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Competing Interests: The authors declare that they have no conflict of interest.

Purpose: To evaluate the clinical characteristics of congenital rubella retinopathy (CRR) with modern fundus imaging., Methods: Single-center case series. Eleven patients (2005-2020) at the Emory Eye Center with known or presumed CRR. Trained image readers reviewed fundus imaging (color fundus photography, widefield pseudocolor imaging, near-infrared reflectance imaging, autofluorescence imaging, and spectral-domain optical coherence tomography) for pre-specified features suggestive of CRR., Results: Eleven patients with confirmed (63.6%) or presumed (36.3%) CRR were identified. All were female with median (range) age of 53 (35-67) years. Six (54.5%) were born during the 1964-1965 United States rubella epidemic. All had congenital hearing loss. Two (18.2%) had a congenital heart defect. Eleven (50.0%) eyes had salt-and-pepper retinal pigmentary changes. Twenty-two eyes (100.0%) had irregularly distributed regions of speckled hypoautofluorescence. One eye (4.5%) had a presumed macular neovascularization., Conclusion: Modern fundus imaging demonstrates characteristic features of CRR, even when pigmentary changes are not readily apparent on examination. Widefield autofluorescence findings of irregularly distributed speckled hypoautofluorescence are particularly revealing. This series of newly diagnosed adults with CRR may represent the milder end of the phenotypic spectrum of this condition, highlighting imaging findings that may aid in diagnostically challenging cases of CRR., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the dysmorphic facial features in congenital rubella syndrome (CRS) and describe their associations with ocular and systemic features., Methods: The medical records of children diagnosed with CRS between 2016 and 2021 were retrospectively reviewed for ocular and systemic features. CRS was diagnosed either on the basis of positive serology for rubella antibodies or with the classic triad of congenital cataract, sensorineural hearing loss, and congenital heart defect. Children with photographic documentation of the face were analyzed independently by three experienced investigators for facial dysmorphic features (triangular face, microcephaly, broad forehead, low anterior hairline, whorl on the anterior hairline, prominent nose, micrognathia). The dysmorphic feature was recorded as present only when at least two of the three examiners confirmed its existence., Results: CRS was diagnosed in 237 children: mean age at presentation, 5.45 ± 4.5 years; 126 males (53%); bilateral cataract, 176 (75%). Positive serology for rubella antibodies was noted in 153 children (65%). Photographic record of facial features was documented in 127 (54%). The most common dysmorphic facial feature was wide forehead (82 [65%]), followed by low anterior hairline with whorl (41 [32%]). However, microcornea (P = 0.9801), cataract (P = 0.8342), pupillary sphincter atrophy (P = 0.7421), and salt and pepper retinopathy (P = 0.8803) were not significantly associated with the presence of facial dysmorphism. Congenital heart disease was significantly associated with facial dysmorphism (P = 0.0308). Sensorineural hearing loss was not associated with the presence of facial dysmorphism (P = 0.8463)., Conclusions: Facial dysmorphism is common in children with CRS, but it was not predictive of the presence of ocular manifestations of CRS in this cohort., (Copyright © 2023 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Following rubella virus control, the most important cause of congenital infections is human cytomegalovirus (HCMV). Congenital CMV (cCMV) may happen both in primary and non-primary maternal infections. The present study aimed to screen cCMV in symptomatic newborns suspected of congenital rubella syndrome (CRS) in Iran., Methods: Out of 1629 collected infants' serum samples suspected of CRS but negative for rubella IgM, 524 samples were selected regarding cCMV complications. These samples were divided into two age groups: 1- one month and younger, 2- older than 1 month up to one year. Anti-HCMV IgM detection was performed on these serums. Then HCMV IgG avidity assay and HCMV DNA detection were carried out on all samples with positive and borderline results in IgM detection., Results: Herein, 3.67% of symptomatic infants aged one month and younger had positive and borderline HCMV IgM, 12.5% of which had a low avidity index (AI). HCMV IgM detection rate among symptomatic infants older than one month to one year was 14.5%. Identified genotypes in this study were gB-1(63.63%), gB2 (18.18%), and gB3 (18.18%), respectively., Conclusions: This comprehensive study was performed on serum samples of symptomatic infants clinically suspected of cCMV from all over Iran. There was a good correlation between serology findings and PCR., (© 2024. The Author(s).)

