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This is a group of tests that detect Epstein-Barr Virus (EBV) antibodies and they are used to help diagnose infectious mononucleosis or glandular fever.
Glandular fever develops in about half of people who are infected with the EB virus. Antibodies are made by the immune system to fight off infection. 

Some people with glandular fever can be diagnosed through their symptoms together with a Full Blood Count test and a Monospot test. However, other people have a negative result to the Monospot and an antibody test is needed instead to make their diagnosis.

EBV antibody testing is also used to differentiate between an EBV infection and other illnesses with similar symptoms.

It is used to assess whether the EBV infection is active or has occurred at some time in the past.

What is being tested?

Epstein-Barr virus (EBV) antibodies are a group of tests that are ordered to help diagnose a current, recent, or past EBV infection. EBV is a member of the herpes virus family. Passed through the saliva, the virus causes an infection that is very common. According to World Health Organisation (WHO), as many as 95% of people in the world adult population has been infected by EBV. After exposure to the virus, there is an incubation period of several weeks. EBV then causes an acute primary infection, followed by resolution and dormancy. Latent EBV remains in the person’s body for the rest of their life, reactivating intermittently, but causes minimal symptoms or complications unless the person’s immune system is significantly compromised.

Most people are infected by EBV in childhood and experience few or no symptoms, even in the acute phase of the infection. However, when the initial infection is delayed until adolescence, EBV causes glandular fever in up to 50% of those infected. Glandular fever is a condition that is associated with fatigue, fever, sore throat, swollen lymph nodes, an enlarged spleen, and, sometimes, an enlarged liver. Those who have it are often symptomatic for a month or two before the initial infection resolves.

Patients with glandular fever are diagnosed by their symptoms and the findings of a full blood count (FBC) and a monospot test (which tests for a heterophile antibody). A certain percentage of those who have glandular fever will have a negative mono test; this is especially true with children. EBV antibodies can be used to determine whether or not the symptoms these patients are experiencing are due to a current infection with the EBV virus.

It can be important to distinguish EBV from other illnesses. Symptoms similar to infectious mononucleosis can also be caused by a number of other viruses including cytomegalovirus (CMV), toxoplasmosis, hepatitis viruses and Human Immunodeficiency Virus (HIV). Confirming glandular fever is important as it is possible the spleen can rupture. Therefore such patients should not be involved in contact sports for several weeks to months after infection, as a ruptured spleen can cause other complications.

It is also important for medical staff to distinguish EBV like symptoms in a pregnant women from other viruses such as cytomegalovirus, toxoplasmosis, or herpes simplex virus infection, as these illnesses can cause complications during the pregnancy.

It can also be important to rule out EBV and to look for other causes for the symptoms in, for example, patients with streptococcal  throat infection who need to be identified and treated with antibiotics.  A person can have  both streptococcal throat infection and have glandular fever at the same time.

To detect the virus there are several EBV antibodies. They are proteins produced by the body in an immune response to several different Epstein-Barr virus antigens. They include IgM and IgG antibodies to the viral capsid antigen (VCA), and antibodies to the nuclear antigen (EBNA). During a primary EBV infection, each of these EBV antibodies appears independently depending on the stage of infection. The VCA-IgM antibody is usually detectable at the time of the first blood test, when symptoms first appear and then tends to disappears after about 4 to 6 weeks. The VCA-IgG antibody develops soon after VCA-IgM, and persists for life. The EBNA antibody usually develops 2-4 months after the initial infection, so does not usually appear until the acute infection has resolved. and persists for life. Using a combination of these EBV antibody tests and the clinical presentation, a doctor is able to diagnose an EBV infection and to determine whether it is a current, recent, or past infection.

How is it used?

Epstein-Barr Virus (EBV) antibodies are used to help diagnose glandular fever if you are symptomatic but have a negative monospot test.

Requesting serology testing for EBV antibodies will include:

  • Viral capsid antigen (VCA)-IgM, and VCA-IgG — to detect a current or recent infection
  • If VCA-IgG is detected then Epstein Barr nuclear antigen (EBNA) may be added — to detect a previous infection

Pregnant women with symptoms of a viral illness, one or more of these EBV antibodies may be ordered along with tests for CMV, toxoplasmosis, and other infections (sometimes as part of a TORCH screen) to help distinguish between EBV and conditions that may cause similar symptoms.

Occasionally, a VCA-IgG or other EBV antibody tests may be repeated 2-4 weeks after the first test, either to see if the test result changes from not detected to detected or to measure the changes in antibody concentrations.

