Zytomegalie (CMV-Infektion) in der Schwangerschaft

@article{Daiminger.2024,

title = {Performance of eight commercial immunoassays for the detection of cytomegalovirus-specific IgM antibodies in pregnancy - no test fits all needs},

author = {A Daiminger and R Beck and S Exler and U Bartelt and M Enders},

doi = {10.1128/jcm.01407-23},

year  = {2024},

date = {2024-04-10},

urldate = {2024-04-10},

journal = {Journal of Clinical Microbiology},

volume = {62},

issue = {4},

pages = {e0140723},

abstract = {Detection of cytomegalovirus (CMV)-specific immunoglobulin M (IgM) antibodies as first-line serologic diagnosis plays an important role in identifying CMV primary infection during pregnancy. The performance characteristics of eight commercially available CMV IgM assays were compared. Sensitivity and IgM antibody kinetics were assessed using 100 acute phase and follow-up sera from 39 pregnant women with a well-defined onset of CMV primary infection. Specificity was analyzed using 50 well-characterized serum samples from pregnant women not infected or latently infected with CMV and from patients with other acute infections. Until 12 weeks after the onset of primary infection, four assays showed sensitivities of 100%, whereas the others had individual gaps to detect all primary infections in this time period. All assays showed a time-dependent decrease of IgM levels. More than 12 weeks after the onset of infection, the IgM-positive rates varied considerably between tests. The specificity was between 92% and 98% in all but one assay. The observed differences in the performance characteristics must be taken into account in CMV screening and diagnosis of primary infection during pregnancy.},

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}

@article{Devlieger.2021,

title = {Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial},

author = {R Devlieger and H Buxmann and G Nigro and M Enders and J J\"{u}ckstock and P Sikl\'{o}s and A Wartenberg-Demand and J Sch\"{u}ttrumpf and J Sch\"{u}tze and N Rippel and M Herbold and G Niemann and K Friese},

doi = {10.1159/000518508},

year  = {2021},

date = {2021-10-01},

urldate = {2021-10-01},

journal = {Fetal Diagnosis and Therapy},

volume = {48},

issue = {8},

pages = {611\textendash623},

abstract = {Introduction: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We pre­sent a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. Methods: CMV-seronegative pregnant women (gestational age [GA] \<14 weeks) were 1:1 randomized to monthly CMV-serostatus monitoring and CMV-HyperIg upon seroconversion (treatment), or routine prenatal care with CMV-serostatus testing at end of pregnancy (control). Ethical considerations required that control subjects with confirmed seroconversion be offered CytotectcircledR. The primary endpoint was the proportion of fetuses/newborns with congenital CMV infection. Secondary endpoints included neonatal CMV disease and safety during the 24-month follow-up. Results: The treatment arm counted 4,800 randomized subjects: 52 seroconverted (median GA 24 [11--35] weeks), of which 45 completed follow-up. The control arm counted 4,735 randomized subjects: 42 seroconverted, of which 34 completed follow-up (evaluable data for 28 newborns) and 8 subjects chose off-label CytotectcircledR. Congenital CMV rates were 13/28 newborns (46.4% [CI 27.51; 66.13]) vs. 16/45 newborns (35.6% [CI 21.87; 51.22]) in control and treated arms, respectively (p = 0.46). Newborn CMV disease was mostly mild and spontaneously resolving. There were no major safety concerns. The target sample was not reached within an acceptable time frame. Conclusions: Serial monitoring of CMV serostatus with CMV-HyperIg treatment was associated with a mild nonsignificant reduction in the vertical CMV transmission rate. Studies on the optimal preventive strategy are hampered by epidemiological and ethical challenges and should focus on GA-dependent transmission rates and accurate dating of infection.},

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}

@article{Kagan.2021,

title = {Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study},

author = {K O Kagan and M Enders and M Hoopmann and A Geipel and C Simonini and C Berg and I Gottschalk and F Faschingbauer and M O Schneider and T Ganzenmueller and K Hamprecht},

doi = {10.1002/uog.23596},

year  = {2021},

date = {2021-01-25},

urldate = {2021-01-25},

journal = {Ultrasound in obstetrics \& gynecology},

volume = {57},

pages = {560-567},

abstract = {OBJECTIVE 

 

In this study we set out to examine the efficacy of the hyperimmunoglobulin (HIG treatment in women with a recent primary CMV infection up to 14 weeks' gestation. 