Rubella infections are rarely seen where immunization programmes are in place. Congenital rubella syndrome is however still observed where the vaccination programme against rubella is not administered or interrupted. We present such a case, with typical clinical anomalies including congenital cataracts, sensorineural hearing loss and bone lesions. The diagnosis was verified by detection of rubella immunoglobulin M positivity in the mother in the first trimester and positive rubella serology in both baby and mother.

Background: Rubella is a common inherited infection resulting in congenital cataracts and a significant cause of permanent vision loss in developing countries. In 2016, Indonesia had the highest number of congenital rubella syndrome (CRS) cases globally. Here, we report the first genotype of the rubella virus extracted from the eye lens from a child with congenital cataracts due to CRS., Case Presentation: A female neonate was delivered by an elective caesarean delivery with normal birth weight at term from a 24-year-old mother in the rural setting. The baby presented with bilateral congenital cataracts, small-moderate secundum atrial septal defect, severe supravalvular pulmonary stenosis, and profound bilateral hearing loss. She also had microcephaly and splenomegaly. The patient's serology showed persistent positive IgG for rubella virus at the age of four years and four months. Following extraction during cataract surgery, viral detection of the lenses identified the presence of rubella. Phylogenetic analysis confirmed that the virus was grouped into genotype 1E., Conclusions: Our study reports the first phylogenetic analysis of the rubella virus extracted from the eye lens of a child with CRS in Indonesia. The detection of the rubella virus from eye lenses is remarkably promising. Our findings also emphasize the importance of molecular epidemiology in tracking the origin of rubella infection toward achieving virus eradication., (© 2022. The Author(s).)

