Neonatal cytomegalovirus infection: Diagnostic modalities available for early disease detection (original) (raw)
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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. [Indian J Pediatr 2010; 77 (1) : 77-79]
Congenital CMV infection in symptomatic infants in Delhi and surrounding areas
The Indian Journal of Pediatrics, 2006
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 ยต-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.
Indian Journal of Medical Microbiology, 2015
in the general population is between 50-70%, [3,4] the corresponding fi gure for the developing nations ranging from 70-100%. In India, this fi gure approaches 98-100%. [5] The rates of congenital infection in developed countries are about 0.6-0.7% of live births, whereas in the developing world, higher rates between 1-5% have been observed. [1,3] Congenital HCMV infection is asymptomatic in more than 90% of infected infants, whereas the remaining 10% show manifestations including microcephaly, small for gestational age (SGA), neonatal hepatitis, hepatomegaly, splenomegaly, chorioretinitis, cataract, thrombocytopenia, etc, Some of these symptomatic infants also develop sensorineural hearing loss (SNHL) in the ensuing few years. [2] A fraction of infants who were asymptomatic at birth also go on to develop complications like SNHL and neurodevelopmental delays in the next few years of their lives. In fact, it is now established that congenital HCMV infection is the leading cause of nonsyndromic SNHL in the developed world. [2] The diagnosis of congenital HCMV infection has traditionally been based on demonstration of the virus in urine by isolation in cell culture. Owing to the slow turnaround time for cell culture and its low sensitivity, demonstration of HCMV DNA in urine by PCR has gradually replaced virus isolation. [2] Demonstration of IgM antibodies to HCMV (anti-HCMV IgM) is a common diagnostic test in neonates or infants, which suggests current infection and supports the diagnosis. Other tests, utilising
Specific and non-specific serological markers in the screening for congenital CMV infection
Epidemiology and Infection, 1988
SUMMARYIgM antibodies specific for cytomegalovirus (CMV) were demonstrated in 15 (2.6%) of 575 umbilical cord sera obtained from newborns in Kuwait. Some 93% and 50% of these CMV-IgM positive cord sera displayed markedly raised (more than normal mean + 2 S.D.) content of total IgM and IgA respectively. In contrast, only 0.2 and 1.8% of the CMV-IgM negative cord sera had elevated total IgM and IgA. respectively. Rheumatoid factor (RF) was demonstrable. at concentrations of 30 IU/ml or more, in 67% of the CMV-IgM positive as compared with 3.2% of the CMV-IgM negative sera whereas interferon alpha was found in the serum of only one of these infants. These results indicate that raised total immunoglobulin. in particular IgM. concentrations and the detection of RF in cord blood are useful non-specific markers for the identification of congenital CMV infection.
Guidelines on CMV congenital infection
Journal of Perinatal Medicine, 2000
Congenital cytomegalovirus (CMV) infection occurs in 0.6-0.7% of all newborns and is the most prevalent infection-related cause of congenital neurological handicap. Vertical transmission occurs in around 30% of cases, but the fetus is not always affected. Symptomatic newborns at birth have a much higher risk of suffering severe neurological sequelae. Detection of specific IgG and IgM and IgG avidity seem to be the most reliable tests to identify a primary infection but interpretation in a clinical context may be difficult. If a seroconversion is documented or a fetal infection is suspected by ultrasound markers, an amniocentesis should be performed to confirm a vertical transmission. In the absence of a confirmed fetal infection with fetal structural anomalies, a pregnancy termination should be discouraged. Fetal prognosis is mainly correlated to the presence of brain damage. Despite promising results with the use of antiviral drugs and CMV hyperimmune globulin (HIG), results have to be interpreted with caution. Pregnant women should not be systematically tested for CMV during pregnancy. Managing CMV screening should be restricted to pregnancies where a primary infection is suspected or among women at high risk. The magnitude of congenital CMV disease and the value of interventions to prevent its transmission or to decrease the sequelae need to be established before implementing public health interventions. In this paper, aspects of CMV infection in the pregnant woman and her infant are reviewed.
