A Rubella Epidemic in Sasebo, Japan in 1957, with Various Complications

Though the rubella vaccination programme for adolescent girls was introduced in Japan in 1977, rubella epidemics have occurred repeatedly. Also in Sasebo, Japan in 1987, we experienced various complications as follows: encephalitis (five cases), meningitis (three), thrombocytopenic purpura (four), vascular purpura (four), hemolytic anemia (two), pneumonia (eight), protein-losing gastroenteropathy (one), multiple organ disorder with encephalitis, purpura, myocarditis, hepatic and renal dysfunction (one), and congenital rubella syndrome (CRS: three). Disorders ranging over multiple organs seem to occur in acquired as well as congenital rubella infection. The incidence of encephalitis was estimated to be 1: 1600 cases of rubella and two of five cases were apparently serious. Though the strategy for preventing rubella has been directed only against CRS, we should note the various and severe complications with acquired rubella infection, and should adopt two-stepped protection: vaccination of young children of both sexes and of adolescent girls.     

Burden of congenital rubella syndrome (CRS) in India: <Emphasis Type="Italic">A systematic review</Emphasis>

Background

Rubella, though a mild, vaccine-preventable disease, can manifest with severe teratogenic effects in the fetus labeled as congenital rubella syndrome (CRS) due to primary maternal rubella infection. Despite a reduction in disease burden of several vaccine-preventable diseases through childhood immunization, CRS continues to account for preventable severe morbidity including childhood blindness, deafness, heart disease, and mental retardation.

Objective

To conduct a systematic review to describe the prevalence of CRS and its contribution to major long-term handicaps in Indian population. Another objective was to estimate the susceptibility to rubella infection in Indian adolescent girls and women of reproductive age-group. We also explored strategies to decrease CRS in India by identifying the immunogenicity of rubella containing vaccines (RCV) in Indian children and women, as well as their coverage in India.

Methods

Publications reporting ‘CRS prevalence in general population as well as selected subgroups i.e., suspected intra-uterine infection, congenital ocular abnormalities, deafness, congenital heart disease, mental retardation, and congenital malformations’, ‘seroprevalence to rubella (IgG) amongst women and adolescents’, and ‘immunogenicity and coverage of RCVs’ in Indian population were retrieved through a systematic search. Primary databases employed were Medline through PubMed and IndMed, websites of the WHO, and UNICEF. No restrictions were applied in terms of study designs. The primary outcome measure was ‘congenital rubella syndrome’ (CRS) which was further categorized as ‘suspected CRS’ and ‘confirmed CRS’ as defined by World Health Organization (WHO).

Results

Comprehensive evidence about the true burden of CRS in India is not available. Almost all studies have been done in institutional/hospital set-ups and community-based studies are grossly lacking. There are no studies assessing the prevalence of CRS in general population. All studies have evaluated the CRS burden in symptomatic cohorts of children. 1–15% of all infants suspected to have intra-uterine infection were found to have laboratory evidence of CRS. About 3–10% of suspected CRS cases are ultimately proven to have confirmed CRS with the aid of laboratory tests. CRS accounts for 10–15% of pediatric cataract. 10–50% of children with congenital anomalies have laboratory evidence of CRS. 10–30% of adolescent females and 12–30% of women in the reproductive age-group are susceptible to rubella infection in India. RCVs are highly immunogenic in Indian adolescents and women. The coverage data of RCVs in India is not available. However, the coverage of MMR vaccine has been reported as 42%, 30% and 5% from Delhi, Chandigarh and Goa, respectively.

Conclusion

This systematic review identifies and explores factors associated with the prevalence of CRS in India. There is a need for urgent action in terms of revamping the national immunization policy and introduction of RCVs in the national immunization program. Active surveillance of rubella and CRS is needed to redress the burden of CRS in India.