Background: Congenital heart disease (CHD) is a common congenital malformation. Antenatal rubella infection in the mother and genetic defects are important causes to which CHD are attributed. Exact contribution of antenatal rubella infection or genetic causes to CHD is still unknown., Objective: To study the epidemiology, etiology and clinical associations of echocardiographically confirmed congenital heart disease in infants in Western Rajasthan enrolled in the congenital rubella syndrome (CRS) surveillance project. To study the utility of clinical diagnostic criteria in identifying congenital rubella infection., Method: This was a prospective observational study, in which 251 patients with echocardiographically confirmed CHD were enrolled. Detailed clinical evaluation was done in all patients. Rubella serology was done in all patients. Genetic and other testing was done as appropriate., Result: The hospital-based prevalence of CHD in infants was 1% at our center. Fifty-seven percent of the babies had acyanotic septal heart defects of which ventricular septal defect (VSD) was the most common (35%). Anti-rubella immunoglobulin M (IgM) antibodies were positive in 8.5% of the CHD patients. A clinically identifiable genetic cause was present in 3.6% of the cases. In patients who tested positive for anti-rubella IgM antibodies also, VSD was the most common (33%) CHD followed by Tetralogy of Fallot (13.2%)., Conclusion: CRS contributes to 8.5% of CHD. CRS is associated with a wide spectrum of CHD. The etiology of a large number of CHD remains elusive. Detailed studies on the cause and mechanism of development of CHD need to be undertaken., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To study the frequency of intrauterine rubella infection in a cohort of neonatal-onset glaucoma (NOG) and its effect on the treatment outcomes., Design: Prospective cohort study., Participants: Infants with NOG presenting to the pediatric glaucoma service at a tertiary care center in northern India at Chandigarh between January 1, and September 30, 2018, with a minimum postoperative follow-up of 1 year were included in this study., Methods: Rubella immunoglobulin-M (IgM) antibodies were tested in all patients. Surgery for intraocular pressure (IOP) control comprised combined trabeculotomy with trabeculectomy or goniotomy. Presenting features and treatment outcomes at 1 year were compared among infants with and without rubella-IgM antibodies., Results: Of 27 eligible infants, 7 (25.9%) were rubella-IgM positive, and all had bilateral glaucoma. One eye in a rubella-positive baby was an unsightly blind eye and required a prosthesis. A total of 13 eyes of 7 patients were compared with 34 eyes of 20 rubella-negative patients. There was no significant difference in mean age and IOP at presentation. Rubella-positive infants had significantly more opaque corneas (P < 0.001), shorter eyes (P < 0.001), and smaller corneal diameters (P = 0.007) at presentation. Two patients in the rubella group had bilateral cataracts, 3 patients had heart disease, and 1 patient had sensorineural deafness. Salt-and-pepper retinopathy was noted in both rubella-positive infants where fundus evaluation was possible. Despite comparable IOP control (P = 0.51), the corneal clarity remained significantly worse in the rubella-positive patients (P = 0.02)., Conclusions: Twenty-five percent of those with newborn glaucoma had underlying intrauterine rubella infection, thus making them susceptible for development of congenital rubella syndrome (CRS). Neonatal-onset glaucoma is an important component of CRS, which may present without buphthalmos and persistent corneal clouding despite good IOP control., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Rubella is an acute illness caused by rubella virus and characterised by fever and rash. Although rubella is a clinically mild illness, primary rubella virus infection in early pregnancy can result in congenital rubella syndrome, which has serious medical and public health consequences. WHO estimates that approximately 100 000 congenital rubella syndrome cases occur per year. Rubella virus is transmitted through respiratory droplets and direct contact. 25-50% of people infected with rubella virus are asymptomatic. Clinical disease often results in mild, self-limited illness characterised by fever, a generalised erythematous maculopapular rash, and lymphadenopathy. Complications include arthralgia, arthritis, thrombocytopenic purpura, and encephalitis. Common presenting signs and symptoms of congenital rubella syndrome include cataracts, sensorineural hearing impairment, congenital heart disease, jaundice, purpura, hepatosplenomegaly, and microcephaly. Rubella and congenital rubella syndrome can be prevented by rubella-containing vaccines, which are commonly administered in combination with measles vaccine. Although global rubella vaccine coverage reached only 70% in 2020 global rubella eradiation remains an ambitious but achievable goal., Competing Interests: Declaration of interests AKW receives funding from the Bill and Melinda Gates Foundation and Gavi, the Vaccine Alliance. AKW is a member of the Vaccine Impact Modelling Consortium. The views expressed in this Seminar reflect those of the author and are not necessarily those of the Vaccine Impact Modelling Consortium. WJM was a member of WHO's Strategic Advisory Group of Experts on Immunization Working Group on Measles and Rubella from 2011 to 2018 and is currently a member of the WHO Measles-containing vaccine Microarray patches Product Development Working Group. The views expressed in this Seminar reflect those of the author and are not necessarily those of WHO or the Strategic Advisory Group of Experts on Immunization Working Group on Measles and Rubella., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Congenital rubella syndrome (CRS) is a devastating condition associated with significant morbidity. Due to universal vaccination programs, it is currently a rare condition, especially in developed countries. We report an infant born in Israel to a foreign worker from the Philippines who presented with a blueberry muffin rash immediately after birth. Initial workup revealed sonographic brain anomalies, abnormal hearing tests, and a patent ductus arteriosus. CRS was subsequently confirmed by laboratory diagnosis. Rubella virus genotype 1E was detected in the infant's nasopharyngeal swab and urine samples. This was the first case of CRS in Israel in 20 years, emphasizing the need to "think outside the box" when dealing with infants of mothers who are foreign workers, refugees, or visitors of foreign relatives, in which rubella immune status is unknown. Additionally, public health authorities should consider the routine assessment of rubella immunity status of foreign workers in order to avoid such tragic, preventable diseases. We present a case of congenital rubella syndrome - rarely seen in developed countries. This emphasis the need to "think out of the box" when dealing with infants of mothers who come from countries in which the vaccination program is not well established., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The aim of this study ws to evaluate prognostic factors associated with final visual outcome in patients with congenital cataract associated with congenital rubella syndrome., Methods: A prospective interventional analysis of preoperative systemic and ocular features of 56 eyes of 28 seropositive infants of less than 12 months presenting to us with bilateral cataract was performed. All infants were surgically treated with cataract extraction, posterior capsulorhexis, and anterior vitrectomy followed by visual rehabilitation. Intraocular lens implantation was done in children after 2 years of age. Outcome data were collected till children reached the fifth chronological age. Chi-square test was used as a test of significance for qualitative data., Results: Of the 56 eyes, 44.6% eyes had vision better than 20/60. Important preoperative factors related to poor visual prognosis were morphology of cataract (P = 0.004), microphthalmos (P < 0.001), features suggestive of iris hypoplasia (P < 0.001), optic atrophy (P < 0.001), nystagmus (P = 0.02), and associated neurological anomalies (P = 0.0023). We found no significant statistical association between postoperative visual outcome and isolated rubella retinopathy, cloudy cornea, cardiological, and ontological abnormalities., Conclusion: Cataract associated with rubella is a common cause of congenital cataract in developing countries. Determining prognostic factors helps us in parent counseling and planning treatment protocols. Nevertheless, early detection and treatment with adequate multidisciplinary approach remains priority for improving long-term visual outcomes., Competing Interests: None

