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ABSTRACT: OBJECTIVE: To analyze the outcome of maternal primary CMV infection. METHODS: Retrospective analysis of a cohort of 238 patients with maternal primary CMV infection detected at routine screening. The cases were managed with serial ultrasound (US) scans and amniocentesis was performed in 36.1% of cases. All prenatal results were confirmed at birth. RESULTS: The average age was 31.9 [18-44] years. Patients were symptomatic in 21% of cases. The rate of intrauterine transmission was 24.9%, and it was 8.8%, 19%, 30.6%, 34.1% and 40% in the preconceptional period, the periconceptional period, the first, second and third trimester of pregnancy, respectively (P = 0.025). There was a significantly higher risk of US abnormalities when maternal infection occurred during the preconceptional or periconceptional period and the first trimester compared with later (p < 0.001). Because of US abnormalities, pregnancy was terminated in 18 cases at the parents' request. Three infected newborns were symptomatic; all three cases were suspected at US before birth. We did not observe any symptomatic fetal infection when maternal infection occurred after 14 weeks of gestation. 5.5% of clinically asymptomatic cases developed hearing loss. CONCLUSION: The rate of materno fetal transmission is linearly correlated to the gestational age at infection. No severe case of congenital infection was observed if maternal infection occurred after 14 weeks of gestation. © 2013 John Wiley & Sons, Ltd.
Prenatal Diagnosis 04/2013; · 2.11 Impact Factor
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ABSTRACT: Cytomegalovirus (CMV) is the most frequent cause of congenital virus infection. CMV infects approximately 1% of newborns at birth with severe consequences among 10% of them and antenatal and postnatal treatments, although promising, are still under evaluation in randomised control trials. Efficacy of hygienic counselling to prevent CMV infection is nowadays established and should be spread.
To evaluate health care providers' awareness of CMV infection during pregnancy in France.
A questionnaire on CMV infection was sent by e-mail to obstetricians, paediatricians, midwives and laboratory physicians, members of medical or midwives association. We evaluated their knowledge concerning CMV epidemiology, transmission, symptoms in adults, newborns and children.
The questionnaire was completed by 800 respondents (half midwives and one third obstetricians). Most of them were unaware of the precise transmission route of CMV. Laboratory physicians had the highest score concerning maternal symptoms and post natal long term effects. 20% of respondents were wrongly convinced that in utero treatment options for congenital CMV infection were already available in France at the time of the study. The mean knowledge scores regarding transmission and neonatal symptoms increased with a more advanced career stage (i.e. older age) among obstetrician.
This study tends to confirm that there is a large gap between knowledge of CMV during pregnancy and the burden of this disease. To bridge this gap, health care providers should improve their knowledge about congenital CMV by various means: medical reviews, continuing medical education, meetings, conferences, the Internet.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2012; 55(2):158-63. · 3.12 Impact Factor
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Prenatal Diagnosis 04/2012; 32(5):496-7. · 2.11 Impact Factor
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ABSTRACT: Although measles is usually considered a benign viral disease of childhood, people may be affected whatever their age with severe pneumologic or neurologic consequences are more frequent before 5 years old and after 20 years old. The consequences of a congenital measles, defined as a newborn eruption within 10 days after birth, can be dramatic. The incidence of measles has significantly decreased since first vaccines were introduced in the late 1960s. In France, active immunization for measles is proposed since 1983. Since the beginning of 2008, France has been experiencing a measles outbreak with more than 17,000 notified cases. The current measles outbreak affects more particularly very young children and young adults and, among these, pregnant women. Measles during pregnancy may be severe mainly due to pneumonia. Measles is associated with a risk of miscarriage and prematurity, but congenital anomalies have not been described. If rash occurs near term, the consequences of congenital measles could be severe. Prevention of measles in pregnant women is based on improving immunization coverage, currently insufficient to eradicate virus circulation. The aim of this review is to state on the latest data concerning measles virus, give latest vaccine recommendations, and also to suggest management of measles contact or measles infection during pregnancy.
