and 8 (3.75%) Parvovirus B19. To test the assay's robustness, 27 samples were kept at 26–30°C. Measles and rubella were still detected after 7 days at 26–30°C, and after 21 days measles and rubella were still detectable in all samples but one. Sequencing indicated the circulation of the B3 measles genotype, as expected in West Africa. This study highlights the robustness of the measles/rubella diagnostic test on saliva samples stored in VTM. The high level of rubella detection questioned the single valence measles vaccination strategy. [ABSTRACT FROM AUTHOR]

Background A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but data on long-term immunity are limited. We assessed neutralizing antibody levels against measles and rubella among adults up to 11 years after receipt of a third MMR dose. Methods In this longitudinal study, healthy adults who received a third MMR dose as young adults (ages 18–28 years) were recalled around 5 years and 9–11 years after the third dose. Measles and rubella antibody levels were assessed by plaque-reduction and immunocolorimetric neutralization assays, respectively. Antibody concentrations <120 mIU/mL and <10 U/mL were considered potentially susceptible to measles and rubella, respectively. Geometric mean concentrations (GMCs) and 95% confidence intervals (CIs) over time were estimated from generalized estimating equation models. Results Approximately 5 and 9–11 years after receipt of the third dose, 405 and 304 adults were assessed, respectively. Measles GMC was 428 mIU/mL (95% CI, 392–468 mIU/mL) 5 years postvaccination, declining to 381 mIU/mL (95% CI, 339–428 mIU/mL) 11 years postvaccination. At the last follow-up visit (9–11 years postvaccination), 10% of participants were potentially susceptible to measles infection. Rubella GMCs were stable throughout the follow-up period (63 U/mL to 65 U/mL); none of the participants was susceptible to rubella at the last follow-up visit. Conclusions Eleven years after receiving a third MMR dose, measles and rubella neutralizing antibody levels remained high in adults. However, on the basis of waning antibody levels, some adults may become susceptible to measles infection over time despite receipt of 3 vaccine doses. [ABSTRACT FROM AUTHOR]

This study included the detection of the spread of the Rubella virus and some causes of abortion among women of childbearing age in the city of Samarra. Ninety samples were collected from women with recurrent abortions for the period from the beginning of October 2019 to the end of January 2020. Their ages ranged between (16-45) years. Anti-rubella IgG, IgM, antiphospholipid (APL), anticardiolipin (ACL), and antinuclear antibody (ANA) were investigated for (60) samples of women who were infected with the rubella virus, and (30) samples from no infected women. The results showed that 86.7% of the women infected with German measles had anti-rubella IgG and 35% had anti-rubella IgM. While the other group had 38.4% of IgG and 0% of IgM anti-rubella antibodies. The results showed that 71.7%, 78.3%, and 11.7% of patients with rubella infection gave positive results for APL, ACL, and ANA antibodies, respectively. 16.6%, 6.7%, and 3.4% of the cases that were suffering from repeated miscarriages and without rubella gave a positive result for APL, ACL, and ANA antibodies, respectively. [ABSTRACT FROM AUTHOR]

Since the initial identification of vaccine-derived rubella virus (RuV) in the cutaneous granulomas of pediatric patients with inborn errors of immunity in 2014, more than 80 cases of RuV granulomas have been reported implicating both vaccine-derived and wild type RuV. Previously thought to arise exclusively in patients with significant immunocompromise, the identification of RuV granulomas in clinically immunocompetent patients adds nuance to our understanding of the interplay between host environment, immune dysregulation, and RuV granuloma formation. This review summarizes the literature on RuV granulomas including clinical and histopathologic features, proposed pathomechanisms supporting granuloma development, and potential therapeutic options. There is no standardized algorithm to guide the workup and diagnosis of suspected RuV granulomas. We highlight the importance of contributing RuV granuloma cases to ongoing Centers for Disease Control and Prevention surveillance efforts to monitor wild type and vaccine-derived RuV transmission. Studies advancing our understanding of RuV granulomas may provide insights into the role of viral infectious agents in granulomatous disease pathogenesis and guide the development of improved therapeutic options. [ABSTRACT FROM AUTHOR]

