Avidity of immunoglobulin G directed against human cytomegalovirus during primary and secondary infections in immunocompetent and immunocompromised subjects.

Diagnosis of primary human cytomegalovirus (HCMV) infection is accomplished exclusively by serologic testing. Among the possible methods, the determination of immunoglobulin G (IgG) avidity is one of the least explored. In this work, we used a commercially available kit to test anti-HCMV IgG avidity in 336 serum samples from pregnant women and transplant recipients undergoing virologically proven HCMV primary or nonprimary infections and from latently infected blood donors. Our results demonstrate that the anti-HCMV IgG avidity test differentiates primary from nonprimary HCMV infections in both pregnant women and solid organ transplant recipients. In fact, 88.6% of primary infections and no secondary infections showed low-avidity IgG to HCMV. In particular, low IgG avidity is a marker of primary infection for 18 to 20 weeks after onset of symptoms in both immunocompromised and immunocompetent subjects.     

Comparative evaluation of eight commercial human cytomegalovirus IgG avidity assays

BackgroundThe interpretation of a positive IgM antibody result to human cytomegalovirus (HCMV) in a pregnant woman is of major importance for the correct management of the pregnancy. Determination of HCMV-specific IgG avidity is considered an useful approach for distinguishing IgM antibody due to primary HCMV infection from IgM antibody elicited during non-primary infection.ObjectiveComparative evaluation of eight commercial HCMV IgG avidity assays currently available in Europe.Study designA panel of 198 sequential samples collected from 65 pregnant women at 0–90, 91–180, and >180 days after the onset of primary HCMV infection was retrospectively tested by Abbott, BioMérieux, Bio-Rad, DiaSorin, Diesse, Euroimmun, Radim, and Technogenetics HCMV IgG avidity assays according to the manufacturer's instructions.ResultsNone of the 198 samples tested yielded identical scores by the kits under evaluation. The Euroimmun and Radim assays showed the best correlation with expected results in terms of low (0–90 days), intermediate (90–180 days) and high (>180 days) avidity results, respectively. The best accuracy in diagnosing a recent (<90 days after the onset) or non-recent (>180 days after the onset) primary HCMV infection was shown by Radim followed by Euroimmun and Diesse. The best correlation with a well established in-house developed HCMV IgG avidity assay was shown by Radim.ConclusionsHCMV IgG avidity kits need to be improved and standardized. In the meantime, highly specific IgM assays are preferable for screening purposes in pregnant women.     

温州市区育龄妇女孕前巨细胞病毒感染现状调查

目的了解温州地区育龄妇女孕前人巨细胞病毒（HCMV）感染的状况。方法收集2008年10月至2010年6日参加温州市龙湾区免费孕前优生筛查的妇女血标本2869份,采用酶联免疫吸附试验（ELISA）检测血清HCMV IgG/IgM抗体;HCMV IgM抗体阳性标本,采用实时荧光定量聚合酶链反应（FQ-PCR）检测血HCMV DNA载量;HCMV IgG/IgM抗体双阳性标本,采用尿素变性结合ELISA技术检测IgG抗体亲和力指数（AI）。结果 2869份孕前妇女血清中HC-MV IgG抗体阳性检出率为97.77%（2805/2869）,HCMV IgM抗体阳性检出率为0.77%（22/2 869）,IgG/IgM抗体均阳性检出率占0.17%（5/2 869）;22份HCMV IgM阳性标本中,血HCMV DNA阳性检出率为68.18%（15/22）;5份HCMVIgG/IgM双阳性标本中,检出低亲和力IgG抗体1份,中等亲和力IgG抗体2份,高亲和力IgG抗体2份。结论温州市区育龄妇女孕前HCMV IgG抗体阳性率高;对HCMV IgM抗体阳性孕前妇女应进行多指标检测以判断HCMV感染的状态,为减少出生缺陷、做好优生优育服务提供依据。     

