IgG Avidity Index Research Articles

Neutralizing and ELISA IgG antibodies to human cytomegalovirus glycoprotein complexes may help date the onset of primary infection in pregnancy

BackgroundDefinition of onset for primary human cytomegalovirus (HCMV) infection during pregnancy is critical for several reasons, including diagnosis of pre-conceptional infections and definition of gestational age at the time of infection. ObjectiveTo determine the onset of primary HCMV infection, differential kinetics of antibodies neutralizing infection of epithelial and fibroblast cells, as well as ELISA IgG antibodies to HCMV glycoprotein complexes (gC) gH/gL/pUL128L, gH/gL/gO, and gB were exploited and compared with conventional assays. Study designIn a series of 40 pregnant women with primary HCMV infection and ascertained HCMV-related mild clinical symptoms, the kinetics of different types of neutralizing and ELISA IgG antibodies were investigated with the aim of establishing criteria for dating the onset of primary infection in pregnant women without clinical symptoms. ResultsIgG antibodies to gB and gH/gL/pUL128L, as well as antibodies neutralizing infection of epithelial cells appeared early after infection onset (within 2–3 weeks) and increased rapidly, whereas antibodies to gH/gL/gO and antibodies neutralizing infection of fibroblasts appeared later (>30 days) and increased slowly. Both the conventional diagnostic assays (IgG, and IgM antibody, and IgG avidity index) and the novel assays for determination of antibody responses directed against HCMV gC allowed the definition of an algorithm indicating the onset of primary HCMV infection in asymptomatic women within a period of 1–2 months. ConclusionNew neutralization and ELISA IgG assays to HCMV gC provide additional tools for dating the onset of primary infection in pregnancy.

Lack of evidence for a role of HHV-6 in the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD), the most common form of dementia worldwide, is associated with impairment in the mechanisms of the clearing of amyloid-β within a scenario of neuroinflammation. The etiopathogenesis of the AD is unclear, but a role for viral infection is suspected to play a role in initiating the disease. We recently described a positive correlation between high titers of HSV-1-specific antibodies (Ab) and the volumes of brain regions typically affected in disease. The exploration of a possible role for Herpesviridae in AD was extended by analyzing HHV-6-specific humoral immunity in individuals with AD or a diagnosis of amnestic mild cognitive impairment (aMCI), a condition that is often prodromic of the development of AD. 59 AD, 60 aMCI, and 61 age-matched healthy controls were enrolled in the study. Serum HHV-6 IgG antibody titers and avidity index were tested by ELISA. Two randomly selected subgroups of AD and aMCI in whom HHV-6 serum antibodies were detected underwent brain magnetic resonance imaging (MRI) by 1.5 T scanner. HHV-6 seroprevalence, antibody titers, and avidity were similar in the three groups. No correlation was found between Ab titers or avidity and brain volumes, either overall or in the regions typically affected by disease. The lack of any relation between humoral immune response against HHV-6 and AD and aMCI seems to rule out a role for this virus in the pathogenesis of AD.

ATPS-33EVIDENCE OF ABSENCE FOR CYTOMEGALOVIRUS IN PATIENTS WITH GLIOBLASTOMAS AND OTHER HIGH-GRADE GLIOMAS BY REAL-TIME PCR FOR DNA, IMMUNOHISTOCHEMISTRY FOR PROTEIN ANDIN-SITUHYBRIDIZATION FOR mRNA

