scholarly journals Pitfalls in the Serological Diagnosis of Primary Human Cytomegalovirus Infection in Pregnancy Due to Different Kinetics of IgM Clearance and IgG Avidity Index Maturation

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 396
Author(s):  
Antonella Sarasini ◽  
Alessia Arossa ◽  
Maurizio Zavattoni ◽  
Chiara Fornara ◽  
Daniele Lilleri ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Serological Diagnosis ◽  
Avidity Index ◽  
Igm Antibody ◽  
Igg Avidity ◽  
Kinetics Of ◽  
In Pregnancy

Primary infection occurs when seronegative women are infected by human cytomegalovirus (HCMV). Diagnosis of primary infection is based on the following: antibody seroconversion, presence of IgM and low IgG avidity index (AI), and presence of DNAemia. The kinetics of HCMV-specific IgM antibody and maturation of AI might be very rapid or long-lasting during primary infection, which makes serological diagnosis insidious. The aims of this study were as follows: (i) to report atypical kinetics of HCMV-specific IgM antibody and AI early after onset of primary HCMV infection in a population of pregnant women, and (ii) to assess the frequency of such results. Altogether, 1309 sequential serum samples collected from 465 pregnant women with primary HCMV infection were included in the study. As a general rule, using the LIAISON®CMVIgMII and LIAISON®CMVIgGAvidityII assays, virus-specific IgM antibody levels decreased, while IgG AI increased over time during the first three months after infection onset. However, early clearance of IgM antibody and/or early IgG AI maturation occurred in 46/426 (10.7%) women. In more details, 20/426 (4.7%) and 26/418 (6.2%) women had undetectable IgM antibody or high IgG AI, respectively, when tested within 1–3 months after well-defined infection onset. Twenty sera from as many women with high IgG AI by the LIAISON assay were further tested for IgG AI by VIDAS®CMVIgGAvidityII and Mikrogen recomLineCMVIgG Avidity assays. Comparable results were obtained with VIDAS, whereas 14/20 sera gave low AI with the Mikrogen assay. In conclusion, about 11% of pregnant women undergoing a primary HCMV infection showed misleading serological results. Additional and appropriate testing might help in reducing the risk of missing HCMV primary infection in pregnancy. Furthermore, preconceptional testing should be strongly recommended.

scholarly journals Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy

2021 ◽  
Vol 9 (8) ◽  
pp. 1749
Author(s):  
Giuseppe Gerna ◽  
Chiara Fornara ◽  
Milena Furione ◽  
Daniele Lilleri
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Cytomegalovirus Infection ◽  
Hcmv Infection ◽  
Antiviral Treatment ◽  
Virus Transmission ◽  
Immune Correlates ◽  
Maternal Immune Response ◽  
In Pregnancy

Congenital cytomegalovirus infection (cCMV) may affect about 1% of all newborns all over the world as a result of either a primary or recurrent human cytomegalovirus (HCMV) infection. While about 90% of infants affected by cCMV are asymptomatic at birth, the remaining 10% are symptomatic often with neurodevelopmental impairment and sensorineural hearing loss. In view of identifying the best approach to vaccine prevention of cCMV, this review will examine the most important steps made in the study of the immune response to, and diagnosis of, HCMV infection. The maternal immune response and immune correlates of protection are being partially identified with a partial contribution given by our laboratory. The diagnosis of primary infection is often difficult to achieve in the first three months of pregnancy, which is the time primarily involved in virus transmission to the fetus in association with the most severe symptoms and sequelae. Prevention of cCMV is anticipated by prevention of primary infection in early pregnancy by means of different measures, such as (i) behavioral-educational measures, (ii) immunoglobulin administration, (iii) antiviral treatment with valaciclovir. However, the most promising approach to cCMV prevention appears to be the development of a non-living vaccine, including at least three viral antigens: gB, pentamer complex gHgLpUL128L, and pp65, which have been shown to be able to stimulate both the humoral and the cellular arms of the maternal immune response. Primary HCMV infection may be managed in pregnancy by counseling of the couples involved by a team of specialists that includes virologists, obstetricians, infectivologists and neonatologists.

scholarly journals Role of Toxoplasma gondii IgG Avidity Testing in Discriminating between Acute and Chronic Toxoplasmosis in Pregnancy

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Aref Teimouri ◽  
Sina Mohtasebi ◽  
Elham Kazemirad ◽  
Hossein Keshavarz
Keyword(s):  
Toxoplasma Gondii ◽  
Primary Infection ◽  
Diagnostic Technique ◽  
Acquisition Time ◽  
Avidity Index ◽  
Recent Infection ◽  
Content Type ◽  
Avidity Assay ◽  
Igg Avidity ◽  
In Pregnancy