Measurement of EBV-IgG anti-VCA avidity aids the early and reliable diagnosis of primary EBV infection

Current serological methods for the diagnosis of Epstein-Barr virus (EBV) infection still differentiate poorly between primary infection and reactivation. This is particularly true when IgG and IgM antibodies are present simultaneously and only a single serum sample is provided for analysis. The demonstration of the IgG avidity state has the potential to distinguish recent from past or reactivated infection. An analysis of the kinetics of avidity maturation of anti-VCA antibodies in primary EBV infection was undertaken with longitudinally collected sets of sera from 28 well-characterised EBV cases and in sera from 35 cases with previous EBV infection and recent primary infection due to HIV, CMV, or hepatitis A. Antibodies directed against the viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA-1) were sought, using a commercial enzyme immunoassay (EIA). In parallel with standard IgG anti-VCA detection, serum was incubated with 8 M urea to disrupt low-avidity complexes to allow calculation of the percentage avidity. In cases with primary EBV infection, the mean avidity rose from 54% at 6 weeks to 82% by 28 weeks after the onset of symptoms, but remained lower than that of the control sera (96%). The addition of the avidity measurement improved the sensitivity of IgG and IgM anti-VCA testing in diagnosis of primary EBV infection from 93% to 100%. The specificity of IgM anti-VCA testing alone was poor, with 14 of 35 cases (49%) demonstrating false-positive results, but it improved to 97% by the demonstration of high-avidity IgG anti-VCA. The combination of negative IgG anti-EBNA and low-avidity IgG anti-VCA had a sensitivity and specificity of 100%. The routine addition of IgG anti-VCA avidity estimation to diagnostic EBV serology is recommended.     

Evaluation of serological markers for the immunodiagnosis of acute acquired toxoplasmosis

The detection of specific IgM antibodies has been the most frequently used serological marker for diagnosing recent toxoplasmosis. However, the persistence of specific IgM antibodies in some patients and the use of tests with a low specificity have complicated the interpretation of serological results when toxoplasmosis is suspected. The purpose of the present study was to determine the value of newer serological techniques in the diagnosis of acute acquired toxoplasmosis. Sixty-four sera, 31 from patients with Toxoplasma gondii infection and 33 from patients with latent infection, were tested. Anti-T. gondii IgA was measured by two antibody capture ELISA tests (Platelia Toxo IgA and ETI-TOXOK A) and an automated direct ELISA (IMx Toxo IgA); all three assays detected antibody levels compatible with a recent infection in sera from all 31 patients with acute toxoplasmosis. However, significant levels of IgA were also detected with high frequency by all three assays in sera from patients with latent infection. IgE antibodies detected by IgE immunosorbent agglutination assay (ISAGA) were present in 26 (84%) of 31 patients with acute toxoplasmosis and in sera from two subjects with latent infection taken >1 year after the beginning of the clinical symptoms of infection. Thirty (97%) of 31 patients with a recent T. gondii infection and 15 (45%) of 33 subjects with latent infection had an AC/HS pattern compatible with acute toxoplasmosis. The avidity of T. gondii IgG was evaluated by two methods. One method was based on the titration of each serum sample and calculation of the titres, in the absence and presence of urea, in relation to a defined cut-off value. In the other method, a single serum dilution was used and the absorbances of the reactions in the presence and absence of urea were compared. The titration method was more sensitive for diagnosing recent primary infection; all 31 sera from patients with acute toxoplasmosis had avidity indices compatible with acute toxoplasmosis by the titration method, whereas with the single dilution method, sera from four patients had equivocal results. In the 33 individuals with latent infection, similar results were obtained with the two avidity methods; only one serum sample had a non-compatible avidity value with the titration method. The results obtained in the present study show that the current serological markers used for diagnosing acute acquired toxoplasmosis have significant limitations. The data suggest that determination of the avidity of T. gondii-specific IgG by the titration method in patients with detectable IgM antibodies defines most accurately the stage of infection by T. gondii.     