Medical Sciences, 2016
Human cytomegalovirus (CMV) is a member of the herpesviridae family. It is a double stranded, enveloped and ubiquitous DNA virus that rarely causes disease in healthy individuals yet can cause serious diseases in the fetus and in immunosuppressed individuals [1]. Most CMV infections are inapparent, but the virus can cause a wide range of diseases in susceptible individuals. Fetal CMV infection is of great public health concern because it is the most common cause of congenital infection worldwide, affecting 0.2% to 2.4% of all live births [2]. The overall birth prevalence of congenital CMV infection was reported to be 0.64% but varied considerably among different study location [3]. CMV is now the most common viral cause of mental retardation and hearing deficit of children in developed countries [4]. It causes deformation of preformed tissues rather than malformation of developing organs [4], so CMV can affect fetuses beyond the first trimester, although earlier primary infection is usually more severe [5]. Primary infection is defined as CMV infection in a previously seronegative person. Secondary infection is defined as intermittent excretion of the virus in the presence of host immunity and may be due to either reactivation of an endogenous virus [4, 5] or exposure to a new virus strain from an exogenous source [4]. Primary maternal infection is most likely to cause severe symptomatic congenital infection [4, 5] but recurrent infection may also rarely do so. Perinatal CMV infection is usually not associated with clinical illness in term babies, but may also cause serious problems in preterm infants. [4, 5]. Although the diagnosis of congenital CMV infection is very complex and challenging, important landmarks have been achieved in recent years, these included tests to determine the avidity index of anti-CMV IgG, allowing differential diagnosis of primary from non-primary CMV infections and innovative molecular techniques to detect the CMV in amniotic fluid. In this review, we sort to present the concepts of mother-to-fetus in-utero transmission of CMV and clinical significance of IgG avidity testing i n d i a g n o s i s o f c o n g e n i t a l C M V i n f e c t i o n s .
Journal of Clinical Microbiology, 2016
Congenital cytomegalovirus (CMV) infection represents a relevant cause of deafness and neurological damage in newborns. Intrauterine CMV transmission might result after primary or nonprimary infections, though at different rates (30% versus 0.2%, respectively). At present, a prenatal diagnosis of CMV infection is based mainly on maternal serology, the detection of CMV-DNA in amniotic fluid and fetal blood, and ultrasound (US) and magnetic resonance imaging (MRI). Recent evidences suggest that congenital CMV infection may be an immune-mediated disease and that evaluation of humoral and especially T-cell immunities may improve the overall prenatal diagnosis. This review summarizes the most recent advancements in the diagnosis of maternal and prenatal CMV infections.
Cytomegalovirus (CMV) remains the most common cause of viral intrauterine infection. The objective of this research was to determine the prevalence of at-risk pregnancies for congenital cytomegalovirus transmission in a randomly selected pregnant women and their newborns. Enzyme Link Immunosorbent Assay (ELISA) and real-time polymerase chain reaction (PCR) were utilized to screen the sera of mothers (n = 100) and consecutive umbilical cord blood samples from their newborn (n = 100). Of the 100 mother's sera analyzed, 100 (100%) and 3 (3%) were positive for cytomegalovirus IgG and IgM antibodies, respectively. Of the 100 cord serum specimens analyzed, 99 (99%) and 2 (2%) were positive for cytomegalovirus IgG and IgM antibodies, respectively. Cytomegalovirus DNA was detected in 4 out of 100 (4%) cord blood samples of newborns. From four CMV DNA positive cases, Case 1 had no IgM in cord serum, but had IgM in mother's sera. Cases 2 and 4 were positive for IgM in both mother's sera and cord serum. Case 3 had no detectable CMV IgM in sera and cord serum. As many as 66 and 100% of CMV IgM-positive women in this study also had CMV IgM and CMV DNA in their delivery cord blood samples, respectively suggesting an increased risk of congenital CMV infection in those pregnancies. A paired women sera/cord blood CMV IgM-negative was found to be positive for CMV DNA. The data may also suggest the utility of PCR in place of CMV IgM as a diagnostic method for congenital CMV infection.
Newborn Screening for Congenital Cytomegalovirus Infection in Iran
Pediatric Infectious Disease Journal, 2016
Cytomegalovirus (CMV) infection is the most frequent congenital infection in developed countries and the main cause of non-hereditary sensorineural deafness. We report the case of a 27-week-old newborn (NB) with symptomatic congenital CMV infection. The pregnancy was monitored and CMV seroconversion was detected in the first trimester maternal serum screening. At 10 weeks of gestation the mother was diagnosed with breast carcinoma, submitted to a tumorectomy at 17 weeks and started chemotherapy by the 21 st week. CMV fetal infection was confirmed by positive DNA detection in amniotic fluid at 21 weeks of gestation. The mother received valaciclovir therapy from the 22 nd week of pregnancy until delivery. The NB was delivered by cesarean section at 27 weeks with a birth weight of 950 g. In the first day of life, the NB suffered severe thrombocytopenia and congenital CMV infection was confirmed by positive PCR for CMV DNA in both urine and blood samples. The NB completed six weeks of ganciclovir treatment with progressive clinical and analytical recovery. Auditory evoked potentials were absent in the left ear. On the 84 th day of life, the infant, due to clinical and laboratory assessments deterioration, started valganciclovir, completing a total of 6 months of treatment. Currently, at 36 months, the infant presents an appropriate development for the corrected age and has no indication for cochlear implantation. The authors intend to point out the difficulty of treating this infection associated with a high morbimortality, as there is no definitive evidence about the potential benefit of fetal infection treatment during pregnancy, the evidences regarding the effectiveness of antiviral therapy in NB refer to a restricted group of NBs, and this therapy may be associated with important