A case of congenital rubella syndrome and epidemiology of related cases in China, 2014-2023.

Rubella is a major cause of congenital defects, and the presence of rubella infection in a pregnant woman may lead to fetal death or congenital defects known as congenital rubella syndrome(CRS). Since China has not yet established a national CRS surveillance system, the true incidence cannot be determined. To understand the disease burden and epidemiological characteristics of CRS cases in China, the article reports the first case of CRS in Quzhou, China, and conducts a retrospective analysis of related cases that have been reported in China over the past decade. Because the availability of rubella-containing vaccines (RCV) was not widespread in China before 2008, women of childbearing age born before 2008 are generally unvaccinated against RCV. Due to the lack of routine CRS monitoring and screening, CRS is underreported in China. Vaccination of nonimmune women of childbearing age with RCV and establishing a sensitive and timely case-based CRS surveillance system can accelerate the elimination of rubella and CRS.

Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Progress Toward Rubella and Congenital Rubella Syndrome Elimination - Worldwide, 2012-2022.

Rubella virus is a leading cause of vaccine-preventable birth defects. Infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects, including cataracts, deafness, heart defects, and developmental delay, known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine can provide lifelong protection against rubella. The Global Vaccine Action Plan 2011-2020 included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions by 2020, and rubella elimination is a critical goal of the Immunization Agenda 2030. This report updates a previous report and describes progress toward rubella and CRS elimination during 2012-2022. During 2012-2022, among 194 WHO countries, the number that included rubella-containing vaccine (RCV) in their immunization schedules increased from 132 (68%) to 175 (90%) and the percentage of the world's infants vaccinated against rubella increased from 40% to 68%. Reported rubella cases declined 81%, from 93,816 in 2012 to 17,407 in 2022. Verification of rubella elimination was achieved in 98 (51%) of 194 countries by 2022, an increase from 84 (43%) countries in 2019. Despite significant progress in the introduction of RCV into routine immunization programs worldwide, approximately 25 million infants annually still do not have access to RCV. Nevertheless, even in complex settings, the increasing number of countries that have achieved and sustained rubella elimination demonstrates progress toward global rubella elimination.

Priorities for hearing loss prevention and estimates of global cause-specific burdens of hearing loss: a systematic rapid review.

BACKGROUND: Hearing loss affects approximately 1·6 billion individuals worldwide. Many cases are preventable. We aimed to estimate the annual number of new hearing loss cases that could be attributed to meningitis, otitis media, congenital rubella syndrome, cytomegalovirus, and ototoxic medications, specifically aminoglycosides, platinum-based chemotherapeutics, and antimalarials. METHODS: We used a targeted and a rapid systematic literature review to calculate yearly global incidences of each cause of hearing loss. We estimated the prevalence of hearing loss for each presumed cause. For each cause, we calculated the global number of yearly hearing loss cases associated with the exposure by multiplying the estimated exposed population by the prevalence of hearing loss associated with the exposure, accounting for mortality when warranted. FINDINGS: An estimated 257·3 million people per year are exposed to these preventable causes of hearing loss, leading to an estimated 33·8 million new cases of hearing loss worldwide per year. Most hearing loss cases were among those with exposure to ototoxic medications (19·6 million [range 12·6 million-27·9 million] from short-course aminoglycoside therapy and 12·3 million from antimalarials). We estimated that 818 000 cases of hearing loss were caused by otitis media, 346 000 by meningitis, 114 000 by cytomegalovirus, and 59 000 by congenital rubella syndrome. INTERPRETATION: The global burden of preventable hearing loss is large. Hearing loss that is attributable to disease sequelae or ototoxic medications contributes substantially to the global burden of hearing loss. Prevention of these conditions should be a global health priority. FUNDING: The US National Institute on Deafness and Other Communication Disorders and the US National Institute on Aging.

Congenital cytomegalovirus infection in newborns suspected of congenital rubella syndrome in Iran: a cross-sectional study.

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.

Facial dysmorphism in congenital rubella syndrome.

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.

Fundus imaging features of congenital rubella retinopathy.

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.

Effect evaluation of rubella knowledge attitudes and practices (KAP) intervention on parents of 0 to 2 year old children in Chongqing, China.

OBJECTIVE: To evaluate the effect of rubella elimination publicity and communication project intervention activities on rubella related knowledge attitudes and practices (KAP) on parents of 0 to 2 year old children in Chongqing, and to provide basis for the formulation of rubella elimination strategies and measures. METHOD: We choose 7 townships (streets) of parents of 0 to 2 year old children who live for more than 6 months in Chongqing to investigate the status of rubella knowledge, attitude and practice. Parents' cognition and behavior related to rubella, congenital rubella syndrome (CRS) and rubella component vaccine (RCV) were analyzed and evaluated before and after intervention. RESULTS: 420 people were surveyed before and after the intervention. The awareness rate of rubella prevention knowledge of parents after intervention was significantly higher than that before intervention, with statistical significance (P < .05). After intervention, parents' support rate of "rubella antibody test before pregnancy" and "RCV vaccination for children" were 89.52% and 72.14%, respectively, which were higher than those of parents before intervention (84.05% and 27.38%, P < .05). The RCV timely vaccination rate of children after intervention was 92.78%, which was higher than that of children before intervention (83.90%, P < .05). CONCLUSION: Targeted publicity and communication methods should be adopted for urban and rural areas to create a good publicity atmosphere, popularize rubella and CRS related popular science knowledge, and improve the RCV timely vaccination rate of school-age children and high-risk population.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2022.