Predictive value of maternal-IgG avidity for congenital human cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus (HCMV) is now the most common cause of viral intrauterine infection. Fetal damage is mostly linked to maternal primary infection. It is therefore important to differentiate primary from recurrent or persistent HCMV infection in pregnant females. For this purpose, IgM tests are not reliable enough and the measurement of the IgG avidity appears to be presently the best method. OBJECTIVE: To evaluate the performance of the measurement of HCMV-IgG avidity by a 8 M urea denaturation assay in predicting congenital infection in the offspring. STUDY DESIGN: Seventy-eight women were included in this study on the basis of a HCMV IgM positive or equivocal result on a first serum during pregnancy, but without a documented seroconversion history. The IgG avidity was measured and correlated with the outcome of the pregnancy. RESULTS: In eight cases of HCMV in utero infection the maternal HCMV-IgG avidity index was below 50%. One case of HCMV in utero infection was observed despite a high avidity index during the second trimester of the pregnancy. High or intermediate HCMV-IgG avidity indexes during the first trimester of pregnancy were not associated with a congenital infection. CONCLUSIONS: Even in the presence of an IgM positive result, an HCMV IgG avidity index above 65% on a serum obtained during the first trimester of pregnancy could reasonably be considered as a good indicator of past HCMV infection. In these conditions invasive prenatal diagnosis is not necessary.     

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.     

Relevance of the toxoplasma IgG avidity test in the serological surveillance of pregnant women

In addition to the serological systematic screening tests, kits to measure the avidity of toxoplasma IgG antibodies are currently available. Since high-avidity IgG toxoplasma antibodies have been shown to exclude recent infection, IgG avidity determination is especially useful in ruling out acute infection having occurred in the 3-4 prior months of pregnancy. We therefore compared the efficacy of two toxoplasma IgG avidity ELISA kits: SFRI (SFRI Laboratoire) and VIDAS Toxo-IgG avidity kit (bioMérieux). The agreement of the results from the 2 commercial assays were analysed using 55 serum samples, in terms of global mother-child Toxoplasma results and outcome, specially with light of the results of Toxoplasma antenatal, postnatal assays and of clinical follow up of children.     

An antigen fragment encompassing the AD2 domains of glycoprotein B from two different strains is sufficient for differentiation of primary vs. recurrent human cytomegalovirus infection by ELISA.

Primary human cytomegalovirus (HCMV) infection during pregnancy is a frequent cause of fatal damage in populations with low prevalence of HCMV. Differentiation of primary vs. recurrent HCMV infection is an important issue in prenatal counseling. Antibodies specific for viral glycoproteins become detectable only with considerable delay with relation to HCMV infection or IgG seroconversion. Thus, lack of glycoprotein specific (gp-specific) antibodies can serve as a convenient indicator to identify those pregnant women that bear an elevated risk for HCMV transplacental transmission and fetal sequelae. In the opposite case, presence of gp-specific antibodies virtually excludes HCMV primary infection several weeks before sampling. However, no standardized screening assay for HCMV gp-specific antibodies had been available thus far. For this reason, an ELISA based on procaryotically expressed fragments of HCMV glycoprotein B (gB; gpUL55) was developed. Small fragments of gB from two different laboratory strains, encompassing the antigenic domain 2 (AD2) sufficed for sensitive and specific detection of gp-specific antibodies. The gB-ELISA titers correlated with titers of virus neutralizing antibodies in serum samples from primary or recurrent HCMV infections. Seroconversion kinetics of the gB-ELISA in samples from patients with primary HCMV infection closely paralleled the delay in seroconversion of gp-specific antibodies as determined by neutralization assay. Thus this assay provides a diagnostic tool that is easy to perform and can significantly add to available methods for the timely identification of primary HCMV infection during pregnancy. In addition, the gB-ELISA may be helpful in other clinical settings for the differentiation of primary HCMV infection from diseases caused by other pathogens.     