Since 1969, rubella and its harmful effect on fetuses infected in utero can be prevented by rubella vaccine, usually given in combination with measles vaccine. The rubella vaccine is highly protective both in children and in adults including women intending to become pregnant. Owing to the use of combined measles and rubella vaccines, congenital rubella infection has been eliminated from the Western Hemisphere and nearly all of Europe. Such combined vaccination is now being applied throughout the world, posing the possibility of eventual rubella eradication. The existence of viruses of animals related to rubella does not appear to be a barrier to eradication of the human virus. However, persistent rubella virus in infants infected in utero and of immunosuppressed patients with granulomas may pose a problem for eradication. Nevertheless, this review posits that eradication of rubella is now feasible if routine vaccination of infants and surveillance for chronic infection are correctly applied. [ABSTRACT FROM AUTHOR]

Background/Objective: Miscarriage is often a result of maternal infection with pathogens, including Toxoplasma gondii, Rubella virus, Cytomegalovirus, and Herpes Simplex Virus (TORCH). This study aimed to investigate the seroprevalence of TORCH agents in women with spontaneous miscarriage in Jizan, Kingdom of Saudi Arabia. Methods: A retrospective, cross-sectional study was conducted at a maternity hospital in the Jizan region. The study included 201 pregnant women who visited the hospital between 2018 and 2022. Blood samples were collected, and TORCH IgG and IgM antibodies were measured using indirect ELISA kits. Descriptive statistics and chi-square tests were used for data analysis. Results: The majority of pregnant women fell within the 31-40 age range (49.3%) and had a graduate education level (54.2%). Among the participants, 40.3% tested positive for Toxoplasma IgG antibodies, 11.9% tested positive for Toxoplasma IgM antibodies, 24.9% tested positive for Rubella IgG antibodies, 4% tested positive for Rubella IgM antibodies, 28.9% tested positive for Cytomegalovirus IgG antibodies, and 4% tested positive for Cytomegalovirus IgM antibodies. For Herpes Simplex Virus type 1, 9% tested positive for IgG antibodies, and 0.5% tested positive for IgM antibodies. For Herpes Simplex Virus type 2, 4.2% tested positive for IgG antibodies, and 0.5% tested positive for IgM antibodies. Conclusion: The study revealed a significant seroprevalence of TORCH agents among women with spontaneous miscarriage in Jizan, Kingdom of Saudi Arabia. The findings highlight the importance of screening for TORCH infections during prenatal care to identify potential risks to the fetus and implement appropriate management strategies. [ABSTRACT FROM AUTHOR]

Rubella virus infection can cause vertical transmission to the fetus during pregnancy. In China's Henan province, rubella surveillance needs to be well‐established. In this research, a total of 1933 neonates and 2502 pregnant women were enrolled, and their sera for IgG and IgM antibodies against rubella were tested by chemiluminescence assay. Of 1933 neonates' sera tested, the seropositive of rubella IgG was 68.7%. The seroprevalence of rubella IgM in neonates was 0.4%. 30.9% of neonates had negative results for IgG and IgM antibodies. Two thousand five hundred and two pregnant women participated in the serosurvey, and 79.3% were rubella IgG positive. Rubella IgG seropositivity in pregnant women differed by age and number of births. 0.8% of the pregnant women had positive results for IgM against the rubella virus. The seronegative of rubella IgG and IgM antibodies in pregnant women was 19.8%. Due to the negative rubella‐specific IgG antibody, many neonates remain at risk of rubella virus infection. Rubella virus continues to spread since some neonates and pregnant women with rubella‐specific IgM antibody positive have been detected. Rubella vaccination may be introduced for childbearing‐age women to increase immunity levels against rubella with periodic sero‐surveillance. [ABSTRACT FROM AUTHOR]