A VCA-IgG test, and sometimes an EBNA test, may be ordered on an asymptomatic patient to determine if that person has been previously exposed to EBV or is susceptible to a primary EBV infection. This is not routinely requested, but it may be ordered when a patient, such as an adolescent or an immune compromised patient, has been in close contact with someone who has glandular fever.

When is it requested?

EBV antibodies may be ordered when you have symptoms suggesting glandular fever, and had a negative monospot test or when a pregnant woman has flu-like symptoms or the doctor wants to determine whether the symptoms are due to EBV or another microorganism.

Signs and symptoms of EBV infection may include:

  • Fatigue
  • Fever
  • Sore throat
  • Swollen lymph glands
  • Sometimes enlarged spleen and/or liver

VCA-IgG and EBNA may be ordered whenever your doctor wants to establish previous exposure. Testing may occasionally be repeated when the first test was negative, but your doctor still suspects that your symptoms are due to EBV.

What does the result mean?

If you have positive VCA-IgM antibodies, then it is likely that you have a current, or had a very recent, EBV infection. If you also have symptoms associated with glandular fever, then it is likely that you will be diagnosed with and EBV infection, even if your monospot test was negative. If you also have a reactive VCA-IgG test result, then it is highly likely that you have, or recently had, an EBV infection.

If the VCA-IgM is negative but the other antibodies including EBNA antibody are detected, then it is likely that you had a previous EBV infection. If you are asymptomatic and have a negative VCA-IgG test, then you have not been previously exposed to EBV and could be infected. Below, results are provided in table form.

Test result most likely indicate the following:

EBV ANTIBODY TEST

SUSCEPTIBLE TO EBV

CURRENT EBV INFECTION

PAST EBV INFECTION

COMMENTS

VCA-IgM

 

+

+

Appears first, disappears in 4-6 weeks. 

Can be falsely positive with some other infections

VCA-IgG

-

+

+

If not present, then you are susceptible.

It appears within a week of infection, then persists for life

EBNA-IgG

 

 

+

becomes reactive in 2-4 months, then persists for life

Heterophile IgM (Mono test)

 

+

 

Associated with glandular fever.

Note: False positives can occur with other conditions. 
False negatives are common in children

 

is there anything else I should know?

There are other antibodies that arise during an EBV infection including an IgG antibody to EBV D early antigen (EA-D IgG), an IgA antibody to the EBV viral capsid antigen (EBV VCA-IgA) and an IgG antibody to the EBV early antigen restricted (EA-R IgG). While it is possible to test for these antibodies as part of the EBV diagnostic workup, it is rarely necessary to do so.

Complications of EBV infection that can occur include trouble breathing due to a swollen throat associated with or without a bacterial infection, rarely a ruptured spleen, jaundice, skin rashes, pancreatitis, seizures, and/or encephalitis can occur. EBV is also associated with, and may play a role in, several rare forms of cancer, including Burkitt’s lymphoma and nasopharyngeal carcinoma.

Reactivation of the virus is rarely a health concern unless the patient is immunocompromised, as may happen in those who have HIV/AIDS or in those who have received an organ transplant. Primary infections in these patients can be more severe, and some may experience chronic EBV-related symptoms or complications.

Common questions

  • How is EBV infection treated?

Care is largely supportive - rest, treating the symptoms such as sore throat, and avoiding any contact sports or heavy lifting for several weeks to months to avoid spleen rupture. There are no anti-viral medications or vaccines available to speed healing or prevent infection.

  • Do adults get glandular fever?

They do, but it is rare because most have already been infected 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 glandular fever occur throughout the world?

Yes. However, in less developed nations, it is not as common because most of the population is infected with EBV earlier in life when symptoms are minimal.

  • Can EBV be prevented?

Not at this time. It is very common in the population, with almost everyone being infected and therefore being infectious at one time or another. The virus may also reactivate intermittently in a previously infected person, usually without causing any symptoms.

  • If I have had EBV infection, can I still get glandular fever?

No. Once you have recovered from an EBV infection, you will not get glandular fever (again). However you could experience similar symptoms from another viral illness.

  • Why is glandular fever sometimes called "the kissing disease"?

This is because EBV is passed on through saliva from mouth-to-mouth contact (such as kissing) or through saliva transfer to hands and/or toys, etc.

  • Are there other types of tests available for EBV?

Yes. There are molecular tests that can detect and measure EBV DNA. They can be helpful in diagnosing and monitoring EBV-related diseases such as Burkitt’s lymphoma, Hodgkin’s lymphoma and post-transplant lymphoproliferative disease (PTLD).

Last Updated: Thursday, 1st June 2023

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