BACKGROUND: Several groups have suggested a potential causative role of cytomegalovirus (CMV) in the development of high-grade gliomas (HGG), while others have not found any evidence of CMV in these cancers. We used 3 different molecular technologies to assay for the presence of CMV DNA, mRNA and protein in tumor tissue and blood samples of patients with HGG. METHODS: Part A: Fresh-frozen tissues from 27 glioblastomas (GBM) were analyzed for CMV by real-time PCR of US17. Part B: Prospective study of patients with newly-diagnosed HGG (grades III or IV) who underwent standard chemoradiation. Plasma and serum were collected at baseline, and plasma at follow-up visits. FFPE tumor tissue was analyzed for CMV proteins by genetically validated immunohistochemistry (IHC), in-situ hybridization assays targeting 1E1/2 and pp65, and by real-time PCR for US17 (tissue and plasma). RESULTS: Part A: CMV was detected in 0/27 fresh-frozen GBM tissue samples using real-time PCR. Part B: Eighteen patients with HGG (12 grade IV, 6 grade III) were enrolled. CMV tissue testing was negative in all samples by both probes for in-situ hybridization, both antibodies for IHC (n = 11 available samples), and CMV US17 real-time PCR (PCR successful in 8/14 samples). Serum CMV IgG avidity index was positive (0.55-0.82) in 8/15 cases, consistent with rates in the general population. CMV was detected in baseline plasma samples of 3/16 patients and in 1 single follow-up sample. All other plasma samples were negative for CMV (n = 34). CONCLUSION: CMV was not detected in any HGG tissue. Half of the patients with HGG did not have an exposure to CMV prior to their diagnosis, and viremia was rare at presentation and follow-up. An independent, unbiased investigation of CMV positivity rates using a central reference laboratory with standardized tissue samples and controls is warranted before further consideration of CMV-targeted therapy in HGG.

Immunodiagnostic approaches for the detection of human toxocarosis

Human toxocarosis is an important zoonosis caused by larvae of Toxocara canis/cati. The objective was to evaluate the role of IgG anti-Toxocara antibody detection and the specific IgG avidity in diagnostics of human toxocarosis. Anti-Toxocara IgG antibodies and IgG avidity were evaluated by excretory-secretory (ES)-enzyme-linked immunosorbent assay (ELISA). The IgG anti-Toxocara seroprevalence in people (n = 7678) from western Slovakia was 15.3% and found to be highest in the oldest age groups. The presence of low- IgG avidity in 179 suspected patients for toxocarosis was evaluated in relation to sex, age, IgG antibody levels, eosinophilia, increased total IgE, domicile, geophagia, dog/cat ownership, anamnesis. Low- IgG avidity index was found in 30.7% of the patients. The low- IgG avidity in eosinophilic group (42.1%) was significantly higher than in non-eosinophilic group (22.0%; P = 0.043). Substantially higher eosinophilia was detected in children (under 10 years old; 55.6%) than in adults (aged ≥ 41 years; 17.6%; P = 0.009). Significant difference between seroprevalence of total IgE in patients coming from towns (48.8%) and patients from villages (21.3%) was established (P = 0.007). Mild negative correlation (r = −0.477, P = 0.043) was observed between the amounts of eosinophils and the values of IgG avidity. The sensitivity and specificity of IgG avidity assay were 43.8% and 83.3%, respectively. Our results suggest that besides anti-Toxocara IgG, measurement of IgG avidity may be useful for the determination of acute toxocarosis. Moreover, these tests should be accompanied by other immunological markers and determinants of examined patients such as eosinophilia, increased total IgE and age.

Serological Investigation of Toxoplasma gondii on Pregnant Women and Toxoplasmosis Suspected Patients Between 2012-2014 Years on a Tertiary Training Hospital

Toxoplasmosis is a zoonotic disease which is still an important health issue in both developing and developed countries. We aimed to evaluate Toxoplasma gondii (T. gondii) seropositivity on toxoplasmosis suspected patients and pregnant women, retrospectively. Blood samples taken from toxoplasmosis suspected patients (n=1296) and pregnant women (1737) on our tertiary training hospital between 2012-2014 years. Anti-T. gondii IgG and IgM seropositivity analyzed with chemiluminescent microparticle immunological assay (CMIA) method. Also IgG avidity index were evaluated on patients who had both antibodies. Of 1269 toxoplasmosis suspected patients, 37% (n=479) had only T. gondii IgG positive while 1.9% (n=25) had both IgG and IgM antibodies. Of 1737 pregnant women, 24.2% (n=421) had only T. gondii IgG positive while 0.7% (n=13) of women were found positive for both antibodies. None of the total 3033 patients were seropositive for sole IgG antibody. Avidity tests were applied to the double positive patients and low avidity were detected on only one person from each group. Nationwide, high throughput, systemic seroprevalance studies is needed in order to take precautions for the public health to protect sensitive groups and pregnant women especially because of congenital toxoplasmosis risk.