For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.

Estimates of the global burden of Congenital Rubella Syndrome, 1996-2019.

OBJECTIVES: Many countries introduced rubella-containing vaccination (RCV) after 2011, following changes in recommended World Health Organization (WHO) vaccination strategies and external support. We evaluated the impact of these introductions. METHODS: We estimated the country-specific, region-specific, and global Congenital Rubella Syndrome (CRS) incidence during 1996-2019 using mathematical modeling, including routine and campaign vaccination coverage and seroprevalence data. RESULTS: In 2019, WHO African and Eastern Mediterranean regions had the highest estimated CRS incidence (64 [95% confidence intervals (CI): 24-123] and 27 [95% CI: 4-67] per 100,000 live births respectively), where nearly half of births occur in countries that have introduced RCV. Other regions, where >95% of births occurred in countries that had introduced RCV, had a low estimated CRS incidence (<1 [95% CI: <1 to 8] and <1 [95% CI: <1 to 12] per 100,000 live births in South-East Asia [SEAR] and the Western Pacific [WPR] respectively, and similarly in Europe and the Americas). The estimated number of CRS births globally declined by approximately two-thirds during 2010-2019, from 100,000 (95% CI: 54,000-166,000) to 32,000 (95% CI: 13,000-60,000), representing a 73% reduction since 1996, largely following RCV introductions in WPR and SEAR, where the greatest reductions occurred. CONCLUSIONS: Further reductions can occur by introducing RCV in remaining countries and maintaining high RCV coverage.

Congenital Rubella Syndrome Following Rubella Vaccination During Pregnancy.

Rubella vaccine is usually given in combination with measles and mumps vaccines as a measles-mumps-rubella vaccination. Because it contains live attenuated virus, its use is contraindicated during pregnancy. However, since the introduction of rubella vaccine, no cases of congenital rubella syndrome have been reported following vaccination during pregnancy. We report a case of a female infant, born to a woman inadvertently vaccinated with measles-mumps-rubella vaccination early in pregnancy, who manifested a phenotype of cardiac and neurologic defects, neurodevelopmental delay, and lymphocytopenia consistent with congenital rubella syndrome.

Progress Toward Rubella Elimination - World Health Organization South-East Asia Region, 2013-2021.

During 2013, the 11 countries of the World Health Organization (WHO) South-East Asia Region* (SEAR) adopted the goals of measles elimination and rubella and congenital rubella syndrome (CRS) control† by 2020. During 2019, SEAR countries declared a broader goal for eliminating both measles and rubella§ by 2023 (1). Before 2013, only five SEAR countries had introduced rubella-containing vaccine (RCV). This report updates a previous report and describes progress toward rubella elimination in SEAR during 2013-2021 (2). During 2013-2021, six SEAR countries introduced RCV; all countries in the Region now use RCV in routine immunization. Routine immunization coverage with the first dose of a rubella-containing vaccine (RCV1) increased >600%, from 12% during 2013 to 86% during 2021, and an estimated 515 million persons were vaccinated via RCV supplementary immunization activities (SIAs)¶ during 2013-2021. During this time, annual reported rubella incidence declined by 80%, from 5.5 to 1.1 cases per million population. Maldives and Sri Lanka are verified as having achieved rubella elimination; Bhutan, North Korea, and Timor-Leste have halted endemic transmission of rubella virus for >36 months. SEAR has made substantial progress toward rubella elimination; however, intensified measures are needed to achieve elimination.

Considerable doubt about rubella screening and vaccination among unvaccinated orthodox protestant women: a mixed-methods study.

