Epstein Barr Virus (EBV) Tests & Result Interpretation

The Epstein-Barr Virus (EBV) test is often used to diagnose people suffering from symptoms of mononucleosis. Read on to discover what an abnormal result means and how to tell if you have a current or past infection.

Epstein-Barr Virus Basics

The Epstein-Barr virus (EBV)or human herpesvirus 4is one of eight types of herpes viruses that are known to infect humans. EBV is extremely common: it is estimated that up to 90% of adults worldwide carry the virus [12].

The virus usually does not cause any symptoms in children. Howeverbetween 30-50% of adolescents and adults who have the virus will develop infectious mononucleosis (mono) [2].

Because EBV is spread through salivamono has earned the nickname “the kissing disease.” It causes sore throatfatigueand feveramong other symptoms [3].

EBV can increase the risk for certain cancers and immune system disorders and has been linked to multiple autoimmune disorders [45678].

What is the Epstein-Barr Virus Test?

The Epstein-Barr virus test is a blood test that determines if your body is producing antibodies and mounting an immune response against EBV [2]. It is also known as the Epstein-Barr virus antibody profile.

If you have the virusyour body will produce different types of antibodies to help combat the infection. These antibodies circulate in your blood and can be detected with the EBV test [2].

By revealing which types of antibodies you havethe test can determine if you have a current or a past infection [2].

About 70% of people tested will have antibodies indicative of past infections [9].

After your body successfully fights the virusit remains dormant in your cells and doesn’t cause any symptoms. Howeverit can be reactivated by stress or a weakened immune system [10].

When is it Ordered?

Your doctor will order an Epstein-Barr virus test if they suspect that you have mono. Symptoms to watch for include [11]:

• Sore throat
• Swollen lymph glands
• Fatigue
• Headache
• Poor appetite
• Fever

Symptoms of mono usually last 2 to 3 weeksthough certain symptoms such as fatigue and muscle pain may last longer [312].

Because the disease is most common in young adults between the ages of 15 and 24your doctor may take your age into account when deciding whether to order the test [13].

Procedure

To test for EBV-specific antibodiesyou will need to get your blood drawn. Results usually take a few days to come back.

Monospot test is a more rapid test that can give you results within minutes. For this testyou may also need to have your blood drawn. Howeverin most commercially-available testsyou will only need to give a small blood sample from a finger prick [14].

Within the first week of symptomsthe monospot test may give you a false-negative result. If the initial result is negative and your doctor still suspects monohe may ask you to repeat the test a week or so later [13].

Types of Epstein-Barr Tests

EBV-Specific Antibody Tests

Your immune system produces antibodies against different partsor antigensof EBV. The type of antibodies that are detected in your blood helps your doctor determine if you have a current or past infection [9].

VCA IgG antibody (EBV AB VCA IgG)

Viral capsid antigen (VCA) IgG antibodies are directed against the protein shell (capsid) of the virus. These antibodies typically appear at the same time as infection symptoms [2].

Once they are madeVCA IgG antibodies will stay in your blood for life. This means they will always be detectableeven if you are not suffering from a current infection [15].

This also means thatby themselvesthey are unhelpful in determining if you have a current or past infection.

IgG Avidity Test

In some cases where a clear diagnosis can’t be madethe IgG avidity test may be used. It measures how mature VCA IgG antibodies are by seeing how strongly they bind to EBV antigens [2].

During the early stages of an infectionVCA IgG antibodies are immature and don’t bind as strongly to EBV antigens. As the infection progressesthey start to develop and mature [2].

This makes the avidity test useful for estimating how long the infection has lasted as well as determining if it’s a current or past infection [2].

VCA IgM antibody (EBV AB VCA IgM)

VCA IgM antibodies are also directed against the virus shell and usually appear at the same time as VCA IgG antibodies. Howeverunlike VCA IgG antibodiesthey disappear within a few weeks [1617].

In some casesVCA IgM antibodies may be detectable for several months [18].

They are found in up to 75% of people with mono [19].

Epstein-Barr Nuclear Antigen Antibody (EBNA)

Epstein-Barr nuclear antigen (EBNA) antibodies are directed against proteins that the virus uses to survive and replicate its DNA after it enters into a dormant phase [20221].

EBNA antibodies are only detectable 3-4 weeks after the onset of symptomsafter mono has run its course and the virus is no longer active. In most casesthey stay in circulation for life and are a sign of a past infection [29].

Early Antigen Antibody (EBV EA)

Epstein-Barr early antigen antibodies (EA) are directed against proteins that control how the protein shell (capsid) of the virus is made [22].

Like their name suggeststhey are found in the first 3-4 weeks of the infection and are no longer detectable after 3-4 months in most people [223].

In some casesthey may be detectable for years after the initial infection [2].

EA antibodies are also detected in people who have a reactivated infection or in cases of certain cancers linked to EBV [23].

They are not usually tested for in routine practicebut they may be used in cases where a diagnosis can’t be made using VCA or EBNA antibodies [2].

Monospot Test

The EBV-specific antibody test is the gold standard when it comes to diagnosing mono. Howeverit usually takes a few days for the results to come back [14].

With an illness like monowhich is short-lived and has symptoms very similar to those of other illnessestime is of the essence. Diagnosing it quickly can help reduce complications and prevent the use of unnecessary treatments such as antibiotics [14].

