Epstein-Barr Virus Infection

Epstein-Barr virus is one of the most common infections in the world, affecting up to 95% of adults at some point in their lives. While many people never experience symptoms, this highly contagious virus can cause infectious mononucleosis and, in rare cases, has been linked to various cancers and autoimmune conditions.

Table of contents

• What is Epstein-Barr Virus?
• Medical Identification Codes
• Other Names
• How Common is EBV?
• How the Virus Spreads
• Signs and Symptoms
• Stages of Infection
• Diagnosis and Testing
• Treatment and Recovery
• Potential Complications
• Prevention
• Chronic Active EBV
• Related Health Conditions

What is Epstein-Barr Virus?

Epstein-Barr virus (EBV) is a very common viral infection that spreads through saliva and other body fluids^[1]. It belongs to the family of herpesviruses (viruses that can remain dormant in the body for life) and is specifically known as human herpesvirus 4^[2]. EBV was first discovered in 1964 in cells from Burkitt lymphoma, making it the first identified virus known to cause cancer in humans^[3].

Once you get EBV, the infection stays within your body for your entire life in a dormant state where it is inactive or sleeping^[1]. The virus primarily infects B lymphocytes, which are white blood cells that help the body fight off infections. When the virus attaches to these white blood cells, your cells are unable to fight the infection properly and you experience symptoms^[1].

Most cases of EBV do not cause symptoms. However, other cases, especially in teenagers and young adults, can lead to infectious mononucleosis (a disease commonly known as “mono” or the “kissing disease”)^[1].

B27.0
XNOR2, 1D81.0
40168006, 240530001

Human herpesvirus 4, HHV-4, EBV, Epstein-Barr virus

How Common is EBV?

Epstein-Barr virus is very common worldwide. In the United States, an estimated 50% of all children up to 5 years of age and about 95% of adults have experienced an EBV infection in their lifetime^[1]. EBV is one of the most common human viruses in the world, and most people will get infected with EBV at some point in their lives, especially in childhood^[2].

The virus affects children, teenagers, and young adults most commonly, but anyone can get the virus^[1]. EBV affects both sexes equally and all races, although the age of first infection varies widely between ethnic groups^[8]. Infection occurs globally and has no seasonal preference^[8].

How the Virus Spreads

Epstein-Barr virus is highly contagious and easily spreads through close person-to-person contact^[1]. The virus spreads primarily through bodily fluids, especially saliva (spit)^[2]. You can get EBV from an infected person in several ways:

• Kissing someone with the virus
• Coughing or sneezing near you
• Sharing drinks, food, or eating utensils
• Sharing drinking cups or toothbrushes
• Sexual contact (through blood and semen)
• Touching items a child might have put in their mouth or drooled on
• Blood transfusions or organ transplants

The virus can spread during the incubation period (the time between when someone is exposed to the virus and when they experience symptoms), which is between four to six weeks^[1]. This means you can pass the virus to others even before you know you are sick. The virus probably survives on an object at least as long as the object remains moist^[2].

If you have EBV, you do not have to show symptoms to pass the virus onto someone else. When you first get EBV, you can spread it for weeks and even before you have symptoms. Once EBV is in your body, it stays inactive, but if it reactivates, you can potentially infect others no matter how much time has passed since the first infection^[2].

Signs and Symptoms

Symptoms range in severity for each person diagnosed with Epstein-Barr virus. Many people who get EBV, especially young children, either do not show symptoms or their symptoms are similar to short-term illnesses like a cold or the flu^[1]. EBV infections in children usually do not cause symptoms, or the symptoms are not distinguishable from other mild, brief childhood illnesses^[2].

Teenagers or adults who get the virus may show symptoms between two to four weeks, but symptoms could linger for months, especially fatigue^[1]. Common symptoms of EBV infection include:

• Fatigue or feeling extremely tired
• Fever
• Sore throat and throat inflammation (swelling)
• Swollen lymph nodes (bean-shaped organs in your neck)
• Enlarged spleen and liver
• Rashes on your skin
• Lack of appetite
• Weak and sore muscles

About 35 to 50% of teenagers and young adults who become infected with EBV will develop infectious mononucleosis^[3]. People who get symptoms from EBV infection usually get better in 2 to 4 weeks. However, some people may feel fatigued for several weeks or even months^[2].

