Interpretive Handbook

Toxoplasma:

Toxoplasma gondii is an obligate intracellular 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 soil and become infectious. Toxoplasmosis is acquired by humans via ingestion of food or water contaminated with cat feces or undercooked meats containing oocysts.

Infection of the normal adult is commonly asymptomatic. In cases with clinical manifestations, the most common symptom is lymphadenopathy, which may be accompanied by an array of other symptoms making differential diagnosis difficult.

Severe-to-fatal infections do occur in adults immunocompromised by cancer chemotherapy or other immunosuppressive treatment and in patients with AIDS. These infections are thought to be caused by reactivation of latent infections and often involve the central nervous system.

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. 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.

Cytomegalovirus (CMV):

CMV is a significant cause of morbidity and mortality, especially in organ transplant recipients and individuals with AIDS. CMV is also responsible for congenital disease of the newborn.

Infections with CMV result from reactivation of latent virus from a previous infection, transmission of the virus from a donor organ or blood product, or initial or primary contact with the virus in a seronegative patient. Infection in immunologically normal patients can cause mononucleosis similar to that produced by infection with Epstein-Barr virus. Infection in immunocompromised hosts commonly results in more severe disease.

Herpes Simplex Virus (HSV):

HSV types 1 and 2 produce infections that are expressed in various clinical manifestations ranging from mild stomatitis to disseminated and fatal disease. The more common clinical conditions 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 is the cause of the majority of urogenital infections and is almost exclusively found in adults. Type 1 HSV is associated closely with orolabial infection, although genital infection with this virus can be common in some populations.

Aids in the diagnosis of both congenital and acute acquired toxoplasmosis, cytomegalovirus, and herpes simplex virus

Toxoplasma:

Diagnosis of acute central nervous system, intrauterine, or congenital toxoplasmosis is difficult by routine serological methods. Active toxoplasmosis is suggested by the presence of IgM antibodies, but elevated anti-IgM titers are often absent in immunocompromised patients. In addition, elevated IgM can persist from an acute infection that may have occurred as long ago as 1 year.

A suspected diagnosis of acute toxoplasmosis should be confirmed by further testing at a toxoplasmosis reference laboratory or by detection of Toxoplasma gondii DNA by PCR analysis of cerebrospinal fluid or amniotic fluid specimens (PTOX/81795 Toxoplasma gondii, Molecular Detection, PCR).

For confirmation of a diagnosis, the FDA issued a Public Health Advisory (7/25/1997) suggesting that sera found to be positive/equivocal for Toxoplasma gondii IgM antibody be sent to a Toxoplasma reference laboratory. CDC or Jack Remington, M.D., Palo Alto Medical Foundation, 860 Bryant Street, Palo Alto, CA 94301, were recommended. (reviewed 12/2011)

Specimens interpreted as equivocal may contain very low levels of IgM. A second specimen should be drawn and tested.

Cytomegalovirus (CMV):

Negative CMV IgM results suggest that an individual is not experiencing a recent infection. However, a negative result does not rule out primary CMV infection. It has been reported that CMV-specific IgM antibody was not detectable in 10% to 30% of cord blood sera from infants demonstrating infection in the first week of life. In addition, up to 23% of pregnant women with primary CMV infection did not demonstrate detectable CMV IgM responses within 8 weeks postinfection. In cases of primary infection where the time of seroconversion is not well defined, as high as 28% of pregnant women did not demonstrate CMV IgM antibody.

Positive CMV IgM results indicate a recent infection (primary, reactivation, or reinfection).

IgM antibody responses in secondary (reactivation) CMV infections have been demonstrated in some CMV mononucleosis patients, in a few pregnant women, and in renal and cardiac transplant patients with secondary rather than primary infections.

Herpes Simplex Virus:

Presence of IgM class antibodies indicates recent infection.

Results must be used in conjunction with clinical symptoms and patient history.

Positive test results may not be valid in persons who have received blood transfusions or other blood products in the past several months.

Toxoplasma:

Negative results do not preclude recent primary Toxoplasma gondii infection. A negative result could indicate either no previous exposure or also could be seen in cases of remote exposure with subsequent loss of detectable antibody. A second specimen drawn at a later point in time may be needed to rule out a recent infection.

Positive serologic results alone are not diagnostic of Toxoplasma gondii infection. For example, infections with Epstein-Barr virus (EBV) have been suspected to elicit antigen-specific IgM responses (eg, false-positive IgM Toxoplasma reactions) in individuals previously sensitized to a variety of non-EBV infectious agents.

Since persisting IgM levels may be detected long after the onset of acquired infection, the use of a single serological test result must be used with caution in those cases when it is critical to establish the time of infection. This applies to the diagnosis of acute Toxoplasma gondii infection acquired during pregnancy. Determination of the date of infection based solely on the results of detectable IgM antibody to Toxoplasma gondii is not recommended. That determination should include clinical history and previous serology, since low levels of IgM antibody may persist for a year or more. The use of a test to determine a rise in IgG antibody to Toxoplasma gondii (TOXOG/8267 Toxoplasma Antibody, IgG, Serum or TOXGM/81647 Toxoplasma Antibody IgG and IgM, Serum) may provide additional information as to the date of infection. Therefore, the Food and Drug Administration (FDA) has instructed commercial suppliers of Toxoplasma IgM kits to recommend Toxoplasma IgG testing also be performed.

Cytomegalovirus (CMV):

IgM responses can vary from patient-to-patient. A negative result does not preclude the possibility of recent primary CMV infection.

Serum specimens with total IgG concentrations of > or =20 mg/mL may cause interference in the CMV IgM assay.

A specimen drawn late after the convalescent stage of infection may not contain detectable levels of IgM antibodies to CMV. Because CMV IgM antibody may persist for many months after primary infection, its detection in a single serum specimen is of limited value in determining the timing when infection occurred. Negative results do not preclude recent infection by CMV.

This test should not be used as a general screen in the absence of clinical symptoms or known exposure.

EBV is known to be a potent B-cell stimulator. Infections with EBV have been suspected to elicit antigen-specific IgM responses in individuals previously sensitized to a variety of non-EBV infectious agents.

Herpes Simplex Virus (HSV):

Individuals infected with HSV may not exhibit detectable levels of IgM antibody in the early stages of infection.

This assay does not discriminate between antibodies to HSV-1 and HSV-2.

Toxoplasma ANTIBODY, IgM

Test value threshold <0.55 is negative

Test value threshold > or =0.55-<0.65 is equivocal

Test value threshold > or =0.65 is positive

CYTOMEGALOVIRUS (CMV) ANTIBODIES, IgM

Negative (reported as positive or negative)

The presence of IgM class antibodies indicates recent infection.

HERPES SIMPLEX VIRUS (HSV) ANTIBODY, IgM, BY IMMUNOFLUORESCENCE ASSAY (IFA)

Negative

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