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Government of India is committed to eliminate measles and control rubella/congenital rubella syndrome (CRS) by 2020. In 2016, CRS surveillance was established in five sentinel sites. We analyzed surveillance data to describe the epidemiology of CRS in India., Methodology/principal Findings: We used case definitions adapted from the WHO-recommended standards for CRS surveillance. Suspected patients underwent complete clinical examination including cardiovascular system, ophthalmic examination and assessment for hearing impairment. Sera were tested for presence of IgM and IgG antibodies against rubella. Of the 645 suspected CRS patients enrolled during two years, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. The median age of laboratory confirmed CRS infants was 3 months. Common clinical features among laboratory confirmed CRS patients included structural heart defects in 108 (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy) in 82 (59.9%) and hearing impairment in 51. (38.6%) Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. Surveillance met the quality indicators in terms of adequacy of investigation, adequacy of sample collection for serological diagnosis as well as virological confirmation., Conclusions/significance: About one fifth suspected CRS patients were laboratory confirmed, indicating significance of rubella as a persistent public health problem in India. Continued surveillance will generate data to monitor the progress made by the rubella control program in the country., Competing Interests: The authors have declared that no competing interests exist.

Neonates with congenital rubella syndrome (CRS) are known to have associated congenital cardiac malformations. Patent ductus arteriosus (PDA) is one the most common cardiac anomalies associated with CRS. PDA refractory to medical management and associated with ventilatory dependence is considered for surgical ligation. However, the management of PDA can be challenging in the presence of underlying lung disease or pulmonary vascular disease. Outcomes after closure in neonates are dependent upon age, weight, nutritional status, pre-operative pulmonary arterial hypertension and presence of chronic lung disease. We present a neonate with CRS who required surgical PDA closure. The neonate developed severe pulmonary arterial hypertension which led to fatal outcome. The clinical course is corroborated with histo-pathological changes observed on the autopsy of this neonate.

Background: Rubella is an RNA virus in the genus Rubivirus within the Matonaviridae family. Rubella remains a leading vaccine-preventable cause of birth defects. Most African countries including Liberia do not currently provide rubella-containing vaccine (RCV) in their immunization program. We analyzed the existing surveillance data to describe rubella cases and identify the at-risk population., Methods: We conducted a retrospective descriptive statistics on the suspected-measles case-based surveillance data that obtained from the national database. Suspected-measles cases who were negative and indeterminate for measles IgM and tested for rubella IgM were extracted from the database. We used only rubella IgM positive cases to calculate trends and percentages by person, place and time. The cumulative-percent curve was used to visually describe the age distribution of rubella cases., Results: During 2017-2018, a total of 2027 suspected-measles cases with known laboratory results were reported; of which, 1307 were tested for rubella IgM. Among tested cases, 472 (36%) were positive, 769 (59%) were negative and 66 (5%) were indeterminate for rubella IgM. Female contributed 269 (57%) of the confirmed rubella cases respectively. The median age was 7 years with an interquartile range of 5-10 years. From the total rubella cases, 6 (1%) were under 1 year, 109 (23%) were 1-4 years, 207 (44%) were 5-9 years, 87 (18%) were 10-14 years and 56 (12%) were more than or equal to 15 years. Women in their reproductive-age contributed 23 (5%) of rubella cases with 17% positivity rate. Two-thirds or 307 (65%) of the cases were reported from February to May which is dry season in Liberia., Conclusions: Our analysis revealed that rubella was widely circulating in Liberia. Majority of the cases were reported among children < 15 years. However, rubella was also reported among women of reproductive age and infants < 1 year with no report of congenital rubella syndrome (CRS). Detail investigation of rubella cases among infants of < 1 year and women of reproductive age is important to uncover CRS. Establishment of CRS surveillance and the introduction of RCV in the immunization program are crucial to prevent rubella infection and avert the risk of CRS.

A retrospective survey of medical records of children discharged with a diagnosis of congenital rubella syndrome (CRS) from our hospital between January 2005 and December 2015 was performed. There were 28 clinically diagnosed cases of CRS during this period. A total of 17 children (61%) out of 28; had laboratory evidence of immunoglobulin M (IgM) rubella positivity in their serum sample. There were 24 male and 4 female infants (M:F = 6:1; mean age, 2.8 ± 3.5 months). None of the mothers received rubella vaccination in the past. All the infants had low birth weight; 21 had microcephaly. Structural heart defects (21 of 28) was the most prominent manifestation in these infants; of these, patent ductus arteriosus (PDA; 15/28) was the most common one. Other manifestations included cataract (18 of 28), hearing impairment (8 of 28), purpuric rash (6 of 28), developmental delay (8 of 28) and hepatosplenomegaly (26 of 28). Of the 18 children with cataract, 12 had bilateral and 6 had unilateral cataract. There is an urgent need to start effective CRS surveillance and preventive measures including appropriate vaccination against rubella., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens., (Copyright: © 2019 Permanyer.)