 

METHODS 

 

Ongoing observational study at the prenatal medicine departments of Tuebingen, Bonn, Cologne and Erlangen, Germany as well as the laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tuebingen. Enrollment criteria were the presence of confirmed, very recent primary CMV infection in the first trimester and a gestational age at first HIG administration of $\leq$ 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti-IgG levels, low anti-CMV-IgG avidity in the presence of a positive CMV IgM test and no or just seroconversion anti-gB2-IgG-reactivity. The HIG administration (Cytotect CPcircledR, Biotest, Germany) was started as soon as possible within few days after the first visit in the four units. HIG was administered at 200 IU per kilogram bodyweight intravenously and repeated every two weeks until about 18 weeks' gestation. Maternal-fetal transmission at the time of amniocentesis was considered as relevant primary outcome measure. Multivariate logistic regression analysis was used to determine significant covariates that could be used for the prediction of maternal-fetal transmission. 

 

RESULTS 

 

149 pregnant women and 153 fetuses were treated. Median maternal age and weight was 32.0 years and 65.0 kg, respectively. Median gestational age at the time of the first referral to one of the four centers was 9.4 weeks. Median anti-CMV-IgG levels, the anti-CMV-IgM index and the CMV IgG avidity was 5.7 U/ml, 2.5, and 22.3%, respectively. Treatment with HIG started at a median gestational age of 10.6 weeks and ended at 17.9 weeks. Within this time frame, HIGs were administered on average 4 times. Amniocentesis was carried out at a median gestational age of 20.4 weeks. In 143 (93.6%) of the 153 cases, the fetus was not infected. Maternal-fetal transmission occurred in 10 cases (6.5%, [95% CI 3.2 - 11.7]). In the uni- and multivariate logistic regression analysis, only the level of the anti-IgM index was significantly associated with maternal-fetal transmission at the time of the amniocentesis. However, only four (40.0%) of the 10 cases with maternal-fetal transmission had an anti-IgM level above 11.4 which corresponds to the 95th centile of the pregnancies without transmission. 

 

CONCLUSION 

 

HIG is a treatment option to prevent maternal-fetal transmission in a case of a primary CMV infection. However, treatment is only beneficial in women with a very recent primary infection in the first trimester or during the periconceptional period, a timely start and an appropriate treatment interval. This article is protected by copyright. All rights reserved.},

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pubstate = {published},

tppubtype = {article}

}

@article{Exler.2019,

title = {Primary cytomegalovirus (CMV) infection in pregnancy: Diagnostic value of CMV PCR in saliva compared to urine at birth},

author = {S Exler and A Daiminger and M Grothe and G Schalasta and G Enders and M Enders},

doi = {10.1016/j.jcv.2019.05.015},

year  = {2019},

date = {2019-05-01},

journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},

volume = {117},

pages = {33--36},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kohmer.2019,

title = {Laboratory diagnosis of congenital CMV infection in newborns: Impact of pre-analytic factors},

author = {N Kohmer and A Nagel and A Berger and M Enders and K Hamprecht and K Korn and M Kortenbusch and K \"{U}berla and H F Rabenau},

doi = {10.1016/j.jcv.2019.03.017},

year  = {2019},

date = {2019-04-01},

journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},

volume = {115},

pages = {32--36},

abstract = {BACKGROUND 

 

To identify infants with congenital cytomegalovirus (cCMV) saliva polymerase chain reaction (PCR) is an ideal screening method. However, there are only few data on the influence of pre-analytic factors on the analytical sensitivity of the CMV PCR. 

 

OBJECTIVES 

 

This study aimed to evaluate the performance of different swabbing materials, transport time and initial virus concentration regarding to the efficacy of recovery of CMV-DNA. 