Stages of Infection

Infection with Epstein-Barr virus happens in three phases^[4]:

Infection: The virus copies itself in your body, and you may or may not have symptoms. During this stage, the virus attaches to white blood cells and begins to multiply.

Latency: EBV goes to sleep in your body. Once you get the infection, it will live in your body in a dormant (sleeping or inactive) state^[1]. The virus becomes latent (inactive) in your body after the initial infection^[2].

Reactivation: The virus can sometimes “wake up” and cause symptoms again. In some cases, the virus may reactivate, though this does not always cause symptoms. People with weakened immune systems are more likely to develop symptoms if EBV reactivates^[2]. Certain events can trigger EBV to wake up and make it contagious to others, potentially causing symptoms. Events that trigger EBV reactivation include stress, a weak immune system, and menopause or hormone changes^[1].

Diagnosis and Testing

Diagnosing EBV infection can be challenging because the symptoms are similar to other illnesses like the flu or a cold^[2]. Your doctor may suspect mononucleosis based on your signs and symptoms, how long they have lasted, and a physical exam. He or she will look for signs such as swollen lymph nodes, tonsils, liver or spleen^[4].

EBV infection can be confirmed with a blood test that detects antibodies (substances your immune system makes against the virus)^[2]. About 9 out of 10 adults have antibodies that show that they have a current or past EBV infection^[2]. There are several types of blood tests used:

Antibody tests: These tests look for specific antibodies to the Epstein-Barr virus. The tests can show if you currently have EBV, or if you had an infection in the past^[4]. Different antibodies appear at different stages of infection, helping doctors determine whether the infection is new, current, or past.

White blood cell count: Your doctor may use blood tests to look for an elevated number of white blood cells (lymphocytes) or abnormal-looking lymphocytes. These blood tests will not confirm mononucleosis, but they may suggest it as a possibility^[4].

Monospot test: A screening test that checks your blood for antibodies to the Epstein-Barr virus. This test gives results within a day, but it may not detect the infection during the first week of the illness^[4]. The CDC does not recommend using this test at home because it is not very accurate. The test can have false-positive and false-negative results, which means that it could find EBV when you do not have the virus or miss EBV when you do have it^[4].

Treatment and Recovery

There is no specific treatment for EBV. Most people get better in 2 to 4 weeks without medical treatment^[2]. As with other viruses, Epstein-Barr cannot be treated with antibiotics because antibiotics do not work against viral infections^[4]. Treatment mainly involves taking care of yourself and managing symptoms^[1].

Things you can do to help relieve symptoms include:

• Drinking fluids to stay hydrated
• Getting plenty of rest
• Taking over-the-counter medications for pain and fever

Do not fight the fatigue. Try to increase your sleep overnight and take naps when you can to give your body a chance to heal^[4]. If you have symptoms like a fever or sore throat, take acetaminophen or ibuprofen consistently until you feel better^[4].

Short courses of corticosteroids (medications that reduce swelling) are indicated for EBV infectious mononucleosis with severe complications such as hemolytic anemia, low platelet count, involvement of the central nervous system, or extreme tonsillar enlargement. However, corticosteroids are not indicated for uncomplicated EBV infectious mononucleosis^[12]. Corticosteroids should be considered in those with impending airway obstruction^[12].

No effective antiviral therapy is available for EBV infectious mononucleosis in immunocompetent persons. Acyclovir and ganciclovir may reduce EBV shedding, but are ineffective clinically^[12].

Because mono can enlarge the spleen, avoiding contact sports for four weeks is recommended to prevent injury^[7]. Most people will feel better after one to two weeks, but sometimes symptoms can affect you for up to four weeks or longer^[7].

Potential Complications

While most people recover from EBV without any long-term complications, some individuals may experience lingering symptoms or develop more serious conditions. EBV is implicated in many health problems beyond infectious mononucleosis^[5].