The IgG avidity value for the prediction of Toxoplasma gondii infection in the amniotic fluid.

Primary Toxoplasma gondii (T. gondii) infection during pregnancy may lead to congenital toxoplasmosis. Maternal screening using T. gondii IgG avidity measurement and multiplex nested PCR was performed. The aim of this prospective cohort study was to determine a cut-off value of IgG avidity index (AI) for the prediction of the presence of T. gondii DNA in the amniotic fluid. One hundred thirty-nine women with positive or equivocal tests for IgM underwent both serum IgG avidity measurement and PCR analysis for the amniotic fluid. Nine had positive PCR results, and three of them were diagnosed as having congenital infection. A cut-off value of IgG AI was determined using receiver operating characteristic analysis. IgG AI (mean 13%) in women with positive PCR results was significantly lower than that (39%) in women with negative results. A cut-off value of <25% IgG AI yields the best results with 77.8% sensitivity and 81.5% specificity for the presence of T. gondii DNA in the amniotic fluid. None of women with IgG AI of ≥30% had a positive PCR result or congenital infection. This study firstly demonstrated that a cut-off value of 25-30% IgG AI might be useful for the prediction of the presence of T. gondii DNA in the amniotic fluid and congenital infection.

Age-dependent immune responses and immune protection after avian coronavirus vaccination

Infectious bronchitis virus (IBV) is an endemic disease of chickens and a major contributor to economic losses for the poultry industry despite vaccination. Recent observations indicated that chicks may have an immature immune system immediately after hatching when vaccinated for IBV. Therefore we hypothesized that early IBV vaccination will generate an immature, poorly protective IBV-specific immune response contributing to immune escape and persistence of IBV. To test this hypothesis the IBV-specific immune response and immune protection were measured in chicks vaccinated at different ages. This demonstrated a delayed production of IgG and IgA plasma antibodies in the 1, 7 and 14-day-old vaccination groups and also lower IgA antibody levels were observed in plasma of the 1-day-old group. Similar observations were made for antibodies in tears. In addition, IgG antibodies from the 1-day-old group had lower avidity indices than day 28 vaccinated birds. The delayed and/or lower antibody response combined with lower IgG avidity indices coincided with increased tracheal inflammation and depletion of tracheal epithelia cells and goblet cells upon IBV field strain challenge. The lack of vaccine-mediated protection was most pronounced in the 1-day-old vaccination group and to a lesser extent the 7-day-old group, while the 14-day-old and older chickens were protected. These data strongly support IBV vaccination after day 7 post hatch.

Rapid increase in the serum Cytomegalovirus IgG avidity index in women with a congenitally infected fetus

BackgroundHuman Cytomegalovirus (CMV) is the virus most frequently responsible for severe diseases of the fetus and newborn. The reported intrauterine transmission rate of CMV following primary maternal infection is approximately 40%. Invasive techniques are needed for the prenatal diagnosis of congenital CMV infection. ObjectivesThe aim of this study was to evaluate whether the rapidity of change in the CMV IgG avidity index (AI) is associated with the presence of congenital CMV infection among mothers with suspected primary CMV infection. Study designThe serum CMV IgG AI was repeatedly measured in 17 pregnant women with positive or borderline test results for CMV IgM together with an initial IgG AI value of <40%. Their neonates underwent polymerase chain reaction analyses for the presence of CMV DNA in the urine. The rapidity of change in the IgG AI per 4 weeks was defined as the ΔAI (%). The ΔAI of women with congenital CMV infection was compared with that of women with no infection. ResultsThe ΔAI of nine mothers with congenital CMV infection (median,15.7%; range,7.8–42.8%) was significantly higher than that of eight mothers with no infection (median, 6.5%, range, 2.0–8.8%; p<0.001). The incidences of congenital CMV infection were 100.0%, 16.7%, and 0.0% among mothers with a ΔAI of >10, 5–10, and <5%, respectively. ConclusionsMeasurement of the ΔAI in pregnant women might be useful for estimating the risk of mother-to-neonate CMV transmission.