Abstract Uveitis is a process of intraocular inflammation that may involve different sections of the uveal tract. Apart from systemic or localized immune-mediated diseases, infections are key players in the etiology of uveitis and entail different treatment strategies. Rubella virus (RuV) is a recognized causative agent for the development of Fuchs uveitis, representing a major cause of virus-associated intraocular inflammation. A cohort of 159 patients diagnosed with different forms of uveitis between 2013 and 2019 was subjected to diagnostic antibody testing of the aqueous or vitreous humor. The diagnostic panel included RuV, cytomegalovirus, herpes simplex virus, varicella-zoster virus, and toxoplasmosis. Within this cohort, 38 RuV-associated uveitis (RAU) patients were identified based on a pathologic Goldman-Witmer coefficient indicative of an underlying RuV infection. With a mean age of 45.9 years, the RAU patients were younger than the non-RAU patients (56.3, p

Background: Measles and rubella are vaccine-preventable diseases targeted for elimination in most World Health Organization regions, and China is considered to have momentum towards measles elimination. Therefore, this study aimed to assess the population immunity levels against measles and rubella in Zhejiang Province in China in order to provide valuable insights for informing future public health measures and contributing to the ongoing global campaign against these diseases. Materials and methods: A cross-sectional serological survey was conducted in 2022. A total of 2740 blood samples were collected from healthy individuals spanning the age range of 0–59 years, representing diverse demographic strata across 11 prefectures in Zhejiang Province in China. The sera were tested for measles and rubella IgG antibodies to determine positivity rates and geometric mean concentrations (GMCs). Results: The overall positivity rate for the measles IgG antibody was 85.3%, with a GMC of 588.30 mIU/mL. The positivity rate for the rubella IgG antibody was 70.9%, and the GMC was 35.30 IU/mL. Measles IgG antibody positivity rates across the 0–11 months, 12–23 months, 24–35 months, 3–5 years, 6–9 years, 10–14 years, 15–19 years, 20–29 years, and 30–59 years age groups were 63.1%, 92.5%, 97.0%, 94.0%, 85.8%, 77.3%, 86.9%, 84.9%, and 88.7%, respectively (trend χ2 = 118.34, p < 0.001). Correspondingly, rubella antibody positivity rates for these same age brackets were 55.9%, 87.9%, 94.7%, 88.2%, 69.9%, 54.2%, 72.6%, 67.5%, and 74.3% (trend χ2 = 199.18, p < 0.001). Both univariate and multivariate analyses consistently demonstrated that age, immunization history, and differing economic levels were significant factors contributing to variations in antibody levels. Conclusions: The seroprevalence of measles and rubella was lower than that required for herd immunity. Periodic vaccination campaigns should be launched to increase immunity.

TORCH infections usually result in mild maternal morbidity, but may cause severe congenital abnormalities. Therefore, it is important to detect maternal infections, monitor the fetus after the disease has been recognized, and define the seronegative women who are at risk of primary infection during pregnancy. From 2014 to 2023, serum samples from 1032 childbearing-aged and pregnant women (16–45 years) were tested for IgM/IgG antibodies to the most common TORCH pathogens: Toxoplasma gondii, rubella virus (RUBV), cytomegalovirus (CMV), and herpes simplex viruses (HSV-1 and HSV-2). The overall IgG seroprevalence rates were 20.1% for T. gondii, 91.3% for RUBV, 70.5% for CMV, 66.8% for HSV-1, and 3.5% for HSV-2. Only HSV-2 seroprevalence was age-related, with a significant progressive increase in seropositivity from 0% in those aged less than 26 years to 9.3% in those older than 40 years. The seroprevalence of T. gondii was higher in residents of suburban/rural areas than in residents of urban areas (27.4% vs. 17.1%). In addition, participants from continental regions were more often toxoplasma-seropositive than those from coastal regions (22.2% vs. 15.3%). HSV-1 seroprevalence was also higher in suburban/rural areas (71.7% vs. 64.7%). Obstetric history was not associated with TORCH seropositivity. Univariate and multivariate risk analysis showed that suburban/rural areas of residence and continental geographic regions were significant risk factors for T. gondii seroprevalence. Furthermore, suburban/rural area of residence was a significant risk factor for HSV-1 seroprevalence, while older age was a significant risk factor for HSV-2 seroprevalence. A declining trend in the seroprevalence of all TORCH pathogens was observed compared to previous Croatian studies (2005–2011). Similarly, the proportion of women simultaneously IgG-seropositive to two or three pathogens decreased over time. The maternal serology before pregnancy could potentially reduce the burden of congenital TORCH infections.