 

STUDY DESIGN 

 

Two CMV suspensions containing a high or low concentration of the laboratory strain AD 169 were prepared as test samples. Sampling was simulated by immersion of different swabs in these CMV suspensions and storing the swabs dry or in specified transport media. Transport conditions were modeled by storing the samples for defined time periods prior to DNA extraction and quantitative PCR analyses. Parallel analyses in two different laboratories allowed determination of lab to lab consistency. 

 

RESULTS 

 

The duration of storage under the conditions analysed did not have a major effect on the recovery efficiency for the swabbing materials tested. With exception of flocked dry swabs, all tested swabbing materials demonstrated good recovery of CMV DNA. The flocked swab/eNAT system showed the best overall performance. 

 

CONCLUSIONS 

 

All tested swabbing materials (with exception of the flocked dry swabs) seem to be well suited for recovery of CMV DNA and appropriate for use for the diagnosis of cCMV infection in symptomatic cases and in general cCMV screening programs of newborns.},

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pubstate = {published},

tppubtype = {article}

}

@article{Kagan.2019b,

title = {Prevention of maternal-fetal transmission of CMV by hyperimmunoglobulin (HIG) administered after a primary maternal CMV infectionin early gestation},

author = {K O Kagan and M Enders and M S Schampera and E Baeumel and M Hoopmann and A Geipel and C Berg and R Goelz and L de Catte and D Wallwiener and S Brucker and S P Adler and G Jahn and K Hamprecht},

doi = {10.1002/uog.19164},

year  = {2019},

date = {2019-03-01},

journal = {Ultrasound in obstetrics \& gynecology},

volume = {53},

number = {3},

pages = {383--389},

abstract = {OBJECTIVE 

 

To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to women with first trimester CMV infection for preventing maternal-fetal transmission of CMV. 

 

METHODS 

 

Subjects were 40 pregnant women with a primary CMV infection with a median gestational age at diagnosis of 9.6 weeks with a range of 5.1 to 14.3 weeks' gestation. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks' gestation. Within this interval, HIG was administered between 2 and 6 times. While CMV IgG monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV IgG avidity indices remained stable over the whole treatment period. The results were compared with a historic cohort with first trimester CMV infection without treatment that also had an amniocentesis at about 20 weeks RESULTS: Each subject had amniocentesis performed. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5%, [95% CI:0 - 13.2%]). At delivery, two additional subjects had late gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% of 40 cases, [95% CI: 1,6 - 20.4%]). All infected neonates were asymptomatic at birth. Matched historical controls were 108 pregnancies with 38 transmissions (35.2%, [95% CI: 26.2 - 45.0%]), which was significantly higher than in the HIG administration group. 

 

CONCLUSION 

 

After a primary maternal CMV infection in the first trimester, HIG administration prevents maternal-fetal transmission up to 20 weeks of gestation. This article is protected by copyright. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Modrow.2018,

title = {Management der kongenitalen Zytomegalievirus-Infektion bei Neugeborenen},

author = {S Modrow and H Buxmann and M Enders and U Gembruch and R Goelz and K Hamprecht and D Huzly and P Kummer and K O Kagan and M Knuf and T Mertens and U Nennstiel-Ratzel and C Roll and M Wojcinski},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Frauenarzt},

volume = {59},

number = {5},

pages = {394--402},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DelleChiaie.2018,

title = {No evidence of obstetrical adverse events after hyperimmune globulin application for primary cytomegalovirus infection in pregnancy: experience from a single centre},

author = {L Delle Chiaie and P Neuberger and M Vochem and A Lihs and U Karck and M Enders},

doi = {10.1007/s00404-018-4703-y},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Archives of gynecology and obstetrics},

