Burden of congenital rubella syndrome (CRS) in India based on data from cross-sectional serosurveys, 2017 and 2019-20.

BACKGROUND: India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal. METHODS: We conducted serosurveys in 2019-20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS. RESULT: The seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4-84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49-232.41) and 65.47 per 100,000 live births (95% CI: 41.60-104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225-23,100) and 50,028 (95% CI: 48,234-51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively. CONCLUSIONS: Our findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.

Characteristics of Patent Ductus Arteriosus in Congenital Rubella Syndrome.

This study investigated the characteristics of congenital rubella syndrome (CRS)-associated cardiac complications, particularly patent ductus arteriosus (PDA). We reviewed the medical records of patients with CRS who were admitted to the Children's Hospital 1 in Vietnam between December 2010 and December 2012, and patients with CRS who underwent PDA transcatheter occlusion therapy at the cardiology department between December 2009 and December 2015. We compared the characteristics of PDA treated with transcatheter closure between children with CRS (CRS-PDA) and those without CRS (non-CRS-PDA) who underwent PDA transcatheter closure between July 2014 and December 2015. One-hundred-and-eight children with CRS were enrolled. Cardiac defects (99%), cataracts (72%), and hearing impairment (7%) were detected. Fifty CRS-PDA and 290 non-CRS-PDA patients were examined. CRS-PDA patients had smaller median birthweight (p < 0.001), more frequent pulmonary (p < 0.001) and aortic stenosis (p < 0.001), higher main pulmonary artery pressure, and higher aortic pressure in systole/diastole (p < 0.001 for each) than did non-CRS-PDA patients. The proportion of tubular-type PDA was higher in CRS-PDA patients (16%) than in non-CRS-PDA patients (3%) (p = 0.020). Tubular-type PDA was frequently seen in patients with CRS and accompanied by pulmonary/systemic hypertension and pulmonary/aortic stenosis; in these patients, more cautious device selection is needed for transcatheter PDA closure.

Sensory defects and developmental delay among children with congenital rubella syndrome.

This study investigated the features of developmental difficulties combined with sensory defects in children with congenital rubella syndrome (CRS). Following a large rubella outbreak in Khanh Hoa Province, Vietnam, in 2011, we enrolled 41 children with CRS from September 2011 through May 2013. Fourteen participants died and six became untraceable by October 2013; the remaining 21 children were followed up from 2013 to 2015. Thirteen and seven participants had hearing and functional ophthalmological impairment, respectively. Developmental difficulties were suspected in 19 (95%) children who failed in at least one area of the Ages and Stages Questionnaire (ASQ) and/or Denver II in 2013 and/or 2015. Developmental difficulties were frequently identified in the ASQ communication domain (n = 14 in 2013) and Denver II language area (n = 13 in 2013). Seven (41%) participants were suspected of having autism spectrum disorder (ASD) in 2013 by the Modified Checklist for Autism in Toddlers. In 2015, proportions of children failing the problem-solving (62%) and personal-social (62%) domains had increased and two of 13 were diagnosed with ASD by the Childhood Autism Rating Scale, Second Edition. Developmental difficulties were suspected in most children with CRS, including autism largely combined with sensory dysfunction.

Surveillance of congenital rubella syndrome (CRS) in tertiary care hospitals in Hanoi, Vietnam during a rubella epidemic.

