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Interpretive Handbook

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Test 61859 :
ToRCH Profile IgG, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Toxoplasma gondii:

Toxoplasma gondii is an obligate intracellular protozoan parasite that is 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, Toxoplasma gondii can remain latent for the life of the host; the risk for reactivation is highest among immunosuppressed individuals.

 

Seroprevalence studies performed in the United States indicate that approximately 9% to 11% of individuals between the ages of 6 and 49 have antibodies to Toxoplasma gondii.(2) Infection of immunocompetent adults is typically asymptomatic. In symptomatic cases, patients most commonly 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 involved 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 and self-limited, and is characterized by a maculopapular rash beginning on the face and 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, 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 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 (cdc.gov/rubella). Immunity may however wane with age as approximately 80% to 90% of adults will show serologic evidence of immunity to rubella.

 

Cytomegalovirus (CMV):

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.(9) 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.(10,11) 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 HSV).

 

CMV seroprevalence increases with age. In the United States the prevalence of CMV-specific antibodies increases from approximately 36% to over 91% in adolescents between the ages of 6 and 11 and adults over 80 years old, respectively.(12)

 

Herpes Simplex Virus (HSV) Types 1 and 2:

HSV types 1 and 2 are members of the Herpesviridae, and produce infections that may 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 HSV infections is routinely made based on clinical findings and supported by laboratory testing using PCR 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.(13) 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.(14,15)

Useful For Suggests clinical disorders or settings where the test may be helpful

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

 

As an indication of 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

Interpretation Provides information to assist in interpretation of the test results

Toxoplasma gondii:

A positive Toxoplasma IgG result is indicative of current or past infection with Toxoplasma 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 Toxoplasma 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 Toxoplasma gondii infection subsequent to the first negative specimen.

 

Recent or acute infection with Toxoplasma gondii can be evaluated with TOXMP / Toxoplasma gondii Antibody, IgM, Serum assay.

 

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 (CMV):

Positive 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 (HSV):

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

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Toxoplasma gondii:

Sera drawn very early during the acute stage of infection may have Toxoplasma IgG levels <9 IU/mL.

 

The Toxoplasma IgG assay should not be used alone to diagnose recent Toxoplasma 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 drawn early during the acute phase of infection or shortly (1-2 weeks) following vaccination may be negative for IgG class antibodies.

 

Cytomegalovirus (CMV):

Sera drawn very early during the acute stage of infection may have undetectable levels of 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 Toxoplasma gondii IgG have not be ruled out.

 

Herpes Simplex Virus (HSV) Types 1 and 2:

Detection of IgG-class antibodies to 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 PCR (LHSV / Herpes Simplex Virus [HSV], Molecular Detection, PCR).

 

Serum specimens drawn 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 drawn 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.)

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Toxoplasma ANTIBODY, IgG

Toxoplasma Ab, IgG

Negative

 

Toxoplasma IgG VALUE

< 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

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Tenter AM, Heckeroth AR, Weiss LM: Toxoplasma gondii: from animals to humans. Int J Parasitol 2000;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;77(3):405-410

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

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

5. American Academy of Pediatrics. Rubella. In Red Book. 2012 Report of the Committee on Infectious Diseases. Edited by LK Pickering. Elk Grove Village, IL 2012

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

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

8. Morbidity and Mortality Weekly Report: Notifiable Diseases and Mortality Tables. 2012:61(34):466-479

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

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

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

12. Staras SA, Dollard SC, Radford KW, et al: Seroprevalence of cytomegalovirus infection in the United States, 1998-1994. Clin Infect Dis 2006;43(9):1143-1151

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

14. Ashley RL, Wu L, Pickering JW, et al: Premarket evaluation of a commercial glycoprotein G-based enzyme immunoassay for herpes simplex virus type-specific antibodies. J Clin Microbiol 1998;36:294-295

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

16. Binnicker MJ, Jespersen DJ, Harring JA: Comparative evaluation of three multiplex flow immunoassays to enzyme immunoassay for the detection and differentiation of IgG-class antibodies to Herpes Simplex Virus types 1 and 2. Clin Vaccine Immunol 2010;17(2):253-257


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