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.

Seroprevalence of rubella in pregnant women in Southern Morocco.

Rubella is a generally benign but dangerous viral infection in early pregnancy, due to the teratogenic potential of the virus. Indeed, it causes spontaneous abortions, in-utero fetal death, premature labor and congenital malformations known as congenital rubella syndrome. The purpose of this study is to determine the immune status of rubella in pregnant women in southern Morocco. A prospective, multicentre study was conducted in 2017 for the detection of rubella IgG and IgM antibodies in 380 pregnant women aged 17 to 46 years, using the Architect i1000 chemiluminescent microparticle immunoassay. Eigthy for percent (84.7%) of women were seropositive. Ten percent of multiparous women remained seronegative despite recommendations for vaccination after delivery. Preventive measures against congenital rubella need to be strengthened, and vaccination is needed in non-immunized women. Vaccination awareness campaigns, especially among non-immunized multiparous women, remain essential.

Epidemiology of Congenital Rubella Syndrome (CRS) in India, 2016-18, based on data from sentinel surveillance.

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.

Hospital based surveillance of congenital rubella syndrome cases in the pre-vaccine era in Amhara Regional State, Ethiopia: A base line information for the country.

BACKGROUND: Rubella virus infection in early pregnancy lead to serious multi-organ birth defects known as congenital rubella syndrome (CRS). The incidence of CRS varies in different populations and the highest burden is found in developing countries in which rubella vaccination is not included in their national immunization programs. In Ethiopia, there is scarcity of data about congenital rubella syndrome. Therefore, the aim of this study was to determine the burden of CRS-related birth defects and its incidence in the pre-vaccine era in Amhara Regional State, Ethiopia. MATERIALS AND METHODS: A cross sectional study was conducted in Dessie, Felege-Hiwot and University of Gondar Referral Hospitals, from December 2015 to August 2017. After getting informed assent from each parent/guardian, blood was collected from infants < 1 year of age for laboratory determination of anti-rubella virus antibodies. Their socio-demographic data and clinical information compatible with congenital rubella syndrome were collected using WHO guideline. RESULTS: During the study period, a total of 50 infants suspected for congenital rubella syndrome were included in the study. All infants suspected for CRS were tested against rubella specific IgM and IgG [for infants ≥ 6 months of age] antibodies using ELISA method. Of these, 9/50 (18%) and 4/14 (28.6%) of them were laboratory confirmed and potential CRS cases, respectively. In the present study, the most common laboratory confirmed defect was ocular manifestations 6 (66.7%) followed by heart related problems 5 (55.6%). In the present study, most of the laboratory confirmed cases (66.7%) were reported among 1-5 months of age infants. In addition, 5 (55.6%) of the infants with laboratory confirmed CRS cases were male and 6 (66.7%) of them were from urban settings. In this study, the incidence of CRS was 0.4 per 1000 live births. CONCLUSION: In this study, nearly one fifth of the infants had laboratory confirmed congenital rubella syndrome and most of them had multiple rubella associated congenital defects at a time. Most of these congenital anomalies were reported among infants ≥ 1 month of age. Based on our result, the incidence of the CRS was line with the global incidence of the CRS in the pre-vaccine era. Therefore, establishing strong rubella/CRS surveillance system as well as introducing the rubella containing vaccine in the national immunization program might be important to reduce the burden of rubella and CRS in the country.

Is birth cohort 1985/9-1990/8 a susceptibility window for congenital rubella syndrome in Taiwan?

OBJECTIVE: The worldwide prevalence of congenital rubella syndrome has drastically decreased after the uptake of vaccine to prevent the infection. However, outbreaks have occurred in some countries due to their own vaccination policies, and this phenomenon has not yet been investigated in Taiwan. Our study aims to fill this gap. MATERIALS AND METHODS: We constructed an analytical database containing 10,824 pregnant women at the Taipei City Hospital, Taipei, Taiwan from January 2004 to July 2012. They were categorized into five birth cohorts according to the different vaccination programs in Taiwan: those born before 1971; those born between September 1971 and August 1976; between September 1976 and August 1979; between September 1979 and August 1985; and between September 1985 and August 1990. Differences of the seronegative rate and titers were compared using the Chi-square and Kruskal-Wallis tests among the five cohorts. RESULTS: The seronegative rates for the five cohorts were 15.00%, 4.07%, 2.88%, 4.21%, and 10.98%, respectively, and were statistically significant different (p < 0.001). The first and fifth cohorts were higher than the average of seronegativity (5%). The mean of log transformed titers were 3.69 IU/mL, 4.22 IU/mL, 4.22 IU/mL, 4.05 IU/mL, and 3.44 IU/mL, which were statistically significant different (p<0.001). Our study also found that the equivocal rates (7.58%) were the highest in the cohort born between September 1985 and August 1990, among those who had been vaccinated. Our study showed that women younger than 27 years had a lower geometric mean titer of antibody titer than the average (60.60 IU/mL). CONCLUSION: The previous vaccination policy in Taiwan has created a susceptibility window for rubella and congenital rubella syndrome over the past decades. We recommend having the antibody test before pregnancy for women born between September 1985 and August 1990, and implement a catch-up vaccine for those who were either seronegative or equivocal to prevent reinfection during their childbearing period.