Abstract Background TORCH infections during pregnancy significantly impact neonatal and maternal mortality rates worldwide. This study aimed to gather baseline serological data for pregnant women's immunological status to infection and determine if definite TORCH pathogens (cytomegalovirus, rubella virus, and Herpes simplex virus) were associated with Toxoplasma infection, to improve prenatal care and provide appropriate infection control strategies. Methodology Blood samples were gathered from 210 pregnant women attending Al Zagazig University hospitals from February to May 2023. Samples were examined for specific IgM and IgG antibodies against TORCH pathogens by electrochemiluminescence technique. Results Regarding TORCH infection, 60 (28.6%) cases were seronegative, while 77 (36.7%), 63 (30.0%), 56 (26.7%), and 15 (7.1%) were positive IgG antibodies against Toxoplasma gondii, cytomegalovirus, rubella virus, and Herpes simplex virus, respectively. There was no estimate for IgM for cytomegalovirus, rubella virus, or Herpes simplex virus, indicating that no primary infection had been detected during the pregnancy. There was a statistically significant association between seroprevalence of toxoplasmosis infections (IgM and IgG) and age group ≤ 25 years, which is the most common childbearing age group. Cytomegalovirus seropositivity was found in those beyond 25 years (P-value 0.001). Antibodies to mono-infections were found in 97/210 (46.2%) subjects. It is substantially higher under-25 years age group, 71/97 (73.2%), P-value of 0.001. 45/210 (21.4%) participants had antibodies to two agents, with no significant difference in the age group over 25 years, 26/45 (57.8%). Antibodies to three agents were assessed in eight instances, all under 25 years. Conclusions According to our findings, serological evaluation for the TORCH complex in all pregnant women is recommended to determine infection immunity, current immunization regimens, and infection reactivation. Low TORCH antibodies rates amongst pregnant women in Egypt's Sharqia governorate might be an appropriate starting point for prenatal screening initiatives.

Abstract Background TORCH (Toxoplasma gondii [TOX], Cytomegalovirus [CMV], Rubella virus [RV], and Herpes simplex virus [HSV]) represents pathogens known to traverse the maternal-fetal barrier and cause severe neonatal anomalies. We aimed to assess the prevalence of preconception TOX, CMV, and RV infections among women with fertility desire in southern China, and identify related risk factors. Methods Data were obtained from a population-based cross-sectional study conducted as part of the National Free Preconception Health Examination Project. Women planning to conceive within the next 6 months in Guangdong Province were enrolled between 2014 and 2019. Information on sociodemographic, gynecological, and obstetric characteristics was collected. Sera were analyzed for TOX IgG, CMV IgG, and RV IgG antibodies using an enzyme-linked immunosorbent assay. Descriptive, univariate, and multivariate logistic regression analyses were performed to assess the association between TORCH infections and related factors. Results Among 2,409,137 participants, the prevalence of IgG antibodies for TOX, CMV, and RV was 3.20% (95% CI: 3.18–3.22%), 77.67% (95% CI: 77.62–77.71%) and 76.03% (95% CI: 75.98–76.07%), respectively. Of all participants, 141,047 women (5.85%, 95% CI:5.83–5.88%) reported a history of immunization for RV. Women living in the Pearl River Delta, a more developed region, have significantly lower vaccination rates than those living in other regions. The seropositivity of TOX IgG was highest among women aged 35 years and above, with primary or lower education levels, and rural registration. Factors such as being older, having a higher educational level, and being of other ethnicities were associated with a higher prevalence of naturally acquired CMV and RV infections. Women living in the Pearl River Delta showed a higher risk of TOX, CMV, and RV infections, with aORs of 2.21, 4.45, and 1.76, respectively. A history of pregnancy, gynecological diseases, and sexually transmitted infections were potentially associated with TORCH infections, but this association varied across pathogens. Conclusion The findings of this study update the baseline of preconception TORCH infections among women with fertility desire in southern China, helping to estimate the risk of congenital infection and guide the development and implementation of effective prevention measures for preconception TORCH infections.

