What is being tested?

Cytomegalovirus (CMV) is a common virus that occurs widely but rarely causes symptoms. In Australia, by the age of 20 years, around 50% of adults have been infected with CMV and this proportion increases with age. Most people are infected as children or as young adults and do not experience any significant symptoms or health problems.

CMV may be found in many body fluids during an active infection, including saliva, urine, blood, breast milk, semen, vaginal secretions, and cerebrospinal fluid. It is easily transmitted to others through close physical contact or possibly by contact with infected objects, such as nappies or toys. After the initial "primary" infection has resolved, CMV becomes dormant or latent - like other members of the herpes virus family. Cytomegalovirus remains in a person for the rest of his life without causing any symptoms, unless the person's immune system is significantly weakened. If this happens, the virus can reactivate.

CMV can cause notable health problems in three situations:

• Most people who have symptoms from a primary CMV infection may cause a flu-like or glandular fever-like illness. This condition, which causes symptoms such as extreme fatigue, fever, chills, body aches and/or headaches, usually resolves within a few weeks. 
• CMV infection acquired antenatally (during pregnancy) may cause serious physical and developmental problems that may be first noticed in infants or young children. This occurs most commonly when women are infected for the first time (primary infection) during pregnancy and the infection is passed  to the developing baby across the placenta. Most newborns (around 90%) that are infected before birth appear healthy at birth and most remain well, but a small proportion may develop hearing problems or delayed mental development later. A few babies may be stillborn, while others may have symptoms at birth such as jaundice, anaemia, low platelets, an enlarged spleen or liver, a small head or hearing loss.
• In those with weakened immune systems, CMV can cause serious illness and death. This includes those with advanced HIV/AIDS, those who have had organ or bone marrow transplants and those undergoing chemotherapy treatment for cancer. If these people immune systems who become infected for the first time (primary infection) might experience the most severe symptoms, and their CMV infection may remain active.
• Those who have been exposed to CMV previously may reactivate their infection. This could affect their eyes (causing inflammation of the retina, which can lead to blindness), digestive tract (causing bloody diarrhoea and abdominal pain), lungs (causing pneumonia with a cough and shortness of breath), and brain (causing encephalitis). There can also be spleen and liver involvement, and those who have had organ or bone marrow transplants may experience some degree of rejection. Active CMV also further depresses the immune system, potentially allowing other secondary infections, such as fungal infections, to occur.

CMV testing involves either a measurement of antibodies to CMV, or the detection of the virus itself. The virus can be identified during an active infection by culturing CMV or more commonly, by detecting the virus's genetic material (its DNA) in a fluid or tissue sample with a process known as polymerase chain reaction testing or PCR.

How is it used?

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

There are a few different methods of detecting a CMV infection:

Antibody testing
Antibody testing 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 usually declines. After several months, the level of CMV IgM antibody usually falls below detectable levels. Additional IgM antibodies are produced when CMV is reactivated in an immunocompromised person.
• 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 stabilise as the CMV infection resolves and the virus becomes inactive. After a person has been exposed to CMV, they 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.
• Sometimes, IgM antibodies to CMV remain positive for prolonged periods (many months), in conjunction with positive IgG antibodies. It may be important to determine when primary infection occurred, such as in the case of a pregnant woman, with risk of congenital infection in the foetus. In this situation, another test called IgG avidity may be performed to indicate whether the infection occurred within the last 3-4 months.

CMV antibody testing may be used to determine immunity to primary CMV infections in people prior to organ or bone marrow transplantation and in 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 in some immune-compromised people with flu-like 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, the doctor may be able to distinguish between active and latent CMV.

Testing for IgM antibodies may be used to detect a congenital infection in a newborn, usually in conjunction with tests that detect the virus directly.

Viral detection
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) by PCR.

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 are frequently used to detect CMV in a person's sample. Testing can be qualitative, determining the presence or absence of CMV, or quantitative, measuring the amount of virus present.

The choice of tests and samples collected depends on the age of the person, their general health status and symptoms, and on the doctor's clinical findings and suspicions of organ involvement. For instance, a newborn's urine or saliva may be tested by PCR or cultured to detect CMV, while a pregnant woman may have IgG and IgM (+/- IgG avidity) blood testing to identify the presence of antibodies and to distinguish between a current primary infection and a previous infection. For diagnosis of congenital infection, tests that detect the virus directly must be performed to confirm the diagnosis and these samples should be collected within 21 days of birth to confirm congenital, rather than postnatal infection. Sometimes the baby’s routinely collected newborn screening test card can be tested for virus to make this diagnosis retrospectively.

Immune-compromised people with active CMV may be monitored using a variety of CMV tests. Often doctors want a quantifiable viral (PCR) 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.

When is it requested?

CMV tests may be ordered, along with tests for influenza and EBV (Epstein Barr virus), when a person has flu for glandular fever-like signs and symptoms such as:

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

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

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

CMV testing may be done on a newborn with jaundice, anaemia, low platelets, an enlarged spleen and/or liver, and a small head; or on 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.

What does the result mean?

Care must be taken when interpreting the results of CMV testing. The doctor 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 – their IgM and IgG levels may be lower than expected even though they have 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
If both CMV IgG and IgM are present in a symptomatic person, then it is most likely that they have 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 to 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).

Another test which may be ordered in this setting is IgG avidity testing. This test measures the strength of a person’s IgG antibodies towards CMV, as these antibodies become more “avid” or, tightly binding, with time. Thus, a low avidity suggests recent infection and a high avidity indicates an infection which occurred before to about 4 months prior.

If only IgM is present, then the person may have very recently been infected. If someone is symptomatic but has low or undetectable levels of IgG and/or IgM, it may mean that they either have a condition other than CMV or that their 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 PCR or culture is positive for cytomegalovirus, then the person likely has an active CMV infection. If the PCR 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. 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 PCR 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 but at a different site of the body.

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.

Is there anything else I should know?

CMV is one of the conditions traditionally included in a "TORCH" testing panel. This group 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, Other (usually refers to Syphilis), 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).

Common questions

• How can I tell if my CMV has reactivated?

If you are a reasonably healthy person, you will probably not have a symptomatic reactivation or may have mild flu-like symptoms. If you are immune-compromised, you may have more serious symptoms associated with your lungs, digestive tract, or eyes. In this case, it is important to talk to your doctor about your health concerns.

• If I have or had CMV, can I spread it to others?

If you have a new or prior infection with CMV, you can spread it to others even if you aren't showing signs or symptoms. Nevertheless, you must be in close contact with others in order to transmit the virus. It can be spread through several types of body fluids, including saliva, breast milk, vaginal fluids, semen, urine, and blood.

• Is there any way to prevent getting CMV?

Careful hygiene such as hand washing can help prevent transmission of the virus. However, CMV is very common and many people were infected when they were children. It has been estimated that as many as 70% of children in daycare have been exposed to CMV.

More information

RCPA Manual: Cytomegalovirus detection

RCPA Manual: Cytomegalovirus antibody