Congenital rubella syndrome in child of woman without known risk factors, New Jersey, USA.

We report a case of congenital rubella syndrome in a child born to a vaccinated New Jersey woman who had not traveled internationally. Although rubella and congenital rubella syndrome have been eliminated from the United States, clinicians should remain vigilant and immediately notify public health authorities when either is suspected.

Congenital rubella syndrome: a review of laboratory data from 2002 to 2011.

Rubella infection in pregnant women during the first trimester of pregnancy can lead to fetal anomalies, commonly known as congenital rubella syndrome (CRS). The objective of our study was to analyze the serological test results among infants suspected of having CRS aged < or = 12 months compared with their clinical status. Between January 2002 and December 2011, 3,279 serum samples from infants aged < or = 12 months from government hospitals in Malaysia were examined for rubella specific IgM and IgG antibodies using a Axsym, automated analyzer (Abbott Laboratories). Forty-eight samples were positive for rubella specific IgM antibodies and 494 samples were positive for rubella specific IgG antibodies. These were then age stratified and their clinical history reviewed for any CRS symptoms. Fifteen of 38 rubella IgM positive infants (39.5%) aged < 3 months, had a clinical appearance compatible with CRS. However, only 1 IgM positive infant aged 3 to 6 months and one infant aged 7 to 11 months had clinical appearance compatible with CRS. The most common abnormal findings in these cases were congenital heart defects and cataracts. Forty-eight point eight percent of IgM positive cases and 53.1% of IgG positive cases, had inadequate information in the chart to determine the presence of CRS. Clinical findings and timely laboratory diagnosis to determine the presence of CRS are important in infants born with congenital defects. Physicians should also be aware of the appropriate interpretation of these findings.

Active surveillance for congenital rubella syndrome in Yangon, Myanmar.

OBJECTIVE: Rubella vaccine is not included in the immunization schedule in Myanmar. Although surveillance for outbreaks of measles and rubella is conducted nationwide, there is no routine surveillance for congenital rubella syndrome (CRS). Therefore, we organized a study to assess the burden of CRS. METHODS: From 1 December 2000 to 31 December 2002 active surveillance for CRS was conducted among children aged 0-17 months at 13 hospitals and 2 private clinics in Yangon, the capital city. Children with suspected CRS had a standard examination and a blood sample was obtained. All serum samples were tested for rubella-specific IgM; selected samples were tested for rubella-specific IgG and for rubella RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). FINDINGS: A total of 81 children aged 0-17 months were suspected of having CRS. Of these, 18 children had laboratory-confirmed CRS (7 were IgM positive; 7 were RT-PCR positive; and 10 were IgG positive at > 6 months of age). One additional child who tested positive by RT-PCR and whose mother had had rubella during pregnancy but who had a normal clinical examination was classified as having congenital rubella infection. During 2001-02 no rubella outbreaks were detected in Yangon Division. In the 31 urban townships of Yangon Division, the annual incidence was 0.1 laboratory-confirmed cases of CRS per 1000 live births. CONCLUSION: This is the first population-based study of CRS incidence from a developing country during a rubella-endemic period; the incidence of CRS is similar to endemic rates found in industrialized countries during the pre-vaccine era. Rubella-specific IgG tests proved practical for diagnosing CRS in children aged > 6 months. This is one of the first studies to report on the use of rubella-specific RT-PCR directly on serum samples; further studies are warranted to confirm the utility of this method as an additional means of diagnosing CRS.

Newborn screening for congenital infectious diseases.

