Epstein-Barr Virus

The Epstein-Barr virus is a common virus that infects only humans. It can cause a condition known as infectious mononucleosis, mono or glandular fever. The Epstein-Barr virus is a member of the human herpesvirus family and is also known as human herpesvirus 4 or HHV-4.

It is estimated that up to 90 percent of the world’s adult population has the Epstein-Barr virus, but many people who have the virus in their bodies will experience no symptoms. Many people are infected during childhood or adolescence. In the U.S., about half of the population has contracted EBV by the age of five. Most of the remainder contract the virus during adolescence or early adulthood. 1

People who contract the virus during childhood tend not to show symptoms of infection, but those who contract it during adolescence or adulthood may develop infectious mononucleosis. 2 The symptoms of EBV-related mononucleosis are a severe sore throat, fever and intense fatigue that can last for several months. Once the initial infection has ended, the virus remains latent in the body. 3

Treatment for infectious mononucleosis, which is normally caused by EBV, includes treating the symptoms, and monitoring for complications. The outlook for people with infectious mononucleosis is generally good.

Most people contract the Epstein-Barr virus, or EBV, during childhood and may not show symptoms during that time. Children may show only very mild or non-specific symptoms of infection, but the condition tends to affect teenagers and adults more severely. 3 The condition is most common among people between the ages of 15 and 24. 4 Signs of infection usually develop only some time after the virus has been contracted; this incubation period is usually between a month and eight weeks long. 5

The most common symptoms of infectious mononucleosis are: 1 3 4 6 7 8

• Fatigue
• Fever, but not always chills; the fever caused by an EBV infection is typically low-grade
• Swollen lymph glands, also known as lymphadenopathy
• A sore throat, also known as pharyngitis
• Nausea, vomiting and loss of appetite
• Enlarged tonsils
• Headaches

The sore throat, which is one of the most prominent symptoms of glandular fever, can sometimes be confused with strep throat. It is common for people who have EBV-related pharyngitis to have painful, enlarged tonsils, also.

Good to know: While it is not known for sure whether the Epstein-Barr virus causes chronic fatigue syndrome, most people with infectious mononucleosis experience severe fatigue as a prominent symptom of the condition. However, this fatigue usually resolves within three months. The fatigue associated with chronic fatigue syndrome typically lasts for about one year. 1

Other symptoms include: 1 3 6 7 8

• Body aches
• Enlarged spleen
• Enlarged liver
• Non-itchy skin rash
• Jaundice

Less common symptoms include: 1

• Coughing
• Eye pain
• Chest pain
• Sensitivity to light
• Muscle pain

Although not everyone who is affected by infectious mononucleosis experiences an enlarged spleen and/or liver, these can nevertheless be very serious symptoms. In some cases, the spleen may rupture. 8 A ruptured spleen can in fact sometimes be the first sign that someone has infectious mononucleosis. Signs and symptoms of a ruptured spleen include: 9 10

• Pain in the stomach, often worst on the upper left side
• Pain in the left shoulder
• Muscle-guarding in the abdomen, i.e. tensing the abdominal muscles
• Rapid heartbeat
• Low blood pressure
• Nausea
• Sweating
• Lightheadedness and/or fainting
• Fatigue
• Blurred vision
• Bruising or bloating of the stomach region

The pain from a ruptured spleen can be mild or severe. A ruptured spleen is a medical emergency, and the affected person should go to hospital immediately.

The rash associated with infectious mononucleosis is faint, red and not itchy; it typically disappears quickly. 1 Jaundice is more common among older people affected by infectious mononucleosis; older people may also not always have a sore throat or swollen lymph glands.

Concerned that you or a loved one may have this condition? Start your symptom assessment in the free Ada app.

The Epstein-Barr virus is extremely contagious, and new infections are especially common in populations of high-school and college-age adults. 6 It is spread by contact with infectious bodily fluids, especially saliva, and is therefore sometimes known as the kissing disease. It can also be spread by: 4 11

• Sharing toothbrushes
• Sharing drinking vessels and cutlery, especially if they are not washed between use
• Coughing and sneezing
• Contact with the saliva, blood or semen of someone with EBV
• Organ transplants or blood transfusions from a donor with EBV

Young children may also contract the virus from putting toys into their mouths which have been in contact with the infected saliva of other children, or from the hands of caregivers with infected saliva on them. 11 12 Teenagers and adults can contract EBV by kissing someone who is shedding the virus.

People who have the virus in their bodies can pass it on to others, even when they themselves are not experiencing any symptoms. The incubation period between getting the virus and developing symptoms is also quite long, up to eight weeks. For these reasons, it is sometimes hard to diagnose mono, as the affected person may not remember being near anyone ill and may not have known that they were in contact with someone who was shedding the virus.

