Universal Screening With Use of Immunoglobulin G Avidity for Congenital Cytomegalovirus Infection

Tanimura, Kenji; Tairaku, Shinya; Morioka, Ichiro; Ozaki, Kana; Nagamata, Satoshi; Morizane, Mayumi; Deguchi, Masashi; Ebina, Yasuhiko; Minematsu, Toshio; Yamada, Hideto

doi:10.1093/cid/cix621

Cited by 43 publications

(48 citation statements)

References 36 publications

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“…However, absence of detectable CMV IgM in the mothers' sera does not rule out primary CMV infection. 1,19,23 BaAlawi et al reported that a concordance of low CMV IgG AI values and CMV IgM positivity of 91% among five ELISA kits, varying between 75% and 93% for high AI values and IgM negativity. 17 Further, high CMV IgM titers reportedly correlate well with low CMV IgG AI values.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the indirect and IgM‐capture anti‐human cytomegalovirus IgM ELISA methods as confirmed by cytomegalovirus IgG avidity

Ikuta

Koshizuka

Kanno

et al. 2019

Microbiology and Immunology

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Primary cytomegalovirus (CMV) infection during pregnancy often results in congenital CMV infection with severe clinical complications. IgM antibodies are one of the indices of primary infection. The IgG avidity index (AI) is also known to remain low for 3 months after primary infection. Here, we evaluated and compared the performance of CMV IgM and IgG avidity assays. Because sensitivity and specificity reportedly differ between CMV IgM kits, CMV IgM detection was compared between the two commercially available ELISA kits that are most commonly used in Japan. Sera for CMV IgM were first screened using a traditional indirect ELISA kit. Selected samples were then tested for CMV IgM and CMV AI using a CMV IgM‐capture ELISA kit and a CMV IgG avidity assay, respectively. The rate of concordance between the IgM kits was 89% (42/47), indicating the absence of any significant difference. Most of the CMV IgM‐positive plasma samples showed high CMV IgG AI; however, 18 commercially available plasma samples with low CMV IgG AI were all CMV IgM‐positive. One plausible explanation for this discrepancy is that the duration of low IgG AI is shorter than that of IgM positivity. Alternatively, CMV IgM tests may generate pseudo‐positive readouts in cases of congenital infection. Nevertheless, our study confirms that CMV IgG AI can be a reliable indicator of CMV primary infection.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the indirect and IgM‐capture anti‐human cytomegalovirus IgM ELISA methods as confirmed by cytomegalovirus IgG avidity

Ikuta

Koshizuka

Kanno

et al. 2019

Microbiology and Immunology

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“…And yet protection of seronegative women remains an important goal given the equal contributions of transmissions in the seronegative and seropositive settings to cCMV infections in developed countries. may miss the identification of congenital CMV transmission cases in the setting of nonprimary maternal infection (51). Further support for the idea of a role of neutralizing antibodies in reducing the risk of placental HCMV transmission comes from studies demonstrating that neutralizing titers induced by the HCMV pentameric complex (PC; gH/gL/UL128-131A) against epithelial-cell-tropic viruses are strongly associated with reduced congenital CMV transmission in the setting of nonprimary congenital CMV transmission in HIV/CMV-coinfected pregnant women (48,52).…”

Section: Congenital CMV Transmission In Acutely and Chronically Hcmv-mentioning

confidence: 99%

Advancing Our Understanding of Protective Maternal Immunity as a Guide for Development of Vaccines To Reduce Congenital Cytomegalovirus Infections