     

Congenital rubella syndrome after rubella vaccination in 1–4 weeks periconceptional period

Objective  To examine weather exposure to rubella vaccine during 1–4 wk periconceptional period can cause congenital rubella syndrome (CRS). Methods  This prospective study was performed in 60 pregnant women who received rubella vaccine inadvertently 1–4 wk pre or post conception. Time of conception was determined by last menstrual period (LMP) and first trimester sonography. In addition to gathering mother’s obstetric and demographic information, all neonates were evaluated for CRS signs by systemic physical examination and anti rubella IgG and IgM antibody titers in cord blood samples. Results  A total of 60 pregnant women with the median gestational age of 38 weeks were studied. The mean maternal age was 22 years and 58.3% of pregnancies were unintended. In 90% of mothers there were no post vaccination side effects (fever, lymphadenopathy, arthritis, arthralgia). None of the mothers had a history of drug abuse, smoking or teratogenic exposures. Mean neonatal weight was 3100grs and 6.7% of them were premature. No signs of CRS were found in the neonates based on systemic physical exam at birth and one month later. Mean value of cord blood anti rubella IgG titere was 148/28±67/26 lu/ml. cord blood anti rubella IgM was negative in all of the neonates. Conclusion  In this study inadvertent rubella vaccination 1–4 wk before and after conception did not cause CRS in neonates and according to all reasearches pregnancy termination is not indicated in these cases.     

Estimating the burden of congenital rubella syndrome in Costa Rica, 1996-2001

BACKGROUND: The epidemiology of rubella in Costa Rica changed during recent decades, shifting the susceptible groups to the reproductive age. This study estimates the burden of congenital rubella syndrome (CRS) from 1996 to 2001 in this country. METHODS: Three methods to calculate CRS incidence were used. A retrospective search ("Observed cases") was conducted using hospital discharge records of children born from 1996 to 2001 with selected codes of ICD9 and ICD10 consistent with CRS and children <3 months of age with a positive serologic test for rubella IgM antibody at the National Children's Hospital (NCH). Cases were classified as either suspected, compatible or confirmed CRS and congenital rubella infection. "Expected" incidence of CRS was calculated using reported cases of rubella (women 15-45 years of age) and fertility rates, assuming CRS probability of 0.9 during the first trimester of pregnancy and 0.5 of asymptomatic rubella cases. "Estimated" CRS cases were calculated using incidence rates reported from modeling analysis during epidemic and endemic years. RESULTS: Of the 577 discharge charts reviewed and the 66 children reported as rubella IgM(+), 40 compatible CRS cases, 45 confirmed, and 4 with congenital rubella infection cases were identified. The range of annual incidence rate of CRS (per 1000 live births) was as follows: "Observed" = 0.00-0.33, "Expected" = 0.00-0.35 and "Estimated" = 0.5-1.5. Compared with the estimated number of CRS cases, only 27.2% of CRS cases were detected from the retrospective search and 10.1% would be expected when calculated using rubella reported cases. CONCLUSIONS: The under-detection of CRS cases using rubella reported cases in women of reproductive age and retrospective search of CRS reinforces the importance of suspecting CRS in the presence of a single compatible manifestation. Laboratory confirmation is indispensable to implement CRS elimination strategies and should be done in every suspected case.     

Body mass index percentiles among adolescent girls living in Edirne, Turkey

BACKGROUND: Body mass index (BMI) is the simplest way to measure obesity; therefore, it is chosen by many authorities as a screening method for adolescent obesity. Body mass index is positively correlated with the complications of childhood and adolescent obesity, such as hypercholesterolemia, insulin resistance, hyper-tension and long-term development of cardiovascular diseases. The aim of the present study was to produce percentile curves for bodyweight, height and BMI in a representative sample of adolescent girls living in urban and rural areas of Edirne, Turkey, and to compare these percentile curves with curves from other countries. METHODS: The present study was a cross-sectional study, including a representative sample of 1687 adolescent girls from rural and urban areas of Edirne, who were evaluated between May and July 2001. Bodyweight and height were measured using standard procedures. Body mass index (kg/m2) was calculated as the ratio of bodyweight to body height squared. Smoothed percentiles for these variables were calculated using polynominal regression models. Crude weight, height and BMI percentile values, as well as smoothed percentile curves are presented. RESULTS: Body mass index, weight and height reference curves for adolescent girls were produced. When we compared the BMI values of subjects in the present study with those of other countries, 85th and 95th percentiles of BMI in the present study were found to be generally lower than those for other ethnicities. CONCLUSION: Our findings show ethnic differences in BMI among adolescent girls. It will be usefull for each country to produce its own BMI percentiles.     

