University of Delaware UD Medical Technology National Institutes of Health

Epstein-Barr Virus: A Complete Guide

by Matthew Delmonico
95 % of Adults are infected with EBV worldwide. This image was taken from a copyright free source.
95% of Adults worldwide are infected with EBV
this is a copyright free image

Introduction

The Epstein-Barr Virus (EBV) is most commonly associated with the disease mononucleosis, also known as "the kissing disease" due to its primary mode of infection. Few however realize that  EBV is a very common virus amongst human and often causes no disease at all. According to the World Health Organization (WHO) serologic tests show that approximately 95% of adults worldwide and the United States have been infected by EBV. EBV has been linked to mild childhood sickness, to infectious mononucleosis in adolescent's, and to Burkitt's lymphoma and nasopharyngeal carcinoma.1

Use the links below to navigate throughout the page.

Etiology- Disease Formation
Epidemiology- Distribution of Disease
Pathogenesis- Disease Causation
Signs, Symptoms, and Sequallae of Disease
Diagnosis of Disease
EBV Testing
Treatment and Prevention
About the Author
References

Etiology

The Epstein-Barr Virus (EBV)  according to the WHO website, " belongs to the genus Lymphocryptovirus, in the subfamily Gammaherpesvirinae, family Herpesviridae".  This means that EBV is an enveloped herpes virus which like most herpes viruses causes a life-long latent infection. EBV has a double stranded DNA genome which is more stable than RNA thus having a lower incidence of mutations.1

The Epstein-Barr Virus can cause multiple disease states depending on during which stage of life a person is infected or the effects of a latent infection.

Early Childhood-
 If infected during early childhood children present with symptoms indistinguishable from most other common childhood diseases. A certain percentage of young children may exhibit no symptoms of infection.2

Adolescence and Young Adulthood-
EBV is the most common cause of infectious Mononucelosis in young adults.

Other diseases:
EBV is thought to play a critical role in two cancers:
Burkitt's lymphoma and nasopharyngeal carcinoma.The CDC sites EBV as a factor in these cancers2, but the WHO lists EBV as one of 3 viruses known to be the causative agents in cancer1.  Return to top.

Epidemiology

As stated previously  EBV infects approximately 95% of the world's adult population.

Prevalence of EBV and associated disease states in the United States:

    The CDC states that 95% of adults between 35 and 40 years of age have been infected with EBV. Additionally they state that of those who are infected with EBV during their adolecence or young adulthood between 30 and 50% develop infectious mononucleosis. As for the prevalence of EBV associated with Burkitt's lymphoma and nasopharyngeal carcinoma in the United States, the CDC does not even list the names of these diseases and calls them "rare" and "not normally found".2 The WHO, however, gives a more detailed picture of these diseases prevalence and association in the United states. The WHO reports that Burkitt's lymphoma has only a 10-15% association with the EBV. This shows that in the USA the EBV is not  the causitive agent of the disease rather a contributing factor. The incidence of nasopharyngeal carcinoma  in most populations including the USA is 1 in 100,000. In the USA most cases are is those of Chinese origin and those exposed to fumes, smoke, and chemicals.1 Overall, EBV is a very common disease which most commonly causes non-distinct mild sickness in children, and infectious mononucleosis in young people. Most others infected with EBV are asymptomatic and are carriers of the disease.

Prevalence of EBV and associated disease states Worldwide:

    The WHO does not report any information regarding the incidence of EBV infections during adolescence worldwide and no clear information regarding infectious mononucelosis. The WHO does detail the incidence of Burkitt's lymphoma and nasopharyngeal carcinoma.  Burkitt's lymphoma(BL) is endemic to central Africa which is known as the lymphoma belt. There are 6-7 cases per 100,000 of BL in this region with the peak age if incidence at 6 to 7 years old.  In the "lymphoma belt" which is between the 10th degrees parallel above and below the equator. In this region there is a 97% association between BL and EBV.1 The other cancer associated with EBV, nasopharyngeal carcinoma, is seen in a higher incidence in only a few regions worldwide. The highest incidence, 20 per 100,000, is in Southern China; other regions are Kuwait, Israel, and the "lymphoma belt". Additionally, Nasopharyngeal carcinoma affects men twice as often as men and most common between ages 20 and 50.1 Return to top.

Pathogenesis

    In the case of EBV  both epithelial cells and human B-lymphocytes are infected.Epithelial cells are infected during the active phase of the infection and this is where viral replication occurs. Memory B-lymphocytes on the other hand are where the latent EBV virus resides.1 EBV is often found in human saliva, this can be during an active disease state or most commonly during a periodic reactivation which occurs without any symptoms.2 Due to this fact most infections are due to direct contact with an infected persons saliva. Human beings are the primary reservoir for EBV due to the fact that EBV will stay latent in a person for their lifetime and reactivation.1 Return to top.