ABSTRACT Risk of mother-to-child transmission of Toxoplasma gondii during pregnancy is much greater in women who are exposed to primary T. gondii infection (toxoplasmosis) after conception compared to those who were exposed to the infection before conception. Therefore, laboratory tests that help classify recent primary toxoplasmosis are important tools for the management of pregnant women suspected to have T. gondii exposure. Detection of Toxoplasma IgM (Toxo IgM) is a sensitive indicator of primary toxoplasmosis, but the indicator specificity is low because sometimes natural IgM antibodies react with Toxoplasma antigens in the absence of the infection. Furthermore, Toxo IgM sometimes persists in blood serum for several months or years following the primary infection. In recent decades, Toxo IgG avidity assay has been used as a standard diagnostic technique for a better estimation of the infection acquisition time and identification of the primary T. gondii infection during pregnancy. Avidity is described as the aggregate strength; by which, a mixture of polyclonal IgG molecules reacts with multiple epitopes of the proteins. This parameter matures gradually within 6 months of the primary infection. A high Toxo IgG avidity index allows a recent infection (less than 4 months) to be excluded, whereas a low Toxo IgG avidity index indicates a probable recent infection with no exclusions of the older infections. This minireview is based on various aspects of T. gondii IgG avidity testing, including (i) description of avidity and basic methods used in primary studies on T. gondii IgG avidity and primary infections; (ii) importance of IgG avidity testing in pregnancy; (iii) result summary of the major studies on the use of T. gondii IgG avidity assay in pregnancy; (iv) brief explanation of the T. gondii IgG avidity values in newborns; (v) result summary of the major studies on T. gondii IgG avidity and PCR; (vi) discussion of commercially available T. gondii IgG avidity assays, including newer automated assays; and (vii) current issues and controversies in diagnosis of primary T. gondii infections in pregnancy.

scholarly journals Reactivity to p52 and CM2 Recombinant Proteins in Primary Human Cytomegalovirus Infection with a Microparticle Agglutination Assay

2000 ◽  
Vol 7 (4) ◽  
pp. 536-539 ◽  
Author(s):  
Eric Nulens ◽  
Monique Bodéus ◽  
Fabrizio Bonelli ◽  
Antonio Soleti ◽  
Patrick Goubau
Keyword(s):  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Immunoglobulin M ◽  
Test Format ◽  
Avidity Index ◽  
Serum Samples ◽  
Test Formats ◽  
Human Cytomegalovirus Infection ◽  
Established Infection

ABSTRACT We evaluated the reactivities of sera against p52 and CM2 recombinant antigens of human cytomegalovirus (HCMV), coated on microparticles, for the differentiation of primary HCMV infection from an established infection. Two different test formats of the CMV Multiplex Copalis assay were evaluated. The 214 serum samples tested were immunoglobulin M (IgM) positive or equivocal by our reference assay. Reactivities against p52 and CM2 antigens were tested for sera from 37 patients with a well-documented seroconversion within the preceding 3 months (119 serum specimens), 31 patients known to have had a seroconversion at least 8 months earlier (31 serum specimens), and 57 patients without a documented seroconversion (64 serum specimens). The assay had a sensitivity for the detection of a primary infection of 70 or 86% by the first test format and a sensitivity of 88 or 94% by the second test format, according to the criteria used to indicate a primary infection by this test. A good correlation of the results of the assay with our in-house avidity index was found. The specificity of the assay warrants further evaluation. With IgM-positive sera, the assay was not sufficiently specific to make a distinction between a primary infection and an established infection.

scholarly journals Primary Human Cytomegalovirus (HCMV) Infection in Pregnancy

2017 ◽  
Author(s):  
Horst Buxmann ◽  
Klaus Hamprecht ◽  
Matthias Meyer-Wittkopf ◽  
Klaus Friese
Keyword(s):  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
In Pregnancy

scholarly journals Diagnosis and Management of Human Cytomegalovirus Infection in the Mother, Fetus, and Newborn Infant

2002 ◽  
Vol 15 (4) ◽  
pp. 680-715 ◽  
Author(s):  
Maria Grazia Revello ◽  
Giuseppe Gerna
Keyword(s):  
Prenatal Diagnosis ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Prognostic Markers ◽  
Recurrent Infection ◽  
Congenital Infection ◽  
Immunoglobulin M ◽  
Hcmv Disease ◽  
The Impact

SUMMARY Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy.

scholarly journals Development of Human Cytomegalovirus–Specific T Cell Immunity during Primary Infection of Pregnant Women and Its Correlation with Virus Transmission to the Fetus

2007 ◽  
Vol 195 (7) ◽  
pp. 1062-1070 ◽  
Author(s):  
Daniele Lilleri ◽  
Chiara Fornara ◽  
Milena Furione ◽  
Maurizio Zavattoni ◽  
Maria Grazia Revello ◽  
...  
Keyword(s):  
T Cell ◽  
Pregnant Women ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Virus Transmission ◽  
T Cell Immunity ◽  
Cell Immunity

scholarly journals Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Roberta Rizzo ◽  
Liliana Gabrielli ◽  
Daria Bortolotti ◽  
Valentina Gentili ◽  
Giulia Piccirilli ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Pregnant Women ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Human Leukocyte ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Hcmv Disease ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection. We analyzed 182 blood samples from 130 pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women experiencing primary HCMV infection. The median levels of sHLA-G in maternal serum of women with primary HCMV infection were higher in comparison with nonprimary and uninfected pregnant women (p<0.001). AF from HCMV symptomatic fetuses presented higher sHLA-G levels in comparison with infected asymptomatic fetuses (p<0.001), presence of HLA-G free-heavy chain, and a concentration gradient from amniotic fluid to maternal blood. No significant statistical difference of beta-2 microglobulin median levels was observed between all different groups. Our results suggest the determination of sHLA-G molecules in both maternal blood and amniotic fluid as a promising biomarker of diagnosis of maternal HCMV primary infection and fetal HCMV disease.

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