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 cysts.

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.

Rubella:

Primary postnatal rubella infection (German or 3-day measles) is typically a mild, self-limiting disease characterized by a maculopapular rash, fever, malaise, and lymphadenopathy.

Conversely, primary prenatal rubella infections may have devastating results. In utero infections may severely damage the fetus, particularly if the infection occurs during the first 4 months of gestation. Congenitally infected infants may exhibit 1 or more defects including congenital heart disease and mental retardation.

Prior to the introduction of the rubella vaccines, approximately 15% of childhood sensorineural deafness and 2% of congenital heart defects were attributed to congenital rubella infection in both the United States and the United Kingdom. During the epidemic of 1962 to 1965, rubella infections during pregnancy were estimated to have caused 30,000 stillbirths and 20,000 malformed infants in the United States. The US rubella vaccination program, which calls for vaccination of all children, has significantly reduced the incidence of rubella.

Cytomegalovirus (CMV):

CMV is a significant cause of morbidity and mortality, especially in organ transplant recipients and individuals with AIDS.(1,2) 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 (EBV). Infection in immunocompromised hosts commonly results in more severe disease.

Herpes Simplex Virus (HSV):

The herpes virus family contains HSV types 1 and 2, varicella-zoster virus, CMV, EBV, and human herpesvirus 6, 7, and 8 (Kaposi sarcoma). 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.

Determination of rubella immune status in individuals >6 months of age

As an indication of past or recent infection with Toxoplasma gondii, cytomegalovirus, or herpes simplex virus in individuals >6 months of age

Toxoplasma:

Diagnosis of acute central nervous system, intrauterine, or congenital toxoplasmosis is difficult by routine serological methods. A single positive IgG result is only indicative of recent or previous infection and is present in up to 70% of the adult population in the United States.

The absence of IgG is helpful in that it usually indicates the absence of infection. However, a negative result could mean either no previous exposure or could also be seen in cases of remote exposure with subsequent loss of detectable antibody.

Seroconversion from negative to positive IgG is indicative of recent Toxoplasma gondii infection. Seroconversion indicates infection subsequent to the first negative specimen.

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

Rubella:

By early adulthood, approximately 80% to 90% of the population of the United States show serologic evidence of having experienced rubella diseases. Rubella vaccine is recommended for all children, many adolescents, and some adults (particularly females) unless it is specifically contraindicated. These facts indicate that the expected number of negative rubella serologies will be very low.

A positive result indicates prior immunization or exposure to the virus and immunity against rubella.

Seroconversion indicates infection subsequent to the first negative specimen.

Cytomegalovirus (CMV):

Individuals with negative CMV IgG results are presumed to have not experienced infection with CMV and, therefore, are susceptible to primary infection.

A single positive CMV IgG result indicates past or current CMV infection. Such individuals are potentially at risk of transmitting CMV infection through blood products; the likelihood of transmission by other modes is not known.

Seroconversion, determined by parallel testing of acute and convalescent phase specimens, is required to determine whether the infection is a current active infection or a past exposure. A ratio of > or =2 in paired sera (acute and convalescent) IgG values (ie, seroconversion), along with a convalescent antibody level of >6, is indicative of a recent infection. The infection may either be primary or a reactivation of a preexisting latent process with active viral excretion. Seroconversion indicates infection subsequent to the first negative specimen.

CMV infections are quite common. Approximately 60% to 85% of the population is believed to be infected by age 18.

Herpes Simplex Virus (HSV):

The presence of antibodies specific for HSV type 1 or 2 indicates infection with the corresponding serotype of the virus.

A single positive specimen only indicates exposure at some point in time (past or recent). Seroconversion, determined by parallel testing of acute and convalescent phase specimens, is required to determine whether the infection is a current active infection or a past exposure. Seroconversion indicates infection subsequent to the first negative specimen.

This profile is not useful for diagnosing infection in infants <6 months of age. IgG antibodies in this age group are usually the result of passive transfer from the mother.

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

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

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

Toxoplasma:

-A single Toxoplasma IgG antibody assay cannot be used to diagnose recent infection.

-The IgM assay TOXOM/8865 Toxoplasma Antibody, IgM, Serum should be used to diagnose recent infection.

Rubella:

The presence of antirubella IgG antibodies does not exclude the possibility of an ongoing infection. Testing of acute- and convalescent-phase paired sera may be used to diagnose recent infection.

This assay should be used primarily to determine the immune status of an individual through the detection of antirubella IgG-class antibodies.

For possible congenital rubella infections in infants <6 months of age, communicate directly with your State Health Laboratory or the Centers for Disease Control and Prevention to arrange appropriate testing and follow-up. Mayo Medical Laboratories no longer performs IgM testing for the laboratory assessment of acute rubella infection. Because of the low prevalence of rubella in the United States, testing for antirubella IgM antibodies is of limited clinical value and may yield false-positive results, which can negatively impact patient care.

Cytomegolvirus (CMV):

Sera drawn very early in the acute stage of disease may have IgG levels <4 AU/mL.

The assay demonstrates a linear dilution response to concentration. However, no international standard has been established.

Positive IgG test results from cord blood should be interpreted with caution. The presence of IgG antibodies in cord blood is usually the result of passive transfer from the mother to the fetus. A negative test, however, may be useful in excluding current infection.

The IgG titer of a single specimen should not be used to aid in the diagnosis of recent infection. Paired (acute and convalescent) specimens should be drawn and tested concurrently to detect seroconversion.

Lack of a significant increase in IgG antibody level does not exclude the possibility of CMV infection.

Herpes Simplex Virus (HSV):

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/80575 Herpes Simplex Virus (HSV), Molecular Detection, PCR).

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 or 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-1 and HSV-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 ANTIBODY, IgG

<4 IU/mL (negative)

4-7 IU/mL (equivocal)

> or =8 IU/mL (positive)

RUBELLA ANTIBODIES, IgG

Negative

CYTOMEGALOVIRUS (CMV) ANTIBODIES, IgG

<4 AU/mL (negative)

4-5 AU/mL (equivocal)

> or =6 AU/mL (positive)

A convalescent IgG antibody level of >6 AU/mL combined with a ratio of > or =2 in a paired sera (seroconversion) IgG titer indicates recent infection. The presence of only IgG antibodies generally indicates past infection with CMV.

HERPES SIMPLEX VIRUS (HSV) TYPE 1, IgG

Negative (reported as positive, negative, or equivocal)

HERPES SIMPLEX VIRUS (HSV) TYPE 2, IgG

Negative (reported as positive, negative, or equivocal)

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