Prevalence of rubella virus and cytomegalovirus infections in suspected cases of congenital infections

Although rubella virus and cytomegalovirus (CMV) are important causes of congenital infections, information on their prevalence in our country is scarce. We studied a total of 249 infants suspected of having congenital infections from January 1988 to September 1989. Serum samples of these infants were tested for rubella and cytomegalovirus specific IgM antibodies by mucapture ELISA. Thirty (12%) infants were positive for rubella IgM antibody, and 50 (20%) had CMV specific IgM antibody. In the group presenting with hepatosplenomegaly (n=56) rubella and CMV specific IgM antibodies were detected in 1 (1.7%) and 25 (44.6%) infants respectively. In the group presenting with congenital malformations (n=90), 23 (25.5%) were positive for rubella, and only 9 (10%) had CMV IgM antibodies. Of the infants presenting with mental retardation (n=39), only CMV infection was detected in 3 (7.7%) infants, whereas amongst the group showing intrauterine growth retardation (n=16), 5 (31.25%) had CMV specific IgM antibodies and 2 (12.5%) had rubella specific IgM antibodies. In the miscellaneous group (n=48), 4 (8.3%) and 8 (16.6%) infants had rubella and CMV IgM antibodies respectively. CMV infection was prevalent in a significantly higher number of children with hepatosplenomegaly than rubella while in infants with congential malformations a significantly higher number had rubella infection. It is concluded that rubella and CMV infections are commonly seen in children with intrauterine infections in our population.     

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.     

Rubella and cytomegalovirus (CMV) infections: laboratory aspects of investigation of antenatal, congenital, persistent, and subclinical infections

Rubella specific IgM tests carried out on pregnant women with history of rubella contact or rubella-like rash indicated the presence of rubella-IgM by the second week after contact, persistence to 3-4 weeks followed by a decline and non-detectability around 8-9 weeks and at delivery. Laboratory investigation of cases of rubella infection in infants and children, including clinically proven and suspected congenital rubella revealed distinct patterns of combinations of positivity and negativity of IgM and IgG antibodies. Three cases of persistence of rubella specific IgM antibodies with one even up to 3 years in congenital rubella and a case of CMV-IgM persistence in congenital CMV are described. Rubella-IgM and CMV-IgM were detected in the serum of two patients aged 12 years and 24 years with CMV mononucleosis. Utilization of rubella-IgM/CMV-IgM tests enabled the identification of four cases of subclinical rubella and one of subclinical CMV in a pediatric population.     

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 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.     

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.     

Increased Serum Levels of Anti-Mumps and Rubella Viruses Antibodies in Children with Kawasaki Disease

Serum IgM and IgG antibodies against mumps virus and rubella virus were quantitated serially by enzyme-linked immunosorbent assays in 15 children with Kawasaki disease. IgM antibody against mumps virus and IgG antibody against rubella virus were increased significantly in children with Kawasaki disease who had no previous history of mumps virus or rubella virus infection. Booster-like effect in IgG antibody levels against mumps virus was observed in children with Kawasaki disease who had a previous history of exposure to mumps virus. Since none of the patients manifested clinical symptoms of mumps or rubella, the increased antibody levels against mumps and rubella may represent a part of the nonspecific increase in serum immunoglobulins in children with Kawasaki disease.     

Congenital rubella syndrome in a child born to Liberian refugees: clinical and public health perspectives

We describe a case of congenital rubella syndrome with typical stigmata in an infant born in New Hampshire to Liberian refugees. The infant's clinical specimens were tested for rubella. Rubella immunity status was sought for contacts. The infant's specimen cultures grew wild-type rubella virus; serum immunoglobulin M and G were positive. Eighteen of 20 contacts were rubella-immune. Family's transit history, mother's vaccination history, and infant's estimated gestational age supported congenital infection acquired overseas. Clinicians should maintain vigilance for congenital rubella syndrome in infants with relevant stigmata, particularly those whose mothers are from countries with nonexistent or recently implemented rubella vaccination programs.     

