Cases Of Congenital Rubella Syndrome Research Articles

The burden of congenital rubella syndrome in the Philippines: results from a retrospective assessment.

IntroductionIn line with the regional aim of eliminating rubella and congenital rubella syndrome (CRS), phased introduction of rubella-containing vaccines (RCV) in the Philippines’ routine immunization programme began in 2010. We estimated the burden of CRS in the country before widespread nationwide programmatic RCV use.MethodsWe performed a retrospective chart review in four tertiary hospitals. Children born between 1 January 2009 and 31 December 2014 and identified as possible CRS cases based on the presence of one or more potential manifestations of CRS documented in hospital or clinic charts were reviewed. Cases that met the clinical case definition of CRS were classified as either confirmed (with laboratory confirmation) or probable (without laboratory confirmation). Cases that did not fulfil the criteria for either confirmed or probable CRS were excluded from the analysis.ResultsWe identified 18 confirmed and 201 probable cases in this review. Depending on the hospital, the estimated incidence of CRS ranged from 30 to 233 cases per 100 000 live births. The estimated national burden of CRS was 20 to 31 cases per 100 000 annually.DiscussionThis is the first attempt to assess the national CRS burden using in-country hospital data in the Philippines. Prospective surveillance for CRS and further strengthening of the ongoing measles-rubella surveillance are necessary to establish accurate estimates of the burden of CRS and the impact of programmatic RCV use in the future.

Rubella Seroprevalence and real-time PCR detection of RUBV among Congolese pregnant women

BackgroundRubella is an acute infectious disease caused by Rubella virus (RUBV). RUBV remains an important pathogen worldwide, causing approximately 100 000 cases of congenital rubella syndrome (CRS) every year; and the most severe consequence of rubella is teratogenicity. The aim of this study was to estimate the prevalence of RUBV IgG antibodies and determine RUBV genotypes in Congolese pregnant women in Kongo central province, Democratic Republic of Congo (DRC).MethodsThis was a prospective cross-sectional study that consisted of a laboratory analysis of blood samples from 78 pregnant women to check for the presence of RUBV IgG antibodies, and also determine RUBV genotypes in seropositive samples (using primers targeting RUBV nucleoprotein), with the use of serological and molecular methods, respectively. Participants were pregnant women attending antenatal care clinics (ANC) at two health zones of Kisantu town in DRC. They were followed-up from the first to third trimester. Those who were negative for RUBV antibodies at the initial assay (first trimester) were tested in the second and, eventually, the third trimester.ResultsAn overall rubella seroprevalence of 58.97% was observed, whereas RUBV nucleoprotein was detected in 60% of randomly selected 30 blood samples among the 46 RUBV seropositive pregnant women. Five (27.77%) of positive samples were positive for both RUBV genotypes (RV8633/9112 and RV8945/9577), whereas 11 (61.11%) of them were positive for RV8633/9112 and two (11.11%) were positive for RV8945/9577 only. Regarding rubella clinical signs and complications, two subjects (2.56%) presented with fever, whereas five pregnant women (6.41%) had experienced abortion. None (0%) of the participants has been vaccinated against RUBV.ConclusionsFindings from this study suggest that RUBV is prevalent in Congolese pregnant women. Further research is required to elucidate the molecular epidemiology of RUBV in order to design a rational rubella surveillance and control program in DRC.

Seroepidemiology of Rubella Among Female Students of Sabzevar University of Medical Sciences in 2014

