Test Id : TRCHG

To evaluate recent or acute infection with Toxoplasma gondii, order TXM / Toxoplasma gondii Antibody, IgM, Serum.

For patients presenting with presumed acute infection with herpes simplex virus, order HERPB / Herpes Simplex Virus 1 and 2, Qualitative PCR, Blood.

IgG antibodies in patients younger than 6 months of age are typically the result of passive transfer from the mother. To assess possible infection in patients younger than 6 months, consider ordering IgM testing.

Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL

Collection Instructions: Centrifuge and aliquot serum into plastic vial.

If not ordering electronically, complete, print, and send Infectious Disease Serology Test Request (T916) with the specimen.

1.2 mL

Determining immune status of individuals to the rubella virus following vaccination or prior exposure

Indicating past or recent infection with Toxoplasma gondii, cytomegalovirus, or herpes simplex virus (HSV)

Distinguishing between infection caused by HSV types 1 and 2, especially in patients with subclinical or unrecognized HSV infection

Toxoplasma gondii:

Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting a variety of intermediate hosts, including humans. Infected definitive hosts (cats) shed oocysts in feces that rapidly mature in the soil and become infectious.(1) Toxoplasmosis is acquired by humans through ingestion of food or water contaminated with cat feces or through eating undercooked meat containing viable oocysts. Vertical transmission of the parasite through the placenta can also occur, leading to congenital toxoplasmosis. Following primary infection, T gondii can remain latent for the life of the host; the risk for reactivation is highest among individuals who are immunosuppressed.

Seroprevalence studies performed in the United States indicate approximately 6.7% of individuals between the ages of 12 and 49 have antibodies to T gondii.(2)

Infection of immunocompetent adults is typically asymptomatic. In symptomatic cases, patients most frequently present with lymphadenopathy and other nonspecific constitutional symptoms, making definitive diagnosis difficult to determine.

Severe-to-fatal infections can occur among patients with AIDS or individuals that are otherwise immunosuppressed. These infections are thought to be caused by reactivation of latent infections and commonly involve the central nervous system.(3)

Transplacental transmission of the parasites resulting in congenital toxoplasmosis can occur during the acute phase of acquired maternal infection. The risk of fetal infection is a function of the time at which acute maternal infection occurs during gestation.(4) The incidence of congenital toxoplasmosis increases as pregnancy progresses; conversely, the severity of congenital toxoplasmosis is greatest when maternal infection is acquired early during pregnancy. A majority of infants infected in utero are asymptomatic at birth, particularly if maternal infection occurs during the third trimester, with sequelae appearing later in life. Congenital toxoplasmosis results in severe generalized or neurologic disease in about 20% to 30% of the infants infected in utero; approximately 10% exhibit ocular involvement only, and the remainder are asymptomatic at birth. Subclinical infection may result in premature delivery and subsequent neurologic, intellectual, and audiologic defects.

Rubella:

Rubella (German or 3-day measles) is a member of the Togavirus family, and humans remain the only natural host for this virus. Transmission is typically through inhalation of infectious aerosolized respiratory droplets, and the incubation period following exposure can range from 12 to 23 days.(5) Infection is generally mild, self-limited, and characterized by a maculopapular rash beginning on the face spreading to the trunk and extremities, fever, malaise, and lymphadenopathy.(6)

Primary, in utero rubella infections can lead to severe sequelae for the fetus, particularly if infection occurs within the first 4 months of gestation. Congenital rubella syndrome is often associated with hearing loss and cardiovascular and ocular defects.(7)

The United States 2-dose measles, mumps, rubella (MMR) vaccination program, which calls for vaccination of all children, leads to seroconversion in 95% of children following the first dose.(5) A total of 4 cases of rubella were reported to the Centers for Disease Control and Prevention (CDC) in 2011 without any cases of congenital rubella syndrome.(8) Due to the success of the national vaccination program, rubella is no longer considered endemic in the United States.(9) However, immunity may wane with age as approximately 80% to 90% of adults will show serologic evidence of immunity to rubella.

