If your doctor suspects you presently have, or recently had, a cytomegalovirus (CMV) infection or if it is important to know if you have ever had a CMV infection – such as prior to receiving an organ transplant
When a young adult, a pregnant female, or an immune-compromised patient has typical symptoms that suggest a CMV infection (tiredness, fever, jaundice); when a newborn has multiple congenital anomalies, unexplained jaundice or anaemia, and/or when an infant has seizures or developmental problems that may be due to CMV
The sample required depends on whether testing is being done to determine the presence of antibody or to detect the virus itself and on the health status of the patient. Antibody testing requires a blood sample, obtained by inserting a needle into a vein in the arm. Viral detection may be done on a variety of samples, including urine, blood, or sputum. Some samples may require a special procedure to collect amniotic fluid, duodenal fluid, cerebrospinal fluid, or body tissue (biopsy).
No test preparation is needed.
Cytomegalovirus (CMV) testing is requested to determine whether someone is currently, or has recently been, infected with CMV. It may also sometimes be used to determine whether someone has ever been exposed to CMV. Testing for CMV involves either a measurement of CMV antibodies (immune proteins created in response to CMV exposure) or by the detection of the virus itself. The virus is detected during an active infection by detecting the genetic material of the virus (its DNA).
In the United Kingdom, as many as 50% to 85% of adults have been infected with CMV. Most people are infected as children or young adults and do not experience any significant symptoms or health problems, but the most common symptoms are fever, tiredness and jaundice. CMV is found in many body fluids during an active infection, including saliva, urine, blood, breast milk, semen, cervical secretions, and cerebrospinal fluid. It is easily transmitted to others through sexual contact and sharing saliva or 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 family. Cytomegalovirus remains in a patient for the rest of their life without causing any symptoms, unless the virus reactivates when a patient’s immune system is compromised.
CMV can cause problems in three areas:
- In young adults, the initial primary CMV infection may cause an illness characterised by fever, tiredness or jaundice; it usually resolves within a few weeks but can cause prolonged illness with fever and sweating.
- In infants, primary CMV infection may cause serious physical and developmental problems when women are first infected during pregnancy and then pass the infection to infants across the placental barrier. Most foetuses (about 90%) that are infected appear perfectly normal at birth but may develop hearing or vision problems, pneumonia, seizures, and/or delayed mental development a few months later. A few babies may be stillborn, while others may have symptoms at birth such as jaundice, anaemia, an enlarged spleen or liver, and a small head. Some of these signs and symptoms will resolve with time, but others may persist.
- In those with compromised immune systems, CMV may cause serious illness and death. This includes those with HIV/AIDS, those who have had organ or bone marrow transplants, and those undergoing chemotherapy treatment for cancer. Patients with compromised immune systems who become infected for the first time may experience more severe symptoms, and the CMV infection may remain active. Those who have been exposed to CMV previously may reactivate their infection. This may affect their eyes (causing inflammation of the retina, which can lead to blindness), gastrointestinal tract (causing bloody diarrhoea and abdominal pain), lungs (causing pneumonia with a non-productive 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, allowing other secondary infections, such as fungal infections, to occur.
How is it used?
There are several methods of detecting a cytomegalovirus (CMV) infection:
Two types of CMV antibodies may be found in the blood: IgM and IgG. 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 declines. Eventually, after several months, the level of CMV IgM antibody usually falls below detectible levels. IgM is sometimes produced when latent CMV is reactivated. IgG antibodies are produced by the body several weeks after the initial CMV infection. Levels of IgG rise during the active infection, then stabilize as the CMV infection resolves and the virus becomes inactive. Once 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.
CMV antibody testing may be performed to determine immunity to CMV in pregnant women, in patients 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 intact immune systems, general population screening is rarely done.
IgM and IgG antibody testing and viral CMV detection may be used to help diagnose primary CMV infection in young adults, pregnant women, and some immune-compromised patients with typical symptoms. By comparing the absence or presence of both IgG and IgM in the same sample, the doctor can distinguish between primary, latent, and reactivated CMV in symptomatic patients.
Viral detection involves finding CMV in a blood, fluid, or tissue sample. This can be done either by culturing the virus in a supportive environment or more usually by detecting the virus’s genetic material (CMV DNA).