Uveitis is a process of intraocular inflammation that may involve different sections of the uveal tract. Apart from systemic or localized immune-mediated diseases, infections are key players in the etiology of uveitis and entail different treatment strategies. Rubella virus (RuV) is a recognized causative agent for the development of Fuchs uveitis, representing a major cause of virus-associated intraocular inflammation. A cohort of 159 patients diagnosed with different forms of uveitis between 2013 and 2019 was subjected to diagnostic antibody testing of the aqueous or vitreous humor. The diagnostic panel included RuV, cytomegalovirus, herpes simplex virus, varicella-zoster virus, and toxoplasmosis. Within this cohort, 38 RuV-associated uveitis (RAU) patients were identified based on a pathologic Goldman-Witmer coefficient indicative of an underlying RuV infection. With a mean age of 45.9 years, the RAU patients were younger than the non-RAU patients (56.3, p < 0.001). The evaluation of clinical parameters revealed a predominance of anterior uveitis and late sequalae such as cataract and glaucoma among the RAU patients. In 15 of the patients a history of prior RuV infections could be confirmed. The study underlines the importance of long-term surveillance of RuV associated diseases that originate from infections before the introduction of RuV vaccination programs. [ABSTRACT FROM AUTHOR]

Patients with inborn errors of immunity (IEI) may develop granulomas in multiple organ systems including the skin. Vaccine strain rubella virus (RuV), part of the live attenuated measles, mumps, and rubella (MMR) vaccine, has been identified within these granulomas. RuV is typically found in macrophages; however, recently neutrophils have been identified as a novel cell type infected. Here, we present a case of RuV‐associated cutaneous granuloma with RuV localized to neutrophils. A 46‐year‐old female with common variable immunodeficiency presented with verrucous papules and crusted plaques from the right knee to the distal shin of 20 years duration, associated with prior physical trauma. Biopsy specimen showed palisaded granulomas surrounding central necrosis with scattered aggregates of neutrophils. Vaccine‐derived RuV was detected by molecular sequencing in lesional skin. Fluorescent immunohistochemistry with CD206, myeloperoxidase (MPO), and RV capsid (RVC) antibodies demonstrated that RuV localized to neutrophils but not macrophages. The clinical presentation, cutaneous findings, and likely presence of RVC‐positive granulocytes in bone marrow provide potential support to the evolving hypothesis of persistent RuV within neutrophils contributing to chronic granulomatous inflammation in a milieu of immune dysregulation. [ABSTRACT FROM AUTHOR]

We present a case of cutaneous granulomatous disease associated with rubella virus in a 4‐year‐old girl without an identifiable immunodeficiency. In this case, a combination of anti‐inflammatory, anti‐viral, and anti‐neutrophil therapies successfully treated vision‐threatening eyelid, conjunctival, scleral, and orbital inflammation. [ABSTRACT FROM AUTHOR]

Rubella is a viral disease that can lead to severe health complications, especially in pregnant women and their unborn babies. Understanding the dynamics of the Rubella disease model is crucial for developing effective strategies to control its spread. This paper introduces a major innovation by employing a novel piecewise approach that incorporates two different kernels. This innovative approach significantly enhances the accuracy of modeling Rubella disease dynamics. In the first interval, the Caputo operator is employed to address initial conditions, while the Atangana–Baleanu derivative is utilized in the second interval to account for anomalous diffusion processes. A thorough theoretical analysis of the piecewise derivative for the problem is provided, discussing mathematical properties, stability, and convergence. To solve the proposed problem effectively, the piecewise numerical Newton polynomial technique is employed and the numerical scheme for both kernels is established. Through extensive numerical simulations with various fractional orders, the paper demonstrates the approach's effectiveness and flexibility in modeling the spread of the Rubella virus. Furthermore, to validate the findings, the simulated results are compared with real data obtained from Rubella outbreaks in Uganda and Tanzania, confirming the practical relevance and accuracy of this innovative model. [ABSTRACT FROM AUTHOR]