Journal de Gynécologie Obstétrique et Biologie de la Reproduction 03/2012; 41(3):209-18. · 0.42 Impact Factor
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ABSTRACT: 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.
To evaluate pregnant women's awareness of cytomegalovirus infection in France.
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.
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 hospital's policy concerning CMV infection information, the mother's 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.
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.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2012; 53(4):332-7. · 3.12 Impact Factor
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ABSTRACT: A 34-year-old woman consulted the day before a scheduled caesarean for dry cough. A positive rhinopharyngeal sample for PCR testing for influenza A H1N1 led to a curative oseltamivir (Tamiflu®) treatment. At delivery a direct contact between the newborn and mother lasted only few seconds. The first healthy baby boy developped dry cough with a rhinopharyngeal sample positive for A H1N1. The minimal contact between mother and child and the positive neonatal sample only four hours after birth allow to think that it is a rare case of prenatal transmission of influenza A H1N1 to the fetus.
Journal de Gynécologie Obstétrique et Biologie de la Reproduction 02/2011; 40(5):473-5. · 0.42 Impact Factor
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ABSTRACT: To evaluate the proportion of pregnant women agreeing to cytomegalovirus (CMV) serologic screening. To collect data on CMV infection during pregnancy.
Prospective study.
During two years, all pregnant women were informed on CMV infection. If the patient agreed, serological testing was performed around 12 weeks of gestation (WG) and, if negative, redone around 36 WG.
Four thousand two hundred and eighty-seven pregnant women followed from 12 weeks to delivery.
If the first CMV serologic test was negative, detailed hygiene information was given to the parents. Diagnosis of primary infection was based on the detection of CMV-G, CMV-M and low CMV-G avidity index. When maternal infection was confirmed, diagnosis of CMV congenital infection was done in the newborns by urine culture within the three days following birth. Crude infection-rate data consisted of the number of CMV infection cases and person-time units for both exposed to hygiene CMV information (12 to 36 WG) and unexposed pregnant women (first 12 WG).
Rate of CMV seropositive and seronegative women. Rate of women agreeing for screening. Rate of primary infection. Rate of seroconversion. Number of CMV-infected newborns.
Among the 4287 women followed, 3792 were either seronegative or with an unknown immune status. 96.7% out of them agreed for screening. 53.2% were initially CMV-specific IgG negative. Primary infection was detected in nine women between 0 and 12 WG (0.46%) and seroconversion was diagnosed in five women between 12 and 36 WG (0.26%) (mid P = 0.02, 95% CI [1.07-13.6]).
If clear information on CMV infection during pregnancy is given, patients frequently agree to screening. The rate of seroconversion after information, observed in this study, is low after counselling.
BJOG An International Journal of Obstetrics & Gynaecology 06/2009; 116(6):818-23. · 3.41 Impact Factor
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Prenatal Diagnosis 10/2008; 28(10):971-2. · 2.11 Impact Factor
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Ultrasound in Obstetrics and Gynecology 05/2008; 31(4):481-3. · 3.01 Impact Factor
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ABSTRACT: We measured rubella virus immunoglobulin G (IgG) and IgM levels, as well as IgG avidity indexes, in serum samples taken before or after 6 months either after infection or after vaccination. The results obtained indicate that humoral immune responses are different after primary infection and after vaccination. This may have important consequences on the serological diagnosis of rubella virus infection.