Pregnancy Outcomes of Mothers with Detectable CMV-Specific IgM Antibodies: A Three-Year Review in a Large Irish Tertiary Referral Maternity Hospital.

A retrospective audit was performed for all obstetric patients who had positive CMV IgM results between January 2012 and December 2014 in the Rotunda Hospital, Ireland. In total, 622 CMV IgM positive tests were performed on samples from 572 patients. Thirty-seven patients had a positive CMV IgM result (5.9%) on the Architect system as part of the initial screening. Three patients were excluded as they were not obstetric patients. Of the 34 pregnant women with CMV IgM positive results on initial screening, 16 (47%) had CMV IgM positivity confirmed on the second platform (VIDAS) and 18 (53%) did not. In the 16 patients with confirmed positive CMV IgM results, four (25%) had acute infection, two (12.5%) had infection of uncertain timing, and ten (62.5%) had infection more than three months prior to sampling as determined by the CMV IgG avidity index. Two of the four neonates of women with low avidity IgG had CMV DNA detected in urine. Both these cases had severe neurological damage and the indication for testing their mothers was because the biparietal diameter (BPD) was less than the 5th centile at the routine 20-week gestation anomaly scan.

The evaluation of rubella and sitomegalovirus IgG avidity tests in pregnants: four-year experience

Objective: In this study, we aim to evaluate the retrospective IgG avidity index (AI) test results of the pregnant, who have applied to our hospital and had pregnancy screening test and have been asked for rubella and cytomegalovirus antibody tests and IgG AI test in 4 year period. Methods: Anti-rubella IgM, anti-rubella IgG, anti-CMV IgM and anti-CMV antibodies were performed by IMMULITE 2000XPit Immunoassay System (Siemens, Germany) whereas IgG AI tests were performed by commercial kits of rubella and cytomegalovirus antibody tests (Dia.Pror Diagnostic, Milano-Italy). Results: Between January 2010 and December 2013, 23 (7.32 %) of 314 pregnant women tested rubella IgG AI had low AI, and 266 cases had high AI rate; 14 (17.28%) of 81 pregnant women tested CMV IgG AI, had lower AI rate, 52 of them had high AI. 9 out of 23 pregnant women, who were detected low rubella were requested only AI without any IgM and IgG value; the IgG antibody of 13 pregnant was reactive, and IgM antibody was not requested; IgG and IgM antibody of 1 pregnant was detected positive. When 5 pregnant, who were detected low CMV AI were requested AI without IgG and IgM value; the IgG and IgM of 4 was reactive; 4 of them had IgG reactive but IgM negative; 1 had IgG and IgM negative. Conclusion: As a result, our low rubella AI rate has been detected lower than the rates in our country since our study population contains only the pregnant. Our low CMV AI rate varies due to the same reasons as literature data. During pregnancy scanning, performing of AI testing together with specific IgG and IgM will save both time and will be more meaningful in clinical evaluation for pregnant women. J Clin Exp Invest 2014; 5 (3): 420-423

The IgG avidity value for the prediction of congenital cytomegalovirus infection in a prospective cohort study

Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. To evaluate the maternal IgG avidity value for the prediction of congenital CMV infection. The serum IgG avidity in all mothers was measured, and the urine of their neonates was assessed for CMV DNA in a prospective cohort study. Of 759 women with a positive test for CMV IgG, 14 had congenital CMV infection. CMV IgG avidity indices in the congenital infection group (median 35.1%) were significantly lower than those in the non-congenital infection group (70.4%). A cutoff value of <40% IgG avidity index with 96.1% specificity and 64.3% sensitivity for congenital infection was determined by receiver operating characteristic curve analyses. The highest sensitivity (88.9%), 96.2% specificity, 27.6% positive predictive value, 99.8% negative predictive value, and 96.1% accuracy were found when IgG avidity was measured in <28 weeks of gestation. The IgG avidity measurement with a cutoff value of <40% IgG avidity index might be helpful in predicting congenital CMV infection, especially in <28 weeks of gestation.

