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Diagnosing Mononucleosis


What is EBV?

EBV is one of the most common human viruses across the world, and is a part of the human herpesvirus family. The CDC notes that EBV is the main cause of infectious mononucleosis (IM) and is the causative agent in approximately 80-90% of cases. Other causes of IM may be due to agents including: CMV, streptococcus pyogenes, toxoplasma gondii, hepatitis A and B, just to name a few.


Many of you may know this disease as being referred to as the “kissing disease,” most commonly transmitted through saliva, with the rare potential of being transmitted through blood and sexual intercourse.  It is important to recognize that the incubation period for this disease can be as long as 30-60 days with potential long-term shedding of EBV for as long as 6 months after the onset of symptoms, from the oropharynx.


When evaluating patients in the clinic for suspected mono, the CDC lists several symptoms which may be present including:

  • Fatigue
  • fever
  • inflamed throat
  • cervical or general lymphadenopathy
  • splenomegaly
  • hepatomegaly or
  • rash

Most commonly patients present with a triad of symptoms: fever, pharyngitis posterior lymphadenopathy. Many patients also have tonsillar enlargement and exudate, as well. Symptoms may not be present until at least 1-2 weeks after onset of illness and are more commonly present in teenagers and adults with improvement noted, usually, within a month of onset.


When suspicious for infectious mononucleosis, several options are available to aid diagnosis. Keeping in mind that approximately 90% of adults will be noted to have antibodies that show they have been exposed to EBV, it is important to match laboratory findings with clinical presentation.

  • The most commonly used test in the office to evaluate for IM is the positive agglutination test, ie monospot, which evaluates for the presence of heterophile antibodies. Sensitivity and specificity ranges from 81-95% and 98-100%, respectively.
  • Though the most accurate test to do is a serologic test looking for signs of EBV-specific antibodies that are directed against EBV. This test has much better sensitivity and specificity at 95-99% and 86-100%, respectively.
  • A CBC may also prove to be useful by evaluating for elevated lymphocyte count as well as anemia and reticulocytosis which may be present secondary to EBV.
  • Ultrasonography is reserved for evaluation of splenomegaly and monitoring for changes in spleen size.

Differential: One common differential diagnosis for IM is Group A beta-hemolytic streptococcus (GABHS). Differentiating IM from GABHS may be challenging, since presenting symptoms closely mimic each other. When evaluating a patient, utilizing the Centor clinical scoring criteria may help strengthen a bacterial pharyngitis diagnosis over that of Infectious Mononucleosis, but should never be used in place of diagnostic testing in children or in cases where diagnosis is not clear.

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Notice that GABHS will present with anterior cervical lymphadenopathy, while mononucleosis presents with posterior cervical lymphadenopathy or generalized lymphadenopathy.

Patient education points:

It is important to educate patients and family regarding the potential spread of EBV and encourage patients regarding proper hygiene practices. Examples include avoidance of kissing while actively infected, not sharing drinks and food, and avoid sharing items with people such as kitchen utensils or toothbrushes. Because IM is primarily caused by a virus, abx treatment is not indicated. If antibiotics such as amoxicillin, ampicillin or other beta-lactam antibiotics are prescribed in the presence of EBV, a maculopapular and pruritic rash may present approximately 5 to 10 days after treatment onset. Given that IM has a viral etiology, treatment focus rests in management of symptoms.

By Tracy Lindstrom RN, BSN, DNP-S


Fafi-Kremer, S., Morand, P., Brion, JP et al. (2005). Long-term shedding of infectious Epstein-Barr virus after infectious mononucleosis. Journal of Infectious Disease. 191. 985-989.

Auwaerter, P, (2006). Recent advances in the understanding of infectious mononucleosis: Are prospects improved for treatment or control? Expert Review of Anti Infectious Theory. 4: 1039-1049

CDC (2014). About Epstein-Barr Virus (EBV). Obtained from http://www.cdc.gov/epstein-barr/about-ebv.html

Turabelidze, G., Kalilani, L, Auwaerter, P. (2014). Infectious mononucleosis. Epocrates.

Ruppert, S. (2015). Pharyngitis. The Nurse Practitioner. 40(7). 18-25

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Tracy Lindstrom
Tracy Lindstrom has been a registered nurse for 10 years with experience working in ICU, Home Health, and Case Management. She is currently working on completing her Doctorate in Nursing Practice at Wichita State University (Go Shox!!), with plans to work in family practice after graduation, focusing on underserved populations. She enjoys spending time with her husband, three beautiful daughters and 2 dogs.