Incidence, clinical features and estimated costs of congenital rubella syndrome after a large rubella outbreak in Recife, Brazil, 1999-2000

BACKGROUND: During 1998-2000, a large rubella outbreak was reported from Recife, the capital municipality of Pernambuco State, in northeastern Brazil. In 2002, a study was conducted to assess the burden of congenital rubella syndrome (CRS) after this outbreak. METHODS: To describe the rubella outbreak, we analyzed data available from the National Notifiable Disease System. A retrospective record review for CRS was conducted at 6 maternity hospitals where 53% of Recife's resident live births occurred during 1999-2000 and 1 tertiary health care center. Suspected CRS cases were infants with any manifestation of CRS or maternal infection during pregnancy. Standard international definitions for compatible and confirmed CRS cases were used. Direct CRS costs were based on reimbursements by the National Health System. RESULTS: From October 1998 to July 2000, Recife reported 681 confirmed rubella cases. The highest incidence of rubella was among children 5-11 years of age (5.4 per 1000 population). Forty-five suspected CRS cases were identified; 29 were clinically compatible and 2 were laboratory-confirmed. The average annual incidence of CRS was 0.9 per 1000 live births during 1999-2000. Overall costs for the first year follow-up were estimated at 61,824 US dollars in this cohort. CONCLUSIONS: High rubella vaccination coverage is required to prevent the severe congenital disabilities and high economic costs of CRS. Increased clinician awareness is critical for early CRS detection. Complete reporting is essential to evaluate the impact of vaccination programs and to document progress toward the goal of CRS elimination in the Americas by the year 2010.     

Rubella seronegativity in a low socioeconomic adolescent female population

Ninety low socioeconomic adolescent females (aged 16-22 years, means 18.6 years) were screened for rubella immunity using a rubella IgG enzyme immunoassay. Data concerning past immunizations (with documentation, if possible), prior rubella disease, and previous pregnancies were gathered through direct interviews. Results revealed 20 percent (18/90 girls) were seronegative. Fifty-eight percent (42/72) of the seropositive girls and 50 percent (9/18) of the seronegative girls gave verbal reports of previous rubella immunization, but only 11 subjects (12.2%) could provide documentation of previous vaccination, including one seronegative subject. Thirty-one percent (28/90) of the study population had a history of one or more previous pregnancies (22 therapeutic abortions, 10 live births, and 8 spontaneous abortions). A comparison of the seronegativity rate between the 28 girls who were pregnant previously and the 62 girls who were never pregnant demonstrated a significantly higher seronegativity rate among those who had been pregnant (29% vs. 16%; chi 2 = 5.51; p less than 0.05). The results of this study suggest that the seronegativity rate in this age group is consistent with previous reports of rubella immunity, few adolescents can provide documentation of rubella vaccination, and presentation for abortion is an optimal time to vaccinate rubella susceptible females.     

Burden of congenital rubella syndrome after a community-wide rubella outbreak,Rio Branco,Acre, Brazil, 2000 to 2001

BACKGROUND: During 1999 and 2000 rubella outbreaks were reported in 20 of 27 states in Brazil, many among young adults. We investigated a large rubella outbreak in Rio Branco, Acre, in northwestern Brazil, where rubella vaccination targeting children 1 to 11 years old had been introduced in April 2000. Surveillance for congenital rubella syndrome (CRS) was initiated after the outbreak. METHODS: Suspected rubella cases were detected through active and passive surveillance. Confirmed rubella cases were patients with fever, rash and rubella-specific IgM antibodies. Suspected CRS cases were infants born with CRS-compatible defects or born to mothers with a history of rubella during pregnancy. Confirmed cases were infants with CRS-compatible defects and rubella-specific IgM antibodies. RESULTS: From April 1 to December 31, 2000, 391 confirmed rubella cases were reported. The incidence among persons ages 12 to 19 years (3.3 per 1000 population) was increased 3.7-fold relative to children ages 1 to 4 years (95% confidence interval, 2.4 to 5.8). Of 21 infants with suspected CRS cases, 17 (91%) were tested for rubella-specific antibodies, of whom 7 were IgM-positive and 5 had confirmed CRS. The peak incidence of confirmed CRS (4.3 per 1000) was in March 2001, 7 months after the outbreak peak, with an annualized incidence of 0.6 per 1000. CONCLUSIONS: Vaccination among school age children was insufficient to prevent a rubella outbreak among young adults that resulted in the occurrence of at least 5 cases of CRS. To prevent further cases of CRS, outbreak vaccination of young adults was conducted in November 2000 and among women ages 12 to 39 years in 2001 as part of a national campaign, with a coverage of 98% statewide.     

