What is being tested?
Epstein-Barr virus (EBV) is a virus that typically causes a mild to moderate illness. Blood tests for Epstein-Barr virus detect antibodies to EBV in the blood and help establish a diagnosis of EBV infection.
Epstein-Barr virus causes an infection that is very common. According to the Centers for Disease Control and Prevention (CDC), most people in the United States are infected by EBV at some point in their lives. The virus is very contagious and easily passed from person to person. It is present in the saliva of infected individuals and can be spread through close contact such as kissing and through sharing utensils or cups.
After initial exposure to EBV, there is a period of several weeks before associated symptoms may appear, called the incubation period. During the acute primary infection, the virus multiplies in number. This is followed by a decrease in viral numbers and resolution of symptoms, but the virus never completely goes away. Latent EBV remains in the person’s body for the rest of that person’s life and may reactivate but usually causes few problems unless the person’s immune system is significantly weakened.
Most people are infected by EBV in childhood and experience few or no symptoms. However, when the initial infection occurs in adolescence, it can cause infectious mononucleosis, commonly called mono, a condition associated with fatigue, fever, sore throat, swollen lymph nodes, an enlarged spleen, and sometimes an enlarged liver. These symptoms occur in about 25% of infected teens and young adults and usually resolve within a month or two.
People with mono are typically diagnosed by their symptoms and the findings from a complete blood count (CBC) and a mono test (which tests for a heterophile antibody). About 25% of those with mono do not produce heterophile antibodies and will have a negative mono test; this is especially true with children. Tests for EBV antibodies can be used to determine whether or not the symptoms these people are experiencing are due to a current infection with the EBV virus.
EBV is the most common cause of mono. According to the CDC, examples of other causes of mono include cytomegalovirus (CMV), hepatitis A, hepatitis B or hepatitis C, rubella, and toxoplasmosis. Sometimes, it can be important to distinguish EBV from these other illnesses. For instance, it may be important to diagnose the cause of symptoms of a viral illness in a pregnant woman. Testing can help to distinguish a primary EBV infection, which has not been shown to affect a developing baby, from a CMV, herpes simplex virus, or toxoplasmosis infection, as these illnesses can cause complications during the pregnancy and may harm the fetus.
It can also be important to rule out EBV infection and to look for other causes of the symptoms. Those with strep throat, an infection caused by group A streptococcus, for instance, need to be identified and treated with antibiotics. A person may have strep throat instead of mono or may have both conditions at the same time.
Several tests for different types and classes of EBV antibodies are available. The antibodies are proteins produced by the body in an immune response to several different Epstein-Barr virus antigens. During a primary EBV infection, the level of each of these EBV antibodies rises and falls at various times as the infection progresses. Measurement of these antibodies in the blood can aid in diagnosis and typically provides the healthcare practitioner with information about the stage of infection and whether it is a current, recent, or past infection.
|Antibody||Timing of when the antibody is typically detected in the blood|
|Viral Capsid Antigen (VCA)-IgM antibody||Appears first after exposure to the virus and then tends to disappear after about 4 to 6 weeks|
|VCA-IgG antibody||Emerges during acute infection with the highest level at 2 to 4 weeks, then drops slightly, stabilizes, and is present for life|
|Early Antigen (EA-D) antibody||Appears during the acute infection phase and then tends to disappear; about 20% of those infected will continue to have detectable quantities for several years after the EBV infection has resolved.|
|Epstein-Barr Nuclear Antigen (EBNA) antibody||Does not usually appear until the acute infection has resolved; it develops about 2 to 4 months after the initial infection and is then is present for life.|
How is the test used?
Blood tests for Epstein-Barr virus (EBV) antibodies are used to help diagnose EBV infection, the most common cause of infectious mononucleosis (mono), if a person is symptomatic but has a negative mono test.
In pregnant women with symptoms of a viral illness, one or more EBV antibody tests may be ordered along with tests for cytomegalovirus (CMV), toxoplasmosis, and other infections (sometimes as part of a TORCH screen) to help distinguish between EBV and conditions that may cause similar symptoms.
These tests may be ordered for an asymptomatic person to see if that person has been previously exposed to EBV or is susceptible to a primary EBV infection. This is not routinely done, but it may be ordered when someone, such as an adolescent or an immunocompromised person, has been in close contact with a person who has mono.
The Centers for Disease Control and Prevention (CDC) recommend ordering several tests to help determine whether a person is susceptible to EBV or to detect a recent infection or a prior infection, or a reactivated EBV infection. These tests include:
- Viral capsid antigen (VCA)-IgM
- D early antigen (EA-D)
- Epstein Barr nuclear antigen (EBNA)
When is it ordered?