Incidence, clinical spectrum, and outcome of intrauterine infections in neonates

A prospective study was undertaken on the incidence of intrauterine infections by screening 1302 cord blood samples for total IgM by radial immunodiffusion. Specific IgM against cytomegalovirus (CMV), rubella and Toxoplasma were estimated in cord blood samples found to contain total IgM > 20 mg/dl. All these neonates were examined at birth and at discharge. Cord blood samples with total IgM > 20 mg/dl were further screened for specific IgM against rubella, CMV and Toxoplasma. Neonates found to have positive specific IgM were followed-up for hearing, opthalmological and developmental assessment. Raised cord blood (IgM > 20 mg/dl) was found in 270/1302 (20.6 per cent). Mean birth weight was comparable in babies with raised (> 20 mg/dl) or low (< 20 mg/dl) cord blood total IgM. Incidence of prematurity and low birth weight were not statistically different in babies with raised cord blood IgM when compared to those with low cord blood IgM levels. Similarly, incidence of intrauterine growth retardation (IUGR) idiopathic was similar in two groups. Specific IgM for rubella was found to be positive in eight (0.6 per cent). Of these, three had symptomatic rubella infection. Two mothers of these symptomatic babies had exanthematous viral illness during first trimester. Specific IgM for CMV was found to be positive in 23 (1.8 per cent) while two infants had symptomatic CMV disease. None of the babies was found to have specific IgM against Toxoplasma. One baby with symptomatic CMV disease and one with rubella died. Another baby with symptomatic CMV disease developed neonatal hepatitis which improved on follow-up but the infant went on to develop sensorineural deafness. All other asymptomatic babies with specific IgM positive against rubella and CMV were found to have normal vision, hearing and development on follow-up.     

A prospective study on the incidence and significance of congenital cytomegalovirus infection.

Screening of 3060 neonates for congenital cytomegalovirus (CMV) infection by virus excretion in the urine showed an overall incidence of 0.4%. The incidence was about 1% for mothers between 16 and 25 years and only 0.2% for mothers between 25 and 35. No mothers over 35 years of age gave birth to congenitally infected infants. The percentage of women in the child-bearing age susceptible to CMV infection was estimated by the absence of CMV complement-fixing antibodies in cord sera and ranged from 48% to 33% with increasing age. None of the infected infants showed obvious signs of congenital CMV infection at birth. At follow-up, two infants showed slight, but transient symptoms compatible with a foetal infection; a pair of premature twins exhibited retarded physical and psychomotor development, but this could just as well be ascribed to the prematurity itself. None of the infants had detectable CMV--IgM antibodies in cord sera, but a trend towards elevated total IgM concentration in cord sera and elevated virus excretion titres appeared in the infants with symptoms. With the very low incidence and no signs of sensomotor sequelae the preliminary conclusion is that foetal CMV infection in our population by no means has a significance to deserve screening or a vaccination programme.     

麻疹感染的临床特征及诊断

目的研究广泛麻疹疫苗接种后儿童麻疹的临床特点及诊断。方法研究对象来自2001年4～7月我院隔离门诊的可疑麻疹病例。所有病例就诊时静脉采集全血2.0 mL,分离血清,-20℃保存。用间接ELISA方法检测血清麻疹IgM抗体.若麻疹IgM抗体阴性,同时检测风疹IgM抗体。结果本文共收集85份临床可疑病例,男56例,女29例;年龄46 d～8个月13例.>8个月72例。85份血清麻疹抗体IgM阳性44例,阳性率51.76%,其中年龄46 d～8个月10例,占22 7%;>8个月34例,占77.3%。41份麻疹IgM阴性血清中检测风疹IgM,阳性9例,阳性率为21.95%:占总病例的10. 59%.麻疹和风疹皆阴性32例,占37.65%。麻疹44例中,出疹前发热<3 d 28例(63.6%),≥3 d为16例(36.4%);有Koplik斑35例; 95.5%麻疹病例有结膜炎。风疹9例中,出疹前发热<3 d 8例(89.9%).≥3 d 1例(11.1%):全部风疹病例无Koplik斑;而22.2%风疹病例有结膜炎。结论小儿麻疹的发病年龄及临床表现己发生变化,单凭临床特征易造成较多的漏诊和误诊,血清麻疹IgM抗体检测麻疹病例实用、特异、敏感。     