Viral culture is the traditional method of virus detection, but is seldom used these days. It involves inoculating a culture/tube of human cells with the patient’s sample and incubating the culture in an incubator. Positive cultures can often be detected in 7 days, but negatives 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.
Other methods (polymerase chain reaction – PCR) may be used to detect and measure the amount of viral DNA in a patient’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 body samples collected depends on the age of the patient, their general health status and symptoms, and on the doctor’s clinical findings and suspicions of organ involvement. For instance, a newborn’s urine may be cultured to detect CMV virus, while a pregnant woman may have IgG and IgM blood testing to identify the presence of antibodies and to distinguish between a current primary infection and a previous infection. A second IgG test on a new blood sample requested 2 to 3 weeks after the initial test (called a convalescent sample) is performed to determine whether antibody levels are rising/falling, indicating a recent CMV infection.
Immune-compromised patients with active CMV may be monitored using a variety of CMV tests. Often doctors want a quantifiable viral test to be able to track the amount of virus present (viral load). They can use a quantitative test to predict and monitor the patient’s response to antiviral therapy.
When is it requested?
CMV tests may be requested, along with tests for influenza, mononucleosis (mono), and EBV (Epstein Barr virus), when a young adult, a pregnant female, or an immune-compromised patient has flu- or mononucleosis-like symptoms such as fatigue, swollen lymph nodes, and fever or jaundice. They may be performed when your doctor suspects that you may have an active primary CMV infection or a CMV reactivation.
CMV tests may be requested when you are immune-compromised and have inflammation of the lungs, eyes, liver, spleen, and/or gastrointestinal tract and when your doctor suspects that you may have active CMV. One or more CMV tests may be requested when your doctor is monitoring the effectiveness of antiviral therapy.
CMV testing may be done on a newborn with jaundice, anaemia, 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 you are a candidate for an organ or bone marrow transplant, CMV IgG and IgM antibody testing may be used as a screening test to determine if you have been exposed to CMV in the past.
What does the test result mean?
Care must be taken when interpreting the results of CMV testing. The doctor evaluates the results in conjunction with clinical findings. It can sometimes be difficult to distinguish between a latent and active CMV infection. This is due to several reasons, including:
- A healthy patient who has been infected with CMV at one time will continue to harbour the virus. The CMV can reactivate intermittently, often sub-clinically, shedding small amounts of virus into body fluids but not causing symptoms.
- An infant and some immune-compromised people 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. Ironically, patients who have received solid organ transplants - kidney, liver, heart or lung - produce a strong and prolonged IgM response.
- The virus may not be present in sufficient numbers in the particular fluid or tissue tested to able to be detected.
If both CMV IgG and IgM are present in a symptomatic patient, then it is likely that he or she 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 patient has an active CMV infection (primary or reactivated).
If only IgM is present, then the patient may have very recently been infected. If a newborn has IgM antibodies, then they have a congenital CMV infection. If a patient 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. CMV IgM tests can be non-specific (as can those for EBV), which makes it essential that these tests are interpreted by an experienced healthcare professional.
If the patient is symptomatic and the culture is positive for cytomegalovirus, then the patient likely has an active CMV infection. If the culture is negative, then the patient’s symptoms may be due to another cause or the CMV virus is not detectable in this sample.
If a test for CMV DNA is positive, then CMV is present. High levels of viral DNA tend to indicate an active infection. Low levels indicate a CMV infection but may not indicate a symptomatic condition. Decreasing concentrations (diminishing viral loads) reflect response to antiviral treatment. Levels that do not drop in response to antiviral treatment may reflect a resistance to the therapy being used. Negative results 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.
How can I tell if my CMV has reactivated?
If you are a reasonably healthy person, you will probably not have a symptomatic reactivation. If you are immune-compromised, you may have more serious symptoms associated with your lungs, gastrointestinal tract, or eyes. In this case, it is important to talk to your doctor about your health concerns.
Is there any way to prevent getting CMV?
Careful hygiene can help prevent transmission of the virus. But, since CMV is very common, is present in most body fluids, and is passed through close contact, most people are infected when they are babies. It has been estimated that as many as 70% of children in daycare have been exposed to CMV. Not sharing drinking vessels and bottles is wise, since CMV is readily transmitted via saliva.