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Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis.

ABSTRACT: Development of congenital rubella syndrome associated with rubella virus infection during pregnancy is clinically important, but the pathogenicity of the virus remains unclear.Pathological examination was conducted on 3 aborted fetuses with congenital rubella infection.At autopsy, all 3 aborted fetuses showed congenital cataract confirmed by gross observation. Rubella virus infection occurred via systemic organs including circulating hematopoietic stem cells confirmed by immunohistochemical and molecular investigations, and major histopathogical changes were found in the liver. It is noteworthy that the virus infected the ciliary body of the eye, suggesting a possible cause of cataracts.Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

SUBMITTER: Nguyen TV

PROVIDER: S-EPMC4484509 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis.

Nguyen Thong Van TV Pham Van Hung VH Abe Kenji K

EBioMedicine 20141030 1

<h4>Background</h4>Development of congenital rubella syndrome associated with rubella virus infection during pregnancy is clinically important, but the pathogenicity of the virus remains unclear.<h4>Methods</h4>Pathological examination was conducted on 3 aborted fetuses with congenital rubella infection.<h4>Findings</h4>At autopsy, all 3 aborted fetuses showed congenital cataract confirmed by gross observation. Rubella virus infection occurred via systemic organs including circulating hematopoie ...[more]

PMID: 26137534

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Project description:Rubella vaccines have been used to prevent rubella and congenital rubella syndrome (CRS) in several World Health Organization (WHO) regions. Mathematical modelling studies have simulated introduction of rubella-containing vaccines (RCVs), and their results have been used to inform rubella introduction strategies in several countries. This systematic review aimed to synthesize the evidence from mathematical models regarding the impact of introducing RCVs. We registered the review in the international prospective register of systematic reviews (PROSPERO) with registration number CRD42020192638. Systematic review methods for classical epidemiological studies and reporting guidelines were followed as far as possible. A comprehensive search strategy was used to identify published and unpublished studies with no language restrictions. We included deterministic and stochastic models that simulated RCV introduction into the public sector vaccination schedule, with a time horizon of at least five years. Models focused only on estimating epidemiological parameters were excluded. Outcomes of interest were time to rubella and CRS elimination, trends in incidence of rubella and CRS, number of vaccinated individuals per CRS case averted, and cost-effectiveness of vaccine introduction strategies. The methodological quality of included studies was assessed using a modified risk of bias tool, and a qualitative narrative was provided, given that data synthesis was not feasible. Seven studies were included from a total of 1393 records retrieved. The methodological quality was scored high for six studies and very high for one study. Quantitative data synthesis was not possible, because only one study reported point estimates and uncertainty intervals for the outcomes. All seven included studies presented trends in rubella incidence, six studies reported trends in CRS incidence, two studies reported the number vaccinated individuals per CRS case averted, and two studies reported an economic evaluation measure. Time to CRS elimination and time to rubella elimination were not reported by any of the included studies. Reported trends in CRS incidence showed elimination within five years of RCV introduction with scenarios involving mass vaccination of older children in addition to routine infant vaccination. CRS incidence was higher with RCV introduction than without RCV when public vaccine coverage was lower than 50% or only private sector vaccination was implemented. Although vaccination of children at a given age achieved slower declines in CRS incidence compared to mass campaigns targeting a wide age range, this approach resulted in the lowest number of vaccinated individuals per CRS case averted. We were unable to conduct data synthesis of included studies due to discrepancies in outcome reporting. However, qualitative assessment of results of individual studies suggests that vaccination of infants should be combined with vaccination of older children to achieve rapid elimination of CRS. Better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Guidelines for reporting of outcomes in mathematical modelling studies and the conduct of systematic reviews of mathematical modelling studies are required.

Project description:PurposeMany retinal disorders present with pigmentary retinopathy, most of which are progressive conditions. Here we present over nine years of follow up on a case of stable pigmentary retinopathy that is suspected to stem from a congenital rubella infection. Parafoveal cone photoreceptors were tracked through this period to gain insight into photoreceptor disruption in this pigmentary retinopathy.MethodsThe patient was examined at 8 visits spanning a total of 111 months. Examination at baseline included clinical fundus examination, full-field electroretinography (ERG), kinetic visual field assessment (Goldmann), and best corrected visual acuity; all of these except ERG were repeated at follow up visits. Imaging was performed with fundus photography, spectral-domain optical coherence tomography (SD-OCT) and confocal adaptive optics scanning light ophthalmoscopy (AOSLO). For the latter four time points AOSLO imaging also included split-detector imaging.ResultsThere were no defects in hearing or cardiac health found in this patient. There were minimal visual deficits found at baseline, with mild rod suppression on ERG; best corrected visual acuity was 20/25 OD and 20/20 OS at baseline, which was stable throughout the follow-up period. Retinal thickness as measured by OCT was within the normal range, though foveal hypoplasia was present and outer nuclear layer thickness was slightly below the normal range at all time points. Cone density was relatively stable throughout the follow-up period. A number of cones were non-reflective when observed with confocal AOSLO imaging and density was markedly lower than expected values (foveal cone density was 43,782 cones/mm2 on average). Genetic analysis revealed no causative variations explaining the phenotype.Conclusions and importanceThis patient appears to have a stable pigmentary retinopathy. This case is likely due to a congenital insult, rather than progressive retinal disease. This finding of stability agrees with other reports of rubella pigmentary retinopathy. Imaging with AOSLO enabled observation of two notable phenotypic features. First is the observation of dark cones, which are seen in many retinal disorders including color vision defects and degenerative retinal disease. Second, the cone density is well below what is expected - this is especially interesting as this patient has near-normal visual acuity despite this greatly decreased number of normally-waveguiding cones in the fovea.

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Dataset Information

Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis.

Publications

Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis.

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