Cytomegalovirus:

Cytomegalovirus (CMV) is a member of the Herpesviridae family of viruses and usually causes asymptomatic infection after which it remains latent in patients, primarily within bone marrow derived cells.(10) Primary CMV infection in immunocompetent individuals may also manifest as a mononucleosis-type syndrome, similar to primary Epstein-Barr virus infection, with fever, malaise, and lymphadenopathy.

CMV is a significant cause of morbidity and mortality among bone marrow or solid organ transplant recipients, individuals with AIDS, and other immunosuppressed patients due to virus reactivation or from a newly acquired infection.(11,12) Infection in these patient populations can affect almost any organ and lead to multi-organ failure. CMV is also responsible for congenital disease among newborns and is 1 of the ToRCH infections (toxoplasmosis, other infections including syphilis, rubella, CMV, and herpes simplex virus [HSV]).

CMV seroprevalence increases with age. In the United States, the prevalence of CMV-specific antibodies increases from approximately 36% to over 91% in children between the ages of 6 and 11 and adults over 80 years old, respectively.(13)

Herpes Simplex Virus Types 1 and 2:

HSV types 1 and 2 are members of the Herpesviridae family and produce infections that range from mild stomatitis to disseminated and fatal disease. Clinical conditions associated with HSV infection include gingivostomatitis, keratitis, encephalitis, vesicular skin eruptions, aseptic meningitis, neonatal herpes, genital tract infections, and disseminated primary infection.

Infections with HSV types 1 and 2 can differ significantly in their clinical manifestations and severity. HSV type 2 primarily causes urogenital infections and is found almost exclusively in adults. HSV type 1 is closely associated with orolabial infection, although genital infection with this virus can be common in certain populations.

The diagnosis of HSV infections is routinely made based on clinical findings and supported by laboratory testing using a polymerase chain reaction (PCR) assay or viral culture. However, in instances of subclinical or unrecognized HSV infection, serologic testing for IgG-class antibodies to type-specific HSV glycoprotein G (gG) may be useful. There are several circumstances in which it may be important to distinguish between infection caused by HSV types 1 and 2.(14) For example, the risk for reactivation is highest for HSV type 2, and the method of antiviral therapy may be different depending on the specific type of HSV causing disease. In addition, the results of HSV type specific IgG testing is sometimes used during pregnancy to identify risks of congenital HSV disease and allow for focused counseling prior to delivery.(15,16)

Toxoplasma ANTIBODY, IgG

Negative

Toxoplasma IgG

< or =9 IU/mL (Negative)

10-11 IU/mL (Equivocal)

> or =12 IU/mL (Positive)

RUBELLA ANTIBODY, IgG

Vaccinated: Positive (> or =1.0 AI)

Unvaccinated: Negative (< or =0.7 AI)

CYTOMEGALOVIRUS

Negative

HERPES SIMPLEX VIRUS (HSV), TYPE 1 AND TYPE 2 ANTIBODIES, IgG

Herpes Simplex Virus (HSV) Type 1, IgG

Negative

Herpes Simplex Virus (HSV) Type 2, IgG

Negative

Toxoplasma gondii:

A positive Toxoplasma IgG result is indicative of current or past infection with T gondii. A single positive Toxoplasma IgG result should not be used to diagnose recent infection.

Equivocal Toxoplasma IgG results may be due to very low levels of circulating IgG during the acute stage of infection. A second specimen should be submitted for testing if clinically indicated.

Individuals with negative Toxoplasma IgG results are presumed to not have had previous exposure to T gondii. However, negative results may be seen in cases of remote exposure with subsequent loss of detectable antibody. Seroconversion from negative to positive IgG is indicative of T gondii infection subsequent to the first negative specimen.

Rubella:

Positive: The presence of detectable IgG-class antibodies to rubella indicates prior exposure through infection or immunization. Individuals testing positive for IgG-class antibodies to rubella are considered immune.