The heterophile antibody monospot test (more commonly known as just “monospot test”) was developed to deliver rapid results within 5 to 10 minutes [142].

It’s also cheaper and only requires a blood sample from a finger prick [142].

The test detects the presence of antibodies in the blood called heterophile antibodieswhich are made in response to EBV infection. Unlike EBV-specific antibodiesthey are not unique to EBV and will also bind to other antigensincluding cells of other animal species [2].

In factmost monospot tests use sheepgoator horse red blood cells to detect the presence of heterophile antibodies. When these cells are added to a blood sample they will bind to any heterophile antibodies present. When this occursthe sample “clumps” togetheryielding a positive result [2].

Heterophile antibodies peak 2-5 weeks after symptoms begin and then decline rapidly [2].

The monospot test does have some drawbacksthe biggest being the relatively high frequency of false-negative results. In other wordseven if you are infected with EBVthere is a good chance the test will give you a negative result [14].

On the other handa positive result almost always means you have an infection.

The CDC does not recommend using the monospot test to diagnose mono due to its poor accuracy [14].

In cases where the monospot test is negative but the doctor still suspects monofurther testing using the EBV-specific antibody test may be required [24].

Complete Blood Count

A complete blood count (CBC) is frequently ordered alongside the monospot test to help confirm a positive result orin the case of a negative resultand to determine if further tests are needed [24].

The CBC will tell you whether specific white blood cells called lymphocytes are elevatedwhich is commonly the case with mono [24].

It will also reveal if a subset of large lymphocytes called atypical lymphocytes is also elevated. Atypical lymphocytes greatly increase in response to viral infections such as mono [12].

Result Interpretation

Normal Result

A normal result means that the test did not find any antibodies in your blood. In the case of the EBV-specific antibody testa negative result likely means that you have never been infected with EBV [24].

In the case of the monospot testa negative result may mean that you are still in the early stages of the infection and that the test will have to be repeated [24].

There are a few other viruses and parasites that can cause mono. If you are experiencing symptoms of mono and your EBV test results come back normalyou may need additional tests to identify the cause [2].

Abnormal Result

An abnormal result means that the test has found antibodies to EBV in your blood. This means that you are currently infected with EBV or have been infected in the past.

Like any lab testfalse-positives and false-negatives can occur. For examplean acute infection with another herpesvirus called cytomegalovirus or the parasite Toxoplasma gondii can cause a false-positive VCA IgM result [25].

Your doctor will interpret your results in conjunction with your symptomsmedical historyand other test results.

Below is a table displaying the most common combinations of results from the EBV-specific test and their interpretations [25].

Levels of antibodies detected in the bloodcalled titerscan’t tell how long you’ve had the infection or how severe it is.

Sometimesdoctors are unable to make a diagnosis given the antibody pattern. This occurs when a person has the following results [2]:

• Positive for VCA IgG and negative for both VCA IgM and EBNA
• Positive for VCA IgM and negative for both VCA IgG and EBNA
• Positive for EBNA and negative for both VCA IgG and VCA IgM
• Positive for all three antibodies (further testing required to determine whether the infection is late acute or reactivated)

If you have any of these antibody patternsyour doctor will usually do further testing. They may check IgG avidity testthe EA antibody testor another test that detects the presence of DNA belonging to EBV [2].

Acute vs. Chronic Infection

Acute

An acute EBV infectionalso called a primary infectioncauses mono. The associated symptoms usually resolve within weeks of catching the virus; howeversome symptoms may last longer [1113].

After the symptoms go awaythe virus is contained and enters a dormant phase wherein it stops reproducing itself and spreading.

Chronic

Chronic active EBV disease (CAEBV) is a rare disorder in which a person is unable to successfully fight and contain the virus [26].

It is defined as a chronic illnesslasting longer than 3 monthsin which a patient has high levels of EBV DNA in their blood in the absence of a weak immune system [26].

Symptoms of the disease mirror many of those of an acute infectionsuch as fever and swollen lymph glands. More serious complications such as an enlarged spleen and low red blood cellwhite blood celland platelet counts occur frequently in these patients [26].

Most of those with a chronic infection will test negative for EBNA antibodiesor they may have very low levels [27].

Over timetheir immune systems may failand if left untreatedthey will develop opportunistic infectionsmultiorgan failureand cancer [26].

The only effective treatment for chronic active EBV is bone marrow transplantation [26].

Abnormal Results: What Now?

The most important thing is to work with your doctor to get an accurate diagnosis and to monitor your condition.

There are currently no vaccines to prevent mono nor drugs approved for treating mono. The symptoms usually just run their course.

Antiviral drugs have been suggested for treating mono; howevera recent review found no proof of their effectivenessand concluded that the studies in support of the treatment were of low quality [28].

Howeverthere are steps you can take to manage the symptoms of monoincluding [29]:

• Getting enough rest
• Avoiding intense exercise
• Drinking plenty of fluids and consuming enough food
• Taking Tylenol and NSAIDs (aspirin is not recommended for those with mono) to address fever and pain – remember to discuss your medication with your doctor
• Gargling with salt water and using pain-relieving throat lozenges

After your symptoms resolvethe virus will remain in a dormant state in your bodyusually without causing any further symptoms. Howeveryou will still test positive for some EBV-specific antibodiesand the virus may reactivate under certain conditions.

If you suspect that you have a reactivated EBV infectioncheck out this post for more strategies to get back to full health.