Abnormalities of immunglobulins in infants with congenital heart disease.

Twenty-eight infants had their serum immunoglobulins estimated (by radial immunodiffusion) in early infancy. The IgG level was abnormal in twelve infants. Elevated levels of IgA were found in ten and IgM in fourteen. These variations, mostly obvious in the first ten days of life, were detected in the absence of clinical or immunological evidence of congenital rubella infection.     

Congenital CMV infection in symptomatic infants in Delhi and surrounding areas

Many viral infections are associated with significant maternal and fetal consequences during pregnancy among which cytomegalovirus is one of the most important agent, globally. Both primary and recurrent infection due to this virus can result in fetal infection. Samples from Congenital Anoammaled babies are referred to NICD from Delhi based Government hospitals and surrounding areas for diagnosis of congenital infections like Toxoplasm, Rubella, CMV and Herpes. In the present study, accumulated data is presented for the most common teratogenic virus—Cytomegalovirus prevalence as a causative agent for congenital infection in New Born babies at Delhi and surrounding areas. 96 samples from symptomatic babies in the age group of few days to 6 months exhibiting different congenital anomalies, were reported between 1 st Jan 04 to 30 th April/05. All the blood samples were tested for the detection of CMV (IgM) antibodies using μ-capture ELISA technique. 18(18.75%) samples from babies showed positive titres for CMV-IgM antibodies. None of the mothers of positive babies were found positive for CMV-IgM antibodies but all were serologically exposed to CMV virus previously as their serum samples were positive for CMV-IgG antibodies indicating primary infection in the past or reactivation/reinfection with a different strain of CMV in the early pregnancy.     

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.     

ABNORMALITIES OF IMMUNOGLOBULINS IN INFANTS WITH CONGENITAL HEART DISEASE

Abstract. Twenty-eight infants had their serum immunoglobulins estimated (by radial immunodiffusion) in early infancy. The IgG level was abnormal in twelve infants. Elevated levels of IgA were found in ten and IgM in fourteen. These variations, mostly obvious in the first ten days of life, were detected in the absence of clinical or immunological evidence of congenital rubella infection.     

A PROSPECTIVE STUDY ON THE INCIDENCE AND SIGNIFICANCE OF CONGENITAL CYTOMEGALOVIRUS INFECTION

Abstract. Screening of 3060 neonates for congenital cytomegalovirus (CMV) infection by virus excretion in the urine showed an overall incidence of 0.4%. The incidence was about 1 % for mothers between 16 and 25 years and only 0.2% for mothers between 25 and 35. No mothers over 35 years of age gave birth to congenitally infected infants. The percentage of women in the child-bearing age susceptible to CMV infection was estimated by the absence of CMV complement-fixing antibodies in cord sera and ranged from 48% to 33% with increasing age. None of the infected infants showed obvious signs of congenital CMV infection at birth. At follow-up, two infants showed slight, but transient symptoms compatible with a foetal infection; a pair of premature twins exhibited retarded physical and psychomotor development, but this could just as well be ascribed to the prematurity itself. None of the infants had detectable CMV-IgM antibodies in cord sera, but a trend towards elevated total IgM concentration in cord sera and elevated virus excretion titres appeared in the infants with symptoms. With the very low incidence and no signs of sensomotor sequelae the preliminary conclusion is that foetal CMV infection in our population by no means has a significance to deserve routine screening or a vaccination programme.     

