CMV Tests

Cytomegalovirus (CMV) testing is used to determine whether someone with signs and symptoms has an active CMV infection. Sometimes it may be ordered to help determine whether someone had a prior CMV infection.

CMV is a common virus that occurs widely throughout the population but rarely causes noticeable symptoms or significant health problems. However, primary CMV infection may cause serious illness and complications in newborns and people with weakened immune systems, such as transplant recipients, cancer patients, people receiving immunosuppressive drugs, and people with HIV. (See the "What is being tested?" section for more on this.)

There are a few different methods of detecting a CMV infection. The choice of tests and samples collected depends on the age of the person, their general health status and symptoms, and on the health practitioner's clinical findings and suspicions of organ involvement.

Antibody testing (serology)
Antibody testing is done on blood samples and can be used to determine if someone has had recent or past exposure. There are two types of CMV antibodies that are produced in response to a CMV infection, IgM and IgG, and one or both may be detected in the blood.

• IgM antibodies are the first to be produced by the body in response to a CMV infection. They are present in most individuals within a week or two after the initial exposure. IgM antibody production rises for a short time period and then declines. After several months, the level of CMV IgM antibody usually falls below detectable levels. Additional IgM antibodies are produced when latent CMV is reactivated.
• IgG antibodies are produced by the body several weeks after the initial CMV infection and provide protection from primary infections. Levels of IgG rise during the active infection, then stabilize as the CMV infection resolves and the virus becomes inactive. After a person has been exposed to CMV, the person will have some measurable amount of CMV IgG antibody in their blood for the rest of their life. CMV IgG antibody testing can be used, along with IgM testing, to help confirm the presence of a recent or previous CMV infection.

CMV antibody testing may be used to determine immunity to primary CMV infections for people prior to organ or bone marrow transplantation and for a person diagnosed with HIV/AIDS. Since CMV infection is widespread and causes few problems to those with healthy immune systems, general population screening is rarely done.

Antibody testing and viral CMV detection may be used to help diagnose primary CMV infection in young adults, pregnant women, and some immune-compromised people with flu- or mononucleosis-like symptoms. By comparing the absence or presence of IgG and IgM antibodies in the same sample or the amount of antibody present in samples collected on different days, a health practitioner may be able to distinguish between active and latent CMV.

Direct detection of CMV
Viral detection involves determining the presence of CMV in a blood, fluid, or tissue sample. This can be done either by culturing the virus or by detecting the virus's genetic material (CMV DNA). Viral detection is used to diagnose congenital infections in newborns and may be used to detect and/or confirm active infections in others.

Viral culture is the traditional method of virus detection. Presence of the virus (positive cultures) can often be determined in as little as 1 to 2 days, but cultures that are negative for the virus must be held for 3 weeks to confirm the absence of CMV because the virus may be present in very low numbers in the original sample and/or the CMV strain may be slow-growing.

Molecular methods such as polymerase chain reaction (PCR) may be used to detect and measure the amount of viral DNA in a person's sample. Testing can be qualitative, determining the presence or absence of CMV, or quantitative, measuring the amount of virus present.

Immune-compromised people with active CMV may be monitored using a variety of CMV tests. Often, health practitioners want a quantifiable viral test to be able to track the amount of virus present (viral load). They can use a quantitative test to monitor a person's response to antiviral therapy.

CMV tests may be ordered, along with tests for influenza, mononucleosis (mono), and EBV (Epstein-Barr virus), when a young adult, a pregnant woman, or an immune-compromised person has flu- or mono-like signs and symptoms such as:

• Fatigue, weakness
• Sore throat
• Swollen lymph nodes
• Fever
• Headache
• Muscle aches

Other less common but more serious signs include inflammation of the lungs, eyes, liver, spleen, and/or digestive tract.

One or more CMV tests may be ordered at intervals when a health practitioner is monitoring the effectiveness of antiviral therapy.

CMV culture or molecular testing may be done for a newborn with jaundice, anemia, an enlarged spleen and/or liver, and a small head; or for an infant with hearing and vision problems, pneumonia, seizures, and/or signs of delayed mental development.

When a person is a candidate for an organ or bone marrow transplant, CMV antibody testing may be ordered as a screening test to determine if the person has been exposed to CMV in the past.

Care must be taken when interpreting the results of CMV testing. A health practitioner evaluates the results in conjunction with clinical findings, including signs and symptoms. It can sometimes be difficult to distinguish between a latent, active or reactivated CMV infection. This is due to several reasons, including:

• A healthy person who has been infected with CMV at one time will continue to harbor the virus. The CMV can reactivate intermittently, often sub-clinically, shedding small amounts of virus into body fluids but not causing symptoms. 
• An immune-compromised person may not have a strong antibody response to the CMV infection; the person's IgM and IgG levels may be lower than expected even though the person has an active case of CMV. 
• The virus may not be present in sufficient number in the particular fluid or tissue tested to able to be detected.

Antibody testing
A positive CMV IgG and IgM in a symptomatic person means it is likely that the person has either recently been exposed to CMV for the first time or that a previous CMV infection has been reactivated. This can be confirmed by measuring IgG levels again 2 or 3 weeks later. A high level of IgG is not as important as a rising level. If there is a 4-fold increase in IgG between the first and second sample, then the person has an active CMV infection (primary or reactivated).

A positive CMV IgM and negative IgG means the person may have very recently been infected.

A negative IgG and/or IgM or low levels of the antibodies in someone who is symptomatic may mean that the person either has a condition other than CMV or that the person's immune system is not responding normally (not producing an adequate amount of antibody even if CMV is present).

The following table summarizes possible antibody testing results:

Viral detection
If a person is symptomatic and the culture is positive for cytomegalovirus, then the person likely has an active CMV infection. If the culture is negative, then the person's symptoms may be due to another cause or the amount of CMV virus in the sample is too low to detect.

If a test for CMV DNA is positive, then CMV is present and the person has an active infection. High levels of viral DNA tend to indicate a more invasive infection accompanied by serious symptoms while low levels indicate a CMV infection, usually one with no symptoms or ones that are mild. Like culture, negative results on a DNA test do not rule out CMV infection; the virus may be present in very low numbers or may not be present in the body sample tested.

When used to monitor effectiveness of treatment, decreasing viral loads reflect a response to antiviral treatment. Levels that do not drop in response to antiviral treatment might reflect a resistance to the therapy being used.

CMV is one of the conditions included in a TORCH testing panel. This panel of tests screens for a group of infectious diseases that can cause illness in pregnant women and may cause birth defects in their newborns. TORCH is an acronym for: Toxoplasmosis, Rubella, Cytomegalovirus, and Herpes simplex virus.

When blood transfusion is needed, certain patients, such as CMV-negative HIV/AIDS patients and CMV-negative heart/lung transplant candidates, should receive cellular blood products that have been tested negative for CMV antibodies (so-called CMV seronegative blood products).