volume = {297},

number = {6},

pages = {1389--1395},

abstract = {PURPOSE: To determine the frequency of obstetrical adverse events and clinical outcome in infants following antenatal hyperimmune globulin (HIG) treatment for primary cytomegalovirus (CMV) infection in pregnancy. METHODS: Data from 50 women including three twin pregnancies were retrospectively evaluated. Primary infection was defined by seroconversion or the presence of CMV-specific IgM and low IgG avidity. All women received two or more infusions of HIG (200 U/kg). Congenital CMV (cCMV) infection was diagnosed by detection of CMV in amniotic fluid and/or neonatal urine. We compared gestational age (GA) at birth, head circumference (HC) and birth weight (BW) of infants in our study cohort with those of live-born infants delivered in our clinic between 2015 and 2016. RESULTS: Median gestational age at time of maternal CMV diagnosis was 13 weeks. One-hundred-forty-one maternal HIG doses were given. No HIG-related severe adverse reactions occurred. Preterm birth rate was 4.2% (2/47) in singleton pregnancies. None of the neonates had birth weight or head circumference textless 3rd percentile (textless 3P) for gestational age. There was no statistically significant difference regarding GA, BW and HC between our study cohort and the total population of live-born infants. The frequency of CMV-related sequelae in infants with cCMV infection was 10.5% (2/19) (one with bilateral hearing loss and one with mild motoric delay), both cases following first trimester maternal infection. CONCLUSION: Antenatal HIG treatment was well tolerated and not associated with prematurity or decreased birth weight. HIG application might have a favorable effect on the clinical course of congenital CMV infection},

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pubstate = {published},

tppubtype = {article}

}

@article{Kagan.2018b,

title = {Behandlungsoptionen bei einer vorgeburtlichen CMV-Prim\"{a}rinfektion},

author = {K O Kagan and M Enders and M Hoopmann and K Hamprecht},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Frauenarzt},

volume = {59},

number = {11},

pages = {854--858},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Enders.2017b,

title = {Prenatal diagnosis of congenital cytomegalovirus infection in 115 cases: a 5 years' single center experience},

author = {M Enders and A Daiminger and S Exler and K Ertan and G Enders and R Bald},

doi = {10.1002/pd.5025},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {Prenatal diagnosis},

volume = {37},

pages = {1--10},

abstract = {OBJECTIVE: The objective of this study is to investigate the diagnostic value of invasive prenatal diagnosis (PD) of congenital cytomegalovirus (CMV) infection from amniotic fluid (AF) and fetal blood (FB). METHODS: A retrospective study was conducted on 115 pregnancies with CMV primary infection. A total of 111 AF and 106 FB samples were investigated for various virological and non-virological markers. Detailed ultrasound examinations were performed at time of PD. RESULTS: Overall sensitivity of CMV PCR in FB (75.6%; 95%CI 60-87) and AF (72.7%; 95%CI 57-85) was comparable. In women with amniocentesis textgreater8 weeks between seroconversion and PD, we did not observe significant differences between amniocentesis performed textgreater/=17 + 0 (sensitivity 90.9%; 95%CI 71-99) and textgreater/=20 + 0 gestational weeks (sensitivity 90.0%; 95%CI 68-99). Virological markers in FB were higher in symptomatic compared with asymptomatic fetuses (p textless 0.05). No significant differences were observed for non-virological markers. However, platelet counts textless120 x 10e9/L and beta-2 microglobulin values textgreater14 mg/L were more frequently found in fetuses with severe ultrasound abnormalities compared with fetuses with no or mild abnormalities (p textless 0.001). CONCLUSION: Optimal timing of amniocentesis in women with primary infection in early gestation should be reevaluated in a prospective study. Analysis of FB markers may be beneficial in the individual management of pregnant women with confirmed congenital CMV infection. (c) 2017 John Wiley \& Sons, Ltd},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Enders.2013e,

title = {The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy},

author = {G Enders and A Daiminger and U B\"{a}der and S Exler and Y Schimpf and M Enders},

doi = {10.1016/j.jcv.2012.09.015},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},