An epidemic of congenital rubella in Barbados

Rubella and congenital rubella syndrome (CRS) are preventable, but epidemics of rubella and CRS are not infrequent in the Caribbean and other developing countries. As a result of a surveillance system initiated after an epidemic of rubella in the Barbadian population in 1996, cases of CRS were identified and investigated. A total of seven cases of CRS were proven to be rubella IgM-positive. The infants were found to have a mean birthweight of 2587 g and a mean gestational age of 38 weeks. The clinical course, complications and outcome of those infants were documented and the cost of acute hospital care for each patient was also recorded. Cataracts in four infants, congenital heart disease in three and central nervous system abnormalities in five were the major clinical abnormalities. In four infants, two or more clinical systems were affected. The combined total hospital stay was 105 days (mean 15, range 0-44). A national effort to immunize all those at risk and a strict surveillance programme are essential to prevent future epidemics. This would lead to a significant reduction in the number of cases of rubella and CRS and could effect substantial savings in the national health budget.     

Fetal risk associated with rubella vaccination during pregnancy

BACKGROUND: Costa Rica implemented a nationwide measles-rubella vaccination campaign among men and women (15-39 years old) in May 2001. A protocol was developed to follow-up the vaccinated women who were unknowingly pregnant, to determine the risk of congenital rubella syndrome (CRS) or congenital rubella infection only associated with the administration of the rubella vaccine RA27/3 during pregnancy. METHODS: To classify the prevaccination maternal immune status, a serum sample was taken at the initial evaluation to detect IgM and IgG rubella antibodies (enzyme-linked immunosorbent assay). All pregnancies were followed up and all newborns were evaluated. A cord serum sample of their children was taken at birth. We calculated odds ratio, OR (95% confidence interval, 95% CI) associated with miscarriage, stillbirth, prematurity, low birth weight, and the presence of defects compatible with CRS. RESULTS: The prevaccination immune status was established in 797 women and 1191 mother and child pairs were analyzed. Adjusted OR for miscarriage (OR = 0.60, 95% CI = 0.26-1.39), stillbirth (OR = 1.32, 95% CI = 0.10-16.81), prematurity (OR = 0.25, 95% CI = 0.03-2.39), low birth weight (OR = 0.25, 95% CI = 0.03-2.23) and defects compatible with CRS (OR = 1.09, 95% CI = 0.34-3.54) showed no association between immune and susceptible maternal status. There were no cases of CRS and no children were IgM positive. CONCLUSIONS: No adverse pregnancy outcome such as miscarriages or CRS was documented in women who were vaccinated and unknowingly pregnant. These results support RA27/3 rubella vaccine safety.     

Molecular epidemiology of rubella virus in Asia: Utility for reduction in the burden of diseases due to congenital rubella syndrome

BACKGROUND: Rubella is a mild disease mainly of infants, involving a rash and a fever. However, when women who have no immunity to rubella are infected during the early stage of pregnancy, their babies are often born with congenital rubella syndrome (CRS), which is characterized by a few disorders including deafness, cataracts and heart malformations. To prevent CRS, several strains of live attenuated rubella vaccine have been developed and introduced into immunization programs in many countries. In most Asian countries except Japan, Singapore and Taiwan, rubella remains uncontrolled, and the burden of diseases from CRS is high. In order to develop a control program to reduce the number of CRS cases in Asian countries, it is necessary to conduct a survey of rubella and CRS cases, and to then determine the genotype of the circulating rubella virus in each country. METHODS: Cases of rubella and CRS, based on national reporting systems or active surveillance in the Asian countries, are summarized. Sequences of the E1 gene of the virus isolates from the Asian countries were compared by phylogenic analysis. RESULTS: Recent studies of the molecular epidemiology of rubella virus worldwide revealed that there are two genotypes, and that genotype I is circulating almost worldwide, while genotype II is an Asian prototype restricted to the Asian continent. Genotype I viruses fall into a number of groups, some of which are geographically localized. Antigenically these two genotypes are cross-reactive and immunization with either virus results in immunity to all rubella viruses. DISCUSSION: The hypotheses that rubella virus has evolved on the Asian continent is proposed. The World Health Organization (WHO) has recognized that a rubella immunization program can be combined with the measles immunization program. Inclusion of rubella in the expanded program of immunization (EPI) of measles would be ideal in Asian countries, as it would be efficient and cost effective to administer one injection containing a three-combined vaccine (MMR). It would also be desirable given that WHO require laboratory tests to confirm the presence of measles or rubella as part of it's measles control project, because rubella is often misdiagnosed as measles.     