Permar

Schleiss

Plotkin

2018

J Virol

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Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. Congenital HCMV (cCMV) infection is a major global contributor to long-term neurologic deficits, including deafness, microcephaly, and neurodevelopmental delay, as well as to fetal loss and occasional infant mortality. Accordingly, design of a maternal vaccine to prevent cCMV continues to be a top public health priority. Nevertheless, we remain without a licensed vaccine. Maternal immunity provides partial protection, as the risk of vertical HCMV transmission from chronically infected mothers is reduced compared to settings in which the mother is newly infected during pregnancy. Therefore, an understanding of the maternal immune correlates of protection against cCMV is critical to informing design of an efficacious maternal vaccine. Although vaccine development is being assiduously pursued by a large number of pharmaceutical manufacturers, biotechnology organizations, and academic researchers, some pessimism has been expressed regarding the issue of whether a vaccine to protect against cCMV is possible. This pessimism is based on observations that natural immunity is not completely protective against maternal reinfection and congenital transmission. However, we assert that optimism regarding vaccine development is indeed justified, on the basis of accruing evidence of immune correlates of protection-readily achievable by vaccination-that are associated with reduced transmission of HCMV to the fetus in seronegative women. In light of the substantial burden on society conferred by cCMV infection, even a modest reduction in the occurrence of this fetal disease is an important public health goal and justifies aggressive clinical evaluation of vaccines currently in the pipeline.

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“…By contrast, a prospective cohort study of 2193 pregnant women at low risk showed that the prediction accuracy for congenital CMV infection of maternal screening based on a CMV IgG AI of less than or equal to 45% or less than 35% was similar to that based on CMV IgM (>1.2 index) . Additionally, in this study, 10 (0.5%) of the 2193 pregnant women had newborns with congenital CMV infection, and three of these were born to mothers who had primary infection during pregnancy (as defined by a CMV IgG AI of <35% and/or a CMV IgM index of >1.2 or the detection of CMV IgG seroconversion).…”

Section: Maternal Screening For Predicting Congenital CMV Infectionmentioning

confidence: 99%

“…Figure shows a proposed screening algorithm for congenital CMV infection based on the results of our prospective cohort studies …”

Section: Maternal and Neonatal Screening Algorithm For Congenital CMVmentioning

confidence: 99%

Maternal and neonatal screening methods for congenital cytomegalovirus infection

Tanimura

Yamada

2018

J of Obstet and Gynaecol

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Human cytomegalovirus (CMV) is a common cause of congenital infection that may lead to severe long-term sequelae. Because there are no established vaccines, fetal interventions or neonatal treatments, neither maternal nor neonatal screening is recommended. However, recent studies have indicated that early antiviral treatment may improve neurological outcomes in symptomatic infants with congenital infection. Therefore, prenatal detection may be important in newborns at high risk of such infection. Polymerase chain reaction for CMV DNA in the amniotic fluid is considered the gold standard for diagnosis of intrauterine infection, but its use is limited because amniocentesis is an invasive procedure. In a prospective cohort study, we have reported that the presence of CMV DNA in secretions of the maternal uterine cervix were predictive of congenital infection in groups at high risk. However, we also recently demonstrated that maternal serological screening for primary CMV infection using specific immunoglobulin G, the immunoglobulin G avidity index or specific immunoglobulin M can overlook many cases. Previous research has indicated that the combination of early detection by universal neonatal screening of urinary CMV DNA combined with early antiviral therapy can improve outcomes in infants with symptomatic congenital infection. In this article, we review the current state of maternal and neonatal screening for congenital CMV infection.

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Universal Screening With Use of Immunoglobulin G Avidity for Congenital Cytomegalovirus Infection

Abstract: Maternal screening using CMV IgG and AI can identify pregnancies with CCI from primary infection, but overlooks a number of those from nonprimary infection.

Cited by 43 publications

References 36 publications

Evaluation of the indirect and IgM‐capture anti‐human cytomegalovirus IgM ELISA methods as confirmed by cytomegalovirus IgG avidity

Evaluation of the indirect and IgM‐capture anti‐human cytomegalovirus IgM ELISA methods as confirmed by cytomegalovirus IgG avidity

Advancing Our Understanding of Protective Maternal Immunity as a Guide for Development of Vaccines To Reduce Congenital Cytomegalovirus Infections

Maternal and neonatal screening methods for congenital cytomegalovirus infection

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