Christelle Vauloup-Fellous

Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy?: Results of a 3-year prospective study in a French hospital.

BACKGROUND Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection in developed countries. OBJECTIVES The objective of this study was to evaluate the impact of our prenatal CMV infection screening and counseling policy. STUDY DESIGN Since 2005, all pregnant women in our obstetric center have been informed about CMV infection, and if they agree, given a serological test at around 12 weeks of gestation (WG). If this first test is negative, the women and their partners are given hygiene counseling on how to prevent CMV infection, and a second test is performed at around 36 WG. RESULTS Among the 5312 women who had an unknown immune status, or were known to be seronegative when they had their first visit to our center for their current pregnancy, 97.4% agreed to CMV screening. Primary infection was detected in 11 women between 0 and 12 WG (0.42%), and seroconversion was diagnosed in five women between 12 and 36 WG (0.19%). CONCLUSIONS These results suggest that if clear information is given on CMV infection during pregnancy, the rate of seroconversion is lower following counseling than before counseling.

A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome

To analyze the outcome of maternal primary cytomegalovirus (CMV) infection.

Evaluation of Different Cytomegalovirus (CMV) DNA PCR Protocols for Analysis of Dried Blood Spots from Consecutive Cases of Neonates with Congenital CMV Infections

ABSTRACT Two protocols for the extraction of cytomegalovirus (CMV) DNA and two methods for the amplification of CMV DNA in dried blood spots were evaluated for the retrospective diagnosis of congenital CMV infection. During the period from 1996 to 2006, a urine screening program detected 76 congenitally infected neonates. Stored Guthrie cards with blood from 55 cases and 12 controls were tested. Two spots of dried blood were cut from each card and evaluated in two centers. CMV DNA was extracted from a whole single spot. Center 1 used phenol-chloroform extraction and ethanol precipitation followed by a conventional PCR. Center 2 used the NucliSens easyMAG automated DNA/RNA extraction platform (bioMérieux) followed by a real-time PCR. For evaluation of the extraction method, DNA extracted from each blood spot was evaluated by the amplification method used by the collaborating center. The sensitivities were 66% for center 1 and 73% for center 2. None of the controls were positive. A sensitivity as high as 82% could be obtained by combining the most sensitive extraction method (the phenol-chloroform procedure) with the most sensitive PCR method (real-time PCR). The detection rate was not influenced by the duration of storage of the spots. The sensitivity was higher with blood from congenitally infected cases due to a primary maternal CMV infection, regardless of the protocol used. However, the difference reached significance only for the least-sensitive protocol (P = 0.036).

Evaluation of Cytomegalovirus (CMV) DNA Quantification in Dried Blood Spots: Retrospective Study of CMV Congenital Infection

ABSTRACT We compared two protocols for extracting DNA from dried blood spots for cytomegalovirus (CMV) DNA detection and quantification by real-time PCR. Both extraction methods were reliable for the retrospective diagnosis of CMV congenital infection. Quantification of CMV DNA was valuable after normalization of viral loads with albumin gene PCR amplification results.

Inner ear lesions in congenital cytomegalovirus infection of human fetuses

Congenital cytomegalovirus (CMV) infection is the leading cause of non-hereditary congenital sensorineural hearing loss (SNHL). The natural course and the pathophysiology of inner ear lesions during human fetal CMV infection have not yet been reported. Inner ear lesions were investigated in six CMV-infected fetuses aged 19–35 postconceptional weeks and correlated with central nervous system (CNS) lesions. All the fetuses had high viral loads in the amniotic fluid and severe visceral and CNS lesions visible by ultrasound. Diffuse lesions consisting of both cytomegalic cells containing inclusion bodies and inflammation were found within all studied structures including the inner ear, brain, other organs, and placenta, suggesting hematogenous dissemination. Cochlear infection was consistently present and predominated in the stria vascularis (5/6), whereas the supporting cells in the organ of Corti were less often involved (2/6). Vestibular infection, found in 4/6 cases, was florid; the non-sensory epithelia, including the dark cells, were extensively infected. The endolymphatic sac was infected in 1 of 3 cases. The severity of inner ear infection was correlated with the CNS lesions, confirming the neurotropism of CMV. This study documenting infection of the structures involved in endolymph secretion and potassium homeostasis in fetuses with high amniotic fluid viral loads suggests that potassium dysregulation in the endolymphatic compartment of the inner ear may lead to secondary degeneration of the sensory structures. In addition, the occurrence of SNHL depends on the intensity and duration of the viral infection and inflammation.

Prospective Identification of Congenital Cytomegalovirus Infection in Newborns Using Real-Time Polymerase Chain Reaction Assays in Dried Blood Spots

BACKGROUND Congenital cytomegalovirus (CMV) infection is a public health issue, and implementation of neonatal screening has been debated. Detection of CMV DNA by polymerase chain reaction (PCR) of dried blood spots (DBS) routinely collected for metabolic screening from all newborns has been proposed for congenital CMV infection screening. The goal of this study was to prospectively assess the performance of 2 CMV PCR assays of DBS for CMV neonatal screening in a selected population of neonates. METHODS We studied prospective congenital CMV screening in a population of neonates either born with symptoms compatible with congenital CMV or born to mothers with a history of primary infection during pregnancy. For each neonate, 2 CMV PCR assays of DBS were blindly performed in parallel with a gold standard technique (ie, CMV PCR of a urine sample). RESULTS Two hundred seventy-one neonates were studied, and CMV infection, defined by a positive urine sample in the first week of life, was confirmed in 64 (23.6%). Nineteen infected (29.7%) neonates were symptomatic, and 45 (70.3%) were asymptomatic. The ranges of sensitivity, specificity, positive predictive value, and negative predictive value for the 2 CMV PCR assays of DBS were 95.0%-100%; 98.1%-99.0%; 94.1%-96.9%, and 98.5%-100%, respectively. CONCLUSIONS The sensitivity and specificity of both CMV PCR assays of DBS to identify congenital CMV were very high in this population of neonates with a high risk of sequelae. These new data should be considered in the ongoing debate on the appropriateness of the use of DBS as a sample to screen for congenital CMV infection.