Equivocal: Submit an additional specimen for testing in 10 to 14 days to demonstrate IgG seroconversion if recently vaccinated or if otherwise clinically indicated.

Negative: The absence of detectable IgG-class antibodies to rubella suggests no prior exposure to this virus or the lack of a specific immune response to immunization.

Cytomegalovirus:

Positive cytomegalovirus (CMV) IgG results indicate past or recent CMV infection. These individuals may transmit CMV to susceptible individuals through blood and tissue products.

Equivocal CMV IgG results may occur during acute infection or may be due to nonspecific binding reactions. Submit an additional specimen for testing if clinically indicated.

Individuals with negative CMV IgG results are presumed to not have had prior exposure or infection with CMV and are therefore considered susceptible to primary infection.

Herpes Simplex Virus:

The presence of IgG-class antibodies to herpes simplex virus (HSV) types 1 or 2 indicates previous exposure and does not necessarily indicate that HSV is the causative agent of an acute illness.

Toxoplasma gondii:

Sera collected very early during the acute stage of infection may have Toxoplasma IgG levels less than 9 IU/mL.

The Toxoplasma IgG assay should not be used alone to diagnose recent T gondii infection. Results should be considered in conjunction with clinical presentation, patient history, and other laboratory findings.

The performance characteristics of this assay have not been evaluated in immunocompromised individuals and have not been established for cord blood or for testing of neonates.

Rubella:

Specimens collected early during the acute phase of infection or shortly (1-2 weeks) following vaccination may be negative for IgG class antibodies.

Cytomegalovirus:

Sera collected very early during the acute stage of infection may have undetectable levels of cytomegalovirus (CMV) IgG.

The CMV IgG assay should not be used alone to diagnose CMV infection. Results should be considered in conjunction with clinical presentation, patient history, and other laboratory findings. In cases of suspected diseases, submit a second specimen for testing in 10 to 14 days.

The performance characteristics of this assay have not been evaluated in immunosuppressed or organ transplant recipients and have not been established for cord blood or for testing of neonates.

Immune complexes or other immunoglobulin aggregates present in patient specimen may cause increased nonspecific binding and produce false-positive results.

Potential cross-reactivity for CMV with human chorionic gonadotropin, HIV IgG, multiple myeloma IgG, rheumatoid factor IgM, and T gondii IgG have not be ruled out.

Herpes Simplex Virus Types 1 and 2:

Detection of IgG-class antibodies to herpes simplex virus (HSV) should not be used routinely as the primary means of diagnosing HSV infection. For patients presenting with presumed acute infection with HSV, a clinical specimen (eg, oral, dermal, or genital lesion) should be sampled and submitted for detection of HSV types 1 and 2 by rapid polymerase chain reaction (PCR) (HERPB / Herpes Simplex Virus 1 and 2, Qualitative PCR, Blood).

Serum specimens collected too early in the course of infection may not have detectable levels of HSV IgG. In cases of suspected early disease, a repeat serum specimen should be collected 14 to 21 days later and submitted for testing.

The presence of IgG-class antibodies to either HSV type 1 or 2 does not differentiate between remote infection and acute disease.

HSV serology cannot distinguish genital from nongenital infections.

The predictive value of positive or negative results depends on the prevalence of disease and the pretest likelihood of HSV type 1 and HSV type 2. False-positive results may occur. Repeat testing, or testing by a different method, may be indicated in some settings (eg, patients with low likelihood of HSV infection).