Clinical and Vaccine Immunology 06/2007; 14(5):644-7. · 2.55 Impact Factor
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ABSTRACT: Out of the 90% of cytomegalovirus (CMV) congenitally infected children that are asymptomatic at birth, 5 to 15% will later develop complications, mainly neurodevelopmental defects and/or deafness. Unfortunately, after the first 2 weeks of life, usual diagnostic techniques for CMV detection (viral culture and serology) are useless to differentiate congenital infection from post-natal acquired infection, whereas detection of viral DNA from dried blood spots (DBS; Guthrie cards), systematically collected from all newborns in the first days of life, has been described for late diagnosis of CMV congenital infection. The aim of our study was to choose and optimise a viral DNA extraction method from DBS and to study if CMV DNA detection is reliable when DBS are stored for 1 year at room temperature or 2 months at 37 degrees C. 10 reference cards (blood collected from CMV seronegative newborns (IgG/IgM negative) were "infected" with serial dilutions of virus and spotted on Guthrie cards) were tested. 3 extraction methods were evaluated, products of PCR were analyzes by agarose gel electrophoresis and quantification of CMV from DBS was also performed. Analysis of the results obtained from reference cards showed higher sensitivity of phenol/chloroform extraction following treatment with proteinase K, compared to heat extraction in cell culture medium or extraction with a commercial kit. We did not observe quantitative loss of viral DNA after 1 year storage at room temperature. CMV DNA detection from Guthrie cards could become a very useful tool for retrospective diagnosis of congenital CMV infection when sequelae are diagnosed in the first years of life. We are pursuing this study with DBS from congenitally infected children.
Pathologie Biologie 01/2007; 54(10):551-5. · 1.53 Impact Factor
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L Adalid-Peralta, L Grangeot-Keros,
A Rudent,
N Ngo-Giang-Huong,
R Krzysiek,
C Goujard,
C Deveau,
M Le Gall,
L Meyer,
D Emilie,
C Rouzioux
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ABSTRACT: To study the impact of highly active antiretroviral therapy (HAART) on isotype switching and avidity maturation of HIV-1-specific immunoglobulin G (IgG) in patients with primary HIV-1 infection (PHI).
We studied the emergence and the evolution of anti-HIV IgG antibodies by quantitative immunoblotting to analyse IgG subclasses and IgG avidity. Serum samples were obtained from 16 PHI patients from the French PRIMO Cohort Study at various points in the first year of infection: eight patients received no treatment (group I), and eight patients received efficient HAART (group II) during the study period.
Early initiation of HAART in PHI patients partially prevented an increase in anti-HIV-1 IgG levels. Within IgG subclasses, the amount of anti-HIV-1 IgG1 gradually increased with time in both groups, although levels remained lower in treated patients. The anti-p24 IgG2 level was always lower in group II. We observed a decrease in anti-p24 IgG3 over time in both groups. Treatment did not affect the maturation of HIV-1 IgG avidity, which increased in both groups until month 3 and then remained high until the end of the 12-month follow-up period.
HAART in PHI partially prevents the emergence of HIV-1 IgG antibodies, but does not affect the quality of these antibodies, as reflected in their isotype and avidity.
HIV Medicine 12/2006; 7(8):514-9. · 3.01 Impact Factor
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ABSTRACT: Serological diagnosis of CMV primary infection is usually based on the detection of specific IgM antibody. However, as the presence of IgM antibody is not always correlated with primary infection, measurement of IgG avidity must be performed. The aim of our study was to evaluate the best procedure for serological diagnosis of CMV primary infection. In other words, is it better to first search for IgM antibody, and, if positive, then measure IgG avidity, or first measure IgG avidity without the detection of IgM antibody?
CMV-IgM detection and CMV-IgG avidity measurement were performed on 310 IgG positive sera from pregnant women.
CMV-IgM antibody was detected positive for 9 of 310 sera. Using CMV-IgG avidity index (AI), dating of infection was difficult in 81/310 cases (26%), while it failed in only 3/310 cases using CMV-IgM plus CMV-IgG AI.
The diagnosis of primary CMV infection can be based on the detection of CMV-IgM antibody first and then on the measurement of CMV-IgG AI.
Prenatal Diagnosis 12/2004; 24(11):861-3. · 2.11 Impact Factor
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ABSTRACT: To assess the diagnostic value of RT-PCR on amniotic fluid (AF) for prenatal diagnosis of congenital rubella infection.