BACKGROUND: Women who are susceptible to rubella are advised to vaccinate against rubella to prevent infection in future pregnancies, and thus avert the risk of congenital rubella syndrome in their unborn child. Rubella outbreaks periodically occur in the under-vaccinated orthodox Protestant community in the Netherlands. The objective of this mixed-methods study was to determine and understand personal experience with rubella, perceived rubella susceptibility, and intention to accept rubella screening and vaccination among unvaccinated orthodox Protestant women. The ultimate aim of this study was to inform policy and practice and contribute to the prevention of cases of congenital rubella syndrome. METHODS: A mixed-methods study was conducted combining an online survey and semi-structured interviews among unvaccinated Dutch orthodox Protestant women aged 18-40 years. Descriptive analysis was used for quantitative data. Qualitative data was analysed using codes and categories. RESULTS: Results of the survey (167 participants) showed that most participants had personal experience with rubella (74%, 123/167) and 101 women (61%, 101/167) indicated they had had rubella themselves. More than half of the women were undecided whether to accept rubella susceptibility screening (56%; 87/156) or rubella vaccination (55%; 80/146). Qualitative findings (10 participants) showed that most women thought they were not susceptible to rubella. Indecisiveness and negative attitudes to accept rubella vaccination were related with religious arguments to object vaccination and with women's perception of absence of imminent threat of rubella. Furthermore, results showed presence of misconceptions among women in the interpretation of their susceptibility and high confidence in their parents' memory that they had experienced rubella as a child although no laboratory screening had been conducted. CONCLUSIONS: In light of an imminent rubella outbreak in the Netherlands, a tailored education campaign should be prepared aimed at and established in cooperation with the under-vaccinated orthodox Protestant community. Health care providers should provide adequate information on rubella and support decision-making in order to stimulate women to make a deliberate and informed decision on rubella screening and, if necessary, subsequent vaccination.

Comparison of population-based measles-rubella immunoglobulin G antibody prevalence between 2014 and 2019 in Lao People's Democratic Republic: Impacts of the national immunization program.

OBJECTIVES: We evaluated the effectiveness of the Lao People's Democratic Republic's measles-rubella immunization program using the seroprevalence from two cross-sectional surveys. METHODS: The nationwide surveys occurred in 2014 and 2019 using a multistage cluster sampling, both requiring samples from 2184 individuals from 52 randomly selected villages. Immunoglobulin G titers, measured using enzyme-linked immunosorbent assay, were considered positive at ≥120 mIU/ml (measles) and ≥10 IU/ml (rubella). We calculated the vaccination-related reduction in the force of rubella infection and the number of congenital rubella syndrome cases averted in 2019. RESULTS: We collected 2135 (women: 55.2%, mean age: 23.2 years) and 2001 (52.7%, 23.1 years) samples in 2014 and 2019, respectively. During 2014-2019, immunoglobulin G prevalence increased from 83.9% (95% confidence interval [CI]: 83.8-84.0) to 98.3% (97.7-98.8) for measles and from 75.4% (75.3-75.5) to 87.8% (86.4-89.2) for rubella. The most plausible reduction in the average force of rubella infection was 100% (95% CI: 28-100) since vaccination started, averting 78 (95% CI: 42-128) congenital rubella syndrome cases in 2019. CONCLUSION: This is the first population-based study for measles and rubella at two different time points in developing countries. Measles and rubella seroprevalence increased significantly during 2014-2019, greatly exceeding the immunity thresholds for their elimination.

Congenital Rubella syndrome: A short report and literature review.

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.

Progress Toward Measles and Rubella Elimination - India, 2005-2021.

In 2019, India, along with other countries in the World Health Organization (WHO) South-East Asia Region,* adopted the goal of measles and rubella elimination by 2023,† a revision of the previous goal of measles elimination and control of rubella and congenital rubella syndrome (CRS) by 2020§ (1-3). During 2017-2021, India adopted a national strategic plan for measles and rubella elimination (4), introduced rubella-containing vaccine (RCV) into the routine immunization program, launched a nationwide measles-rubella supplementary immunization activity (SIA) catch-up campaign, transitioned from outbreak-based surveillance to case-based acute fever and rash surveillance, and more than doubled the number of laboratories in the measles-rubella network, from 13 to 27. Strategies included 1) achieving and maintaining high population immunity with at least 95% vaccination coverage by providing 2 doses of measles- and rubella-containing vaccines; 2) ensuring a sensitive and timely case-based measles, rubella and CRS surveillance system; 3) maintaining an accredited measles and rubella laboratory network; 4) ensuring adequate outbreak preparedness and rapid response to measles and rubella outbreaks; and 5) strengthening support and linkages to achieve these strategies, including planning and progress monitoring, advocacy, social mobilization and communication, identification and utilization of synergistic linkages of integrated program efforts, research, and development. This report describes India's progress toward the elimination of measles and rubella during 2005-2021, with a focus on the years 2017-2021.¶ During 2005-2021, coverage with the first dose of a measles-containing vaccine (MCV) administered through routine immunization increased 31%, from 68% to 89%. During 2011-2021, coverage with a second MCV dose (MCV2) increased by 204%, from 27% to 82%. During 2017-2021, coverage with a first dose of RCV (RCV1) increased almost 14-fold, from 6% to 89%. More than 324 million children received a measles- and rubella-containing vaccine (MRCV) during measles-rubella SIAs completed in 34 (94%) of 36 states and union territories (states) during 2017-2019. During 2017-2021, annual measles incidence decreased 62%, from 10.4 to 4.0 cases per 1 million population, and rubella incidence decreased 48%, from 2.3 to 1.2 cases per 1 million population. India has made substantial progress toward measles and rubella elimination; however, urgent and intensified efforts are required to achieve measles and rubella elimination by 2023.

Phylogenetic analysis of congenital rubella virus from Indonesia: a case report.

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.