Rubella infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). The 11 countries in the World Health Organization (WHO) South-East Asia Region are committed to the elimination of measles and control of rubella and CRS by 2020. Until 2016, when the Government of India's Ministry of Health and Family Welfare and the Indian Council of Medical Research initiated surveillance for CRS in five sentinel sites, India did not conduct systematic surveillance for CRS. During the first 8 months of surveillance, 207 patients with suspected CRS were identified. Based on clinical details and serologic investigations, 72 (34.8%) cases were classified as laboratory-confirmed CRS, four (1.9%) as congenital rubella infection, 11 (5.3%) as clinically compatible cases, and 120 (58.0%) were excluded as noncases. The experience gained during the first phase of surveillance will be useful in expanding the surveillance network, and data from the surveillance network will be used to help monitor progress toward control of rubella and CRS in India., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Rubella was declared eliminated in the United States in 2004. During 2013-2015, 2 infants with congenital rubella syndrome (CRS) were born in New York State. Both mothers were foreign born and traveled to Yemen during their pregnancy. Delayed consideration of CRS led to preventable exposures and a substantial public health response.

Rubella vaccination has been included in the United Kingdom's (UK) routine childhood schedule for nearly 30 years. The UK achieved World Health Organization (WHO) elimination status in 2016 and acute rubella infections are rare. In the period 2003-16, 31 rubella infections in pregnancy (0.23 per 100,000 pregnancies) were identified through routine surveillance, of which 26 were in women who were born abroad. Five of the 31 rubella infections led to congenital rubella syndrome in the infant and three had confirmed congenital rubella infection without congenital rubella syndrome. An additional seven babies were identified with congenital rubella syndrome, although rubella infection in pregnancy had not been reported. Place of birth was known for six of these seven mothers, all of whom were born outside the UK, and in five cases maternal infection was acquired abroad. WHO Europe has set targets for measles and rubella elimination and prevention of congenital rubella syndrome by 2015. Vaccination uptake and rubella immunity is high in the UK population and most infections in pregnancy since 2003 were acquired abroad and in unvaccinated women. Every contact with a health professional should be used to check that women are fully immunised according to UK schedule.

Background: Congenital rubella syndrome (CRS) has many severe neurological manifestations and other systemic consequences. Although various studies have been done in Indonesia, there are no conclusive results on CRS incidence. The aim of this study was therefore to investigate the incidence, clinical manifestations and outcomes of CRS in Yogyakarta, Indonesia., Methods: A descriptive study involving a review of congenital anomalies associated with CRS was carried out at Dr Sardjito Hospital, Yogyakarta, Indonesia, from July 2008 to June 2013. CRS was categorized according to the World Health Organization (WHO) classification. This study involved children aged <1 year old, and was conducted at the outpatient clinic, pediatric and neonatology wards., Results: A total of 201 children met the criteria for suspected CRS during the 5 year study. Of those patients, 6% were classified as having laboratory-confirmed CRS, 21.4% as having clinically compatible CRS, and 72.6% as having discarded CRS (i.e. a suspected case that does not meet the criteria for CRS). The estimated incidence of laboratory-confirmed CRS and laboratory-confirmed and clinically compatible CRS in Yogyakarta, Indonesia during the study period was 0.05:1,000 and 0.25:1,000 live births, respectively. Of the laboratory-confirmed CRS patients, 83.3% of children had congenital heart disease (CHD), 75% had hearing impairment, 66.7% had congenital cataract and 50% had microcephaly. Furthermore, none of the mothers was vaccinated against rubella., Conclusions: The incidence of CRS in infants in Yogyakarta Indonesia is considered high, with most clinical manifestations being CHD, hearing impairment and congenital cataract. This emphasizes the necessity for epidemiological study of CRS in other hospitals and the importance of establishing a national rubella vaccination program in Indonesia., (© 2017 Japan Pediatric Society.)

