Pediatric Mononucleosis and Epstein-Barr Virus Infection Follow-up

Updated: Mar 22, 2021
  • Author: Jaya Sureshbabu, MBBS, MRCPCH(UK), MRCPI(Paeds), MRCPS(Glasg), DCH(Glasg); Chief Editor: Russell W Steele, MD  more...
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Inpatient & Outpatient Medications

Nonspecific treatment includes saline gargles and acetaminophen or ibuprofen for sore throat, fever, and myalgia. Constipation may be treated with a laxative.

Acyclovir has no demonstrable benefit for treatment of uncomplicated infectious mononucleosis in placebo-controlled trials.

Various therapies are used for complications of Epstein-Barr virus (EBV) infection, although only a few have been studied in controlled trials. Corticosteroids are used for treatment of severe airway obstruction due to tonsillar enlargement, hemolytic anemia, and severe thrombocytopenia. They may decrease the duration of febrile illness and constitutional symptoms, but their routine use for treatment of a virus known to be related to tumor development is discouraged.

Interferon-alfa decreases shedding of Epstein-Barr virus in renal transplant recipients. [62]

Acyclovir and desciclovir can reverse Epstein-Barr virus–associated hairy leukoplakia in patients with HIV. [63] Acyclovir has been used to treat interstitial pneumonitis, [64] X-linked lymphoproliferative syndrome, and lymphoproliferative disorders. Posttransplant lymphoproliferative disorder (PTLD) has been treated with ganciclovir and cytomegalovirus (CMV) intravenous immunoglobulin (CytoGam). High-dose (20mg/kg/dose q8 hours, IV) is probably required to be effective.

Immune thrombocytopenia has been treated with intravenous immunoglobulin. [65]

Whether corticosteroids are beneficial or harmful in patients with encephalitis, pericarditis, and myocarditis is unclear.

Combination therapy with corticosteroids and acyclovir has been reported, with varying outcomes.



Patients with primary infectious mononucleosis do not require any isolation. Epstein-Barr virus has low transmissibility and cannot be acquired from environmental surfaces or fomites.

Avoid contact with saliva. Epstein-Barr virus is present in throat washings of individuals with acute infectious mononucleosis. Virus can be cultured from the oropharynx for up to 18 months. It can be recovered from the oropharynx of 10-20% of healthy adults. Epstein-Barr virus infection is usually acquired through contact between a susceptible individual and the saliva of an asymptomatic individual who is shedding Epstein-Barr virus. In young children, saliva is spread by drooling and hand-to-mouth behaviors. In adolescents, infected saliva may be transferred by kissing, hence the label "kissing disease."

Use good hand washing techniques with adequate soap and water 

Do not kiss children on the mouth.

Maintain clean conditions, especially when young children are present (eg, in daycare), and avoid children sharing the toys.

Epstein-Barr virus can be transmitted by blood transfusion and by bone marrow transplantation. However, because the organism is so common, no procedures are in place to prevent this.

Vaccine development is proceeding, although the role of a vaccine is unclear. [13, 66, 67, 68]



Complications encountered after infectious mononucleosis include the following:

  • Acute interstitial nephritis
  • Hemolytic anemia
  • Myocarditis and cardiac conduction abnormalities
  • Neurologic abnormalities, multiple sclerosis
  • Cranial nerve palsies
  • Encephalitis
  • Aseptic meningitis
  • Mononeuropathies
  • Retrobulbar neuritis
  • Thrombocytopenia
  • Upper airway obstruction due swollen tonsils

Hepatitis develops in more than 90% of patients with infectious mononucleosis. Liver function test results are mildly elevated but are usually no more than 2-3 times the reference range. Bilirubin levels are elevated in approximately 45% of patients, but jaundice occurs in only 5%. Liver abnormalities are most pronounced in the second and third weeks of illness.

Approximately 50% of patients with infectious mononucleosis develop mild thrombocytopenia. The platelet count is usually 100,000-140,000/mL. The platelet count usually reaches its nadir approximately 1 week after symptom onset and then gradually improves over the next 3-4 weeks. Thrombocytopenia may be caused by the production of antiplatelet antibodies and peripheral destruction, especially in the enlarged spleen.

Hemolytic anemia occurs in 0.5-3% of patients with infectious mononucleosis. Hemolytic anemia has been associated with cold-reactive antibodies, with anti-I antibodies, and with autoantibodies to triphosphate isomerase. Hemolysis is usually mild and is most significant during the second and third weeks of symptoms.

Upper airway obstruction due to hypertrophy of tonsils and other lymph nodes in the Waldeyer ring occurs in 0.1-1% of patients. Treatment with corticosteroids may be beneficial. Patients with severe tonsillar and lymph node enlargement with impending airway obstruction may require intubation or tracheostomy. Patients who require hospitalization may have concurrent streptococcal pharyngitis. Two thirds of patients admitted with infectious mononucleosis with upper airway obstruction and dehydration have alpha-hemolytic Streptococcus infection, usually due to group C streptococci.

