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To our knowledge, this is the first report of the use of real-time reverse transcription–polymerase chain reaction to assess changes in viral load in a patient with congenital rubella syndrome (CRS). Rubella-specific antibody titers were also determined. The patient was a male neonate born to a primipara with rubella infection at 10 weeks of gestation. He had no symptoms at birth, but rubella virus was detected in his pharynx, blood, and urine. His mental and physical development was normal for 1 year; however, he was diagnosed with deafness at 13 months of age. Thus, the patient was diagnosed with CRS. Rubella infection in the pharynx was almost constant until 5 months of age; however, it increased dramatically at 6 months of age. No infection was detected at 13 months. Rubella-specific immunoglobulin M titer was consistently low until 9 months of age and then decreased gradually until it became negative at 20 months of age. Rubella-specific immunoglobulin G titer was high at birth. However, it decreased at 3 months and increased again at 4 months. This titer peaked at ∼9 months and then decreased again at 13 months. This case shows that the period after the decline in maternal antibody titers, not the neonatal period, may be the most contagious period in patients with CRS.

OBJECTIVE: Outbreaks of rubella and congenital rubella syndrome (CRS) continue to arise in various countries where a rubella-containing vaccine is not included in the national immunization program. After a large-scale rubella outbreak in 2011, CRS cases emerged in Vietnam. The aim of this study was to clarify the clinical features of these cases with an emphasis on cardiovascular complications and outcomes. METHODS: From October 2011 to September 2012, we conducted a prospective surveillance study of infants RESULTS: We enrolled 38 cases of CRS characterized by a low birth weight (71%), cardiovascular defects (72%), cataracts (13%), hearing impairment (93%), purpura (84%), hepatosplenomegaly (68%), and thrombocytopenia (76%). Patent ductus arteriosus, the most common cardiovascular complication, was often associated with progressive pulmonary hypertension (PH). As of January 2013, 13 infants (34%) had died, and PH was significantly more frequent among the fatalities (P = .004); however, therapeutic closure of the ductus reversed the PH in several cases. CONCLUSIONS: PH-associated mortality is high among infants who have CRS in Vietnam. Providing proper assessments, continuous follow-up, and timely intervention for cardiovascular defects is critical for the management of CRS patients. Echocardiography is of diagnostic and prognostic value and can support better clinical management of CRS, even in a developing country setting.

Routine rubella vaccination was begun in the United States in 1969 with the goal of preventing congenital rubella infection. In October 2004, 35 years after initiation of the program, an independent panel of international experts was convened by the Centers for Disease Control and Prevention to assess progress toward elimination of rubella and congenital rubella syndrome (CRS). Based on available data, panel members concluded unanimously that rubella is no longer endemic in the United States. The national objective of elimination of rubella and CRS by 2010 from the United States has been attained.1 Rubella was first described as a mild exanthematous illness of childhood early in the 19th century by German physicians, resulting in the name German measles. In 1941, Sir Norman Gregg, an Australian ophthalmologist, recognized that a number of children developed cataracts after an epidemic of rubella and proposed an association between maternal rubella infection and the development of cataracts, deafness, heart disease, and mental retardation in the infant.2 In addition, Gregg is credited with introducing the concept of an intrauterine viral infection as having teratogenic potential. In 1962, rubella virus was isolated in cell culture.3,4 This was the same year as the start of a worldwide pandemic that spread to the United States in 1964-1965 and resulted in >12 million cases of rubella. This was the last rubella epidemic to occur in the United States, but it resulted in thousands of infections in pregnant women, causing … Address correspondence to H. Cody Meissner, MD, Division of Pediatric Infectious Disease, Tufts-New England Medical Center, 750 Washington St, Boston, MA 02111. E-mail: cmeissner{at}tufts-nemc.org