اهداف علی‌رغم واکسیناسیون، هنوز هم سرخجه به‌عنوان یک بیماری مهم و تهدید‌کننده سلامت جهانی، کانون توجه است. بر اساس آمارها، سالانه حدود 100‌هزار نمونه سندرم سرخجه مادرزادی در جهان اتقاق می‌افتد. هدف این مطالعه، بررسی وضعیت ایمنی دانشجویان دختر دانشگاه علوم پزشکی سبزوار نسبت به بیماری سرخجه بود.مواد و روش ها در این مطالعه توصیفی‌مقطعی، تعداد 143دانشجوی دختر، پرسشنامه‌ای را شامل پرسش‌های جمعیت‌شناختی و همه‌گیرشناختی (محل سکونت، سابقه دریافت واکسن سرخجه، سابقه عفونت سرخجه خود و خانواده) پر کردند. در ادامه، پس از دریافت رضایت‌نامه کتبی از دانشجویان خون‌گیری شد و با استفاده از روش الایزا، تیتر آنتی‌بادی‌های IgM و IgG ضدسرخجه اندازه‌گیری شد. تجزیه‌و‌تحلیل اطلاعات در نرم‌افزار SPSS نسخه 16 و با استفاده از روش‌های آماری توصیفی و همچنین آزمون آماری »مجذور کای« انجام گرفت.یافته ها 8/45درصد دانشجویان شرکت‌کننده در مطالعه، سبزواری و بقیه ساکن دیگر شهرهای ایران بودند. براساس اظهارات، 3 درصد دانشجویان، واکسن سرخجه را دریافت نکرده بودند. نتایج الایزا نشان داد تمامی نمونه‌های سرمی از نظر IgM اختصاصی ضد‌سرخجه، منفی بودند. همچنین، 3/99 درصد آن‌ها دارای تیتر درخور پذیرش (بیشتر از 10 IU/ml) آنتی‌بادی IgG اختصاصی ضد‌سرخجه بودند.نتیجه گیری نتایج مطالعه ما نشان داد که وضعیت ایمنی دانشجویان دختر دانشگاه علوم پزشکی سبزوار نسبت به بیماری سرخجه، در وضعیت کاملا لوبی قرار دارد.

Rubella in Sub-Saharan Africa and sensorineural hearing loss: a case control study

BackgroundRubella infection can affect several organs and cause birth defects that are responsible for congenital rubella syndrome (CRS). Congenital hearing loss is the most common symptom of this syndrome, occurring in approximately 60% of CRS cases. Worldwide, over 100 000 babies are born with CRS every year. There is no specific treatment for rubella, but the disease is preventable by vaccination. Since 1969, the rubella vaccine has been implemented in many countries, but in Africa, only a few countries routinely immunize against rubella. The aim of this study was to estimate the rate of infection from the wild-type rubella virus in São Tomé and Príncipe by determining rubella seroprevalence with a DBS method. The goal of this study was to reinforce the need for implementation of the rubella vaccine in this country. As secondary objectives, the validation of a DBS method was first attempted and an association between seroprevalence and hearing loss was assessed.MethodsWe collected samples from individuals observed during humanitarian missions in São Tomé and Príncipe. All individuals underwent an audiometric evaluation, and a drop of blood was collected for the dried blood spot (DBS).We define two groups: the case group (individuals with unilateral or bilateral hearing loss (HL)) and the control group (individuals with two normal ears). Patients were excluded if they suffered from conductive HL, if they showed evidence of possible causes of HL, if they had developmental delay or if they refused to participate in the study.ResultsAmong the 315 subjects, we found 64.1% individuals with IgG for the rubella virus, 32.1% without immunity for the rubella virus and 3.8% who were borderline.In the control group, 62.6% were positive for the rubella IgG, whereas in the case group, 72% were positive. Analyzing both groups, with ages ranging from 2 to 14 years of age and from 15 to 35 years of age, we found a seroprevalence of 50.3% to rubella in the younger group and 82.1% in the older group, with a significant difference between cases and control group noted within the younger patients (p = 0.025).ConclusionsRubella is a disease that can be prevented. Rubella infections are still very common in São Tomé and Príncipe, and women of child-bearing age are still at risk for rubella infection during pregnancy, justifying the urgency of vaccination against rubella.A statistically significant association between the group of children under 14 years of age with HL and immunity for rubella was observed in this country, although this study did not allow us to establish a cause-effect relationship between rubella infection and SNHL.

Hospital-based surveillance of congenital rubella syndrome in Indonesia.

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.

External Quality Assessment for Rubella Virus RNA Detection Using Armored RNA in China.