Evaluation of virological procedures to detect fetal human cytomegalovirus infection: Avidity of IgG antibodies,virus detection in amniotic fluid and maternal serum

Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection and fetal damage largely due to maternal primary infection. Virological procedures which are able to detect HCMV fetal infection were evaluated. HCMV IgG antibodies were detected in 62.5% of the pregnant women and 1.47% had a primary infection. From March, 1992 to August, 1995, 29 seroconversions were observed, and in 64 other cases. HCMV IgM antibodies were detected in the first serological test. The mean IgG antibody avidity test (AI) was 31% for the 11 seroconversions tested and 74% in 32 cases where IgG and IgM HCMV antibodies were detected in the first serum. In the 29 HCMV seroconversions, 19 amniocentesis were carried out and 12 fetuses (41.4%) were infected in utero. In four amniotic fluids positive in culture and PCR, the fetus or newborns were infected and in one out of the two cordocentesis undertaken, hepatitis, anemia, and thrombocytopenia were noted. In four other cases, investigations seeking HCMV in amniotic fluid were negative whereas infants were infected at birth. Among the 64 cases with positive HCMV IgM and IgG antibodies detected in the first serological test, three fetuses were infected in utero, but no amniotic fluid was available in these cases. Amniotic fluids were studied in 39 cases, and HCMV detection by culture and PCR-hybridization was negative. HCMV DNA was detected in the maternal sera of five out of 21 pairs of seroconversions and in two cases on the first negative serum. The assay was also carried out on 50 of the 64 HCMV IgM positive sera. Two had detectable HCMV DNA. © 1996 Wiley-Liss, Inc.     

Antibody avidity following varicella-zoster virus infections.

The avidity of IgG antibodies following varicella-zoster virus (VZV) infections was investigated using urea treatment of antigen-bound serum antibody by indirect radioimmunoassay (RIA) and immunoblotting techniques. Sequential sera from 16 patients with varicella and 17 patients with zoster were tested, as well as sera from 80 seropositive individuals without a recent history of VZV disease. Both types of assay showed that low-avidity antibodies predominate early after primary infection, but that antibody avidity increases markedly during convalescence. Using RIA, all sera taken up to 12 weeks after the onset of varicella showed greater than 50% reduction in antibody titre after treatment with 8 M urea but thereafter the proportion of urea resistant antibody increased with time. In contrast, after recurrent infection, high avidity antibodies were found to predominate at all times. Only 6 of 47 sera tested from zoster cases showed greater than 30% reduction after urea treatment and all these were taken within 2 weeks after onset of rash. Immunoblotting also showed that the highly immunogenic p32/p36 nucleoproteins appear to induce predominantly low avidity antibodies, even after recurrent VZV infection. The results of this study indicate that treatment with 8 M urea in RIA for IgG antibodies may be a simple and reliable method for distinguishing primary and anamnestic antibody responses against VZV.     

Immunoglobulin G Avidity in Diagnosis of Toxoplasmic Lymphadenopathy and Ocular Toxoplasmosis

