CAN INFECTION WITH CYTOMEGALOVIRUS, PARVOVIRUS B19 AND HERPES SIMPLEX VIRUS CAUSE RECURRENT PREGNANCY LOSS?

ABSTRACT During an outbreak of parvovirus B19 we collected serum samples from 68 nonpregnant patients in the region of Antwerp (Belgium). Fifty-seven (84%) of the parvovirus B19 immunoglobulin M (IgM)-positive sera had a positive result for Epstein-Barr virus (EBV) IgM by Liaison testing, 61 (90%) had a positive result for herpes simplex virus (HSV) IgM, 20 (29%) samples were positive for cytomegalovirus IgM, and 15 (22%) had a positive result for Borrelia burgdorferi sensu lato IgM. As assay interference was suspected, sera were further investigated by using additional infectious-disease serology tests and by performing various interference elimination procedures. We could show that the EBV IgM and HSV IgM results were false positives due to aspecific IgM reactions with the solid phase. All samples were also analyzed by a modified Liaison EBV IgM assay, based on the addition of polyvinylpyrrolidone and polyvinyl alcohol to the dilution buffer, which partially eliminated this type of assay interference. Although the Liaison is a very convenient, automated immunoassay platform, this study demonstrates the potential for improvement of mainly the EBV IgM and HSV IgM tests.

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Lights and Shadows of TORCH Infection Proteomics

Genes ◽

10.3390/genes11080894 ◽

2020 ◽

Vol 11 (8) ◽

pp. 894

Author(s):

Janaina Macedo-da-Silva ◽

Claudio Romero Farias Marinho ◽

Giuseppe Palmisano ◽

Livia Rosa-Fernandes

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Pathological Condition ◽

Parvovirus B19 ◽

Total Protein Content ◽

Interconnected System ◽

Congenital Diseases ◽

Post Translational Modifications ◽

Varicella Zoster ◽

Simplex Virus

Congenital abnormalities cause serious fetal consequences. The term TORCH is used to designate the most common perinatal infections, where: (T) refers to toxoplasmosis, (O) means “others” and includes syphilis, varicella-zoster, parvovirus B19, zika virus (ZIKV), and malaria among others, (R) refers to rubella, (C) relates to cytomegalovirus infection, and (H) to herpes simplex virus infections. Among the main abnormalities identified in neonates exposed to congenital infections are central nervous system (CNS) damage, microcephaly, hearing loss, and ophthalmological impairment, all requiring regular follow-up to monitor its progression. Protein changes such as mutations, post-translational modifications, abundance, structure, and function may indicate a pathological condition before the onset of the first symptoms, allowing early diagnosis and understanding of a particular disease or infection. The term “proteomics” is defined as the science that studies the proteome, which consists of the total protein content of a cell, tissue or organism in a given space and time, including post-translational modifications (PTMs) and interactions between proteins. Currently, quantitative bottom-up proteomic strategies allow rapid and high throughput characterization of complex biological mixtures. Investigating proteome modulation during host–pathogen interaction helps in elucidating the mechanisms of infection and in predicting disease progression. This “molecular battle” between host and pathogen is a key to identify drug targets and diagnostic markers. Here, we conducted a survey on proteomic techniques applied to congenital diseases classified in the terminology “TORCH”, including toxoplasmosis, ZIKV, malaria, syphilis, human immunodeficiency virus (HIV), herpes simplex virus (HSV) and human cytomegalovirus (HCVM). We have highlighted proteins and/or protein complexes actively involved in the infection. Most of the proteomic studies reported have been performed in cell line models, and the evaluation of tissues (brain, muscle, and placenta) and biofluids (plasma, serum and urine) in animal models is still underexplored. Moreover, there are a plethora of studies focusing on the pathogen or the host without considering the triad mother-fetus-pathogen as a dynamic and interconnected system.

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Laboratory assessment and diagnosis of congenital viral infections: Rubella, cytomegalovirus (CMV), varicella-zoster virus (VZV), herpes simplex virus (HSV), parvovirus B19 and human immunodeficiency virus (HIV)

Reproductive Toxicology ◽

10.1016/j.reprotox.2006.02.001 ◽

2006 ◽

Vol 21 (4) ◽

pp. 350-382 ◽

Cited By ~ 50

Author(s):

E MENDELSON ◽

Y ABOUDY ◽

Z SMETANA ◽

M TEPPERBERG ◽

Z GROSSMAN

Keyword(s):

Human Immunodeficiency Virus ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Varicella Zoster Virus ◽

Viral Infections ◽

Parvovirus B19 ◽

Laboratory Assessment ◽

Varicella Zoster ◽

Immunodeficiency Virus ◽

Simplex Virus

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Performance of the Epstein-Barr Virus and Herpes Simplex Virus Immunoglobulin M Assays on the Liaison Platform with Sera from Patients Displaying Acute Parvovirus B19 Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00142-09 ◽

2009 ◽

Vol 16 (8) ◽

pp. 1247-1248 ◽

Cited By ~ 7

Author(s):

Elisa Costa ◽

Nuria Tormo ◽

María Ángeles Clari ◽

Dayana Bravo ◽

Beatriz Muñoz-Cobo ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

False Positive ◽

Parvovirus B19 ◽

Immunoglobulin M ◽

Barr Virus ◽

Parvovirus B19 Infection ◽

Epstein Barr ◽

Simplex Virus ◽

Positive Results

ABSTRACT Acute parvovirus B19 infection has been reported to cause false-positive results frequently in the Epstein-Barr (EBV) and herpes simplex virus (HSV) immunoglobulin M (IgM) assays from DiaSorin performed on the Liaison platform. We tested 65 sera from patients with a presumptive or conclusive diagnosis of acute parvovirus B19 infection in both assays and obtained no false-positive results in the EBV IgM test and 10.4% nonspecific reactivities in the HSV IgM assay. Our data support the specificity of both assays in this clinical setting.