Congenital rubella syndrome (CRS) has serious consequences, such as miscarriage, stillbirth, and severe birth defects in infants, resulting from rubella virus infection during pregnancy. However, rubella vaccine has not yet been implemented in Indonesia. This study aimed (1) to estimate the incidence of CRS in Indonesia, (2) describe the clinical features of CRS at our referral hospital, and (3) pilot a CRS surveillance system to be extended to other hospitals. We conducted a 4-month prospective surveillance study of infants aged <1 year with suspected CRS in 2013 at an Indonesian hospital. Infants with suspected CRS were examined for rubella-specific IgM antibody or rubella IgG antibody levels. Of 47 suspected cases of CRS, 11/47 (23.4%), 9/47 (19.1%), and 27/47 (57.5%) were diagnosed as laboratory-confirmed, clinically compatible, and discarded CRS, respectively. The most common defects among laboratory-confirmed CRS cases were hearing impairment (100%), congenital cataracts (72.7%), microcephaly (72.7%), and congenital heart defects (45.5%)., Conclusion: The number of laboratory-confirmed CRS cases among Indonesian infants is high. Furthermore, hearing impairment is the most common clinical feature of CRS in infants. Our findings indicate the importance of implementation of rubella vaccine in Indonesia. Conducting hospital-based surveillance of CRS in other hospitals in Indonesia may be appropriate. What is Known: •Congenital rubella syndrome (CRS) has serious consequences in infants resulting from rubella virus infection during pregnancy. •The incidence of CRS in most developed countries has greatly decreased since implementation of rubella vaccination. •Rubella vaccine has not yet been implemented in many developing countries. What is New: •The number of laboratory-confirmed CRS cases among Indonesian infants was high. •Implementation of rubella vaccine into immunization programs in Indonesia is important because of the high number of CRS cases. •Our study highlights the need for ongoing prospective surveillance of CRS in Indonesia.

Objective: Rubella virus infection during the first trimester of pregnancy can cause congenital rubella syndrome (CRS). We aimed to describe the abnormalities in order to define the ultrasound features to look for when performing prenatal scans. The goal of this review is to focus specifically on the signs of CRS accessible to prenatal diagnosis., Methods: We analyzed every case of CRS described before and/or after birth that we identified in the Pubmed database and classified them as accessible or not to prenatal diagnosis., Results: The most frequently reported malformations accessible to prenatal diagnosis were: cardiac septal defects, pulmonary artery stenosis, microcephaly, cataract, microphtalmia, and hepatosplenomegaly., Conclusion: This extensive literature review shows that the ultrasound features of CRS are not well known, even though rubella was the first teratogenic virus described. This review will help clinicians in the management of rubella during pregnancy by clarifying the findings to be sought.

Background: A pre-anaesthestic echocardiogram (echo) is requested for most non-cardiac surgeries to identify possible cardiac structural anomalies., Objective: To describe the prevalence and spectrum of structural cardiac abnormalities seen in various non-cardiac conditions., Methods: We carried out a retrospective review of pre-anaesthetic echos performed over five years on children scheduled for non-cardiac surgery. The requests were categorised according to referring specialities, and the biodata and echo findings were noted., Results: A total of 181 children and 181 echocardiograms were studied, and 100 (55.2%) of the patients were male. Most of the children (87, 48.1%) with oro-facial clefts were referred from dentistry. Of the 181 children, 39 (21.5%) had cardiac abnormalities, most (34, 87.2%) of whom had congenital heart disease (CHD). Ophthalmic requests with suspected congenital rubella syndrome (CRS) had the highest prevalence of 8/12 (66.7%) while the lowest was oro-facial clefts at 15/87 (17.2%). Atrial septal defect was the commonest abnormality, found in 14 patients (35.9%)., Conclusion: Pre-anaesthetic echo should be performed, especially for children with suspected CRS and other congenital anomalies, requiring non-cardiac surgery.

We describe a rubella outbreak that occurred in Romania between September 2011 and December 2012. During this period 24,627 rubella cases, 41.1% (n=10,134) of which female, were notified based on clinical criteria, and a total of 6,182 individuals were found serologically positive for IgM-specific rubella antibody. The median age of notified cases was 18 years (range: <1-65) and the most affected age group 15 to 19 years (n=16,245 cases). Of all notified cases, 24,067 cases (97.7%) reported no history of vaccination. Phylogenetic analysis of 19 sequences (739 nucleotides each), from 10 districts of the country revealed that the outbreak was caused by two distinct rubella virus strains of genotype 2B, which co-circulated with both temporal and geographical overlap. In addition to the 6,182 IgM-positive rubella cases, 28 cases of congenital rubella syndrome (CRS) were identified, including 11 neonatal deaths and one stillbirth. The outbreak underscores the need to encourage higher vaccination uptake in the population, particularly in women of reproductive age, and to strengthen epidemiological and laboratory investigations of suspected rubella cases. Genetic characterisation of wild-type rubella virus is an essential component to enhance surveillance and here we report rubella virus sequences from Romania., Competing Interests: Conflicts of Interest: None declared, (This article is copyright of The Authors, 2016.)