Traditional serological techniques have some limitations in evaluating the duration of Toxoplasma gondii infection in pregnant women, patients with lymphadenopathy, and older children suspected of having congenital toxoplasmosis. In these three groups of patients, two variants of T. gondii immunoglobulin G (IgG) avidity tests were used: an EIA Kit (Labsystems) and a noncommercial enzyme-linked immunosorbent assay specially elaborated in the laboratory. The avidity of specific IgG in sera from 23 patients with a known recently acquired infection (mainly pregnant women) was low (less than 30%), whereas that in sera from 19 patients with toxoplasmic lymphadenopathy of 3 weeks to 6 months in duration (mean, 8.3 weeks) covered a large range (between 0.2 and 57.8%; mean, 25.7%); high avidity results were observed for 10 of 19 patients (52.6%). The large range of IgG avidity in patients with toxoplasmic lymphadenopathy suggests various durations of infection in these patients, with a tendency for a chronic phase of toxoplasmosis. According to the avidity marker, five patients with lymphadenopathy for less than 3 months did not have a recent Toxoplasma infection. In 6 of 19 patients with lymphadenopathy (31.6%), low IgG avidity values persisted until 5 months after the first serological examination. In all four patients with a documented chronic course of Toxoplasma infection (6 months to 8 years after the first positive serology), high IgG avidity values were observed. Among sera from 10 children and young immunocompetent adults suspected of having ocular reactivation of congenital toxoplasmosis, all had high IgG avidity values (over 40%), suggesting congenitally acquired ocular infection rather than noncongenital infection. In conclusion, the avidity of IgG is a valuable marker of recent toxoplasmosis in pregnant women, suggests the duration of invasion in patients with lymphadenopathy, and may be helpful for differentiation between reactivation of congenital infection and recently acquired ocular toxoplasmosis in immunocompetent patients. A low IgG avidity does not always identify a recent case of toxoplasmosis, but a high IgG avidity can exclude primary infections of less than 5 months’ duration.     

Rubella-specific IgG1 avidity: a comparison of methods

Two methods of determining the avidity of specific IgG1 were compared with sera from different categories of rubella infection. Both methods were based on an antiglobulin enzyme-linked immunosorbent assay. In one method the absorbances were compared with and without diethylamine (DEA) in the serum diluent over a range of serum dilutions and the difference between the dilution curves measured (DEA-shift). In the other, the absorbances at a single serum dilution were compared with and without urea in the wash fluid used after the antigen/serum incubation (avidity index). Various concentrations of DEA were also assessed in the avidity-index method, as this method is simpler to perform. The DEA-shift method was shown to be more sensitive for diagnosing recent primary rubella or immunization by demonstrating specific IgG1 of low avidity. The avidity-index method, however, was more specific when sera from cases of reinfection or non-specific rubella IgM reactivity were tested. 35 mM DEA was found to be the optimal concentration of DEA when DEA was substituted for urea in the avidity index method.     

Early neutralizing and glycoprotein B (gB)-specific antibody responses to human cytomegalovirus (HCMV) in immunocompetent individuals with distinct clinical presentations of primary HCMV infection.

BACKGROUND: Antibodies with functional anti-Human Cytomegalovirus (HCMV) activity are likely to be involved in preventing virus dissemination and thus may contribute to minimize the clinical manifestations of infection. OBJECTIVES: To investigate the role of humoral immunity in modulating the clinical expression of primary Human Cytomegalovirus (HCMV) infection in immunocompetent persons. STUDY DESIGN: Neutralizing (NA) and glycoprotein B (gB)-specific antibodies were quantitated in acute-phase and late-convalescence phase sera from 19 individuals who developed either HCMV mononucleosis (12) or oligosymptomatic hepatitis (seven). RESULTS: The levels of NA in sera drawn early after infection were significantly lower in the former patients than in the latter (P=0. 032). This difference was not related to either the total serum IgG levels and anti-HCMV IgGs avidity or to the presence of higher viral loads in blood, as assessed by detecting serum HCMV DNA by PCR, in patients experiencing mononucleosis. Increased NA titers were seen in all available late-convalescence sera. In these sera, median NA levels were not significantly different among the study groups. Antibodies to HCMV gB of both IgG and IgM classes were detected in all acute-phase sera analyzed. Median anti-gB IgG and IgM titers did not differ significantly between study groups. Likewise, the IgG subclass reactivity pattern against gB was found to be similar for both groups. CONCLUSIONS: The data revealed that an intense and early antibody response to gB developed in patients undergoing primary HCMV infection irrespective of the clinical manifestation of the disease. In contrast, a deficient NA response was observed in patients with HCMV mononucleosis versus that observed in patients displaying a milder form of disease-suggesting that the strength of NA response to HCMV generated early after infection might determine the severity of primary HCMV infection.     