To estimate the prevalence of congenital toxoplasmosis, Chagas disease, cytomegalovirus, and rubella, blood samples on dried blood spot (DBS) from neonates (day 3-20 of life) were screened for immunoglobulin (Ig) M against Toxoplasma gondii, cytomegalovirus, rubella virus, and IgG against Trypanosoma cruzi by methods used for serum and adapted for use with DBS. Positive samples were further analyzed for IgM and IgG in serum from neonates and mothers. DBS samples from 364,130 neonates were tested for Toxoplasma gondii-specific IgM, and 15,873 neonates were also tested for IgM against cytomegalovirus and rubella virus and for Trypanosoma cruzi-specific IgG. A total of 195 were diagnosed with congenital toxoplasmosis, 16 with cytomegalovirus, and 11 with congenital rubella. One newborn had a confirmed result for Chagas disease, and 21 mothers had positive serum antibodies. These results suggest that infectious diseases should be considered for future inclusion in programs for newborn screening of metabolic diseases in disease-endemic areas.

Congenital hearing impairment associated with rubella: lessons from Bangladesh.

Infection with rubella virus during pregnancy may cause fetal death or the multiple congenital fetal abnormalities that are known as congenital rubella syndrome (CRS). Studies have demonstrated that congenital hearing impairment is the most frequent abnormality associated with intrauterine rubella infection. In the present study, the first of its kind in Bangladesh, we investigated the presence of rubella antibody in hearing-impaired children in order to understand the possible role of rubella infection in the development of hearing impairment. A total of 198 hearing-impaired children and 200 children without hearing problems were studied. After taking a detailed history from the parents, blood samples were collected from both mothers and children; sera were subjected to enzyme-linked immunosorbent assay (ELISA) for anti-rubella IgG. Rubella antibody was detected in 74% of the hearing-impaired children and in 18% of those with normal hearing: this finding correlated with the presence of rubella antibody in the mothers (67%) of rubella seropositive hearing-impaired children. In contrast, we observed rubella antibody in only 14% of the mothers of the children without hearing problems. Consistent with the presence of antibody, 41% of the seropositive mothers who had hearing-impaired children gave a history of fever and rash during early pregnancy. Our study indicates a strong association between rubella infection and hearing impairment in Bangladeshi children. In addition, it also indicates that infection by rubella virus is common in Bangladesh: this suggests that priority should be given to implementing appropriate measures for the control of rubella.

Unseen blindness, unheard deafness, and unrecorded death and disability: congenital rubella in Kumasi, Ghana.

OBJECTIVES: Although rubella serosusceptibility among women of reproductive age in West Africa ranges from 10% to 30%, congenital rubella syndrome has not been reported. In Ghana, rubella immunization and serologic testing are unavailable. Our objectives were to identify congenital rubella syndrome cases, ascertain rubella antibody seroprevalence during pregnancy, and recommend strategies for congenital rubella syndrome surveillance. METHODS: Congenital rubella syndrome cases were identified through prospective surveillance and retrospective surveys of hospital records. A rubella serosurvey of pregnant urban and rural women was performed. RESULTS: Eighteen infants born within a 5-month period met the congenital rubella syndrome case definitions, coinciding with a 9-fold increase in presentation of infantile congenital cataract. The congenital rubella syndrome rate for this otherwise unrecorded rubella epidemic was conservatively estimated to be 0.8 per 1000 live births. A postepidemic rubella immunity rate of 92.6% was documented among 405 pregnant women; susceptibility was significantly associated with younger age (P = .000) and ethnicity (northern tribes, P = .024). CONCLUSIONS: Congenital rubella syndrome occurs in Ghana but is not reported. Information about congenital rubella syndrome and rubella in sub-Saharan Africa is needed to evaluate inclusion of rubella vaccine in proposed measles control campaigns.

Laboratory diagnosis of congenital and maternal rubella infection: a review.

Physicians are aware of the congenital rubella syndrome. Serodiagnosis is usually used to detect rubella infection in pregnant women and their fetuses. Although being considered the cornerstone of serodiagnosis, the hemagglutination inhibition test is gradually being replaced by new more convenient methods. Tests to detect IgM eliminate the need for paired sera to diagnose acute rubella infection. However, because of the possibilities of false positive, IgM results should be interpreted with caution. Detection of IgM in cord blood and new genetic technology made the diagnosis of infection in utero possible. The evidence of reinfection in people considered to be immune is abundant; however, discovering new antigenic determinants correlating with immunity may solve the problem and a new vaccine and antibody test that is truly associated with immunity will be available in the future.