Splenic rupture occurs in 0.1-0.2% of patients with infectious mononucleosis. A literature review by Bartlett et al indicated that the risk of splenic rupture is greatest in males under 30 years with infectious mononucleosis symptom onset within the previous 4 weeks. [69] Rupture may be spontaneous, although the patient often has a history of some antecedent trauma. Rupture is most likely during the second and third weeks of clinical symptoms. Patients can present with mild-to-severe abdominal pain below the left costal margin, sometimes with radiation to the left shoulder and supraclavicular area. Massive bleeding may be accompanied by peritoneal irritation and shifting dullness. Shock may be the only presenting symptom. Because bradycardia is common in infectious mononucleosis, tachycardia with pulse of faster than 100 beats per minute is an important sign. Neutrophilia (instead of lymphocytosis) can occur. Surgical intervention is usually required.

Hematologic complications are as follows:

  • Epstein-Barr virus has been implicated in hemophagocytic syndrome. [70, 71, 72]

  • Immune thrombocytopenic purpura occurs and may evolve to aplastic anemia. Aplastic anemia and neutropenia are sometimes associated with antineutrophil antibodies.

  • Epstein-Barr virus infection may accelerate hemolytic anemia in individuals with congenital spherocytosis or hereditary elliptocytosis.

  • Disseminated intravascular coagulation associated with hepatic necrosis has occurred.

Neurologic complications are as follows:

  • Neurologic complications occur in less than 1% of patients with Epstein-Barr virus infections and usually develop during the first 2 weeks. In some patients, especially children, the neurologic symptoms are the only clinical manifestation of infectious mononucleosis [73] . Patients are often negative for the heterophile antibody. However, these complications are often severe. Complete recovery is the rule, but fatalities do occur.

  • Primary Epstein-Barr virus infection has been associated with aseptic meningitis, acute viral encephalitis,and meningoencephalopathy. Hypoglossal nerve palsy, Bell palsy, brachial plexus neuropathy, and multiple cranial nerve palsies have been described. Guillain-Barré syndrome, autonomic neuropathy, GI dysfunction secondary to selective cholinergic dysautonomia, acute cerebellar ataxia, and transverse myelitis also have been reported. Metamorphopsia (ie, Alice in Wonderland syndrome) has been described.rarely.

Cardiac and pulmonary complications are as follows:

  • Pulmonary complications are extremely rare, although upper airway obstruction due to lymphoid hypertrophy is relatively common. Chronic interstitial pneumonitis and pleural effusion have been associated with Epstein-Barr virus infection.

  • Cardiac abnormalities that can occur with Epstein-Barr virus infection include myocarditis and pericarditis.

Autoimmune complications are as follows:

  • Haemolytic anaemia is reported in patients who had infectious mononucleosis

  • Infectious mononucleosis stimulates production of many antibodies not directed against Epstein-Barr virus. These include autoantibodies, anti-I antibodies, cold hemolysins, antinuclear antibodies, rheumatoid factors, cryoglobulins, and circulating immune complexes. These antibodies may precipitate autoimmune syndromes.

Miscellaneous complications are as follows:

  • Renal disorders associated with Epstein-Barr virus infection include interstitial nephritis, renal failure, and paroxysmal nocturnal hemoglobinuria.

  • After cardiac bypass or transfusion, an infectious mononucleosis–like syndrome has been described. Epstein-Barr virus may cause this, but it is more commonly associated with primary CMV infection.

  • Chronic fatigue syndrome- 20 % feel fatigue at 2 months and 13% at 6 months after primary infectious mononucleosis [73] . Myalgias, depression and hypersomnia is also reported to be associated with Epstein-Barr virus infection.



Immunocompetent individuals with acute infectious mononucleosis have a good prognosis, with full recovery expected within several months.

The common hematologic and hepatic complications resolve in 2-3 months.

Neurologic complications usually resolve quickly in children. Adults are more likely to be left with neurologic deficits.

All individuals develop latent infection, which usually remains asymptomatic.

Long-term fatigue can occur, is more common in females, and can last 1-2 years or longer. This is separate from the chronic fatigue syndrome mentioned above (although post–Epstein-Barr virus fatigue can occur, chronic fatigue syndrome has not been causally linked to Epstein-Barr virus).


Patient Education

Educate patient and family about risk of splenic rupture and the need to refrain from contact sports for 2 months.

Inform patient and family about usual course of symptoms with acute infectious mononucleosis.

For patient education resources, see the CDC website and hand-out, Bacterial and Viral Infection Center .



An effective vaccine gainst EBV is currently unavailable.

The prevalence of EBV infection is so coommon and the fact that EBV act as cofactor for development of several epithelial and lymphoid cell malignancies, the necessity for an effective vaccine is so desirable even though the feasibilty seems to difficult now.

The first EBV vaccine trial in humans used live recombinant vaccinia virus expressing gp350. [74]

A monomeric EBV gp350 vaccine in a phase 2 trial was shown to reduce the incidence of infectious mononucleosis, but not the rate of EBV infection, hence newer formulations of gp350 including multimeric forms, virus-like particles, and nanoparticles may be more effective. [14]