Introduction: Congenital and perinatal infections are a leading cause of neonatal and infant morbidity and mortality. Maternal screening, vaccines or treatment where available, constitute effective prevention strategies to reduce the burden of these diseases. Data on the burden of congenital and perinatal infections are very limited for low and middle-income regions., Areas Covered: This review aims to summarize the burden of congenital and perinatal infections and the main challenges for their control in resource-limited settings. Articles were identified through the main electronic databases and cover the period 1971-2016. Expert commentary: Estimates from low and middle-income countries indicate that the burden of congenital infections may be higher in these regions than in industrialized countries. As preventive and curative strategies are available to tackle some of these infections, efforts at the international and national levels must be made to implement those and thus reduce their burden in resource-limited countries.

To our knowledge, this is the first report of the use of real-time reverse transcription-polymerase chain reaction to assess changes in viral load in a patient with congenital rubella syndrome (CRS). Rubella-specific antibody titers were also determined. The patient was a male neonate born to a primipara with rubella infection at 10 weeks of gestation. He had no symptoms at birth, but rubella virus was detected in his pharynx, blood, and urine. His mental and physical development was normal for 1 year; however, he was diagnosed with deafness at 13 months of age. Thus, the patient was diagnosed with CRS. Rubella infection in the pharynx was almost constant until 5 months of age; however, it increased dramatically at 6 months of age. No infection was detected at 13 months. Rubella-specific immunoglobulin M titer was consistently low until 9 months of age and then decreased gradually until it became negative at 20 months of age. Rubella-specific immunoglobulin G titer was high at birth. However, it decreased at 3 months and increased again at 4 months. This titer peaked at ∼9 months and then decreased again at 13 months. This case shows that the period after the decline in maternal antibody titers, not the neonatal period, may be the most contagious period in patients with CRS., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: An estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants., Methods: Cells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls., Results: RV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV., Conclusions: The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.

Background: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months., Methods: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals., Results: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity., Conclusions: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Rubella remains an important pathogen worldwide, with roughly 100,000 cases of congenital rubella syndrome estimated to occur every year. Rubella-containing vaccine is highly effective and safe and, as a result, endemic rubella transmission has been interrupted in the Americas since 2009. Incomplete rubella vaccination programmes result in continued disease transmission, as evidenced by recent large outbreaks in Japan and elsewhere. In this Seminar, we provide present results regarding rubella control, elimination, and eradication policies, and a brief review of new laboratory diagnostics. Additionally, we provide novel information about rubella-containing vaccine immunogenetics and review the emerging evidence of interindividual variability in humoral and cell-mediated innate and adaptive immune responses to rubella-containing vaccine and their association with haplotypes and single-nucleotide polymorphisms across the human genome., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

TORCH infections classically comprise toxoplasmosis, Treponema pallidum, rubella, cytomegalovirus, herpesvirus, hepatitis viruses, human immunodeficiency virus, and other infections, such as varicella, parvovirus B19, and enteroviruses. The epidemiology of these infections varies; in low-income and middle-income countries, TORCH infections are major contributors to prenatal, perinatal, and postnatal morbidity and mortality. Evidence of infection may be seen at birth, in infancy, or years later. For many of these pathogens, treatment or prevention strategies are available. Early recognition, including prenatal screening, is key. This article covers toxoplasmosis, parvovirus B19, syphilis, rubella, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Rubella is a mild viral disease that typically occurs in childhood. Rubella infection during pregnancy causes congenital rubella syndrome, including the classic triad of cataracts, cardiac abnormalities and sensorineural deafness. Highly effective vaccines have been developed since 1969, and vaccination campaigns have been established in many countries. Although there has been progress, the prevention and diagnosis of rubella remain problematic. This article reviews the implications and management of rubella during pregnancy., (© 2014 John Wiley & Sons, Ltd.)