Immunoglobulin G avidity in differentiation between early and late antibody responses to West Nile virus

In 1999 West Nile virus (WNV) surfaced in the United States in the city of New York and spread over successive summers to most of the continental United States, Canada, and Mexico. Because WNV immunoglobulin M (IgM) antibodies have been shown to persist for up to 1 year, residents in areas of endemicity can have persistent WNV IgM antibodies that are unrelated to a current illness with which they present. We present data on the use of IgG avidity testing for the resolution of conflicting data arising from the testing of serum or plasma for antibodies to WNV. Thirteen seroconversion panels, each consisting of a minimum of four samples, were used. All samples were tested for the presence of WNV IgM and IgG antibodies, and the avidity index for the WNV IgG-positive samples was calculated. Panels that exhibited a rise in the WNV IgM level followed by a sequential rise in the WNV IgG level were designated "primary." Panels that exhibited a marked rise in the WNV IgG level followed by a sequential weak WNV IgM response and that had serological evidence of a prior flavivirus infection were designated "secondary." All samples from the "primary" panels exhibited low avidity indices (less than 40%) for the first 20 to 30 days after the recovery of the index sample (the sample found to be virus positive). All of the "secondary" samples had elevated WNV IgG levels with avidity indices of > or =55%, regardless of the number of days since the recovery of the index sample. These data demonstrate that it is possible to differentiate between recent and past exposure to WNV or another flavivirus through the measurement of WNV IgG avidity indices.     

Avidity determination of IgG directed against tick-borne encephalitis virus improves detection of current infections

Recently, avidity determination of IgG has been introduced successfully into virus serology as an additional and specific means for confirmation or exclusion of current infections. This simple and highly reproducible method can compensate for problems arising by classical serology, which include lack of detectable IgM responses during primary infections and persistent IgM responses after past infections. We show that avidity determination can be applied successfully for serological diagnosis of TBEV infection. Using the urea denaturation method, primary TBEV infections showed anti-TBEV IgG of low avidity (avidity index < 0.4), whereas sera from individuals with past infections exhibited high avidity IgG. The retrospective analysis of cases with clinical symptoms of TBEV infection in the absence of detectable anti-TBEV IgM showed that a significant number of these cases (5/45) had anti-TBEV IgG of low avidity, indicating current infection. We recommend the use of avidity determination as a method for routine TBEV serology. J. Med. Virol. 51:242–251, 1997. © 1997 Wiley-Liss, Inc.     

Immunoglobulin G antibody avidity assay for serodiagnosis of hepatitis C virus infection

It has been reported that the avidity of specific IgG antibody is lower in primary viral infection than in chronic viral infection. However, few studies have been reported on the IgG avidity in hepatitis C virus (HCV) infection. In the present study, 36 patients with antibody to HCV (anti-HCV) were examined for IgG avidity by an enzyme immunoassay with or without urea elution. The avidity index was significantly low in patients with primary HCV infection (7.7 +/- 6.8%, mean +/- SD), compared with patients with chronic HCV infection (77.0 +/- 21.8%) and individuals with past HCV infection (44.5 +/- 12.6%). Temporal changes of IgG avidity were examined in six patients with primary HCV infection. The avidity index was low in the acute phase of the infection and then increased with time. These results suggest that the avidity assay for IgG anti-HCV is a useful method for distinguishing primary HCV infection from chronic or past HCV infection.     

Persistence of specific IgM and low avidity specific IgG1 following primary rubella.

Persistence of specific IgM in sera following primary rubella infection was compared with the maturation of the specific IgG1 response. 206 sera, from 171 patients with primary rubella, taken 1 day to 2.5 years after onset of illness, were tested. Rubella-specific IgM was detected by M-antibody capture radioimmunoassay in 100% of sera taken 15-28 days after onset, but in only 9% taken 3-4 months after onset. However, using the diethylamine (DEA) shift value (DSV) method, low avidity specific IgG1 was detected in 91% sera taken at 3-4 months and at 5-7 months 21% of sera remained positive. Using an avidity index method, with urea in the wash buffer, none of the sera were positive for low avidity specific IgG1 beyond 3 months after onset. With DEA in the wash buffer, the number of sera positive rose to 38% at 3-4 months. Thus, the DSV method for detecting low avidity specific IgG1 is a useful additional test for confirming or refuting a diagnosis of primary rubella and is of particular value for assessing pregnant patients.     