EBV antibody tests may be ordered when someone has symptoms suggesting mono but a negative mono test and when a pregnant woman has flu-like symptoms and her healthcare provider wants to determine whether the symptoms are due to EBV or another microbe. Some signs and symptoms associated with mono include:
- Extreme weakness or fatigue
- Sore throat
- Swollen lymph glands in the neck and/or armpits
- Enlarged spleen and/or liver (sometimes)
Testing may be ordered when a healthcare practitioner wants to establish previous exposure to EBV. Testing may occasionally be repeated when the healthcare provider wants to track antibody concentrations (titers) and/or when the first test was negative but the healthcare practitioner still suspects that the person’s symptoms are due to EBV.
What does the test result mean?
Care must be taken when interpreting results of EBV antibody testing. The signs and symptoms as well as the medical history of the person tested must be taken into account. A healthcare practitioner may consult a specialist in infectious diseases, specifically one who is experienced with EBV testing.
If someone is positive for VCA-IgM antibodies, then it is likely that the person has an EBV infection and it may be early in the course of the illness. If the individual also has symptoms associated with mono, then it is most likely that the person will be diagnosed with mono, even if the mono test was negative.
If someone has positive VCA-IgG and EA-D IgG tests, then it is highly likely that the person has a current or recent EBV infection.
If the VCA-IgM is negative but VCA-IgG and an EBNA antibody are positive, then it is likely that the person tested had a previous EBV infection.
If an individual is asymptomatic and negative for VCA-IgG, then that person has likely not been previously exposed to EBV and is vulnerable to infection.
In general, rising VCA-IgG levels tend to indicate an active EBV infection, while falling concentrations tend to indicate a recent EBV infection that is resolving. However, care must be taken with interpreting EBV antibody concentrations because the amount of antibody present does not correlate with the severity of the infection or with the length of time it will last. High levels of VCA-IgG may be present and may persist at that concentration for the rest of a person’s life.
Below, examples of some results are provided in table form.
|VCA-IgM||VCA-IgG||EA-D, IgG||EBNA, IgG||Possible Interpretation|
|Negative||Negative||Negative||Negative||No infection, symptoms due to another cause, susceptible to EBV infection|
|Positive||Positive||Negative||Negative||Early, primary infection|
|Negative or positive||Positive||Positive||Negative||Active infection, though EA-D IgG may persist for life in about 20% of people|
|Negative||Positive||Positive||Positive||May indicate reactivation of virus|
Is there anything else I should know?
The most common complication of mono is a ruptured spleen. Other complications of EBV infection that can occur include trouble breathing due to a swollen throat and, rarely, jaundice, skin rashes, pancreatitis, seizures, and/or encephalitis. EBV is also associated with, and may play a role in, several rare forms of cancer, including Burkitt’s lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma, as well as multiple sclerosis and fibromyalgia.
Reactivation of the virus is rarely a health concern unless the person is significantly and persistently immunocompromised, as may happen in those who have HIV/AIDS or organ transplant recipients. Primary infections in these people can be more severe, and some may experience chronic EBV-related symptoms.
How is Epstein-Barr virus (EBV) infection or infectious mononucleosis (mono) treated?
Care is largely supportive and typically includes plenty of rest and fluids as well as treatment of the symptoms. Avoiding any contact sports or heavy lifting for several weeks to months may be recommended to avoid spleen rupture. There are no anti-viral medications available to speed healing; however, anti-virals and steroids can be used to treat symptoms in severe cases. At present, there is no vaccine for EBV, but clinical trials are underway.
Do adults get mono?
They do, but it is rare because most have already been infected with EBV at an earlier age. When they do, they tend to have less lymph node swelling and sore throat and more liver enlargement and jaundice.
Do EBV infection and mono occur throughout the world?
Yes. In emerging nations, however, mono is not as common because most of the population is infected with EBV earlier in life when symptoms are minimal.
If I have had EBV infection, can I still get mono?
No. Once you have had an EBV infection, you will not get mono. You could, however, experience similar symptoms from another viral illness. In individuals with weakened immune systems, the virus can reactivate and cause illness.
Why is mono sometimes called "the kissing disease"?
This is because EBV is present in the saliva of an infected individual and is commonly spread through kissing. It can also be spread, especially in the case of children, through saliva transfer to hands and/or toys and by sharing utensils or cups.
Are there other types of tests available for EBV?
Yes. There are molecular tests that can detect and measure EBV DNA.