Pediatric Mononucleosis and Epstein-Barr Virus Infection Treatment & Management

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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Approach Considerations

The mainstay of treatment for infectious mononucleosis is supportive care, including adequate hydration, nonsteroidal anti-inflammatory drugs or acetaminophen, and throat lozenges or sprays. [46]

If diagnosis is firmly established, only supportive care is required in the absence of significant complications.

There is no currently accepted specific treatment for infectious mononucleosis. Acyclovir and valacyclovir have an antiviral effect in vivo. A clinical benefit has not been convincingly demonstrated to date. [53]  Acyclovir combined with prednisolone inhibited oropharyngeal Epstein-Barr virus (EBV) replication without affecting duration of clinical symptoms or development of EBV-specific cellular immunity. [54]

Ganciclovir and valganciclovir have been used to treat EBV infections in immunocompromised hosts, but there are no controlled trials demonstrating clinical efficacy. Corticosteroids are often prescribed to treat inflammatory complications, such as airway obstruction, or autoimmune phenomena, such as anemia and thrombocytopenia, but the value of these drugs is controversial and they may impair clearance of the viral load. [22]

Patients with uncomplicated infectious mononucleosis rarely require inpatient therapy.

Hospitalization is warranted in the presence of splenic rupture, airway compromise, dehydration, significant thrombocytopenia or hemolytic anemia, and neurologic or other major complications.

Transfer to a tertiary care center may be necessary for the treatment of significant complications.


Medical Care

Infectious mononucleosis is a self-limited illness that does not usually require specific therapy in patients with mild or moderate illness. However, if the tonsils are markedly enlarged (kissing tonsils) or if the patient has prolonged illness, most experts recommend a short course of steroids (1-2 mg/kg of prednisone daily for 3-7 days).

Because of low transmissibility of Epstein-Barr virus (EBV), isolation is not indicated.

Most affected individuals can be evaluated and treated as outpatients. Inpatient therapy of medical and surgical complications may be required.

Patients with chronic post–Epstein-Barr virus fatigue (chronic fatigue syndrome [CFS]) may benefit from psychological and behavioral approaches. [55]


Surgical Care

Splenic rupture is an acute abdominal emergency that usually requires surgical intervention. [34]  Rupture may occur with trauma as minor as palpation, and is occasionally the presenting symptom.

Diagnosis can be confirmed using imaging procedures or peritoneal lavage in an unstable patient.

Splenectomy is usually required. Occasionally, observation and supportive measures are adequate treatment for a hemodynamically stable patient.

Although partial splenectomy or suturing the capsular tear has been advocated to preserve splenic function, the acute changes that led to rupture militate against the success of this approach.



Surgical consultation should be sought when the patient has abdominal pain or evidence of shock.

Consultation with the appropriate subspecialist is indicated for management of significant complications (eg, infectious diseases, hematology/oncology, immunology).


Diet and Activity


No dietary modifications are required.


Acceptable activity level during the acute illness depends on severity of the patient's symptoms.

Extreme fatigue may require bed rest for 1-2 weeks or even more.

Malaise may persist for 2-3 months, and activity can increase as tolerated.

Patients should not participate in contact sports or heavy lifting for at least 2-3 weeks, although some authors recommend avoiding activities that may cause splenic trauma for 2 months. [33, 34]








Long-Term Monitoring

Monitoring for long-term complications

EBV infection has been associated with a number of different malignancies of both lymphoid and epithelial origin and accounts for 1.8% of all cancer-related deaths worldwide. 

The criteria for association of EBV with cancer includes the following:

  • Finding the viral genome in every tumor cell
  • Presence of viral gene expression
  • Evidence that EBV is clonal (or oligoclonal) in the tumor cells

Each year worldwide there are about 84,000 cases of gastric carcinoma, 78,000 cases of nasopharyngeal carcinoma, 29,000 cases of Hodgkin lymphoma, 7000 cases of Burkitt lymphoma, and 2000 cases of lymphoma in transplant recipients associated with EBV [56] . About 9% of gastric carcinomas are associated with EBV; 90% of gastric lymphoepitheliomas, 7% of moderately to well-differentiated adenocarcinomas, and 6% of poorly differentiated gastric adenocarcinomas are EBV-positive. Virtually all anaplastic nasopharyngeal carcinomas contain EBV genomes. The incidence of nasopharyngeal carcinoma is particularly high in southern China with a rate of 80 per 100,000 in men > 40 years old. In developed countries about 30-40% of Hodgkin lymphomas are EBV-positive, whereas 80-90% of these lymphomas are EBV-positive in developing countries. About 85% of Burkitt lymphomas in Africa are EBV-positive, whereas about 15% of these tumors in the United States are virus-positive. [14]

In sub-Sahara Africa, the incidence of Burkitt lymphoma is 20 per 100,000 in children between the ages of 5 and 9 years old. The rate of EBV post-transplant lymphomas varies among the type of transplant ranging from about 1% in renal and hematopoietic stem cell transplant recipients to about 10% in intestinal transplant recipients.

Up to 10% of seronegative children receiving a solid organ transplant may develop EBV post-transplant lymphoproliferative disease. Patients with primary or aquired immunodeficiency are at increased risk for potentially fatal EBV-related lymphoproliferative disorders, such as post-transplant lymphoproliferative disorder, and B-cell lymphoma. Patients with HIV are at increased risk for EBV-associated malignancies including Burkitt lymphoma, diffuse large B cell lymphoma, Hodgkin lymphoma, immunoblastic lymphoma, primary central nervous system lymphoma, and smooth muscle tumors. [14]