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 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 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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.

     

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.     

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     

Congenital rubella syndrome with death from interstitial pneumonia

There was a rubella epidemic in Japan in 2012–2013, which led to an increased number infants being born with congenital rubella syndrome (CRS). Symptoms of CRS are varied and include cataracts, congenital heart disease, and hearing impairment, but case reports of CRS complicated by interstitial pneumonia are rare. We report the case of a patient with CRS who died of respiratory failure caused by interstitial pneumonia. Thrombocytopenia had been present for approximately 1 month after birth, and the patient presented with sudden lung hemorrhage at 64 days old. Thereafter, respiratory condition deteriorated, and the patient died at 107 days old. Given that infants with CRS who have thrombocytopenia and interstitial pneumonia have a high risk of death, they should be monitored carefully for potential complications.     

Enquête sur le statut vaccinal des parents de jeunes nourrissons

Since 2004, in France, pertussis booster is recommended in parents of young infants and adults likely to become parents. This recommendation adds to others such as rubella vaccination in unvaccinated or seronegative women and decennial dT-IPV booster. The objective of this study is to evaluate the impact of these recommendations in parents of young infants. Pediatricians had to include parents of infants at the first well-baby visit after birth. Vaccination data were secondary recorded from parent's health record or called upon their memory. Between June and October 2006, 41 pediatricians included parents of 400 infants (median age: 36 days). dT-IPV booster was recorded or recalled in 37.4% within the 10 previous years and 17.7% within the 3 previous years. Among this last group, only 11.8% had received a combination including pertussis. Rubella serology was declared as positive by 94% of the mothers, but the physicians obtained the information of a previous rubella vaccination in only 71.7% of the mothers. Among the 9 seronegative mothers during pregnancy, only 3 were vaccinated in postpartum. Adults' immunization guidelines are not well known and poorly applied in France. The unavailability of monovalent pertussis vaccine reduces the eligible population. Two years after the launch of the pertussis cocoon strategy, the coverage of eligible young parents remains low and many opportunities are too frequently missed on the opportunity of decenial dTPolio booster. Rubella catch up strategy should be improved. Adults' vaccination strategies and guidelines need to be better broadcasted to health care professionals and also families.     

Pneumococcal meningitis in Western Australian children: epidemiology, microbiology and outcome

OBJECTIVES: Pneumococcal meningitis is now vaccine-preventable but continues to cause high rates of neurological sequelae internationally. Population-based epidemiology, outcome and microbiology data are necessary to target vaccination strategies. This study outlines these key areas for Western Australian children diagnosed 1990-2000. METHODS: The charts of all rural and metropolitan children with International Classification of Disease 9 and 10 discharge codes of pneumococcal or streptococcal meningitis from the Health Department's Hospital Morbidity Data System were reviewed. RESULTS: Over 10.5 years, 94 episodes were confirmed. The average annual incidence for children under 2 years was 13.45 per 100 000 and 0.66 per 100 000 for children 2 years or older. Indigenous children had an almost seven-fold increased risk compared to non-Indigenous (with 78.55 per 100 000 in the under two-year Indigenous group). Eight children died and 24 of the survivors had neurological sequelae. Penicillin resistance occurred in four of 87 isolates. One quarter of the cohort qualify under the current Australian policy of vaccination of high-risk children with seven-valent conjugate (7vPCV) vaccine. Most isolates (49/58) were 7vPCV serotypes, however, Indigenous populations were less well-covered (58.3% covered vs 91.3% of isolates from non-Indigenous children). Indigenous coverage would be improved to 75% with 11-valent conjugate vaccine. CONCLUSIONS: Indigenous children and those under 2 years are most affected by pneumococcal meningitis and remain primary vaccination targets. Three quarters of these children would not be protected by a policy of vaccination of only high-risk children with 7vPCV--improved protection requires higher valencies for Indigenous populations and universal infant vaccination.     

Screening for rubella IgG and IgM using an ELISA test applied to dried blood on filter paper

IgG and IgM rubella antibodies were measured in dried blood samples from the neonatal metabolic screening program. Of 6613 samples from four central screening laboratories, 289 did not contain rubella IgG antibodies, indicating that only 4.3% of the mothers at term were not immune to the rubella virus in the spring of 1984. The proportion of women at term who were not immune was 9.3% in 1979. Rubella IgM was detected in nine of 37,000 samples; congenital rubella infection was confirmed serologically in eight infants. Of the infected babies, three showed severe clinical findings. We suggest that rubella IgG and IgM should be determined regularly in the surplus material of metabolic screening centers, thus giving the opportunity to detect infected infants. The screening procedure is also useful as a serologic tool for monitoring immunity patterns in women, and thus the effectiveness of vaccination programs.     

Hepatitis A vaccination options for Australia

The epidemiology of hepatitis A is changing, with an increasing proportion of the population becoming susceptible to infection. The burden of hepatitis A is comparable to that of other vaccine-preventable diseases for which new vaccines are available. Options for vaccination include selective programmes for high-risk groups, which could involve screening prior to vaccination, or universal programmes for infants and/or adolescents. Selective programmes have been shown to be highly cost-effective if well implemented, but there is evidence that they might be poorly implemented. If a universal vaccination programme were considered for Australia, an infant programme, with doses at 18 months and 2 years, possibly with an additional adolescent programme, would be the recommended option. Universal hepatitis A vaccination for infants and/or adolescents is of comparable cost-effectiveness compared with other preventive strategies, but needs to be considered in the context of competing vaccination options.     

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.