In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV‐6) and 7 (HHV‐7), parvovirus B19 (B19V), enterovirus (EV), Epstein−Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS‐CoV‐2. Differential diagnosis was carried out on 289 discarded cases by multiplex real‐time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV‐7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV‐6, EV, HAdV, and HCMV‐positive cases were found in children aged 0−4 years and HHV‐7 was most frequent in the 15−39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus‐positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities. [ABSTRACT FROM AUTHOR]

There are 13 globally recognized rubella virus genotypes of which only 2 (1E and 2B) have been detected recently. The largest percentage of all reported rubella virus sequences come from China and Japan with Africa reporting limited data. In a bid to address the lack of rubella genotype data in Uganda and the World Health Organization Africa region, we sought to characterize rubella viruses retrospectively using sera collected from suspected measles patients that turned out rubella IgM positive. Seven sequences belonging to genotype 2B sub-lineage 2B-L2c were obtained. These sequences clustered with other genotype 2B sequences previously reported from Uganda. None of the other genotypes (1E and 1G) reported from Uganda in the earlier years were detected. In addition, none of the sequences were obtained after the introduction of the measles-rubella containing vaccine. The above highlight the need for continuous rubella virological surveillance to confirm interruption of endemic rubella genotype circulation. [ABSTRACT FROM AUTHOR]

This article, published in the journal Pediatric Allergy & Immunology, discusses the presence of rubella virus (RuV) in individuals without immunodeficiencies. The study found that patients with cutaneous granulomas, a type of skin condition, have been found to contain RuV in lesions and shed recoverable virus. While most cases of RuV-associated granulomas have been found in individuals with immunodeficiencies, there have also been cases in individuals without clear host defense compromise. The study surveyed the presence of vaccine strain RuV (VDRV) in samples from non-immune-deficient individuals and found no evidence of the virus. These findings suggest that VDRV is not a common commensal and support the idea that it is a pathogen. The study also discusses the need for further research to understand the variables governing VDRV-associated inflammatory disease. [Extracted from the article]

Background: TORCH infections during pregnancy significantly impact neonatal and maternal mortality rates worldwide. This study aimed to gather baseline serological data for pregnant women's immunological status to infection and determine if definite TORCH pathogens (cytomegalovirus, rubella virus, and Herpes simplex virus) were associated with Toxoplasma infection, to improve prenatal care and provide appropriate infection control strategies. Methodology: Blood samples were gathered from 210 pregnant women attending Al Zagazig University hospitals from February to May 2023. Samples were examined for specific IgM and IgG antibodies against TORCH pathogens by electrochemiluminescence technique. Results: Regarding TORCH infection, 60 (28.6%) cases were seronegative, while 77 (36.7%), 63 (30.0%), 56 (26.7%), and 15 (7.1%) were positive IgG antibodies against Toxoplasma gondii, cytomegalovirus, rubella virus, and Herpes simplex virus, respectively. There was no estimate for IgM for cytomegalovirus, rubella virus, or Herpes simplex virus, indicating that no primary infection had been detected during the pregnancy. There was a statistically significant association between seroprevalence of toxoplasmosis infections (IgM and IgG) and age group ≤ 25 years, which is the most common childbearing age group. Cytomegalovirus seropositivity was found in those beyond 25 years (P-value 0.001). Antibodies to mono-infections were found in 97/210 (46.2%) subjects. It is substantially higher under-25 years age group, 71/97 (73.2%), P-value of 0.001. 45/210 (21.4%) participants had antibodies to two agents, with no significant difference in the age group over 25 years, 26/45 (57.8%). Antibodies to three agents were assessed in eight instances, all under 25 years. Conclusions: According to our findings, serological evaluation for the TORCH complex in all pregnant women is recommended to determine infection immunity, current immunization regimens, and infection reactivation. Low TORCH antibodies rates amongst pregnant women in Egypt's Sharqia governorate might be an appropriate starting point for prenatal screening initiatives. [ABSTRACT FROM AUTHOR]