While infectious mononucleosis is usually diagnosed by a physical examination and consideration of the symptoms shown by the the affected person, 7 laboratory tests can also be used to confirm an Epstein-Barr virus infection as well as infectious mononucleosis. Tests that can be done include: ref7 13

• Complete blood counts
• Heterophile antibody/monospot tests
• Polymerase chain reaction (PCR) tests
• EBV-specific blood tests

The complete blood count results give information on the immune response that the body is mounting against the EBV virus, as well as whether unusual white blood cells typical of EBV infection are present.

The test most commonly used to diagnose an EBV infection is known as a heterophile antibody test, which is usually accompanied by a complete blood count (CBC). This test, also known as a monospot test, looks for the antibodies the body produces to fight off EBV itself. 13 This is usually the first test done. However, this test can take up to two weeks to become positive, meaning that people in the early stages of the condition may test negative. ref1 In the event of an initial negative test, these monospot tests can be carried out weekly for six weeks if the initial tests come back negative; after six weeks, however, a specific EBV serological test should be done. ref1

In some cases, especially in the case of a child with suspected mono, a polymerase chain reaction (PCR) test may be done; this tests for the DNA of EBV viruses. It is more sensitive, but also more expensive. A PCR test can also be used to diagnose indeterminate EBV infections. 1

All of these tests are done on blood samples from the affected person.

The blood test results of someone with infectious mononucleosis may show: 7

• More white blood cells than usual
• Unusual-looking white blood cells
• A lower numbers of platelets than would be usual
• Signs of abnormal liver function

If these tests are inconclusive, a test specifically designed to test for Epstein-Barr viruses may be ordered. These tests are very specific and are designed to determine whether the person being tested has EBV and whether they have infectious mononucleosis. They are typically only done if other tests do not prove or disprove that EBV infection is present, as they are quite expensive and require specialized staff to interpret the results. 14

No known tests for infectious mononucleosis or EBV can tell from whom the infection was contracted.

Most cases of EBV infection are asymptomatic and therefore do not require treatment. Treatment for infectious mononucleosis centers around relieving the symptoms. Medications such as aciclovir have not been shown to be effective against glandular fever. 1

People with infectious mononucleosis should: 1 15

• Be careful to stay well-hydrated and well-nourished
• Manage pain and discomfort using over-the-counter acetaminophen, also known as paracetamol, or ibuprofen
• Gargle with salt water and/or suck lozenges to relieve throat pain
• Take bed rest and avoid doing anything strenuous

Good to know: Because infectious mononucleosis is caused by a virus, it cannot be treated with antibiotics. In fact, mistakenly treating infectious mononucleosis with antibiotics, especially penicillins, can cause a rash. 7

Most people with infectious mononucleosis recover within two to four weeks, but the fatigue that is characteristic of the condition may last for longer. Rarely, symptoms may persist for up to six months. 7

After glandular fever, it is very important to avoid contact sports, heavy lifting or rough activity until given the all-clear by a physician. The spleen and liver can stay enlarged for some time after the sore throat and fever are gone, so the risk of rupturing them remains higher than usual. Once they have gone back to normal size, the affected person can resume their sports or exercise regime.

Although most cases of infectious mononucleosis resolve without complications, they can occur. Severe complications include meningoencephalitis, splenic rupture and extreme tonsillar enlargement; less severe complications include sinus infections or tonsillitis.

It is quite rare for severe complications to occur. f they do, because of their potential severity, they should be considered medical emergencies and promptly treated.

The Epstein-Barr virus seldom affects the nervous system. Neurological involvement is more likely to occur among children than adults, but is exceedingly rare in both groups. 16 In rare cases, EBV can lead to swelling of the meningeal membranes and brain. Signs and symptoms of meningoencephalitis include:

• Headache
• Confusion and/or disorientation
• Difficulty thinking clearly
• Unusual clumsiness or lack of coordination
• Unusual or out-of-character behaviour
• Fever
• Light sensitivity
• Stiffness of the neck
• Painful neck

It is very important that anyone showing these symptoms receives prompt medical care. This condition can be fatal if it is not treated. In severe cases, people who recover may have long-term problems. 16

Although an enlarged spleen is common among people affected by glandular fever, actual rupture of the spleen is rare. 17 However, because the other symptoms of infectious mononucleosis can be mild or vague, it can happen that a ruptured spleen is the first sign that someone has the condition. The pain from a ruptured spleen can differ, varying between mild and severe. A ruptured spleen is a medical emergency, and the affected person should go to hospital immediately. For more information on the symptoms of a ruptured spleen, see the symptoms section.