The virus has been associated with various cancers. About 200,000 cancer cases globally per year are thought to be attributable to EBV^[3]. These include:

• Burkitt lymphoma
• Hodgkin’s lymphoma
• Nasopharyngeal carcinoma
• Gastric cancer
• Various non-Hodgkin lymphomas in immunocompromised patients

EBV has also been linked to autoimmune conditions. Higher risks of developing certain autoimmune diseases have been associated with EBV infection, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome^[3].

In 2022, a large study following 10 million active US military personnel over 20 years suggested EBV as the leading cause of multiple sclerosis (MS), with a recent EBV infection causing a 32-fold increase in MS risk development^[3].

The virus is also associated with the childhood disorders of Alice in Wonderland syndrome and acute cerebellar ataxia^[3]. Other rare complications can include inflammation of the heart muscles and brain^[6].

Prevention

There is no vaccine to protect against EBV infection^[2]. Various vaccine formulations have been tested in humans and other animals; however, none of them were able to prevent EBV infection, so no vaccine has been approved to date^[3]. Cutting-edge research is underway to develop vaccines to protect against EBV and related herpesviruses^[6].

You can help protect yourself by reducing contact with people who have EBV infection. Make sure you avoid:

• Kissing people who are infected
• Sharing drinks and food
• Using the same personal items (toothbrushes, cups, utensils) that an infected person recently used

Because EBV is so common and spreads easily, there is nothing you can do to completely prevent getting it^[7]. For this reason and because most people will be exposed to the viruses that cause mono at some point in their life, prevention focuses on good hygiene practices.

Continue to wash your hands often using soap and warm water, cover your mouth when you cough or sneeze, and do not share drinks. This will help prevent other more serious infections from spreading, like influenza and COVID-19^[7].

Chronic Active EBV

Chronic active EBV (CAEBV) disease is a very rare disease in the United States and Europe, but occurs more frequently in Asia and South America^[11]. Unlike most EBV disorders, the vast majority of cases of CAEBV in Asia and South America are due to EBV present in either T cells or NK cells (natural killer cells). In contrast, EBV is often in B cells in patients with CAEBV in the United States^[11].

This disease is defined as beginning with an acute EBV infection, having markedly elevated antibodies against EBV, or having a markedly elevated EBV DNA level in the blood^[11]. There must also be evidence of organ infiltration with virus-infected cells and detection of EBV protein or nucleic acid in tissue.

Most patients with CAEBV present with fever, liver dysfunction, and enlarged spleen. About half of patients have swollen lymph nodes, low platelet count, and anemia^[11]. Other frequent symptoms include hypersensitivity to mosquito bites, rash, hemophagocytic syndrome, and coronary artery aneurysms. Less common features include calcification of basal ganglia, oral ulcers, lymphoma, interstitial pneumonia, and central nervous system disease.

Death from CAEBV is frequently due to liver failure, malignant lymphoma, or opportunistic infections^[11]. Treatment of CAEBV is controversial, and several immunologic abnormalities have been noted with this condition. The optimal treatment approach is still being studied^[11].

Related Health Conditions

EBV has been implicated in numerous health conditions beyond infectious mononucleosis and cancer. The virus is best known for causing infectious mononucleosis (glandular fever) in adolescents and young adults, although primary EBV infection can be asymptomatic, particularly in children^[8].

EBV can cause disorders with visible symptoms on the skin and mucous membranes. These include oral hairy leukoplakia (asymptomatic white plaques on the lateral tongue), papular acrodermatitis of childhood (a papular rash over buttocks, thighs, arms, and face), and non-sexually acquired genital ulceration^[8].

The virus has been postulated to trigger a number of autoimmune conditions in genetically predisposed individuals. EBV may be implicated in conditions such as pityriasis lichenoides and Langerhans cell histiocytosis^[8].

EBV is also associated with various non-malignant, premalignant, and malignant EBV-associated lymphoproliferative diseases. These include hemophagocytic lymphohistiocytosis and conditions associated with human immunodeficiency virus such as hairy leukoplakia and central nervous system lymphomas^[3].