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.     

Congenital rubella still exists in Tunisia!

Congenital rubella syndrome resulting from maternal rubella infection can cause serious multisystemic malformations resulting in severe morbidity and mortality. After immunization, its incidence has been reduced in the developed world, though it remains a real problem in developing countries since it causes many handicaps. In Tunisia, despite including rubella immunization in the routine national program on immunization for girls once they reach the age of 12, the congenital rubella syndrome still exists. We describe the clinical pattern and the outcome of congenital rubella syndrome in 2 infants and emphasize the necessity of recommending universal screening and follow-up vaccination of susceptible females and including rubella immunization in the routine national immunization program, especially in developing countries.     

A profile of mothers giving birth to infants with congenital rubella syndrome. An assessment of risk factors

To formulate strategies for elimination of congenital rubella syndrome, it is important to identify risk factors for delivering an infant affected by it. We analyzed cases of congenital rubella syndrome in infants born from 1970 to 1985 and reported to either one of two independent Centers for Disease Control surveillance systems. Mothers of infants with congenital rubella syndrome identified in both surveillance systems were disproportionately younger than mothers giving birth in the United States. The risk for delivering an infant with congenital rubella syndrome was approximately 2.5 times higher for blacks compared with whites for both reporting systems. A total of 18% of infants with congenital rubella syndrome born since 1979 were Hispanic (national population average, 7%). Both surveillance systems showed that, although primiparous mothers were at highest risk, 39% of women delivering infants affected by congenital rubella syndrome had had at least one previous live birth, suggesting that postpartum immunization could have prevented these congenital rubella syndrome cases. Young, black, and Hispanic primiparous women represent populations at elevated risk for delivering a congenital rubella syndrome-affected infant and should be specifically targeted for immunization.     

35-year measles, mumps, rubella vaccination assessment in France]

AIM: The setting-up and the follow-up of a vaccination programme require important human and economical investments. Our study objective consists of the clinical benefit evaluation given by measles, mumps and rubella (MMR) vaccination since monovalent and combined vaccines availability (35 years for measles, 30 years for rubella and 20 years for mumps). METHOD: Vaccination impact has been evaluated from the modelisation for each disease under the shape of a decision tree relying on epidemiological data and on efficacy data of the vaccines. We have compared the results in terms of complications, sequaela, deaths in the vaccinated population (vaccination period) with the results that we would obtain if this same population had not been vaccinated (non vaccination period). The general model was applied to each of the three diseases excluding congenital rubella syndrome. They have been modelised according to the occurrence, or not, of a complication leading to an evolution towards either recovery or sequaela or death. The estimation of the number of avoided congenital rubella syndromes has been made from the number of protected women by vaccination and incidence figures of congenital rubella syndromes reported in the population considered before and after vaccination. RESULTS: In France over the period of time considered, almost 2 million meningitis, 60 000 encephalitis, 170 subacute sclerosis panencephalitis and more than 5600 neurological sequaela including more than 600 deafness cases have been avoided as a result of the MMR vaccination programme. Moreover, 590 000 pneumonia, more than one million of acute otitis media and 300 000 orchitis, 3000 rubella infection cases occurring during pregnancy have also been avoided. Overall, more than 12 000 deaths that have been avoided as a result of the MMR vaccination. CONCLUSIONS: In France, MMR vaccination programme leads to a huge benefit in terms of public health, which emphasises the true value of vaccination in the daily medical practice.     

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.     

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.     

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.     

Congenital rubella syndrome despite repeated vaccination of the mother: a coincidence of vaccine failure with failure to vaccinate

Braun C, Kampa D, Fressle R, Willke E, Stahl M, Haller O. Congenital rubella syndrome despite repeated vaccination of the mother: a coincidence of vaccine failure with failure to vaccinate. Acta Pzdiatr 1994;83:674–7. Stockholm. ISSN 0803–5253
Congenital rubella syndrome occurred in a boy born to a mother who had been properly vaccinated three times before conception, but developed only low titers of rubella antibody. The non-vaccinated father most likely infected the mother on a home visit during the third to fifth weeks of gestation. He served in the army and fell ill during an outbreak of a rubella-like disease in his military unit. The mother subsequently developed a slight rash, but rubella IgM antibodies were lacking and rubella infection was not suspected. This incidence demonstrates the necessity of vaccinating all children, including boys and young men. in order to reduce the number of infections and prevent further cases of congenital rubella syndrome.     