Immunoglobulin G avidity in diagnosis of toxoplasmic lymphadenopathy and ocular toxoplasmosis.

Traditional serological techniques have some limitations in evaluating the duration of Toxoplasma gondii infection in pregnant women, patients with lymphadenopathy, and older children suspected of having congenital toxoplasmosis. In these three groups of patients, two variants of T. gondii immunoglobulin G (IgG) avidity tests were used: an EIA Kit (Labsystems) and a noncommercial enzyme-linked immunosorbent assay specially elaborated in the laboratory. The avidity of specific IgG in sera from 23 patients with a known recently acquired infection (mainly pregnant women) was low (less than 30%), whereas that in sera from 19 patients with toxoplasmic lymphadenopathy of 3 weeks to 6 months in duration (mean, 8.3 weeks) covered a large range (between 0.2 and 57.8%; mean, 25. 7%); high avidity results were observed for 10 of 19 patients (52. 6%). The large range of IgG avidity in patients with toxoplasmic lymphadenopathy suggests various durations of infection in these patients, with a tendency for a chronic phase of toxoplasmosis. According to the avidity marker, five patients with lymphadenopathy for less than 3 months did not have a recent Toxoplasma infection. In 6 of 19 patients with lymphadenopathy (31.6%), low IgG avidity values persisted until 5 months after the first serological examination. In all four patients with a documented chronic course of Toxoplasma infection (6 months to 8 years after the first positive serology), high IgG avidity values were observed. Among sera from 10 children and young immunocompetent adults suspected of having ocular reactivation of congenital toxoplasmosis, all had high IgG avidity values (over 40%), suggesting congenitally acquired ocular infection rather than noncongenital infection. In conclusion, the avidity of IgG is a valuable marker of recent toxoplasmosis in pregnant women, suggests the duration of invasion in patients with lymphadenopathy, and may be helpful for differentiation between reactivation of congenital infection and recently acquired ocular toxoplasmosis in immunocompetent patients. A low IgG avidity does not always identify a recent case of toxoplasmosis, but a high IgG avidity can exclude primary infections of less than 5 months' duration.     

Multicenter evaluation of a rapid and convenient method for determination of cytomegalovirus immunoglobulin G avidity

An easy, rapid, and reproducible test to distinguish residual cytomegalovirus (CMV) immunoglobulin M (IgM) antibodies from antibodies produced in primary infection could be useful, especially for pregnant women. The CMV avidity of IgG antibodies with the VIDAS automated enzyme-linked fluorescent assay and 6 M urea was evaluated in a multicenter study to differentiate between primary CMV infections and past infections or reactivations. A total of 416 serum specimens were tested: 159 specimens were from follow-up of primary infections, and 257 were from past infections. All of the specimens from primary infections collected within 4 months (17 weeks) after the onset of the infection had an avidity index lower than 0.8. An avidity index higher than 0.8 excludes a recent primary infection of less than 4 months. However, an avidity index higher than 0.8 cannot confirm all past infections, since 48 specimens (18%) from past infections had an avidity index lower than 0.8 (between 0.5 and 0.8). The exclusion capacity could be improved (96.9%) by using a cutoff of 0.7, but this index would decrease the specificity of the technique, since the avidity index was found to be between 0.7 and 0.8 in two patients with recent primary infection. All specimens from primary infections obtained more than 4 months after the onset of infection had an avidity index more than 0.2. In this study, an avidity index less than 0.2 confirms the presence of a recent primary infection of less than 4 months. The VIDAS CMV IgG avidity test is a rapid, reproducible test with very good performance.