Enlarged tonsils, also known as tonsillitis often accompany the painful sore throat that is characteristic of infectious mononucleosis. In rare cases, the tonsils may become so enlarged that they touch one another, partially or almost completely blocking the airway. This can happen with or without a secondary bacterial throat infection and may appear in cases where other severe symptoms of infectious mononucleosis are absent. 18 However, in cases of very enlarged tonsils, lymph nodes in the area are usually also quite enlarged. 19 People with mono should be aware that this complication may occur and seek medical treatment at once if they begin to breathe with difficulty.

There is no vaccine for Epstein-Barr virus infection.

The main ways of preventing Epstein-Barr virus infection are to avoid sharing toothbrushes, cups and other items that may come into contact with saliva or other bodily fluids with anyone who has had infectious mononucleosis. It is always a good idea to cover the mouth and nose while coughing or sneezing and to wash one’s hands after doing so and after using the bathroom.

Q: Does Epstein-Barr virus cause paralysis?
A: Rarely, an Epstein-Barr virus infection can cause a condition in which one side of the face can become temporarily weak or paralyzed. This is caused by inflammation of a branch of the facial nerve; inflammation disrupts the nerve signals and weakness or paralysis affects the facial muscles. 20 People affected by this condition usually recover within six to 12 weeks.

Other infections that can cause a similar disorder, known as Bell’s palsy, include infection with the herpes simplex virus, the flu, middle ear infections, and Lyme disease, as well as chronic conditions such as diabetes, sarcoidosis and high blood pressure. 20 When facial paralysis is caused by Epstein-Barr or herpes zoster infection, it is not called Bell’s palsy, although the symptoms are identical. 21

Epstein-Barr virus may also be a potential cause of Guillain-Barre syndrome, although this is not known for certain, and the exact causes of Guillain-Barre symptom are as yet unknown. 22 Guillain-Barre syndrome is an autoimmune condition in which the body’s immune system attacks the nerves, causing muscle weakness and paralysis. In most cases, the condition is temporary, and the majority of people affected recover well. 23

Q: Does Epstein-Barr virus cause chronic fatigue syndrome?
A: No conclusive link has as yet been found between Epstein-Barr virus infection and chronic fatigue syndrome, although the condition is still being researched. 24 Some studies have shown that some people with CFS have a history of EBV infection, but others do not. 25

Other potential triggers for chronic fatigue syndrome are environmental factors, hormonal imbalances, other viral infections – such as cytomegalovirus infection and rubella, among others – and problems with the immune system. 24 25

Q: Does Epstein-Barr virus infection cause a rash?
A: Epstein-Barr virus infection causes a rash only rarely. Sometimes this is the result of the infection itself. However, in most cases, a rash that affects someone with EBV is the result of attempts to treat the disorder with antibiotics, specifically ampicillin and amoxicillin. 26 27 Developing this rash after being given a penicillin-type antibiotic does not mean that the person is allergic to those antibiotics. Because infectious mononucleosis is a viral condition, antibiotics do not work. Antibiotics are only effective against bacterial infections. Unlike the rash caused by EBV itself, the rash associated with antibiotic use in cases of EBV is itchy, red and can be long-lasting. 1 28

Q: Can Epstein-Barr virus infection be fatal?
A: Epstein-Barr virus infection can be fatal, but this is very rare. In some cases of EBV infection, a rare complication is that the spleen may enlarge and rupture. 29 If the ruptured spleen is not treated as a medical emergency, the affected person may become very seriously ill. In other cases, the infection may lead to hepatitis and subsequently liver failure, although this is also very rare. 30 31

Q: Can Epstein-Barr virus cause cancer?
A: Epstein-Barr virus is thought to be related to several types of cancer: Burkitt lymphoma, Hodgkin lymphoma, some kinds of stomach cancer and some kinds of nasopharyngeal cancer. 32 It may also be involved in the develop of various other cancers, including breast and prostate cancer.

However, investigations into the relationship between cancer and EBV are still ongoing, and it is likely that various factors, not EBV infection alone, are involved in the development of such cancers. 33 Overall, only a tiny minority of people affected with EBV will ever develop cancer as a result of the virus. 34

Q: What is lymphoma and how does it relate to EBV infection?
A: Lymphoma is a form of cancer that affects the body’s lymphatic system, the network of ducts that drain lymph from the tissues into the blood. The lymphatic system is part of the body’s immune system. 35 Lymphoma occurs when lymphocytes, which circulate in the lymphatic system, do not behave normally. 36 In lymphoma, abnormal lymphocytes gather in the lymph nodes. There are two types of lymphocyte, commonly known as B cells and T cells.

Lymphoma has two main subtypes, Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Burkitt lymphoma is a form of non-Hodgkin’s lymphoma and is most common among people of African descent. 37 Most cases of non-Hodgkin’s lymphoma start in the B cells. Epstein-Barr virus infects the B cells, but in most people this does not cause further problems. 38 In some people, however, the EBV infection causes the B cells to begin to multiply abnormally, causing lymphoma.

• Infectious mononucleosis
• Glandular fever