Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>

ABSTRACT Human parvovirus B19 (here B19), human cytomegalovirus (HCMV), and Toxoplasma gondii infections during pregnancy can lead to severe complications. While traditional diagnosis of infections is mostly confined to one pathogen at a time, a multiplex array is a feasible alternative to improve d...

Full description

Bibliographic Details
Main Authors: Yilin Wang, Lea Hedman, Visa Nurmi, Inga Ziemele, Maria F. Perdomo, Maria Söderlund-Venermo, Klaus Hedman
Format: Article
Language:English
Published: American Society for Microbiology 2020-04-01
Series:mSphere
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/mSphere.00905-19
_version_ 1818683609092980736
author Yilin Wang
Lea Hedman
Visa Nurmi
Inga Ziemele
Maria F. Perdomo
Maria Söderlund-Venermo
Klaus Hedman
author_facet Yilin Wang
Lea Hedman
Visa Nurmi
Inga Ziemele
Maria F. Perdomo
Maria Söderlund-Venermo
Klaus Hedman
author_sort Yilin Wang
collection DOAJ
description ABSTRACT Human parvovirus B19 (here B19), human cytomegalovirus (HCMV), and Toxoplasma gondii infections during pregnancy can lead to severe complications. While traditional diagnosis of infections is mostly confined to one pathogen at a time, a multiplex array is a feasible alternative to improve diagnostic management and cost-efficiency. In the present study, for these three pathogens, we developed microsphere-based suspension immunoassays (SIAs) in multiplex and monoplex formats for the detection of antimicrobial IgM antibodies as well as corresponding chaotrope-based IgG avidity SIAs. We determined the diagnostic performances of the SIAs versus in-house and commercial reference assays using a panel of 318 serum samples from well-characterized clinical cohorts. All the newly developed assays exhibited excellent performance compared to the corresponding high-quality reference methods. The positive and negative percent agreements of the IgM SIAs in comparison with reference methods were 95 to 100% and 98 to 100%, and those of the IgG avidity SIAs were 92 to 100% and 95 to 100%, respectively. Kappa efficiency values between the SIAs and the corresponding reference assays were 0.91 to 1. Furthermore, with another panel comprising 391 clinical samples from individuals with primary infection by B19, HCMV, or T. gondii, the IgM SIAs were highly sensitive for the detection of acute infections, and the IgG avidity SIAs were highly specific for the separation of primary infections from past immunity. Altogether, the strategy of IgM multiplex screening followed by IgG avidity reflex testing can provide high-throughput and accurate means for the detection and stage determination of B19, HCMV, and T. gondii infections. IMPORTANCE Human parvovirus B19, human cytomegalovirus, and Toxoplasma gondii are ubiquitous pathogens. Their infections are often asymptomatic or mild in the general population yet may be transmitted from mother to fetus during pregnancy. Maternal infections by these pathogens can cause severe complications to the fetus or congenital abnormalities. As a rule, the risk of maternal transmission is critically related to the infection time; hence, it is important to determine when a pregnant woman has acquired the infection. In this study, we developed new diagnostic approaches for the timing of infections by three pathogens. All the new assays appeared to be highly sensitive and specific, providing powerful tools for medical diagnosis.
first_indexed 2024-12-17T10:37:27Z
format Article
id doaj.art-28b974fb72e341438810fb9cbcc6020a
institution Directory Open Access Journal
issn 2379-5042
language English
last_indexed 2024-12-17T10:37:27Z
publishDate 2020-04-01
publisher American Society for Microbiology
record_format Article
series mSphere
spelling doaj.art-28b974fb72e341438810fb9cbcc6020a2022-12-21T21:52:20ZengAmerican Society for MicrobiologymSphere2379-50422020-04-015210.1128/mSphere.00905-19Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>Yilin Wang0Lea Hedman1Visa Nurmi2Inga Ziemele3Maria F. Perdomo4Maria Söderlund-Venermo5Klaus Hedman6Department of Virology, University of Helsinki, Helsinki, FinlandDepartment of Virology, University of Helsinki, Helsinki, FinlandDepartment of Virology, University of Helsinki, Helsinki, FinlandDepartment of Virology, University of Helsinki, Helsinki, FinlandDepartment of Virology, University of Helsinki, Helsinki, FinlandDepartment of Virology, University of Helsinki, Helsinki, FinlandDepartment of Virology, University of Helsinki, Helsinki, FinlandABSTRACT Human parvovirus B19 (here B19), human cytomegalovirus (HCMV), and Toxoplasma gondii infections during pregnancy can lead to severe complications. While traditional diagnosis of infections is mostly confined to one pathogen at a time, a multiplex array is a feasible alternative to improve diagnostic management and cost-efficiency. In the present study, for these three pathogens, we developed microsphere-based suspension immunoassays (SIAs) in multiplex and monoplex formats for the detection of antimicrobial IgM antibodies as well as corresponding chaotrope-based IgG avidity SIAs. We determined the diagnostic performances of the SIAs versus in-house and commercial reference assays using a panel of 318 serum samples from well-characterized clinical cohorts. All the newly developed assays exhibited excellent performance compared to the corresponding high-quality reference methods. The positive and negative percent agreements of the IgM SIAs in comparison with reference methods were 95 to 100% and 98 to 100%, and those of the IgG avidity SIAs were 92 to 100% and 95 to 100%, respectively. Kappa efficiency values between the SIAs and the corresponding reference assays were 0.91 to 1. Furthermore, with another panel comprising 391 clinical samples from individuals with primary infection by B19, HCMV, or T. gondii, the IgM SIAs were highly sensitive for the detection of acute infections, and the IgG avidity SIAs were highly specific for the separation of primary infections from past immunity. Altogether, the strategy of IgM multiplex screening followed by IgG avidity reflex testing can provide high-throughput and accurate means for the detection and stage determination of B19, HCMV, and T. gondii infections. IMPORTANCE Human parvovirus B19, human cytomegalovirus, and Toxoplasma gondii are ubiquitous pathogens. Their infections are often asymptomatic or mild in the general population yet may be transmitted from mother to fetus during pregnancy. Maternal infections by these pathogens can cause severe complications to the fetus or congenital abnormalities. As a rule, the risk of maternal transmission is critically related to the infection time; hence, it is important to determine when a pregnant woman has acquired the infection. In this study, we developed new diagnostic approaches for the timing of infections by three pathogens. All the new assays appeared to be highly sensitive and specific, providing powerful tools for medical diagnosis.https://journals.asm.org/doi/10.1128/mSphere.00905-19intrauterine infectionB19HCMVT. gondiiIgMIgG avidity
spellingShingle Yilin Wang
Lea Hedman
Visa Nurmi
Inga Ziemele
Maria F. Perdomo
Maria Söderlund-Venermo
Klaus Hedman
Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>
mSphere
intrauterine infection
B19
HCMV
T. gondii
IgM
IgG avidity
title Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_full Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_fullStr Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_full_unstemmed Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_short Microsphere-Based IgM and IgG Avidity Assays for Human Parvovirus B19, Human Cytomegalovirus, and <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_sort microsphere based igm and igg avidity assays for human parvovirus b19 human cytomegalovirus and named content content type genus species toxoplasma gondii named content
topic intrauterine infection
B19
HCMV
T. gondii
IgM
IgG avidity
url https://journals.asm.org/doi/10.1128/mSphere.00905-19
work_keys_str_mv AT yilinwang microspherebasedigmandiggavidityassaysforhumanparvovirusb19humancytomegalovirusandnamedcontentcontenttypegenusspeciestoxoplasmagondiinamedcontent
AT leahedman microspherebasedigmandiggavidityassaysforhumanparvovirusb19humancytomegalovirusandnamedcontentcontenttypegenusspeciestoxoplasmagondiinamedcontent
AT visanurmi microspherebasedigmandiggavidityassaysforhumanparvovirusb19humancytomegalovirusandnamedcontentcontenttypegenusspeciestoxoplasmagondiinamedcontent
AT ingaziemele microspherebasedigmandiggavidityassaysforhumanparvovirusb19humancytomegalovirusandnamedcontentcontenttypegenusspeciestoxoplasmagondiinamedcontent
AT mariafperdomo microspherebasedigmandiggavidityassaysforhumanparvovirusb19humancytomegalovirusandnamedcontentcontenttypegenusspeciestoxoplasmagondiinamedcontent
AT mariasoderlundvenermo microspherebasedigmandiggavidityassaysforhumanparvovirusb19humancytomegalovirusandnamedcontentcontenttypegenusspeciestoxoplasmagondiinamedcontent
AT klaushedman microspherebasedigmandiggavidityassaysforhumanparvovirusb19humancytomegalovirusandnamedcontentcontenttypegenusspeciestoxoplasmagondiinamedcontent