volume = {56},

number = {2},

pages = {102--107},

abstract = {BACKGROUND: Primary CMV infections in pregnancy are usually asymptomatic and only detected by serology. Estimating the onset of infection is a major diagnostic goal, since primary infections around conception and in early gestation hold a higher risk for congenital disease than those in later pregnancy. OBJECTIVES: To assess the ability of serological supplementary CMV assays to date the onset of primary infection. STUDY DESIGN: From our routine diagnosis we identified 61 pregnant women (n=188 serum samples) with precisely determined onset of CMV primary infection either by IgG seroconversion (n=24) or by significant IgG antibody rise (n=37). One hundred and forty-seven sera were investigated using the VIDAS((R)) CMV IgG avidity EIA (BioMerieux) and 83 sera using the recomBlot CMV IgG with avidity (Mikrogen). RESULTS: Both assays proofed to be reliable in terms of timing the onset of CMV primary infection. An avidity index (AI) in the VIDAS avidity EIA of textless40% indicated primary infection within the last 20 weeks (positive predictive value 93.4%; 99/106), whereas an intermediate AI excluded primary infection within the last 12 weeks (negative predictive value 88.2%; 15/17). The recomBlot showed high reliability (PPV 96.9%; 31/33) for timing the onset of infection within the last 14 weeks. Avidity testing by blot however could not be interpreted in 11 of 47 sera (23.4%). CONCLUSION: For timing the onset of infection (before or in early pregnancy) CMV avidity testing is most helpful if carried out within the first trimester up to the beginning of second trimester},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Buxmann.2012,

title = {Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis},

author = {H Buxmann and O M Stackelberg and R L Schlosser and G Enders and M Gonser and M Meyer-Wittkopf and K Hamprecht and M Enders},

doi = {10.1515/jpm-2011-0257},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {Journal of perinatal medicine},

volume = {40},

number = {4},

pages = {439--446},

abstract = {AIMS: The aim of this study was to investigate the current prenatal textquotedbloff-label usetextquotedbl of cytomegalovirus hyperimmunoglobulin (CMV-HIG) in the prevention and treatment of congenital CMV (cCMV) infection, including the long-term outcome of the children. METHODS: This retrospective observational study comprised mothers and their children, born between January 1, 2006, and October 30, 2010. Prenatal CMV-HIG was administered after diagnosis of primary CMV infection of the mother. Clinical and virological data were collected from maternal and pediatric medical and laboratory reports. Follow-up was 12-36 months after birth. RESULTS: Forty-two women and 43 children met the study criteria. In total, 40 mothers and six unborn infants received 115 doses of CMV-HIG. The treatment group (TG; CMV-DNA polymerase chain reaction-positive amniotic fluid) included four mothers; the multinomial group (MG; CMV-positive mother and unknown CMV status of fetus) included 38 mothers (39 infants). For the four unborn infants in TG, CMV-HIG was administered either intraumbilically or into the amniotic fluid; three of the four mothers received intravenous CMV-HIG. Three children in TG remained CMV-positive and were asymptomatic at birth and during follow-up. One infant in TG had symptomatic cCMV infection in utero, at birth, and during follow-up. In MG, 37 of 38 women received intravenous CMV-HIG and two of 39 infants received CMV-HIG in utero. In total, 9 (23.1%) of 39 children in MG were positive for cCMV (including a terminated pregnancy). All eight instances of cCMV infection at birth in MG were asymptomatic at birth and during follow-up. The fetus from the terminated pregnancy showed no sonographic symptoms of cCMV infection. No severe side effect occurred in 115 CMV-HIG applications. CONCLUSION: CMV-HIG was well tolerated. Compared with published untreated mother-child pairs, we observed a trend toward a smaller risk for intrauterine CMV transmission following CMV-HIG application. Signs of prenatal cCMV disease were not reversed after CMV-HIG},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Enders.2011c,

title = {Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age},

author = {G Enders and A Daiminger and U B\"{a}der and S Exler and M Enders},

doi = {10.1016/j.jcv.2011.07.005},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},