Background: TORCH (Toxoplasma gondii [TOX], Cytomegalovirus [CMV], Rubella virus [RV], and Herpes simplex virus [HSV]) represents pathogens known to traverse the maternal-fetal barrier and cause severe neonatal anomalies. We aimed to assess the prevalence of preconception TOX, CMV, and RV infections among women with fertility desire in southern China, and identify related risk factors. Methods: Data were obtained from a population-based cross-sectional study conducted as part of the National Free Preconception Health Examination Project. Women planning to conceive within the next 6 months in Guangdong Province were enrolled between 2014 and 2019. Information on sociodemographic, gynecological, and obstetric characteristics was collected. Sera were analyzed for TOX IgG, CMV IgG, and RV IgG antibodies using an enzyme-linked immunosorbent assay. Descriptive, univariate, and multivariate logistic regression analyses were performed to assess the association between TORCH infections and related factors. Results: Among 2,409,137 participants, the prevalence of IgG antibodies for TOX, CMV, and RV was 3.20% (95% CI: 3.18–3.22%), 77.67% (95% CI: 77.62–77.71%) and 76.03% (95% CI: 75.98–76.07%), respectively. Of all participants, 141,047 women (5.85%, 95% CI:5.83–5.88%) reported a history of immunization for RV. Women living in the Pearl River Delta, a more developed region, have significantly lower vaccination rates than those living in other regions. The seropositivity of TOX IgG was highest among women aged 35 years and above, with primary or lower education levels, and rural registration. Factors such as being older, having a higher educational level, and being of other ethnicities were associated with a higher prevalence of naturally acquired CMV and RV infections. Women living in the Pearl River Delta showed a higher risk of TOX, CMV, and RV infections, with aORs of 2.21, 4.45, and 1.76, respectively. A history of pregnancy, gynecological diseases, and sexually transmitted infections were potentially associated with TORCH infections, but this association varied across pathogens. Conclusion: The findings of this study update the baseline of preconception TORCH infections among women with fertility desire in southern China, helping to estimate the risk of congenital infection and guide the development and implementation of effective prevention measures for preconception TORCH infections. [ABSTRACT FROM AUTHOR]

Rubella virus is an important human pathogen that can cause neurological deficits in a developing fetus when contracted during pregnancy. Despite successful vaccination programs in the Americas and many developed countries, rubella remains endemic in many regions worldwide and outbreaks occur wherever population immunity is insufficient. Intense interest since rubella virus was first isolated in 1962 has advanced our understanding of clinical outcomes after infection disrupts key processes of fetal neurodevelopment. Yet it is still largely unknown which cell types in the developing brain are targeted. We show that in human brain slices, rubella virus predominantly infects microglia. This infection occurs in a heterogeneous population but not in a highly microglia-enriched monoculture in the absence of other cell types. By using an organoid-microglia model, we further demonstrate that rubella virus infection leads to a profound interferon response in non-microglial cells, including neurons and neural progenitor cells, and this response is attenuated by the presence of microglia. [ABSTRACT FROM AUTHOR]

Rustrela virus (RusV; species Rubivirus strelense , family Matonaviridae) was discovered in different zoo animal species affected by fatal encephalitis. Simultaneous RusV RNA detection in multiple yellow-necked field mice (Apodemus flavicollis) suggested this rodent as a reservoir of RusV. Here, we investigated 1,264 yellow-necked field mice and sympatric other small mammals from different regions in Germany for RusV RNA using an optimized reverse transcription-quantitative polymerase chain reaction (RT-qPCR) protocol and high-throughput sequencing. The investigation resulted in the detection of RusV RNA exclusively in 50 of 396 (12.6 per cent) yellow-necked field mice but absence in other sympatric species. RT-qPCR-determined tissue distribution of RusV RNA revealed the highest viral loads in the central nervous system, with other tissues being only very rarely affected. The histopathological evaluation did not reveal any hints of encephalitis in the brains of infected animals despite the detection of viral RNA in neurons by in situ hybridization (ISH). The positive association between the body mass of yellow-necked field mice and RusV RNA detection suggests a persistent infection. Phylogenetic analysis of partial E1 and full-genome sequences showed a high diversification with at least four RusV lineages (1A–1D) in northeastern Germany. Moreover, phylogenetic and isolation-by-distance analyses indicated evolutionary processes of RusV mostly in local reservoir populations. A comparison of complete genome sequences from all detected RusV lineages demonstrated a high level of amino acid and nucleotide sequence variability within a part of the p150 peptide of the non-structural polyprotein and its coding sequence, respectively. The location of this region within the RusV genome and its genetic properties were comparable to the hypervariable region of the rubella virus. The broad range of detected RusV spillover hosts in combination with its geographical distribution in northeastern Germany requires the assessment of its zoonotic potential and further analysis of encephalitis cases in mammals. Future studies have to prove a putative co-evolution scenario for RusV in the yellow-necked field mouse reservoir. [ABSTRACT FROM AUTHOR]