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Adverse reproductive outcome induced by Parvovirus B19 and TORCH infections in women with high-risk pregnancy

The Journal of Infection in Developing Countries ◽

10.3855/jidc.1533 ◽

2011 ◽

Vol 5 (12) ◽

pp. 868-873 ◽

Cited By ~ 12

Author(s):

Janak Kishore ◽

Richa Misra ◽

Abhiruchi Paisal ◽

Yashodhra Pradeep

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

High Risk ◽

Toxoplasma Gondii ◽

Cord Blood ◽

Pregnant Women ◽

Pregnancy Complications ◽

Congenital Malformations ◽

Parvovirus B19 ◽

Simplex Virus

Introduction: The frequency of fetopathogenic viruses and Toxoplasma gondii infections in the TORCH group (Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus) together with Parvovirus B19 (B19) in pregnant women with bad obstetric history (BOH) and/or concurrent pregnancy complications was investigated. Methodology: Sixty women (20-35 years) with BOH and/or antecedent pregnancy complications were studied. Twenty-nine healthy pregnant women matched for age, parity and gestational age served as controls. Sera were analyzed for IgM antibodies for B19 and TORCH agents by ELISA. Cord blood and 33 placental tissues from six malformed newborns were tested for B19 DNA by PCR. Results: Out of 60 high-risk pregnant women, 47 (78%) had BOH while 23 (38.3%) had underlying complications including polyhydramnios (n=10), oligohydramnios (n=6) and intrauterine growth restriction (n=7). Adverse outcomes occurred in 36 (60%) high-risk cases. All 16 cases with polyhydramnios/oligohydramnios resulted in preterm stillbirths while the remaining 20 cases resulted in seven abortions, six newborns with congenital malformations, four full-term stillbirths and three cases of non-immune hydrops fetalis (NIHF). IgM positivity to T. gondii, rubella, cytomegalovirus, herpes simplex virus and B19 virus was 8.3%, 15%, 30%, 3.3% and 13.6% respectively. B19 infection caused NIHF in three cases and cardiac anomaly in one. All placental tissues and cord blood were negative for B19 DNA. None of the controls had IgM antibodies to any pathogen. Conclusions: Women with BOH and/or pregnancy complications had a high frequency of TORCH and parvovirus B19 infections causing fetal wastage, IUGR, NIHF and congenital malformations.

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Relevance of Parvovirus B19, Herpes Simplex Virus 2, and Cytomegalovirus Virologic Markers in Maternal Serum for Diagnosis of Unexplained Recurrent Abortions

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-956-ropbhs ◽

2007 ◽

Vol 131 (6) ◽

pp. 956-960

Author(s):

Maysaa El-Sayed Zaki ◽

Hossam Goda

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Pregnant Women ◽

Viral Infections ◽

Parvovirus B19 ◽

Maternal Serum ◽

Significant Difference ◽

Recurrent Abortions ◽

Simplex Virus ◽

Herpes Simplex Virus 2

Abstract Context.—The impact of viral infections during pregnancy on adverse pregnancy outcomes is not understood fully. Objective.—To assess the frequency of parvovirus B19, herpes simplex 2, and cytomegalovirus infections in relation to late abortions, in sera from Egyptian pregnant women to establish basic knowledge for future pregnancy care. In addition, to study the diagnostic value of specific immunoglobulin M (IgM) against those viruses compared with their genomes detection by polymerase chain reaction in maternal serum as a noninvasive method of laboratory diagnosis. Design.—Patients were recruited at the Women's Clinic, Mansoura University. One group of patients with recurrent spontaneous abortions (RSA) and a second group of pregnant women without a history of RSA were evaluated including demographic, medical, and clinical data. Virologic markers were evaluated for specific IgM and for viral DNA to cytomegalovirus, herpes simplex virus 2, and parvovirus B19. Results.—There was a statistically significant difference between the RSA group and the pregnant women without RSA group in frequency of parvovirus IgM (84% and 16.7%, respectively) (P < .001) and herpes simplex IgM (40% for RSA) (P = .001). Parvovirus B19 viremia was positive in 48% RSA, herpes simplex virus 2 was positive in 32% RSA, and cytomegalovirus was positive in 12% RSA patients. For RSA patients with parvovirus viremia, the mean ± SD of IgM value was 78.5 ± 30.12 IU/mL, and for RSA patients with negative viremia it was 30.02 ± 17.64 IU/mL with statistically significant difference between both levels (P < .001). Conclusions.—From this study, we conclude that viral infections with parvovirus B19 and herpes simplex 2 were frequently associated with recurrent abortions, and careful investigation for this condition must include evaluating these patients for the previously mentioned viruses. Serologic study by specific IgM for parvovirus and herpes simplex seem to be reliable as screening tests for high-risk pregnancy.

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