Although tremendous efforts have been made to reduce rubella incidence, there are still 300 new cases of congenital rubella syndrome daily; thus, rubella infections remain one of the leading causes of preventable congenital birth defects. An effective surveillance system, which could be achieved and maintained by using an external quality assessment program, is critical for prevention and control of this disease. Armored RNAs, which are noninfectious and RNase-resistant, were used for encapsulation of the E1 gene of rubella virus and for preparation of a 10-specimen panel for external quality assessment. Thirty-two laboratories across mainland China that used nucleic acid tests for rubella virus RNA detection were included in the external quality assessment program organized by the National Center for Clinical Laboratories of China. Different kinds of commercial kits were used by the laboratories for nucleic acid extraction and TaqMan real-time reverse-transcription PCR for rubella virus RNA detection; 99.2% sensitivity and 100% specificity were achieved in this external quality assessment program. Most of the participating laboratories obtained accurate results for rubella nucleic acid tests, thereby achieving the quality required for regional rubella and congenital rubella syndrome elimination.

Exploring the HIV-risk practices of men who have sex with men in Port Harcourt city, Nigeria

Background: Eye examination is a routine part of the periodic pediatric assessment. Prevention of visual impairment due to congenital cataract is now an international priority. Objectives: To screen infants with nontraumatic congenital cataract for rubella infection, then to determine the prevalence of congenital rubella syndrome (CRS), and to assess the associated problems. Design, Setting, Participants, and Intervention: A prospective hospital-based study conducted at two eye hospitals in Khartoum, Khartoum, Sudan, from March 15, 2011 to August 15, 2011. The studied group comprised infants, below 1 year of age, presenting with congenital cataract. A properly designed questionnaire was used for the collection of data. Blood samples of the infants were tested for the presence of specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by the enzyme-linked immunosorbent assay (ELIZA) method. The data were statistically analyzed using SPSS software. Results: The number of studied infants with congenital cataract was 104, with the average age being 6.8 months. Male to female ratio in the positive cases was 1.3:1. Of the 104 children, 14 (13.5%) were positive for rubella infection. Of these 14 positive infants, 13 (93%) were below 6 months of age. This indicates that almost all the positive cases can be detected before the age of 6 months. Two (14.3%) mothers had a history of fever and skin rash during pregnancy. Of all the positive infants, 13 (93%) had bilateral congenital cataract. Conclusion and Relevance: Of the studied infants, 14 (13.5%) were positive for rubella infection, indicating a significant prevalence rate. Of the infants who were positive for rubella infection, 93% were below 6 months of age, indicating that the detection of this infection is highly possible early in life. So, taking the test as early as possible is recommended. Introduction of rubella vaccination in our national immunization program is recommended. Proper surveillance and reporting of all cases of CRS with urgent and long-term management programs are recommended. More studies on a larger scale are needed in our country.

Epidemiological Characteristics of Congenital Rubella Syndrome Cases during Rubella Epidemic in Japan, 2012–2014

BackgroundRubella infection during the first 20 weeks of pregnancy can cause congenital rubella syndrome (CRS). The main defects of CRS are known as classic triads; hearing impairment, congenital heart disease, and cataract. In Japan from 2011 to 2013, rubella outbreak occurred mainly among adults in their 20s to 40s, and consequently notification of CRS cases increased.MethodsWe collected information of epidemiological characteristics regarding all reported CRS cases and their mothers retrospectively by questionnaire to the physicians and interview to the several members of patients’ association of CRS. We conducted descriptive analysis to evaluate public health impact on CRS in Japan.ResultsA total of 45 CRS cases were reported from October 2012 to October 2014. Majority of cases (96%: 43/45) were diagnosed at less than three months old, except for two cases whose diagnoses at 9 months old and 13 months old due to late onset of cataract and hearing impairment. Males accounted for 56% (25/45). The median gestational week at birth was 38 weeks (range: 31 to 41 weeks) and mean birth weight was 2,171 g (standard deviation: ± 626 g). Frequencies of clinical manifestations at the time of diagnosis revealed that 67% (30/45) of cases had hearing impairment, 58% (26/45) had congenital heart disease, and 16% (7/45) had cataract. The most frequent heart diseases was patent ductus arteriosus (77%: 20/26), followed by pulmonary stenosis (15%: 4/26), and atrial septal defect (15%: 4/26). Only 7% (3/45) had classic triads. Thrombocytopenia which accounted for 73% (33/45) was the most frequent manifestation developed other than classic triads. Eleven cases died at the time of investigation, indicating 24% of case fatality proportion of reported CRS cases in this outbreak. Among ten cases died before 6 months old, nine were complicated by congenital heart disease. None of the mothers of reported CRS cases had two doses of Rubella Containing Vaccine (RCV) before pregnancy; meanwhile 24% (11/45) of mothers had one dose of RCV.ConclusionHigh case fatality proportion of CRS pointed out obvious high public health impact in Japan. Vaccination of two doses of RCV before pregnancy is necessary to preventing CRS.Disclosures All authors: No reported disclosures.

Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy

BackgroundRubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo’s (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC’s historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country’s strategy for RCV introduction. MethodsA rubella antibody seroprevalence assessment was conducted using serum collected during 2008–2009 from 1605 pregnant women aged 15–46years attending 7 antenatal care sites in 3 of DRC’s provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC. ResultsOverall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p⩽0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS. ConclusionsIn the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10–20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as vaccination of women of child bearing age through routine services.

Progress towards measles, rubella and congenital rubella syndrome elimination: Oman experience

Oman has committed to the goal of eliminating measles, rubella and congenital rubella syndrome (CRS) by 2015 year. Elimination is defined as the absence of endemic measles and rubella transmission in a defined geographical area for ≥ 12 months in the presence of a well-performing surveillance system and for rubella without the occurrence of CRS cases associated with endemic transmission in the presence of high-quality surveillance system. Strategies to reach this goal included: a) achieving and maintenance high rates of vaccination coverage; b) syndromic surveillance programs to monitor fever and rash illness syndromes for effective detection of cases; c) and high-quality surveillance system, and sensitive for CRS. Measles and rubella was a leading cause of infant and child morbidity and mortality in Oman before the introduction of measles vaccine by 1975 and thereafter until 1994. With the introduction of a second dose of measles and first rubella vaccines in 1994, coverage for first and second doses of measles and rubella vaccines increased more than 95% in 1996 and has been sustained thereafter. A national measles and rubella immunization catch-up campaign targeting children ages 15 months to 18 years was conducted in 1994 that achieved 94% coverage. As a result, the incidence of measles and rubella have declined markedly in recent years, to ≤ 1 case per million persons in 2012 and to zero cases for measles and rubella in 2013. Similarly, no case of CRS has been notified since 2007. Oman has made significant progress toward measles and rubella elimination and has met the regional elimination goals. However, new challenges faced by Oman, for instance with increased globalization, has led to issues such as outbreaks from imported cases. Additional challenges still remain with regard to increasing identification and immunization of unvaccinated non-Omani workers and their families.

Epidemiological and molecular investigation of a rubella outbreak, Romania, 2011 to 2012.

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.

Serological evidence of acute rubella infection among under-fives in Mwanza: a threat to increasing rates of congenital rubella syndrome in Tanzania.

BackgroundControl of rubella infection is essential for preventing congenital rubella syndrome (CRS) and one of the important steps is to define a target population for vaccination. Therefore this study was done to determine serological evidence of acute rubella infection among under-fives in order to anticipate the magnitude of rubella virus transmission in Tanzania.MethodsA cross-sectional study involving children aged between 1 and 59 months was conducted between September and October 2014 before national rubella vaccination campaigns commenced. Rubella IgM antibodies were detected using commercial indirect enzyme-linked immunosorbent assay (ELISA). Data were analyzed using STATA version 11.ResultsA total of230 under-fives were enrolled, their median age was 14 (Interquartile range (IQR) 7–26) months. The overall seroprevalence of rubella IgM antibodies was 10.9 % (25/230) with two confirmed cases of CRS. Two-sample Wilcoxon rank-sum test showed that the median age of rubella IgM seropositive children was significantly higher than that of IgM seronegative children (39 IQR: 18-51months vs. 14 IQR: 7–24 months, P < 0.001). On multivariate logistic regression analysis increase in age (OR: 1.07, 95 % CI; 1.03–1.1, P < 0.001) and residing in rural areas (OR: 8.07, 95 % CI; 1.43–45.6, P = 0.018) were independently found to predict acute rubella infection among under-fives.ConclusionOur findings indicate that rubella virus is prevalent in our setting posing a risk of transmitting to childbearing aged women hence increasing the risk of CRS. Increasing prevalence of acute infection with age in under-fives indicates the protective role of maternal antibodies among infants. The sustained vaccination programme of under-fives as effective measure to control CRS should be emphasized in developing countries.

Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review.

BackgroundThe burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries.MethodsWe reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000–2010 for each country, region and globally.ResultsThe estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4–61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46–195) in the Western Pacific, excluding China, to 116 (95% CI: 56–235) and 121 (95% CI: 31–238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000–80,000) and SE Asia (49,000, 95% CI: 11,000–97,000). In 2010, 105,000 (95% CI: 54,000–158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000–169,000) in 1996.ConclusionsWhilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.

An outbreak investigation of congenital rubella syndrome in Solomon Islands, 2013.

IntroductionDuring May 2012, a rubella outbreak was declared in Solomon Islands. A suspected case of congenital rubella syndrome (CRS) was reported from one hospital 11 months later in 2013. This report describes the subsequent CRS investigation, findings and measures implemented.MethodsProspective CRS surveillance was conducted at the newborn nursery, paediatric and post-natal wards, and the paediatric cardiology and ophthalmology clinics of the study hospital from April to July 2013. Retrospective case finding by reviewing medical records was also undertaken to identify additional cases born between January and March 2013 for the same wards and clinics. Cases were identified using established World Health Organization case definitions for CRS.ResultsA total of 13 CRS cases were identified, including two laboratory-confirmed, four clinically confirmed and seven suspected cases. Five CRS cases were retrospectively identified, including four suspected and one clinically confirmed case. There was no geospatial clustering of residences. The mothers of the cases were aged between 20 and 36 years. Three of the six mothers available for interview recalled an acute illness with rash during the first trimester of pregnancy.DiscussionAdditional CRS cases not captured in this investigation are likely. Caring for CRS cases is a challenge in resource-poor settings. Rubella vaccination is safe and effective and can prevent the serious consequences of CRS. Well planned and funded vaccination activities can prevent future CRS cases.

Does Rubella Cause Autism: A 2015 Reappraisal?

In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS), 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today’s world. CRS cases are no longer typically seen; yet, autistic children often share findings of CRS including deafness, congenital heart defects, and to a lesser extent visual changes. Autistic children commonly have hyperactivity and spasticity, as do CRS children. Both autistic and CRS individuals may develop type 1 diabetes as young adults. Neuropathology of CRS infants may reveal cerebral vasculitis with narrowed lumens and cerebral necrosis. Neuroradiological findings of children with CRS show calcifications, periventricular leukomalacia, and dilated perivascular spaces. Neuroradiology of autism has also demonstrated hyperintensities, leukomalacia, and prominent perivascular spaces. PET studies of autistic individuals exhibit decreased perfusion to areas of the brain similarly affected by rubella. In both autism and CRS, certain changes in the brain have implicated the immune system. Several children with autism lack antibodies to rubella, as do children with CRS. These numerous similarities increase the probability of an association between rubella virus and autism. Rubella and autism cross many ethnicities in many countries. Contrary to current belief, rubella has not been eradicated and globally affects up to 5% of pregnant women. Susceptibility continues as vaccines are not given worldwide and are not fully protective. Rubella might still cause autism, even in vaccinated populations.

Assessing herd immunity against rubella in Japan: a retrospective seroepidemiological analysis of age-dependent transmission dynamics

ObjectiveWe aimed to epidemiologically assess rubella herd immunity as a function of time, age and gender in Japan, with reference to the recent 2012–2014 rubella epidemic.DesignThis study is a retrospective...

Late Clinical Manifestations of Congenital Rubella Syndrome (CRS), an experience from Oman, 1980¬¬ 2015