Neonatal cytomegalovirus infection: Diagnostic modalities available for early disease detection

CMV is a ubiquitous virus. In India, there is high seroendemicity with almost 99% adults showing IgG antibodies. Infection or re-activation becomes important in immunocompromised host (Transplant recipients, Cancer therapy patients and patients with HIV/AIDS). Neonates form a distinctive high risk population for congenital CMV infection and suffer disastrous sequlae of the same. Neonatal infections may be congenital in nature or may be acquired after birth during first month of life via infected breast milk or due to exposure to high risk blood products. The risk for transmission of the virus to the fetus is higher in primary infected mothers than in mothers with reactivated disease. Primary CMV infections are reported in 1–4% of seronegative women during pregnancy and the risk for viral transmission to fetus is 30–40%. Reactivation of a CMV infection during pregnancy is reported in 10–30% of seropositive women and the risk of transmitting the virus is about 1–3%. The adverse outcome of congenital neonatal CMV infection includes-microcephaly (70%), intellectual impairment (60%), sensineural hearing loss (35%), choriorenitis (22%), hepatosplenomegaly (70%), jaundice (68%), thrombocytopenia (65%), low birth weight (65%), pneumonitis (2–5%) and congenital heart disease (<5%). About 5–10% of congenitally infected asymptomatic infants will have neurological problems later in life the most common of which is unilateral or bilateral sensory neural hearing loss. All immunocompromised hosts, including pre-term neonates, mount weak antibody responses (IgM), making serological detection of CMV infection in them, fallacious. Thus, it is imperative to use antigen detection methods such as quantitative PCR or PP65 Antigenaemia assays to detect CMV infection in immunocompromised host. Sakhuja et al and Minz et al have demonstrated that PP65 Antigenaemia assay is very good for diagnosing CMV disease in renal transplant recipients. The present review tends to highlight the role of newer diagnostic modalities in early CMV infection detection in neonatal population.     

新生儿室管膜下囊肿的病因研究

为了探讨新生儿室管膜下囊肿（ＳＥＣ）与先天性感染的关系，采用ＥＬＩＳＡ酶标法检测母婴双方囊肿组与对照组各７０例血巨细胞病毒（ＣＭＶ）、风疹病毒、弓形虫的抗体，并应用聚合酶链反应（ＰＣＲ）技术直接检测病原ＤＮＡ（风疹病毒除外），同时作尿ＣＭＶ的ＰＣＲ检测。结果：囊肿组新生儿血ＣＭＶ－ＩｇＭ抗体和ＣＭＶ－ＰＣＲ阳性率显著高于对照组（分别为１７．１％、５．７％和１２．９％、２．９％）；且尿ＣＭＶ－ＰＣＲ的阳性率达４０．０％（２８／７０），高于对照组的１７．１％（１２／７０）；分别进行两组自身对照，尿ＣＭＶ－ＰＣＲ的阳性率显著高于血ＣＭＶ－ＰＣＲ阳性率（Ｐ＜０．０５）。囊肿组母亲的尿ＣＭＶ－ＰＣＲ阳性率亦显著高于对照组（３０％、１０％、Ｐ＜０．０１）。提示新生儿ＳＥＣ是宫内感染损害中枢神经系统的表现之一，与先天性ＣＭＶ感染有关，尿ＣＭＶ－ＰＣＲ检查可作为宫内ＣＭＶ感染的首选实验室诊断方法。     

Decreased production of specific antibodies to cow's milk proteins in premature infants during the first six months of life

Concentrations of IgG and IgM antibodies to casein, β-lactoglobulin, lactalbumin and bovine serum albumin (BSA) in sera of premature infants of less than 36 weeks gestation, at 5 weeks of age, were less than in age-matched term infants. At 6 months of age IgG antibodies to BSA in preterms were still significantly lower than in term infants.