Signs, Symptoms, and Sequallae

Infectious Mononucleosis-
    According to CDC and the WHO the three most notable symptoms of  Mononucleosis are fever, sore throat, and swollen lymph nodes. Sore throat is due to the lysis of the oropharyngeal epithelial cells due to the replication of EBV. Fever is due to the non-specific immune response to the infection, and swollen lymph nodes are due to the infection spreading to resting B-lymphocytes and due to the increased involvement of the immune system. Other notable distinguishing features of mononucleosis are extreme fatigue(asthenia), an enlarged spleen (splenomegaly), enlarged number of white blood cells (wbc), and the presence of atypical lyphocytes.3 EBV can take anywhere from 30 to 50 days to incubate and can be spead during this time. 1
   Streptococcus pyogenese infection of the throat is often found to accompay infectious mononucelosis due to EBV infection.3 As discussed previously EBV does remain latent and can cause Burkett's Lymphoma and nasopharyngeal carcinoma due to infection but these are very rare.1 It was once thought that EBV played a role in chronic fatigue syndrome, but no link has been found.3 Return to top.

Diagnosis of Disease

    Mononucelosis is a common disease that can often be confused with other bacterial and viral diseases because of  its symptoms which often mirror other sicknesses.  The occurrence of fever, sore throat, and swollen lymph nodes which last 1-4 weeks denote infectious mononucleosis.If the patient presents with these symptoms and is between 12-20 mononucleosis is a strong possibility.2 In order to confirm the disease state a "monospot" test can be performed to test for  Paul-Bunnell heterophile antibody. If the "monospot" is positive no additional testing is needed.2 If continued testing is needed then a slightly elevated white blood cell count along with the presence of 10% atypical lymphocytes are sufficient to diagnose infectious mononucleosis, additional antibody testing to other EBV specific antigens are also helpful.3Tissue cultures are used primarily for research and are not used in diagnosis.2  Return to top.

EBV Testing

    In order to diagnose infectious mononucleosis three primary tests are used Monospot, EBVA, and CBC. The Monospot test is used in order to identify heterophile antibody in human serum. This test can be a false negative in children because they do not produce heterophile antibody; false positives can be due to Systemic Lupus or other autoimmune diseases which also produce heterophile antibodies.3 Monospot is a screening test and if it is negative but a patient has symptoms  commonly associated with Mononucleosis Epstein-Barr Virus Antibody test can be used.2 EBVA tests for viral capsid antibody(VCA)-Igm,IgG and early antigen-IgD all of which indicate a recent or current EBV infection. VCA-IgG and Epstein-Barr nuclear antigen (EBNA) indicate past EBV infections. White Blood Cell count is used to diagnose Mononucleosis if there is elevated overall WBC  and 10% atypical lymphocytes indicate EBV infection. 4
Test Reference Range Expected results Screening or Confirmatory
Monospot Negtive Positive Screening
EBVA Negative (for current infection) Negative (for current infection) Confirmatory
White Blood Cell count Lymphocytes 20-50% 10% atypical lymphocytes
Increased WBCs
Screening4
Return to top.

Treatment and Prevention

    Treatment of Mononucleosis is to manage the symptoms. According to the Merck Manual antiviral agents have been proven not to be effective in shortening the course of the infection or alleviating symptoms. It is advised to take Acetomeniphen or a Non-Steroidal Anti-Inflammatory Drug (NSAID) to help with fever and overall discomfort. Corticosteroids can be used to help alleviate swelling of the airway when necessary.3
    Prevention of EBV is almost impossible with 95% of the worlds population infected with EBV. If one is trying to avoid infection they can avoid contact with an infected persons saliva. Overall there are not many methods of EBV infection prevention.1  Return to top.

About the Author

     My hope is that this website provides those looking for a better understanding of the Epstein-Barr Virus with exactly that as well as emphasize the role of clinical testing in the diagnosis of EBV infection.
     I am a Junior Medical Technology Major at the University of Delaware with a concentration in Pre-Med. AtI work as a Resident Assistant in the Dickinson Complex. I am also the Executive Vice President of the National Residence Hall Honorary Chapter here on campus. Additionally, I was recently accepted into the National Society of Collegiate Scholars here at UD. My future career goal is to go to Medical School, osteopathic or allopathic, I really enjoy patient interaction so I am thinking of pursuing Emergency Medicine or Dermatology. Return to top.

References

1. Initiative for Vaccine Research: Epstein-Barr Virus. World Health Organization Website. http://www.who.int/en/. Acessed November 1, 2009.
2. Epstein-Barr Virus and Infectious Mononucelosis. Centers for Disease Control and Prevention Website. http://www.cdc.gov. Updated May 16, 2006. Acessed November 1, 2009.
3.The Merck Manual Online Medical Library: Infectious Mononucleosis. Merck Website. http://www.merck.com/mmpe/. Updated November 2005. Acessed November 1, 2009.
4. Epstein-Barr Virus Antibodies. Lab Tests Online Website. http://www.labtestsonline.org/. Updated October 31, 2009. Acessed November 1, 2009.