RT-PCR on AF was compared to specific IgM antibody detection in foetuses and/or newborns in 45 pregnant women with confirmed primary infection.
specificity of RT-PCR was 100% and sensitivity ranged between 83 and 95%.
RT PCR may be considered as a valuable tool for prenatal diagnosis of foetal rubella infection.
Pathologie Biologie 12/2004; 52(9):540-3. · 1.53 Impact Factor
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L Grangeot-Keros
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ABSTRACT: The main viral infections prenatally detected in fetuses are: cytomegalovirus (CMV), parvovirus B19, rubella virus and varicella-zoster virus infections. Prenatal diagnosis is based on the direct detection of the virus by culture (CMV), of its antigens (CMV) or of its genome, essentially by PCR. This direct detection can be done either on fetal blood or on amniotic fluid. Prenatal diagnosis can also be performed by detection of specific IgM in fetal blood (rubella). Non specific markers of viral infections can also help diagnosis. At the present time, prenatal diagnosis is essentially based on the detection of the viral genome in amniotic fluid. In order to better appreciate the severity of fetal infections, some groups have tried to identify prognostic markers of these infections. The viral load could play a role in certain infections (CMV).
Annales Pharmaceutiques Françaises 08/2003; 61(4):259-64.
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ABSTRACT: A real-time PCR assay was developed to quantify human cytomegalovirus (HCMV) DNA in amniotic fluid (AF) samples collected from 30 pregnant women with primary HCMV infection as detected either from HCMV-immunoglobulin G (IgG) seroconversion or by the presence of HCMV-specific IgG and IgM associated with a low IgG avidity. Clinical information available for each case included ultrasonographic examination and fetal or newborn outcome. HCMV infection of fetuses or newborns was confirmed for the 30 studied cases. AF samples were subdivided into three groups. In group A (n = 13), fetuses presented major ultrasound abnormalities, and pregnancy was terminated. In group B (n = 13), fetuses had normal ultrasound findings, the pregnancy went to term, and the newborns were asymptomatic at birth. In group C (n = 4), fetuses had no or minor ultrasonographic signs, and pregnancy was terminated. The HCMV DNA load values in AF samples were significantly higher in group A (median, 2.8 x 10(5) genome equivalents [GE]/ml) than in group B (median, 8 x 10(3) GE/ml) (P = 0.014). Our findings suggest that HCMV load level in AF samples correlates with fetal clinical outcome but might also be dependent on other factors, such as the gestational age at the time of AF sampling and the time elapsed since maternal infection.
Journal of Clinical Microbiology 06/2002; 40(5):1767-72. · 4.15 Impact Factor
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ABSTRACT: The main viral infections prenatally detected in fetuses are: cytomegalovirus, parvovirus B19, rubella virus and varicellazoster virus infections. Prenatal diagnosis is based on the direct detection of the virus by culture (CMV), of its antigens or of its genome, essentially by PCR. This direct detection can be done either on fetal blood or on amniotic fluid. Prenatal diagnosis can also be performed by detection of specific IgM in fetal blood (rubella). Non specific markers of viral infection can also help in diagnosis. At the present time, prenatal diagnosis is essentially based on the detection of the viral genome in amniotic fluid. In order to better appreciate the severity of fetal infections, some groups have tried to identify prognostic markers of these infections. The viral load as well as the level of specific IgM could play a role in certain infections (CMV).