OBJECTIVE: To describe the epidemiology and clinical features of congenital rubella syndrome (CRS) in Hanoi, Vietnam. METHODS: Prospective surveillance of CRS between May 2011 and March 2012 in Hanoi, Vietnam. CRS burden was assessed by clinical examination and collection of serum samples from infants in neonatology, cardiology and pediatric departments of two tertiary care hospitals in Hanoi. All infants born during the study period with clinical manifestations of CRS and seropositivity (IgM) for rubella were included in this study. RESULTS: During the surveillance period 113 infants were identified with confirmed CRS (clinical features and positive rubella IgM). Their mean age at diagnosis was 38.4 days (range 1-152 days) and 61% were female. Clinical manifestations of CRS included low birth weight<2500 g (86.0%), congenital heart disease (63.7%), hearing impairment (63.7%) and ophthalmological abnormalities (46.9%). Other clinical features at birth included: thrombocytopenia (85.0%), neonatal purpura (74.3%), splenomegaly (63.7%), hepatomegaly (62.8%) and blueberry muffin rash (61.1%). Among the mothers of infants with confirmed CRS none had received a rubella vaccine in the past and 88.4% gave a history of rubella contact during the pregnancy under study. In most cases (84.1%) maternal infection occurred in the first trimester. During the surveillance period the estimated annual incidence of CRS was 1.13/1000 live births (95% CI 0.92-1.34). CONCLUSIONS: These preliminary baseline data show a high burden of CRS in Hanoi, Vietnam and the urgent need for universal vaccination. Surveillance to determine and monitor the national burden of CRS is essential.

Spontaneously regressing leukoencephalopathy with bilateral temporal cysts in congenital rubella infection.

Very little is known regarding neuroimaging findings in patients with congenital rubella syndrome. We report a 1.9-year-old boy with congenital rubella syndrome who presented in the neonatal period with severe multisystem involvement and diffuse leukoencephalopathy with subcortical anterior temporal cysts, which showed spontaneous improvement during a period of 3 years.

Persistent infection of human fetal endothelial cells with rubella virus.

Cardiovascular abnormalities are the leading cause of neonatal death among patients with congenital rubella syndrome (CRS). Although persistence of rubella virus (RV) in fetal endothelium has been repeatedly suggested as a possible cause of cardiovascular birth defects, evidence of the permissiveness of fetal endothelial cells to RV is lacking. In this study we evaluated the ability of RV to infect and persist in primary fetal endothelial cells derived from human umbilical vein (HUVEC). We found that wild type (wt) low passage clinical RV productively infected HUVEC cultures without producing cytopathology or ultrastructural changes. RV did not inhibit host cell protein synthesis, cell proliferation, or interfere with the cell cycle. Persistently infected cultures were easily established at low and high multiplicities of infection (MOI) with both laboratory and wt clinical RV strains. However, synchronous infections of entire HUVEC monolayers were only observed with clinical RV strains. The release of infectious virions into media remained at consistently high levels for several subcultures of infected HUVEC. The results indicate that macrovascular fetal endothelial cells are highly permissive to RV and allow slow persistent RV replication. The findings provide more evidence for the suggestion that vascular pathologies in CRS are triggered by persistent rubella virus infection of the endothelium.

Three cases of congenital rubella syndrome in the postelimination era--Maryland, Alabama, and Illinois, 2012.

Infection with rubella virus during pregnancy, especially during the first trimester, can result in congenital rubella syndrome (CRS). Serious manifestations of CRS include deafness, cataracts, cardiac defects, mental retardation, and death. In the last major rubella epidemic in the United States, during 1964-1965, an estimated 12.5 million rubella virus infections resulted in 11,250 therapeutic or spontaneous abortions, 2,100 neonatal deaths, and 20,000 infants born with CRS. In 2004, after implementation of a universal vaccination program, elimination of endemic rubella virus transmission was documented in the United States; evidence also suggests that endemic rubella has been eliminated in the entire World Health Organization (WHO) Region of the Americas. However, rubella virus continues to circulate elsewhere in the world, especially in regions where rubella vaccination programs have not been established (e.g., the African Region), placing the United States at risk for imported cases of rubella and CRS. During 2004-2012, 79 cases of rubella and six cases of CRS were reported in the United States; all of the cases were import-associated or from unknown sources. Of the three cases of CRS that occurred in 2012, conditions included cardiac defects, cataracts, hearing impairment, and pericardial effusion in one infant; patent ductus arteriosus, cardiomegaly, thrombocytopenia, and pneumonitis in a second infant; and cataracts, thrombocytopenia, and cardiac defects in a third infant. All three mothers had been in Africa early in their pregnancies. While rubella remains endemic elsewhere in the world, imported CRS will continue to be a public health concern in the United States.