Seroprevalence of mumps, varicella and rubella antibodies in children 1-16 years of age in eastern Turkey

In this study, seroprevalence of mumps, varicella and rubella was investigated in 803 unvaccinated children in eastern Turkey whose ages ranged between 1 and 16 years. Mumps IgG, varicella IgG and rubella IgG antibody levels in all children were studied by enzyme-linked immunosorbent assay (ELISA) method. Information regarding socioeconomic characteristics, number of siblings and disease history was gathered for each participant. No significant difference in seropositivity was detected between girls and boys. Seroprevalence of mumps increased with age, with a seropositivity rate of 29.9% in children aged 1-4 years and of 88.8% in those aged 13-16 years. Seroprevalence of varicella increased with age, with a seropositivity rate of 26.8% in children aged 1-4 years and of 90.3% in those aged 13-16 years. Seroprevalence of rubella also increased with age, with a seropositivity rate of 47.3% in the children aged 1-4 years and of 89.2% in those aged 13-16 years. There was a statistically significant increase in the rate of seropositivity with advancing age through the group of 13-16 years old (p < 0.05). In conclusion, in order to avoid mumps, varicella and rubella diseases and their possible complications, children should be vaccinated against these three diseases before the age of two, since seroprevalence increases with age.     

The susceptibility of adolescent girls to rubella. Observations on 297 girls in Toronto.

Since serum rubella H-I antibody titers of 297 adolescent girls showed 25.3 per cent to be susceptible, we support the recommendation that all susceptible girls be immunized, provided of course that after individual evaluation there is no risk of pregnancy at the time of immunization or in the ensuing two months.     

Parenchymal calcification is associated with the neurological prognosis in patients with congenital rubella syndrome

Congenital rubella syndrome (CRS) results from maternal rubella virus infection in early pregnancy. Abnormal neuroimaging findings have been analyzed in a small number of CRS patients in the past; however, their clinical significance has been poorly addressed. Therefore, we have investigated the neuroimaging findings of 31 patients with CRS from previous studies. The most common finding was parenchymal calcification, which was observed in 18 of 31 patients (58.1%). A multivariable logistic regression model showed that it was associated with psychomotor or mental retardation (p = 0.018), suggesting that parenchymal calcification in CRS could be a prognostic factor.     

Congenital rubella syndrome: pattern and presentation in a southern Nigerian tertiary hospital

Background  

Congenital rubella syndrome (CRS) resulting from maternal rubella infection can result in miscarriages, still birth and rubella infection of the infant. The aim of this study was to evaluate the pattern and presentation of CRS over an 8-year period as seen in the University of Port-Harcourt Teaching Hospital (UPTH), Nigeria.     

Congenital rubella syndrome in Western Australia

The birth prevalence of congenital rubella syndrome (CRS) in Western Australia has been around 20 per 10 000 live births with peaks up to 100 per 10 000 in rubella epidemic years. The rate appears to be falling but it is still too soon to know whether the rubella vaccination programme in Western Australia has made a significant impact. The cohorts of young women who would have received the schoolgirl vaccination programme are only now entering the child bearing age groups. Observed falls may be due also to delayed diagnosis particularly of cases of deafness only. The proportion of nonimmune young women who would have been eligible for the programme in one maternity hospital has fallen. This study needs to be repeated to ascertain whether further epidemics of rubella have resulted in peaks of CRS or whether the vaccination programme has started to have an effect.     