Performance of the BioPlex 2200 Flow Immunoassay in Critical Cases of Serodiagnosis of Toxoplasmosis

The BioPlex 2200 automated analyzer (Bio-Rad Laboratories, Hercules, CA) is a recently developed multiplex analyzer that enables the detection of anti-Toxoplasma, -rubella, and -cytomegalovirus antibodies in the same assay. The aim of this study was to compare this new technology (using the BioPlex 2200 ToRC IgG/IgM kit) in critical cases of serodiagnosis of toxoplasmosis (acute, chronic, or congenital infections and cases with discrepant results) to the technologies used in our routine practice, i.e., the Platelia IgG/IgM enzyme-linked immunosorbent assays (ELISAs) (Bio-Rad Laboratories) and the Toxo-Screen direct agglutination assay (bioMérieux, Lyon, France). Overall, most cases of false-positive/negative results obtained with the Platelia IgG or Toxo-Screen assay were corrected by the BioPlex 2200 ToRC IgG (87.5%). Furthermore, the analysis of 35 sequences of sera showed a trend toward a more rapid decrease of IgM titers by BioPlex 2200 than by Platelia. These results for IgM detection can be explained by a weaker detection of residual IgM. Indeed, among 23 serum samples from patients with probable past infection with long-lasting IgM (Platelia M positive and IgG avidity index, ≥0.5), the BioPlex 2200 Toxoplasma IgM assay was positive for only 11 serum samples. In our panel of critical cases comprising 156 serum and 6 cord blood samples from 103 patients with acute, chronic, or congenital infection, the BioPlex 2200 IgG assay was a sensitive (97.8%) and specific (91.3%) method for IgG detection. The high specificity (97.4%) of IgM detection combined with the shorter kinetics of IgM titers may considerably reduce the number of residual IgM detections, thus yielding more precise diagnoses of acute infections.

Primary Cytomegalovirus Infection in Pregnant Egyptian Women Confirmed by Cytomegalovirus IgG Avidity Testing

Objective: To determine the frequency of primary cytomegalovirus (CMV) infection in pregnant Egyptian women using CMV IgG avidity testing. Subjects and Methods: A cross-sectional study was conducted at Suez Canal University Hospital, Ismailia, Egypt. A total of 546 pregnant women, presenting for routine antenatal screening, were tested for CMV IgG and IgM using a commercially available enzyme-linked immunosorbent assay (ELISA). Sera from CMV IgM-positive women were tested by CMV IgG avidity assay. Results: All the 546 pregnant women were seropositive for anti-CMV IgG. Of the 546 women, 40 (7.3%) were positive or equivocal for IgM antibodies. All sera from the 40 women (IgG+/IgM+) showed a high or intermediate CMV IgG avidity index. Of the 40 women, 23 (57.5%) were in the second or third trimesters of pregnancy and had their first-trimester blood retrieved, and the tested CMV IgG avidity assay showed a high avidity index. Conclusion: Women who were IgM positive had no primary CMV infection in the index pregnancy as evidenced by the high CMV IgG avidity testing.