The article presents a progress report on rubella elimination in South-East Asia region from 2013 to 2021. Topics include increase in routine immunization coverage with the first dose of rubella-containing vaccine (RCV1) during the period, possible consequences of rubella infection during pregnancy, and rubella and congenital rubella syndrome (CRS) incidence and rubella virus genotypes.

Introduction. Rubella is a mild infectious disease affecting mainly children and is caused by the rubella virus, part of the Matonoviridae family, genus Rubivirus. Rubella causes congenital rubella syndrome (CRS) and is the main cause of developmental abnormalities, especially blindness and deafness. There is no specific treatment for rubella and CRS. In order to avoid possible complications from rubella infection, a live attenuated rubella vaccine based on the foreign strain of Wistar RA 27/3 rubella virus is used. However, the actual, more effective and preferred vaccine strain the rubella virus for the Russian Federation is considered to be a viral strain of rubella circulating on its territory. The aim of the study was to study the biological properties of the developed domestic cold-adapted strain vRub-Ant circulating in the territory of the Russian Federation. Materials and methods. Following cell cultures were used in the study human embryo lung diploid cell strain LECH-3, transferable cell line from embryonic kidney cells of green monkeys Vero CCL-81 and Vero ECC, human mesenchymal stem cells, human peripheral blood mononuclear cells (PBMC). Cell cultures were grown on a DMEM/F12 nutrient medium with the addition of 5% fetal bovine serum. Swabs from the pharynx and nasal passages from a child with rubella were used as clinical virus-containing material. Monoclonal anti-idiotypic antibodies m(anti-ID)Ab were used to assess the expression level of alpha/beta and gamma interferon receptors (/ and IFN-R)Ab, imitating the biological effects of alpha/beta and gamma interferons (/ and IFN) of humans. The cultural, virological, immunochemical and serological research methods were applied in the study. Results. Attenuation of the vRub-Ant clinical isolate of rubella virus was carried out for 20 consecutive passages on LECH-3 diploid cells at a reduced temperature of 30C. The main biological markers of attenuation were determined to be ts and ca phenotypes. The avirulence of the attenuated viral strain (att-phenotype) was assessed by the level of expression of / and IFN-R. A lower level of / and IFN-R expression was found on the membranes of human PBMC induced by the vaccine strain vRub-Ant in comparison with the parent wild variant of the rubella virus. This trait,the att phenotype, is characteristic of attenuated viral strains. It has been shown that the vaccine strain vRub-Ant has lost neurotropism and was unable to bind to the membrane receptors of the brain (MRB) of guinea pig embryos, unlike its parent rubella virus strain. The high immunogenicity of the domestic cold-adapted strain vRub-Ant was confirmed by high titers of neutralizing rubella antibodies observed in guinea pigs immunized subcutaneously with one vaccination dose of the virus. Conclusion. A domestic attenuated vaccine strain vRub-Ant of the rubella virus that has the main biological markers of attenuation (ts-ca and att phenotypes) has been developed. The vaccine strain vRub-Ant induces a high levels of neutralizing antibodies in guinea pigs following the immunization with a single vaccination dose of the vaccine. The viral strain vRub-Ant has lost its tropism to the MRB of guinea pig embryos, unlike its parent variant.