Congenital rubella syndrome in Western Australia

Abstract The birth prevalence of congenital rubella syndrome (CRS) in Western Australia has been around 20 per 10 000 live births with peaks up to 100 per 10 000 in rubella epidemic years. The rate appears to be falling but it is still too soon to know whether the rubella vaccination programme in Western Australia has made a significant impact. The cohorts of young women who would have received the schoolgirl vaccination programme are only now entering the child bearing age groups. Observed falls may be due also to delayed diagnosis particularly of cases of deafness only. The proportion of nonimmune young women who would have been eligible for the programme in one maternity hospital has fallen.
This study needs to be repeated to ascertain whether further epidemics of rubella have resulted in peaks of CRS or whether the vaccination programme has started to have an effect.     

A longitudinal evaluation of adolescent depression and adult obesity

BACKGROUND: Prior studies have had conflicting results regarding the relationship between adolescent depression and adult obesity. OBJECTIVE: To test the hypothesis that depression in adolescence would increase the risk for obesity in early adulthood. METHODS: We used data from a longitudinal study of a birth cohort of children born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand (N = 1037). These data included regular diagnostic mental health interviews and height/weight measurements throughout childhood and adolescence. We performed logistic regression analyses to assess the relationship between major depression in early or late adolescence and the risk for obesity at 26 years of age. RESULTS: Major depression occurred in 7% of the cohort during early adolescence (11, 13, and 15 years of age) and 27% during late adolescence (18 and 21 years of age). At 26 years of age, 12% of study members were obese. After adjusting for each individual's baseline body mass index (calculated as the weight in kilograms divided by the square of height in meters), depressed late adolescent girls were at a greater than 2-fold increased risk for obesity in adulthood compared with their nondepressed female peers (relative risk, 2.32; 95% confidence interval, 1.29-3.83). A dose-response relationship between the number of episodes of depression during adolescence and risk for adult obesity was also observed in female subjects. The association was not observed for late adolescent boys or for early adolescent boys or girls. CONCLUSIONS: Depression in late adolescence is associated with later obesity, but only among girls. Future studies should address reasons for these age and sex differences and the potential for intervention to reduce the risk for adult obesity in depressed older adolescent girls.     

Need for protection against Rubella in India

Reports from different parts of India highlight the existence of Rubella leading to fetal malformations and wastage. However, the need for routine immunization to control rubella has not been duly recognized. In the present study the prevalence of rubella was determined in different age groups of the population by estimating IgG antibodies to rubella virus using ELISA kit obtained from Diamedix. Two hundred and seventy four pairs of maternal blood samples were collected. Samples were also obtained from one hundred and thirty nine children aged 1–15 years and assayed for rubella antibodies. The sample was read as positive if the Elisa unit/ml was 15 EU/ml. The results showed that 94.9% of mothers and 94.1% of cord blood samples showed seropositivity. Children between 1 and 5 years showed the lowest seropositivity of 69.2% which gradually increased to reach near 95% levels by 15 years. These observations indicate the prevalence of rubeila in children and thus suggest the need to protect susceptible women of reproductive age group.     

Problems related to menstruation amongst adolescent girls

Objective  To study the types and frequency of problems related to menstruation in adolescent girls and the effect of these problems on daily routine. Methods  Girls in the age group 13–19 years who had had menarche for at least one year at the time of study. 198 adolescent girls have been studied. Data was collected by personal interviews on a pre-tested, semi-structured questionnaire. The questions covered menstrual problems, regularity of menses in last three cycles of menstruation and the effect of these problems on the daily routine. Analysis was done using SPSS version 12. Percentages were calculated for drawing inferences. Results  More than a third (35.9%) of the study subjects were in the age group 13–15 years followed by 17–19 years, 15–17 years respectively. Mean age of study participants was calculated to be 16.2 years. Dysmenorrhea (67.2%) was the commonest problem and (63.1%) had one or the other symptoms of Pre-menstrual syndrome (PMS). Other related problems were present in 55.1% of study subjects. Daily routine of 60% girls was affected due to prolonged bed rest, missed social activities/commitments, disturbed sleep and decreased appetite. 17.24% had to miss a class and 25% had to abstrain from work. Mothers and friends were the most common source of information on the issue. Conclusion  Screen adolescent girls for menstruation related problems and provide them with counseling services and relevant information on possible treatment options. Besides, there is a need to emphasize on designing menstrual health programmes for adolescents.