Seroprevalence of Cytomegalovirus infection in children aged 0-8 years in Nanjing

Objective To investigate the seroprevalence of Cytomegalovirus (CMV) infection and ages of the children in primary for better understanding the status of CMV infection in China with evidence-based medicine. Methods Total 837 children randomly selected from Nanjing Children's Hospital, from Jun.to Sep.in 2011, including 513 boys and 324 girls, aged from 1 day to 8 years, with mean age of 3.6 years old , were recruited.Serum samples were tested for CMV IgM, CMV IgG, and CMV IgG avidity index using commercial enzyme-linked immunosorbent assay kits. Results Of the total serum samples from 837 children, 690 cases were CMV IgG positive.The overall seroprevalence of CMV IgG was 82.4%, with 83.2% (427/513 cases) and 81.2% (263/324 cases) in boys and girls, respectively.There was no significant difference in the seroprevalence of CMV IgG between boys and girls (χ2=0.584, P=0.445). Of the 92 infants less than 6 months old, 86 cases were CMV IgG positive, and the positive rate was 93.5%.The prevalence gradually declined in infants after 7 months old, fell to the lowest level of 66.7% at age of 9 months, and then constantly maintained around 80.0% from 1 to 8 years old (χ2=15.4, P<0.001). CMV IgM in 352 serum samples were tested, and 23 (6.5%) cases were CMV IgM positive.The positive rate peaked in infants at age of 2-3 months (7/12 cases, 58.3%), then decreased over the age and none of the children older than 6 years were IgM positive (χ2=5.1, P<0.001). Furthermore, the CMV IgG avidity index assay was performed in all 23 cases of IgM positive indivi-duals to estimate the primary CMV infection rate.The results showed low avidity index (<30%) in 13 infants, the primary infection rate was 56.5% (13/23 cases). Most subjects with primary infection (n=7, 53.8%) were younger than 1 year old. Conclusions The current seroprevalence of CMV IgG in children in China was around 80.0%, lower than that in adults, and the primary CMV infection mostly occurred before 3 months of age. Key words: Cytomegalovirus; Seroprevalence; Primary infection; Child

Unusual Patterns of IgG Avidity in Some Young Children following Two Doses of the Adjuvanted Pandemic H1N1 (2009) Influenza Virus Vaccine

During the 2009-2010 H1N1 influenza pandemic, an adjuvanted monovalent vaccine containing ∼25% of the normal antigen dose and AS03 adjuvant was widely used in Canada. This vaccine was found to be well-tolerated and immunogenic in young children (D. W. Scheifele et al., Pediatr. Infect. Dis. J. 30:402-407, 2011). We report here additional analyses to further characterize the humoral response to this vaccine. We measured standard hemagglutination inhibition (HAI) and microneutralization (MN) titers, as well as influenza virus-specific IgG avidity and subclass distribution by enzyme-linked immunosorbent assay in 73 subjects. Sera were collected before (day 0) and 3 weeks after each dose of vaccine (days 21 and 42). Most children (55/73) had undetectable HAI and MN titers at day 0 (presumed to be antigen naive) and mounted good responses at days 21 and 42. The majority of these children (43/55) had the expected pattern of an increasing IgG avidity index (AI) after each dose of vaccine (not detected [ND], 0.30, and 2.97 at days 0, 21, and 42, respectively). The avidity responses in the remaining children (12/55) were quite different, with AIs increasing abruptly after the first dose and then declining after the second dose of vaccine (ND, 8.83, and 7.15, respectively). These children also had higher concentrations of influenza virus-specific IgG1 and IgG3 antibodies at day 21. Although the antibody titers were similar, some antigen-naive children demonstrated an unusual pattern of avidity maturation after two immunizations with AS03-adjuvanted, low-dose influenza virus vaccine. These data suggest the presence of subtle differences in the quality of the antibodies produced by some subjects in response to this vaccine.

Increase in the IgG avidity index due to herpes simplex virus type 1 reactivation and its relationship with cognitive function in amnestic mild cognitive impairment and Alzheimer’s disease