Gynécologie Obstétrique & Fertilité 01/2002; 29(12):894-9. · 0.52 Impact Factor
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R Krzysiek,
A Rudent,
L Bouchet-Delbos,
A Foussat,
C Boutillon,
A Portier,
D Ingrand,
D Sereni,
P Galanaud, L Grangeot-Keros,
D Emilie
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ABSTRACT: Strains of human immunodeficiency virus (HIV) transmitted between individuals use the CCR5 coreceptor, but no preferential depletion of particular Th-lymphocyte subpopulations has been reported during primary HIV infection (PHI). In contrast, gut-associated Th lymphocytes are preferentially depleted in macaques recently infected by simian immunodeficiency virus. The expression of CCR5 and the intestinal homing receptor integrin alpha4beta7 on subpopulations of Th lymphocytes was studied in 12 patients with PHI. There was a profound decrease of circulating alpha4beta7+ Th lymphocytes and CCR5+ memory Th lymphocytes with nonlymphoid homing potential (CD62L-CD45RO+). Unlike other Th lymphocytes, this cell population remained depleted despite early control of viral replication under antiretroviral treatment. Therefore, HIV preferentially targets a specific CCR5+ subpopulation of Th lymphocytes early during infection, inducing its persistent depletion despite treatment. Protective immunity in vivo depends on Th lymphocytes carrying homing capacity to nonlymphoid tissue, and therefore these data may explain the persistent abnormalities of immune functions in patients infected with HIV.
Blood 12/2001; 98(10):3169-71. · 9.90 Impact Factor
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D Emilie,
M Burgard,
C Lascoux-Combe,
M Laughlin,
R Krzysiek,
C Pignon,
A Rudent,
J M Molina,
J M Livrozet,
F Souala,
G Chene, L Grangeot-Keros,
P Galanaud,
D Sereni,
C Rouzioux
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ABSTRACT: IFN alpha has both antiviral and immunostimulating properties. The ANRS086 Primoferon A Study evaluated in 12 patients with primary HIV infection the tolerance and efficacy of an early and transient administration of pegylated IFN alpha, in addition to highly active antiretroviral therapy. Tolerance was good, and this regimen allowed the early control of HIV replication and rapid decay of the viral reservoir. These results support the initiation of comparative studies with pegylated INF alpha in primary HIV infection.
AIDS 08/2001; 15(11):1435-7. · 6.24 Impact Factor
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ABSTRACT: Human cytomegalovirus (HCMV) infections are frequently observed as well in immunocompetent as in immunocompromised patients. Diagnostic techniques for HCMV detection have greatly improved during the recent years. Detection of HCMV by culture has been bettered by centrifugating samples in a shell vial and by using monoclonal antibody to the immediate early antigen. Detection of antigens in leucocytes was facilitated by using whole blood instead of leucocytes separated by dextran sedimentation. Detection of HCMV recently sharpened by using molecular biology methods mainly based on the detection of the genome. Under certain circumstances, and especially in pregnant women, diagnosis of HCMV infection is essentially based on the detection of IgG and IgM antibodies. However, as IgM antibody is not a marker of primary infection, complementary tests are needed to help in the datation of the infection. Among them, the measurement of IgG avidity greatly improved the diagnosis of primary infections. In immunocompromised patients, very sensitive techniques are needed to diagnose HCMV infections. Detection of antigenemia and HCMV DNA are the methods of choice for an early detection of the infection. Diagnosis of HCMV-organ diseases largely depends on the infected organ and the presence of HCMV in the organ is, sometimes, difficult to interpret. Today, diagnosis of congenital infections is possible by detecting HCMV in the amniotic fluid. However, in order to reliably detect HCMV, amniocentesis must be performed after 21 week's gestation and at least 6 weeks after seroconversion. As all HCMV infections do not induce disease, prognostic markers are needed, as well in immunocompromised patients as in fetuses. Many studies were conducted in immunocompromised patients to find prognostic markers of HCMV infection in order to introduce preemptive therapy when needed. It seems that quantitative determination of HCMV DNA could be very useful to predict HCMV disease. Qualitative determination of mRNA could also be useful as a prognostic marker of HCMV disease. Determination of viral genotypes is more controversial. As for the infected fetuses, little was published about the prediction of sequelae. Some factors, such as viral load in amniotic fluid or in fetal blood or level of IgM antibody in fetal blood, may be predictive of sequelae, but these data require further studies.
Journal of Clinical Virology 07/2001; 21(3):213-21. · 3.97 Impact Factor