Testing for rubella-specific IgG antibody in urine

BACKGROUND: In Japan rubella vaccination is generally done once during a lifetime, and the vaccination rate decreased after a revised vaccination law in 1995. History of rubella or vaccination may still be unreliable. Testing for rubella antibody is significant to prevent the occurrence of congenital rubella syndrome. However, the collection of blood samples to detect antibodies from young children is invasive and difficult. METHODS: For this study we obtained 853 matched serum and urine samples from 904 healthy students 10 or 14 years of age in the Ibara and Yoshii districts of Okayama, Japan, for a comparison of antibodies for rubella in the matched samples. The serum and urine antibodies were measured with hemagglutination-inhibition and enzyme-linked immunosorbent assays, respectively, and with our urine-based antibody test. RESULTS: The sensitivity, specificity and concordance rates of this urine-based antibody test were 96, 99 and 97% based on the serum antibody results of both assays. The coefficiency was 0.627 between the titers of the urinary and serum antibodies by the enzyme-linked immunosorbent assay. The urinary antibodies were stable for at least 5 months at 4 degrees C and 25 degrees C. CONCLUSIONS: Urine-based assay methods are helpful not only because they avoid the invasive approach of venipuncture but also because unprocessed urine specimens can be used and urinary antibody is stable for a long period. Therefore this test is suitable for screening. In addition protective amounts of rubella antibody in blood can be reliably assessed by means of urine samples.     

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.     

Rubella vaccination

Rubella vaccination programmes aim to prevent congenital rubella infections. Previously differing programmes have now converged according to the following principle: First vaccination should be given at the age of 15 months (together with measles and mumps vaccine) to both boys and girls, in order to diminish the circulation of the wild virus. Teenage girls require (re-)vaccination to ensure their immunity. Also non-immune women have to be identified and vaccinated before they become pregnant. A low acceptance rate increases the risk of infection of pregnant women, independent of the vaccination omitted. As a rule natural and vaccine-induced immunity prevents congenital rubella infections. These infections are exceedingly rare in children born to immune mothers, and are always caused by the wild virus. This minimal risk will disappear only with the eradication of rubella virus, still a distant goal in countries offering vaccination only on a voluntary basis.Abbreviations CR congenital rubella - HI haemagglutination inhibition - HIG haemolysis in gel     

Clinical Studies of Patients with Rubella Syndrome Occurring in a High Incidence in the Ryukyu Islands in 1965: On the Diagnostic Significance of Clinical Manifestations

The 620 cases with a history of maternal rubella and/or with one or more of cataract, CHD and deafness born in the Ryukyu Islands in 1965 were subjected to clinical studies and 360 cases were diagnosed as rubella syndrome. Rubella retinopathy makes a reliable diagnostic basis for rubella syndrome. As for the typical combination of clinical manifestations, the cases with cataract have CHD, deafness and retinopathy; the cases with CHD not accompanied by cataract have deafness and retinopathy; and the cases with deafness not accompanied by cataract and CHD either have or have not retinopathy. The cases with cataract alone or with CHD can extremely rarely be denned as having rubella syndrome. There existed the close relationship between the combination of clinical manifestations and the time of maternal rubella infection. The main clinical manifestations of rubella syndrome are cataract, congenital heart disease (CHD), and deafness appearing singly or two or more together¹⁾²⁾. Etiology of the congenital cataract, CHD, or deafness is mostly not explained; and only a small portion of the incidence is due to intrauterine rubella infection. For the future of the patients in the above conditions and for their parents, clarification as to whether they are or are not due to rubella is very important. Current general practice for the diagnosis of rubella syndrome is laboratory diagnosis that measures rubella hemagglutination inhibition (HI) antibodies³⁾⁴⁾. As the infants grows in age, the above mentioned technique may not assure an absolute judgment⁵⁾⁶⁾. This makes it necessary to arrive at diagnosis from the clinical findings. A prompt, direct diagnosis from the clinical findings alone will be very convenient. In the Ryukyu Islands where there was a high incidence of rubella syndrome in infants in the second half of 1965, we analyzed clinical findings of the affected children with cataract, CHD or deafness on the basis of serological diagnosis. The diagnostic significance of the clinical findings was so studied. Hence our report in this paper.     

Congenital rubella syndrome and the occurrence of congenital heart disease

Aiming to document the incidence and type of associated congenital heart disease, 20 children affected with the congenital rubella syndrome have been evaluated during a 5 year period, starting 1988. Congenital heart disease was detected in 45% of the cases. Persistent ductus arteriosus was the most frequent finding, followed by ventricular and atrial septal defects. Hearing disturbances occurred in 83% of the 12 cases studied. Ophthalmic lesions appeared in 69% of the 13 cases analysed, congenital cataracts being the most frequent one. An association of 66% was found between ophthalmic and heart lesions. Regarding the nutritional index, 70% of the cases were situated between the 25th and 50th percentile. The relevant incidence of congenital defects and the documentation of an important number of cases in a short period of time point out to a significant prevalence of the syndrome with imperative need improve the vaccination programs.     

Rubella seroprevalence among Turkish adolescent girls living in Edirne, Turkey

This study was designed to estimate the rubella seroprevalence in unvaccinated Turkish adolescent girls in urban and rural areas of Edirne, and to create preventive strategies for congenital rubella syndrome (CRS). The sample, representing 12- to 17-year-old adolescent girls, consisted of 1,600 subjects selected from school lists by systematic and random sampling, which was matched by age and urban-rural residency strata proportional to the corresponding distributions in the Edirne population. For each participant, a questionnaire was completed and rubella-specific IgG antibodies were measured. After analysis of samples, seropositivity prevalence, equivocal and seronegative samples of adolescent girls in Edirne were determined as 93.1%, 0.6% and 6.3%, respectively. Data from the present study may indicate that 6.9% of adolescent girls have considerable risk for rubella infection during pregnancy. Eliminating rubella and CRS in Turkey will require national health service efforts, including vaccination of all adolescents and all susceptible women of childbearing age.     