BackgroundCongenital rubella syndrome (CRS) is a major cause of severe birth and late onset defects worldwide. A national CRS registry was established in Oman to conduct long term follow-up of CRS cases. MethodsThe CRS national registry includes all CRS cases reported to the Ministry of Health since 1980 and are based on the WHO CRS case definition. CRS patients received annual clinical assessments.ResultsOf 104 reported CRS cases, 85 (82%) were clinically or laboratory-confirmed. Out of the confirmed cases, 46 (54%) patients were successfully contacted and received clinical evaluation. Twenty (24%) of the confirmed cases were lost to follow-up and 19 (22%) were deceased. Among deceased cases, 7 (28%) died from cardiovascular causes, 3 (12%) from meningitis/encephalitis, 2 (9%) from pneumonia, 1 (3%) from, head injury and 12 (48%) had unknown causes.Out of the evaluable patients, 19 (41%) had late-onset symptoms manifestations of CRS detected from 8-23 years of age; 3 (16%) had endocrine function defects: 2 (11%) had thyroid disorders and 1 (5%) had type 2 diabetes mellitus, 3 (16%) had seizures disorders, One (5%) case each of systolic murmur, elevated blood pressure, pulmonary atresia and left ventricular failure were reported. Three (16%) hepatosplenomegaly, 1 (5%) late onset sensorineural hearing impairment, 1 (5%) hypospadias and 1(5%) autism (reported as CRS-related) 18 (39%) had cerebral palsy, 10 (22%) and 5 (11%) had severe to profound and moderate mental retardation were reported. respectively. Seventy two percent of the CRS cases survived up to 30 years.ConclusionsCardiovascular, neurological manifestations and endocrine function defect were the most common late CRS manifestations. The long survival of CRS cases were attributed to early medical and rehabilitation interventions. Identification and follow-up of the CRS cases provided an opportunity to assess late or unrecognised manifestations of congenital rubella and support earlier clinical intervention.Keywords Congenital Rubella Syndrome; CRS; late manifestations of CRS; disability; Expanded Program on Immunization; Oman

Localization of Viral Antigens Improves Understanding of Congenital Rubella Syndrome Pathophysiology

Rubella virus (RV) is responsible for benign postnatal and deadly antenatal infections. Its involvement in developmental defects in children following congenital transmission was first made by Sir Norman McAlister Gregg in 1941. Indeed, the maternal primary infection results in an RV viremia and placental transfer. If it occurs before 12 weeks of gestation, during organogenesis, it can result in severe fetal damage causing miscarriage or malformations primarily affecting the cardiovascular system, eyes, ears and the central nervous system; it is fatal in nearly one third of cases during the first year of life (Tondury and Smith, 1966). This severe RV infection acquired in utero early in pregnancy is named as Congenital Rubella Syndrome or CRS. In 2014, 141 CRS cases were reported from 114 countries mostly from South-East Asia (n = 86/141), although reporting is probably inconsistent according to the authors themselves (Grant et al., 2015). This number had been estimated as closer to 100,000 cases each year in developing countries alone (Cutts and Vynnycky, 1999). To better understand the pathogenesis of CRS in the absence of an animal model, the first histopathological explorations were conducted in some of the 20,000 fetuses infected during the 1964–1965 epidemics in the US when about 12.5 M Rubella cases were reported (National Communicable Disease Center, 1969). Although these studies identified histological lesions in the heart, blood vessels, crystalline lens, ears, brain, teeth and liver consistent with clinical features and sequelae of CRS, they did not solved the mechanisms of virus teratogenicity (Tondury and Smith, 1966, Esterly and Oppenheimer, 1969). In particular, until recently, the exact nature of the cell types infected with RV remained unknown.

Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome

BackgroundAn 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. MethodsCells 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. ResultsRV 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. ConclusionsThe identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.

Shedding of Rubella Virus among Infants with Congenital Rubella Syndrome Born in Tokyo, Japan, 2013-2014.

Rubella is usually a mild illness, with febrile rash being its main symptom. However, serious consequences of rubella infection can result when the infection occurs during the early stages of pregnancy. After the occurrence of a rubella outbreak in Japan that was observed from 2012 to 2013, 45 infants were reportedly born with congenital rubella syndrome (CRS). We prospectively followed the 15 CRS cases reported in Tokyo to determine the virus shedding periods by using nested reverse transcriptase-polymerase chain reaction to detect rubella virus genes. Throast swabs were used for virus detection. The virus shedding period was measured from birth until the time when the sample last tested positive followed by 2 consecutive negative samples. Kaplan-Meier method was used to estimate the proportion of cases remaining positive for rubella virus genes over time. The proportion of CRS cases shedding virus dropped steadily after birth, dropping to 33.8% at 6 months and 16.9% at 12 months. Our findings also suggested that the earlier the mother's onset of rubella during pregnancy, the longer the infant remained positive. Based on our findings, we believe that infants with CRS should be monitored for rubella virus shedding until 1 year of age.