volume = {52},

number = {3},

pages = {244--246},

abstract = {BACKGROUND: The risk of intrauterine cytomegalovirus (CMV) infection and disease in the fetus or newborn largely depends on time of primary maternal infection during pregnancy. OBJECTIVES: Prospective cohort study of pregnancy outcome in relation to gestational age at primary maternal CMV infection. STUDY DESIGN: In a total of 248 pregnancies with primary infection the onset of infection was determined by IgG seroconversion, IgG avidity and/or onset of clinical symptoms. Congenital infection was diagnosed by CMV detection in amniotic fluid, fetal tissue or urine of the neonate in the first 2 weeks of life. Clinical symptoms were retrieved from ultrasound and medical records. RESULTS: The intrauterine transmission rates following primary CMV infection in the pre- and periconceptional period were 16.7% (4/24) and 34.5% (10/29), respectively. For the first, second and third trimester of pregnancy transmission rates were 30.1% (25/83), 38.2% (29/76) and 72.2% (26/36), respectively. The rate of symptomatically infected fetuses or newborns at birth was 22.8% for any symptoms and 10.3% for severe manifestations. No symptoms were observed in infected newborns of mothers with primary infection in the preconceptional period and in the third trimester. CONCLUSIONS: The risk of intrauterine transmission following primary maternal infection in the third trimester is high, but the risk of neonatal disease is low. The highest risk of severe symptoms in the fetus and newborn exists around conception and in the first trimester of pregnancy},

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pubstate = {published},

tppubtype = {article}

}

@article{Dangel.2006,

title = {Improvement of cytomegalovirus avidity testing by adjusting the concentration of CMV-specific IgG in test samples},

author = {V Dangel and U B\"{a}der and G Enders},

doi = {10.1016/j.jcv.2005.09.011},

year  = {2006},

date = {2006-01-01},

urldate = {2006-01-01},

journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},

volume = {35},

pages = {303--309},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Enders.2003b,

title = {Zytomegalievirus- (CMV-) Durchseuchung und H\"{a}ufigkeit von CMV-Prim\"{a}rinfektionen bei schwangeren Frauen in Deutschland},

author = {G Enders and U B\"{a}der and U Bartelt and A Daiminger},

doi = {10.1007/s00103-003-0602-9},

year  = {2003},

date = {2003-01-01},

urldate = {2003-01-01},

journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz},

volume = {46},

number = {5},

pages = {426--432},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Eggers.2000b,

title = {Combination of microneutralization and avidity assays: improved diagnosis of recent primary human cytomegalovirus infection in single serum sample of second trimester pregnancy},

author = {M Eggers and U B\"{a}der and G Enders},

doi = {10.1002/(sici)1096-9071(200003)60:3textless324::aid-jmv11textgreater3.0.co;2-d},

year  = {2000},

date = {2000-01-01},

urldate = {2000-01-01},

journal = {Journal of medical virology},

volume = {60},

number = {3},

pages = {324--330},

abstract = {Estimation of IgG avidity index is a classical serological method. Antibodies with low avidity are detectable at a very early stage of infection whereas high avidity antibodies indicate past infection. Recently, it was shown that the neutralization assay can be routinely used as a reliable method for differentiating between acute primary and non-primary infection in a single serum sample because the first neutralizing titers (NT) appeared after an average of 13 weeks (range, 10-17 weeks). A low positive NT titer in the presence of specific IgM antibodies, however, still represents a diagnostic problem especially if blood sampling occurred after the 12th week of gestation. To overcome this problem the combination of NT and IgG avidity tests was evaluated. Human cytomegalovirus (HCMV) IgG avidity indices of 350 serum samples from 227 pregnant women were investigated using 6M urea in the washing buffer. HCMV specific IgG antibodies reached full maturation approximately 20-22 weeks after seroconversion and low IgG avidity is therefore a marker of primary infection. The combined application of the microneutralization and avidity assays was shown to serve as a helpful tool in diagnosis of a recent primary HCMV infection of second trimester pregnancy particularly when previous serological data were not available.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Daiminger.1998,

title = {An enzyme linked immunoassay using recombinant antigens for differentiation of primary from secondary or past CMV infections in pregnancy},

author = {A Daiminger and U B\"{a}der and G Enders},

doi = {10.1016/S1386-6532(98)00052-X},

year  = {1998},

date = {1998-01-01},

urldate = {1998-01-01},

journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},

volume = {11},

pages = {93--102},

keywords = {},

pubstate = {published},

tppubtype = {article}

}