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 seroprevalence in an unvaccinated population in Izmir: recommendations for rubella vaccination in Turkey.

BACKGROUND: The European Advisory Group on the Expanded Program on Immunization of WHO has recommended that by 2010 or earlier congenital rubella should be well-controlled or eliminated in all countries in Europe. Debate on the introduction of rubella vaccine into national immunization schedules continues to occur, and data on rubella and congenital rubella syndrome in Turkey are insufficient. OBJECTIVE: To determine age-specific rubella seroprevalence in the 1- to 29-year-old unvaccinated population in Izmir, Turkey. METHODS: A total of 600 unvaccinated persons 1 to 29 years old were selected for the study with cluster sampling in Izmir, Turkey. The information on sociodemographic characteristics and disease history was gathered for each participant, and in 580 of them rubella-specific IgG antibodies were assayed quantitatively by the micro-enzyme immunoassay. RESULTS: Of the 580 participants tested for rubella antibodies, 135 (23.3%) were seronegative. The proportions of susceptible individuals were 61.7, 29.5, 12.4, 10.3 and 8.4% in the age groups of 1 to 4, 5 to 9, 10 to 14, 15 to 19 and 20 to 29 years, respectively. Of the young women 15 to 19 years of age, 13.5% were susceptible to rubella infection. CONCLUSIONS: Because a substantial proportion of women in their childbearing years are susceptible to rubella, immunization efforts should be directed at infants or prepubertal children.     

HYPERTHYROIDISM, DIABETES MELLITUS AND THE CONGENITAL RUBELLA SYNDROME

Abstract. Floret, D., Rosenberg, D., Hage, G. N. and Monnet, P. (Clinique Médicate Infantile B, Hopital E. Herriot, Lyon, France). Hyperthyroidism, diabetes mellitus and congenital rubella syndrome. Acta Paediatr Scand, 69: 259, 1980.—A male patient born to a mother who developed rubella during the tenth week of gestation presented a typical congenital rubella syndrome with mental retardation, neuro-sensory deafness, hypoplasia of the dental enamel and chorioretinitis. Hyperthyroidism occurred at the age of 3 10/12 years and was treated successfully with propylthiouracil for 4 years. The course was complicated by premature craniosynostosis and a craniectomy was performed at the age of 7 years. Overt diabetes mellitus developed at 17 years and was well controlled by insulin therapy. Histocompatibility (HLA) antigens were A2, B8, B40. Diabetes mellitus and thyroid disorders have previously been reported after congenital rubella, and recently after congenital cytomegalovirus infection. Our patient had both endocrinopathies. It is possible that HLA B8 antigens might be responsible for increased susceptibility to rubella infection.     

Economic evaluation of the 7-vaccine routine childhood immunization schedule in the United States, 2001

OBJECTIVE: To evaluate the economic impact of the routine US childhood immunization schedule: diphtheria and tetanus toxoids and acellular pertussis; tetanus and diphtheria toxoids; Haemophilus influenzae type b conjugate; inactivated poliovirus; measles, mumps, and rubella; hepatitis B; and varicella vaccines. DESIGN: Decision tree-based analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported for 1995-2001. Costs were estimated using the direct cost and societal (direct and indirect costs) perspectives. Program costs included vaccine, administration, vaccine-associated adverse events, and parent travel and time lost. All costs were inflated to 2001 US dollars, and all costs and benefits in the future were discounted at a 3% annual rate. PARTICIPANTS: A hypothetical 2001 US birth cohort of 3,803,295 infants was followed up from birth through death. MAIN OUTCOME MEASURES: Net present value (net savings) and benefit-cost ratios of routine immunization. RESULTS: Routine childhood immunization with the 7 vaccines was cost saving from the direct cost and societal perspectives, with net savings of 9.9 billion dollars and 43.3 billion dollars, respectively. Without routine vaccination, direct and societal costs of diphtheria, tetanus, pertussis, H influenzae type b, poliomyelitis, measles, mumps, rubella, congenital rubella syndrome, hepatitis B, and varicella would be 12.3 billion dollars and 46.6 billion dollars, respectively. Direct and societal costs for the vaccination program were an estimated 2.3 billion dollars and 2.8 billion dollars, respectively. Direct and societal benefit-cost ratios for routine childhood vaccination were 5.3 and 16.5, respectively. CONCLUSION: Regardless of the perspective, the current routine childhood immunization schedule results in substantial cost savings.     

Blueberry muffin syndrome owing to congenital rubella: case report

A case of congenital rubella is reported in a 22-day-old boy presenting with a 'blueberry muffin' rash. Late-onset blueberry muffin syndrome following congenital rubella is very rare.