An update on cardiovascular malformations in congenital rubella syndrome.

BACKGROUND: Congenital rubella syndrome (CRS) has long been characterized by the triad of deafness, cataract, and cardiovascular malformations (CVMs). While initial reports identified patent ductus arteriosus (PDA) as the primary CVM in CRS, the exact nature of the CVMs found in CRS has not been well established. METHODS: We searched the English literature from 1941 through 2008 to identify studies that used cardiac catheterization or echocardiography to evaluate the CVMs in CRS. RESULTS: Of the 121 patients in the 10 studies with catheterization data, 78% had branch pulmonary artery stenosis, and 62% had a PDA. In 49% of cases, both branch pulmonary artery stenosis and PDA were present, whereas isolated branch pulmonary artery stenosis and isolated PDA were found in 29 and 13% of cases, respectively. Of the 12 patients in the 10 studies with echocardiographic data, PDA was more common than branch pulmonary artery stenosis, but this finding is greatly limited by the small numbers of patients and limitations of echocardiography. Although published studies of CVMs in CRS have in general reported PDA as the CVM phenotype most commonly associated with CRS, among CRS cases evaluated by catheterization, branch pulmonary artery stenosis was actually more common than PDA. Moreover, although the combination of branch pulmonary artery stenosis and PDA was more common than either branch pulmonary artery stenosis or PDA alone, isolated branch pulmonary artery stenosis was twice as common as isolated PDA. CONCLUSION: Among children with suspected CRS, clinical evaluations for the presence of CVMs should include examinations for both branch pulmonary artery stenosis and PDA.

Primary investigation of 31 infants with suspected congenital rubella syndrome in Sudan.

Between 2005 and 2006, clinical specimens were collected from 31 infants with suspected congenital rubella syndrome (CRS) who presented at six hospitals in Khartoum, Sudan. Eleven (35.5%) were laboratory confirmed as CRS cases by testing for anti-rubella IgM, IgG and viral genome. For the first time in Sudan, the rubella virus genome was directly detected in clinical specimens of six CRS cases and two viruses were isolated in cell culture. Phylogenetic analysis suggested that three genotypes of rubella virus (RV; 1E, 2B and 1G) were co-circulating in Sudan. The study introduced the methodology for CRS confirmation and surveillance in Sudan and provides preliminary data.

Confirmed congenital rubella syndrome--A case report.

BACKGROUND: Congenital Rubella Syndrome (CRS) is defined clinically as an illness usually manifesting in infancy, resulting from rubella infection in utero with certain specific signs and symptoms. Confirmed CRS is a clinically consistent case which is laboratory confirmed. A report of a 3 month old male diagnosed with confirmed congenital rubella is here presented on account of its rarity and easy prevention with vaccination. METHOD: The case notes of 3 month old male admitted with features consistent with CRS and managed for overwhelming septicaemia with heart failure and encephalitis and review of literature on the subject using manual library and Medline search. RESULT: The infant's Rubella-specific immunoglobulin M (IgM) antibody demonstrated positive and the rubella antibody level was high at 11.6 IU/ml. CONCLUSION: This is the first report of confirmed CRS in our centre. Though few cases are seen, the effects and defects on the child are severe and irreversible thus, vaccination with Measles-mump-rubella (MMR) vaccine is recommended as part of the National Programme on Immunization and for all females of child bearing age, who did not receive it in childhood.

Indication and surgical consideration of cochlear implantation at Ramathibodi Hospital.