Toxoplasma gondii IgG:

To evaluate the accuracy of the BioPlex Toxoplasma IgG multiplex flow immunoassay, 100 prospective serum specimens submitted for routine Toxoplasma IgG testing by the VIDAS enzyme-linked fluorescence immunoassay (ELFA; bioMerieux, Durham, NC) were also analyzed in a blinded fashion by the BioPlex assay within a 24-hour period. Specimens with discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle. The results are summarized below:

Sensitivity: 100% (33/33); 95% Confidence Interval (95% CI): 87.6%-100%

Specificity: 100% (67/67); 95% CI: 93.5%-100%

Overall Percent Agreement: 100% (100/100); 95% CI: 95.6%-100%

Rubella IgG

To evaluate the accuracy of the BioPlex Rubella IgG multiplex flow immunoassay (MFI), 100 prospective serum specimens were analyzed in a blinded fashion by the SeraQuest Rubella IgG EIA (Quest Int., Doral, FL) and the BioPlex Rubella IgG assay. Specimens with discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle. The results are summarized below:

Sensitivity: 95.4% (83/87); 95% Confidence Interval (95% CI): 89.9%-99.2%

Specificity: 100% (13/13); 95% CI: 73.4%-100%

Overall Percent Agreement: 96.0% (96/100); 95% CI: 89.8%-98.8%

Cytomegalovirus (CMV) IgG:

To evaluate the accuracy of the BioPlex CMV IgG multiplex flow immunoassay, 100 prospective serum specimens submitted for routine CMV IgG testing by the VIDAS enzyme linked fluorescence immunoassay (ELFA; bioMerieux, Durham, NC) were also analyzed in a blinded fashion by the BioPlex assay within a 24-hour period. Specimens with discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle. The results are summarized below:

Sensitivity: 100.0% (67/67); 95% Confidence Interval (95% CI): 93.5%-100%

Specificity: 100.0% (33/33); 95% C.I.: 87.6%-100%

Overall Percent Agreement: 100.0% (100/100); 95% C.I.: 95.6%-100%

Herpes Simplex Virus (HSV) Type 1 and 2

To evaluate the accuracy of the BioPlex HSV assay, 87 prospective serum specimens were tested by EIA (HerpeSelect, Focus Diagnostics, Cypress, CA) and the BioPlex HSV-1/2 IgG assay.

The results are summarized in Tables 1 and 2 below:

Table 1. Comparison of the Bio-Rad BioPlex HSV-1 IgG assay to the HerpeSelect HSV-1 EIA using prospective serum specimens (n=87).

Sensitivity=100% (15/15) 95% Confidence Interval (95% CI):  76.1%-100%

Specificity=100% (72/72); 95% CI: 93.9%-100%

Overall percent agreement=100% (87/87); 95% CI: 94.9%-100%

Herpes Simplex Virus (HSV) Type 2:

Table 2. Comparison of the Bio-Rad BioPlex HSV-2 IgG assay to the HerpeSelect HSV-2 EIA using prospective serum specimens (n=87).

Sensitivity=100% (15/15) 95% Confidence Interval (95% CI): 76.1%-100%

Specificity=100% (72/72); 95% CI: 93.9%-100%

Overall percent agreement=100% (87/87); 95% CI: 94.9%-100%

1. Tenter AM, Heckeroth AR, Weiss LM: Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000 Nov;30(12-13):1217-1258

2. Jones JL, Kruszon-Moran D, Sanders-Lewis K, Wilson M: Toxoplasma gondii infection in the United States, 1999-2004, decline from the prior decade. Am J Trop Med Hyg. 2007 Sep;77(3):405-410

3. Luft BJ, Remington JS: Toxoplasmic encephalitis in AIDS. Clin Infect Dis. 1992 Aug;15(2):211-222

4. Wong SY, Remington JS: Toxoplasmosis in pregnancy. Clin Infect Dis. 1994 Jun;18(6):853-861

5. AAP Committee on Infectious Diseases: Rubella. In: Pickering LK, Baker CJ, Kimberlin DW, eds. Red Book. 2012 Report of the Committee on Infectious Diseases. 29th ed. American Academy of Pediatrics; 2012

6. Best JM: Rubella. Semin Fetal Neonatal Med. 2007 Jun;12(3):182-192

7. Duszak RS: Congenital rubella syndrome-major review. Optometry. 2009 Jan:80(1):36-43

8. Notifiable Diseases and Mortality Tables. MMWR Morb Mortal Wkly Rep. 2012;61(34):466-479

9. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases: Rubella (German measles, three-day measles). CDC; Updated December 31, 2020. Accessed December 27, 2022. Available at www.cdc.gov/rubella/