After infection with herpes simplex virus type 1 (HSV-1), latent infection persists for life in the trigeminal ganglion and reactivation results in an outbreak of cold sores around the mouth. Many previous studies have reported HSV-1 reactivation to be a risk factor for Alzheimer’s disease (AD). This study enrolled subjects with AD (n=85), subjects with amnestic mild cognitive impairment (aMCI; a prodromal stage of AD) (n=34), and healthy controls (n=28). The avidity index of anti-HSV-1 IgG antibodies—a known indicator of HSV-1 reactivation—was measured in order to clarify the relationship between HSV-1 reactivation and symptoms of cognitive function in AD.Cognitive function in AD and aMCI were evaluated using scores from the mini-mental state examination (MMSE) and frontal assessment battery (FAB). The results showed that the subjects with aMCI, for which cerebral function is better preserved than subjects with AD, had a higher anti-HSV-1 IgG antibody avidity index than the AD subjects or healthy controls. Furthermore, the anti-HSV-1 IgG antibody avidity index was even higher in the subjects with high MMSE scores on orientation to time and three-step command subscores. We observed a negative correlation between the anti-HSV-1 IgG antibody avidity index and plasma BDNF concentration, which is an indicator of encephalitis. This suggests that HSV-1 reactivation, as observed through an increase in the anti-HSV-1 IgG avidity index, does not progress to encephalitis. These results suggest that HSV-1 reactivation occurs from the stage of aMCI, which is prodromal to AD, and can affect AD symptoms without an intermediary stage of severe encephalitis. The study demonstrates that the anti-HSV-1 IgG antibody avidity index could be a useful biomarker for the early diagnosis of aMCI as well as AD, and suggests that antiviral medication to treat HSV-1 could play a role in preventing the onset of AD.

Kinetics of IgG antibody to cytomegalovirus (CMV) after birth and seroprevalence of anti-CMV IgG in Chinese children

BackgroundPrevalence of cytomegalovirus (CMV) infection is 90–100% in developing countries; however, the kinetics of anti-CMV IgG in infants remains elusive.MethodsSera from 112 mother-newborn pairs and longitudinal samples from 41 infants up to 2-year old were tested for anti-CMV IgG and IgM. Additionally, samples from 837 healthy children were included.ResultsOf 112 mothers, 108 (96.4%) were anti-CMV IgG positive; their 108 newborns were also seropositive. In a 2-year follow-up among 40 infants of positive mothers, anti-CMV IgG level in 8 individuals decreased with time and became undetectable by age of 3.5–8 months, and that in 32 others decreased at 1- and 3.5-month old, and then increased. Based on the positive IgM, rising IgG levels, and low anti-CMV IgG avidity index, 76.7% of the primary infections were demonstrated to occur during 1–3.5 months of age. The overall seroprevalence of anti-CMV in 837 children was 82.4%, which was generally constant from 2 to 8 years old (χ2 = 3.150, p = 0.790).ConclusionsThe maternally acquired anti-CMV IgG in infants disappears before 8-month old. Primary CMV infection in Chinese children mostly occurs during 1–3.5 months of age. Whether the relatively lower seroprevalence of anti-CMV in Chinese children found in this survey may reflect the positive rate in child-bearing age women in the future remains to be further studied.

Low IgG avidity and ultrasound fetal abnormality predict congenital cytomegalovirus infection

Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. The aim of this study was to assess whether prenatal clinical or laboratory findings in pregnant women who had high risks for primary CMV infection predicted the presence of congenital infection. Fifty pregnant women who had serum CMV IgG and positive or borderline tests for serum CMV IgM were included in this prospective study. Serum IgG avidity was measured, and PCR was conducted for CMV DNA in maternal serum, urine, and uterine cervical secretion. All neonates underwent PCR testing for CMV DNA in the urine for the presence of congenital infection. Risk factors were compared between congenital infection group and group without congenital infection. As a result, nine neonates (18%) were diagnosed as having congenital infection. The frequencies of ultrasound fetal abnormality and positive test for CMV DNA in cervical secretion, CMV IgM titer and IgM/IgG ratio in the congenital infection group were significantly higher than those in the group without congenital infection. Conversely, IgG avidity index in the congenital infection group was significantly lower than that in the group without congenital infection. By multivariate logistic regression analyses, IgG avidity index (Odds ratio 0.91, 95% CI: 0.83-0.99) and ultrasound fetal abnormality (291.22, 2.72-31125.05), were selected independently as significant signs predictive of congenital CMV infection. Among pregnant women with positive or borderline tests for CMV IgM, when they have findings of low serum CMV IgG avidity or ultrasound fetal abnormality, the probability of congenital CMV infection may increase.