OBJECTIVES: To demonstrate selection criteria for cochlear implant candidates as well as the outcome of quality of life (QoL) after cochlear implant surgery. MATERIAL AND METHOD: Retrospective review was performed of all cochlear implants at Ramathibodi Hospital. A total number of 33 cochlear implantations were performed during the period of 10 years from December 1995 to December 2005. Inclusion criteria were established and the audiological criteria were then evaluated using the electrical promontory stimulation test. The etiology of severe sensory neural hearing loss was detected. The CT scan and MRI of the inner ear were studied in the different causes of deafness. RESULTS: The main cause of deafness in the present study (16 adults and 17 children) was suffering from pregnancy rubella. The second one was familial congenital deafness. The CT scan studied in the rubella cases showed anatomical normal cochlea and the hereditary cause of deafness showed abnormal cochlea that caused a strong perilymphatic gusher in a 14 year- old boy. There were 16 cases of adolescent and adult patients who all had good response in the promontory stimulation test. The QoL post implantation was evaluated in regards to improvement in education and communication. CONCLUSION: Multi-channel cochlear implantation in severe profound hearing loss patients could improve the hearing in both normal and abnormal cochlea, congenital rubella deafness and the familial cause of deafness. The outcomes of the QoL after surgery were better in hearing detection, speech perception, school performance, communication and return to work.

Rubella prevalence and its transmission in children.

Rubella is a major cause of birth defects among the TORCH group of agents causing congenital anomalies. Almost all the symptomatic infected infants have long-term neurological sequelae & many asymptomatic infants also develop deafness or psychomotor retardation later in life. In India need for rubella prevention & control is being recognized. Before formulating any kind of rubella vaccination policies, data on the burden of disease is important. Hence the prevalence of rubella in children and their transmission was evaluated. Paired sera of 146 babies with suspected intra uterine infection and their mothers from lower socioeconomic strata was tested for IgM antibodies by commercially available Enzyme immunoassay (EIA) kits. Congenital Rubella Syndrome (CRS) was confirmed in babies presenting with rubella compatible defects with positive IgM antibodies against rubella. It was seen that out of 146-paired samples evaluated, 15-paired samples (10.27%) were positive for IgM antibodies. The transmission rate of rubella virus from mother to child when the mother was infected was around 55.55% according to this study. CRS prevalence of 10.27% among symptomatic infants is significant as a large majority of rubella infection remains undetected and hence the actual burden of the disease may be higher. Since the disease is preventable by an effective vaccination, strategies for rubella immunization should be developed and enhanced.

Surveillance of congenital rubella syndrome in Japan, 1978-2002: effect of revision of the immunization law.

Infection of rubella virus at the early stages of pregnancy in women who are not immune to rubella often induces congenital anomalies in infants, namely congenital rubella syndrome (CRS). This paper is the first comprehensive report of CRS cases in Japan, compiled from a questionnaire to major hospitals, reports to journals and academic meetings, and cases for virus/virus genome verification submitted to the National Institute of Infectious Diseases. CRS incidence in Japan was determined to be 0.2-8.1 cases/100,000 live births per year in epidemic years and 0.1-0.7 in non-epidemic years, respectively. In the last 4 years, the number of CRS cases remarkably decreased to one-three cases per year. This decrease is thought to be because the immunization law was revised in 1994 for changing the focus of rubella immunization from junior high school girls to infants of both sexes.

Rubella virus replication and links to teratogenicity.

Rubella virus (RV) is the causative agent of the disease known more popularly as German measles. Rubella is predominantly a childhood disease and is endemic throughout the world. Natural infections of rubella occur only in humans and are generally mild. Complications of rubella infection, most commonly polyarthralgia in adult women, do exist; occasionally more serious sequelae occur. However, the primary public health concern of RV infection is its teratogenicity. RV infection of women during the first trimester of pregnancy can induce a spectrum of congenital defects in the newborn, known as congenital rubella syndrome (CRS). The development of vaccines and implementation of vaccination strategies have substantially reduced the incidence of disease and in turn of CRS in developed countries. The pathway whereby RV infection leads to teratogenesis has not been elucidated, but the cytopathology in infected fetal tissues suggests necrosis and/or apoptosis as well as inhibition of cell division of critical precursor cells involved in organogenesis. In cell culture, a number of unusual features of RV replication have been observed, including mitochondrial abnormalities, and disruption of the cytoskeleton; these manifestations are most probably linked and play some role in RV teratogenesis. Further understanding of the mechanism of RV teratogenesis will be brought about by the investigation of RV replication and virus-host interactions.