10. Soderberg-Naucler C, Fish KN, Nelson JA: Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell. 1997 Oct;91(1):119-126

11. Kusne S, Shapiro R, Fung J: Prevention and treatment of cytomegalovirus infection in organ transplant recipients. Transpl Infect Dis. 1999 Sep;1(3):187-203

12. Rubin RH: Importance of CMV in the transplant population. Transpl Infect Dis. 1999;1 Suppl 1:3-7

13. Staras SAS, Dollard SC, Radford KW, Flanders WD, Pass RF, Cannon MJ: Seroprevalence of cytomegalovirus infection in the United States, 1998-1994. Clin Infect Dis. 2006 Nov;43(9):1143-1151

14. Ashley RL, Wald A: Genital herpes: review of the epidemic and potential use of type-specific serology. Clin Microbiol Rev. 1999 Jan;12(1):1-8

15. Ashley RL, Wu L, Pickering JW, Tu MC, Schnorenberg L: Premarket evaluation of a commercial glycoprotein G-based enzyme immunoassay for herpes simplex virus type-specific antibodies. J Clin Microbiol. 1998 Jan;36(1):294-295

16. Brown ZA, Selke S, Zeh J, et al: The acquisition of herpes simplex virus during pregnancy. N Engl J Med. 1997 Aug 21;337(8):509-515

17. Binnicker MJ, Jespersen DJ, Harring JA: Evaluation of three multiplex flow immunoassays compared to an enzyme immunoassay for the detection and differentiation of IgG-class antibodies to herpes simplex virus types 1 and 2. Clin Vaccine Immunol. 2010 Feb;17(2):253-257

18. Dioverti MV, Razonable RR: Cytomegalovirus. Microbiol Spectr. 2016 Aug;4(4). doi: 10.1128/microbiolspec.DMIH2-0022-2015

19. Nath P, Kabir MA, Doust SK, Ray A: Diagnosis of Herpes simplex virus: Laboratory and point-of-care techniques. Infect Dis Rep. 2021 Jun 2;13(2):518-539

20. Notifiable Diseases and Mortality Tables. MMWR Morb Mortal Wkly Rep. 2016;65(3):ND-38

21. Wang ZD, Liu HH, Ma ZX, et al: Toxoplasma gondii infection in immunocompromised patients: A systematic review and meta-analysis. Front Microbiol. 2017 Mar 9;8:389

Detection of IgG-class antibodies to Toxoplasma gondii, rubella, cytomegalovirus, and herpes simplex virus types 1 and 2 is performed on the BioPlex 2200 system, which uses multiplex flow immunoassay technology. Five different populations of fluorescent dyed beads are each coated with antigens unique to each infectious organism. Patient sample is combined with sample diluent and the 5 bead set and incubated at 37 degrees C. During this time IgG antibodies will bind to the antigen-coated beads. After a wash cycle, a fluorescently labeled antihuman IgG antibody conjugate is added to the mixture and incubated at 37 degrees C. Following a wash step to remove unbound conjugate, the bead mixture is passed through a detector that identifies the bead based on dye fluorescence and determines the amount of antibody captured by the antigen based on fluorescence of the antihuman IgG conjugate. Raw data is calculated in relative fluorescence intensity and is converted to an antibody index (AI) for interpretation. Three additional dyed beads, an internal standard bead, a serum verification bead, and a reagent black bead are present in each reaction mixture to verify detector response, the addition of serum to the reaction vessel and the absence of significant nonspecific binding in serum, respectively.(Package inserts: BioPlex 2200 System, ToRC IgG and MMRV IgG, Bio-Rad Laboratories, Clinical Diagnostics Group, Hercules, CA. March 2012)

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This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

86644-CMV

86695-Herpes simplex, type 1

86696-Herpes simplex, type 2

86762-Rubella

86777-Toxoplasma