Evaluation of the Liaison Automated Testing System for Diagnosis of Congenital Toxoplasmosis

Congenital toxoplasmosis is a worldwide health problem, and different screening strategies exist. Testing of toxoplasma-specific antibodies in infants identifies congenital toxoplasmosis during the first year of life. However, experience with commercial available immunoassays is limited. The aim of this study was to evaluate both the performance and analytical characteristics of the Liaison diagnostic system in infants. In a retrospective study, serum Toxoplasma gondii antibodies were measured in samples from 333 infants, including 212 noninfected infants and 121 infants with congenital toxoplasmosis. A total of 1,157 umbilical cord blood and peripheral serum samples were analyzed. Liaison toxoplasma-specific IgG and IgM antibodies and the IgG avidity index were compared to the infection status of the infant, determined by the Sabin-Feldman dye test and immunosorbent agglutination assay--IgM. All noninfected infants were seronegative by Liaison IgG within the first year of life. The Liaison system showed a sensitivity of 81.8%, a specificity of 100.0%, a positive predictive value of 100.0%, a negative predictive value of 90.6%, and overall agreement of 84.4% by comparison with the dye test. Overall agreement of both IgM test systems was 96.0%. In this study cohort, avidity did not show a potential diagnostic benefit for the detection of congenital infection. In conclusion, the Liaison system is a valuable tool to monitor the serologic course of infants at risk. A final serologic confirmatory test is recommended to improve the rate of detection of congenital toxoplasmosis at 1 year of life. Protocols of routine follow-up testing in infants and accurate diagnostic tools after acute gestational infections are needed to improve medical care.

OC21.02: Lesion size affects the diagnostic performance of the International Ovarian Tumor Analysis (IOTA) logistic regression models, the IOTA simple rules and the risk of malignancy index to estimate the risk of malignancy in adnexal masses

Objectives: Positive CMV IgM in the first trimester of pregnancy mandates IgG avidity assays to exclude or confirm primary infection in pregnancy. Methods: To correlate IgG avidity index actual values and trends with the risk of fetal infection. Sera were obtained from women in the first trimester of pregnancy. CMV serology was performed with the LIAISON CMV IgG kit and the LIAISON CMV IgM. Kit. Positive IgG (>0.6 UI/mL) and equivocal IgM (≥15 UA/mL and <30 UA/mL) or positive IgM (≥ 30 UA/mL) prompted CMV IgG avidity test. LIAISON CMV IgG Avidity assay and VIDAS CMV IgG Avidity assay were used in parallel and results were interpreted as recommended by the manufacturer (PI less than 3 months, PI more than 3 months, Intermediate). When at least one of the 2 avidity results was in favour of a PI dating back more than 3 months, the patient was reassured, in all other cases amniocentesis was recommended for prenatal diagnosis after 20 weeks. Results: 187 women (256 sera) had positive or equivocal IgM. Avidity index values were correlated (r2 = 0.646) but there was only 48% concordance in avidity test interpretations. 61 women (77 sera) had an avidity index low or intermediate in LIAISON or VIDAS CMV IgG Avidity assays. 15 of these 61 women (24.5%) had a positive CMV PCR in amniotic fluid retrieved between 19 and 25 weeks. Logistic regression of IgM levels and LIAISON avidity index values did not show any significant association with fetal infection but VIDAS avidity index values were inversely statistically associated with fetal infection (P = 0.002). Based on this logistic regression model the risk of fetal transmission was 70, 40% and 20% for VIDAS avidity index below 0.10, at 0.2, and at 0.4 respectively. Conclusions: These results could be useful for more accurate counselling of women presenting with positive CMV IgM in the first trimester to help them choose between amniocentesis at 20 weeks or ultrasound follow-up alone.