Purpose: To assess the intraoperative and long-term longitudinal postoperative outcomes of cataract surgery in children with congenital rubella syndrome., Setting: Iladevi Cataract & IOL Research Centre, Ahmedabad, India., Design: Prospective observational clinical study., Methods: Children with congenital rubella syndrome who had cataract surgery were enrolled. All microphthalmic eyes were left aphakic. A 1-piece hydrophobic acrylic intraocular lens was implanted in the capsular bag in eyes without microphthalmos. The postoperative observations included complications and visual assessments up to 5 years., Results: The mean age of the 21 children (37 eyes) was 3.97 months ± 2.1 (SD). Intraocular lens implantation was performed in 12 eyes (32.4%), while 25 eyes (67.6%) were left aphakic. Postoperatively, the median follow-up was 60.79 months. Posterior synechiae were observed in 22 eyes (59.5%) and visual axis opacification in 9 eyes (24.3%). Secondary glaucoma was observed in 16 eyes (43.2%), of which 14 were aphakic and 1 was pseudophakic. Nine eyes required trabeculectomy. Age at surgery and ocular comorbidities were statistically significantly associated with secondary glaucoma (P<.05, χ(2) test and Kendall τB criteria P<.05). The mean corrected distance visual acuity at the final follow-up was 0.72 ± 0.56 logMAR., Conclusions: The long-term results suggest good visual outcomes can be obtained with congenital cataract associated with congenital rubella syndrome after early surgical intervention. The rate of serious postoperative complications was acceptable., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Objective: Outbreaks of rubella and congenital rubella syndrome (CRS) continue to arise in various countries where a rubella-containing vaccine is not included in the national immunization program. After a large-scale rubella outbreak in 2011, CRS cases emerged in Vietnam. The aim of this study was to clarify the clinical features of these cases with an emphasis on cardiovascular complications and outcomes., Methods: From October 2011 to September 2012, we conducted a prospective surveillance study of infants <12 months of age who had manifestations suggesting CRS at the only referral hospital in Khanh Hoa Province. These infants underwent standard examinations, echocardiography, cranial ultrasonography, automated auditory brainstem responses, blood cell count measurements, and rubella-specific antibody testing. Detected cardiovascular defects were regularly followed with echocardiography., Results: We enrolled 38 cases of CRS characterized by a low birth weight (71%), cardiovascular defects (72%), cataracts (13%), hearing impairment (93%), purpura (84%), hepatosplenomegaly (68%), and thrombocytopenia (76%). Patent ductus arteriosus, the most common cardiovascular complication, was often associated with progressive pulmonary hypertension (PH). As of January 2013, 13 infants (34%) had died, and PH was significantly more frequent among the fatalities (P = .004); however, therapeutic closure of the ductus reversed the PH in several cases., Conclusions: PH-associated mortality is high among infants who have CRS in Vietnam. Providing proper assessments, continuous follow-up, and timely intervention for cardiovascular defects is critical for the management of CRS patients. Echocardiography is of diagnostic and prognostic value and can support better clinical management of CRS, even in a developing country setting., (Copyright © 2014 by the American Academy of Pediatrics.)

Background: Epidemiological data about congenital rubella syndrome (CRS) are scarce and rubella vaccine is not yet included in the childhood immunization schedule in Sudan. This study aimed to identify and describe CRS cases among Sudanese infants with congenital eye or heart defects., Methods: Between February and September 2010, paired oral fluid and dried blood spot samples were collected from 98 infants aged up to 12 months. These infants were enrolled during their visits to five hospitals in Khartoum, Sudan. Clinical samples were screened for rubella IgM and for ≥ 6 months old infants also for IgG antibodies by ELISA. The oral fluid of IgM and/or IgG positive patients was tested for rubella RNA by reverse transcriptase PCR., Results: Our findings revealed that two children (2.0%) were IgM positive and another five children (5.1%) were positive for IgG antibodies. None of the five infants of which enough oral fluid was available for RNA investigation was PCR positive., Conclusions: This study documented the presence of CRS in Sudan and highlighted the importance of rubella vaccine introduction for preventing future CRS cases in the country.

Sporadic cases of rubella infection are reported each year in France due to insufficient vaccination coverage. Rubella virus is a very unstable enveloped RNA virus. For this reason, transportation and storage of samples collected for its detection require particular conditions. The genetic stability of rubella virus has allowed the development of very effective vaccines. During the recent rubella outbreaks in Algeria and Tunisia, an unusual high rate of encephalitis was reported. The role of the laboratory is crucial in the management of rubella infection during pregnancy. Rubella serological results must be interpreted with caution. Congenital rubella is a severe disease that should already be eliminated thanks to a very effective vaccine that has been developed. All women of childbearing age should be vaccinated. Rubella vaccination of an unknowingly pregnant woman is not an indication for abortion., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)