Phylogenetic Analysis of Rubella Viruses Involved in Congenital Rubella Infections in France between 1995 and 2009

ABSTRACT Rubella is an acute infectious disease that normally has a mild clinical course. However, infections during pregnancy, especially before week 12 of gestation (WG), can cause severe birth defects known as congenital rubella syndrome (CRS). The aim of this study was to perform genotyping and molecular characterization of rubella viruses involved in congenital infections in France over the past 15 years (1995 to 2009). Amniotic fluid (AF) specimens (n = 80) from pregnant women with congenital rubella infections (CRI) before week 20 of gestation, and a few other samples available from children/newborns with CRS (n = 26), were analyzed. The coding region of the rubella virus E1 gene was amplified directly from clinical specimens by reverse transcriptase PCR, and the resulting DNA fragments were sequenced. Sequences were assigned to genotypes by phylogenetic analysis with rubella virus reference sequences. Sufficient E1 gene sequences were obtained from 56 cases. Phylogenetic analysis of the sequences showed that at least five different genotypes (1E, 1G, 1B, 2B, and 1h) were present in France and were involved in congenital infections, with a strong predominance of genotype 1E (87%). This is one of the very few comprehensive studies of rubella viruses involved in CRI. The results indicated that over the past 15 years, multiple introductions of the dominant genotype E caused most of the CRI cases in France. A few sporadic cases were due to other genotypes (1B, 1G, 1h, 2B).

Re-evaluation of the VIDAS ® cytomegalovirus (CMV) IgG avidity assay: Determination of new cut-off values based on the study of kinetics of CMV-IgG maturation

BACKGROUND In case of cytomegalovirus (CMV) infection, differentiation between primary and non-primary CMV infection can be of major importance for the correct management of pregnant women or immunocompromised patients. Besides CMV-IgM and IgG, CMV-IgG avidity measurement is now commonly used to distinguish primary from non-primary infection. OBJECTIVE To re-evaluate the performance of the VIDAS CMV-IgG avidity assay in comparison with 2 other techniques (Architect Abbott and Liaison DiaSorin) and to study the kinetics of CMV-IgG avidity maturation. STUDY DESIGN A panel of 135 sequential samples collected from 31 patients with a proven primary infection (attested by very recent CMV-IgG seroconversion) was tested with VIDAS, Liaison and Architect CMV-IgG avidity assays. Moreover, 235 routinely collected samples, CMV-IgG and CMV-IgM positive, were analyzed with Liaison, VIDAS and an in-house CMV-IgG avidity assay. RESULTS AND CONCLUSIONS The analysis of all the data allowed suggesting new VIDAS cut-off values of 0.40 for low avidity and 0.65 for high avidity, which significantly increase the test performance and enable better patient managements. Using these VIDAS new cut-off values, all of the 31 primary infections were correctly dated. Comparatively, 25 out of 31 were correctly dated with the Architect assay and 29 out of 31 with the Liaison assay. We also demonstrated that the VIDAS CMV-IgG avidity assay allows observing correctly the maturation of CMV-IgG avidity, which could be useful as an additional parameter for diagnosis of a recent CMV infection.

Detailed in utero ultrasound description of 30 cases of congenital cytomegalovirus infection.

The aim of this research was to describe precisely prenatal ultrasound (US) features in congenital cytomegalovirus (CMV) infection.

Awareness of cytomegalovirus infection among pregnant women in France

BACKGROUND Cytomegalovirus (CMV) is the most frequent cause of congenital virus infection. Approximately 1% of newborns are infected by CMV at birth with severe consequences among 10% of them. Efficacy of hygienic counselling is nowadays established and should be spread. OBJECTIVE To evaluate pregnant womens awareness of cytomegalovirus infection in France. STUDY DESIGN Pregnant women receiving prenatal care, at any moment of their pregnancy, in two different obstetrics clinics with different information policies, were asked to complete a written questionnaire about CMV infection. RESULTS More than half (217/362, 60%) of the pregnant women had heard of congenital CMV infection, and most of them (72%) knew the hygiene measures to use to prevent infection. Nevertheless, most could not correctly identify the symptoms associated with congenital CMV disease. Awareness was associated with hospitals policy concerning CMV infection information, the mothers educational level, parity, and employment in health care. Indeed, when information is supposed to be given (hospital A), 74% (vs 34%) know congenital CMV infection and among them the knowledge is more precise. CONCLUSIONS This study tends to confirm that there is a large gap between knowledge of CMV and the burden of this disease. To bridge this gap, women should receive education about congenital CMV. Hospital-based prenatal education increases awareness and knowledge about CMV and CMV prevention.