Objective. The current epidemiology of rubella reveals an increase in the number of cases among adult Hispanics and an increase in the number of congenital rubella syndrome (CRS) cases among infants of Hispanic mothers. Recent rubella outbreaks have occurred primarily among adult Hispanics, many of whom are foreign-born natives of countries where rubella vaccination is not routine or has only recently been implemented. The objective of this study was to estimate the incidence of CRS in a hospital serving a predominantly Hispanic population. Methods. Hospital charts of infants Results. Of the 182 infants with 1 or more ICD-9 codes consistent with CRS, 6 (3.3%) met either the confirmed or probable case definition for CRS. Two infants met the definition for confirmed CRS. Although laboratory tests for rubella immunoglobulin M antibodies were positive for both of these infants, only 1 of the cases had been reported to the state health department. Four other infants had clinical presentations that met the definition for a probable case. One of these had been tested for rubella immunoglobulin M antibodies, and the test was negative. The other 3 had not been tested. The rate of infants meeting the definition of confirmed and probable CRS was 3.1 per 10 000 hospital births. All confirmed and probable cases were among infants born to Hispanic mothers. Maternal country of origin was Mexico for the 2 confirmed cases and 1 of the probable cases, and unknown for the remaining 3 probable cases. Conclusions. The rate of confirmed and probable CRS among infants in this predominantly Hispanic population is higher than the reported rate in the United States in the vaccine era, which has been reported to range from approximately 0.01–0.08 per 10 000 live births. These findings indicate a need for heightened awareness of CRS among physicians who serve populations at risk for rubella. Physicians should report all confirmed and probable CRS cases to the state health department. The lack of appropriate laboratory testing in 3 infants with probable CRS indicates that physicians should consider a diagnosis of CRS in infants with some signs consistent with CRS, particularly in areas serving high numbers of individuals at risk for rubella.

Recent advances have made it possible to isolate rubella virus from affected persons and to propagate the virus in tissue culture. The virus may be identified by the unique cytopathogenic changes in human amnion tissue culture by interference with ECHO virus type 11 in monkey kidney tissue culture. Thus an even closer correlation between an active rubella infection in the mother in the first trimester of pregnancy and the clinical findings of the rubella syndrome is now feasible. The rubella epidemic of 1964 can be expected to produce significant numbers of infants with the congenital rubella syndrome. This paper reports the clinical history of two cases of rubella associated with thrombocytopenia in the newborn.

As a measure of the affinity of antirubella antibody, the resistance of the antibody to elution was used by increasing concentration of ammonium thiocyanate. The term affinity index has been used to define the molarity of thiocyanate which leads to a reduction of 50% of the initial density. The serum from a group of patients with intrauterine rubella was compared with the serum from a group of deaf children, some of whom could have rubella, and a group of controls with antibody following natural infection. The results show that the affinity index of patients with rubella is significantly lower than that of controls. The other deaf patients span the range of indices of the rubella and control groups suggesting that a number of those children could have deafness caused by intrauterine rubella.

The concepts of sensitivity, specificity, and predictive value can be used to assess patterns of birth defects associated with human teratogens. Although sensitivity of any single defect is generally low for many known teratogens, the presence of specific defect combinations is usually predictive of the teratogen. To evaluate the patterns of birth defects associated with diabetic embryopathy, a sensitivity-specificity analysis was performed on 4929 infants with major defects ascertained by the population-based Metropolitan Atlanta Congenital Defects Program between 1968 and 1980. By reviewing hospital records, maternal insulin-dependent diabetes mellitus was confirmed in 26 infants. Patterns of defects were evaluated among infants born to mothers with insulin-dependent diabetes mellitus and compared with the rest of the Metropolitan Atlanta Congenital Defects Program case population. Multiple logistic regression analysis was used to assess defect combinations that predict for insulin-dependent diabetes mellitus. Of 26 infants, 8 had multiple defects. However, most defects and their combinations were poorly sensitive and predictive for insulin-dependent diabetes mellitus. The predictive value for insulin-dependent diabetes mellitus was greatest for the combination of vertebral and cardiovascular anomalies (6.5%). Also, several pathogenetic mechanisms were noted among patients with insulin-dependent diabetes mellitus, such as cell migration defects, cell death events, deformations, and cardiac flow lesions. The inability to find a clear-cut phenotype for diabetic embryopathy may be due to several etiologic factors and mechanisms associated with diabetic embryopathy.