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Infectious mononucleosis - Diagnosis

, medical expert
Last reviewed: 03.07.2025
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Diagnosis of infectious mononucleosis is based on a complex of leading clinical symptoms (fever, lymphadenopathy, enlarged liver and spleen, changes in peripheral blood).

In addition to examining the blood picture, diagnostics are based on the detection of heterophilic antibodies and specific antibodies to the Epstein-Barr virus.

Heterogeneous antibodies. Modified heterohemagglutination reactions are used: the Paul-Bunnell reaction (sheep erythrocyte agglutination reaction) is currently not recommended due to its low specificity. The Hoff-Bauer reaction is agglutination of formalinized horse erythrocytes (4% suspension) with the patient's blood serum; the reaction is carried out on glass, the results are taken into account after 2 minutes; it can be used for express diagnostics. Heterophile antibody titers reach a maximum at 4-5 weeks from the onset of the disease, then decrease and can persist for 6-12 months. However, this reaction can also give false positive and false negative results.

A more specific and sensitive diagnostics of infectious mononucleosis is based on the determination of antibody markers of Epstein-Barr virus antigens (IRIF, ELISA), which allow determining the form of infection.

Diagnostic value of antibodies to the Epstein-Barr virus

Antibodies

Form of infection

IgM to capsid antigen

Igl to capsid antigen

To nuclear antigen, amount

To early antigens, the sum

Not infected

-

-

-

-

Acute stage of primary infection

--

-+--

-

-+

Infection suffered up to 6 months ago

-

-+-

-

-+

Infection suffered more than 1 year ago

-

+--

-

-

Chronic infection, reactivation

-

----

-

--+

Malignant neoplasms associated with EBV

-

----

-

-++

Antibodies (IgM) to the capsid antigen in infectious mononucleosis are detected from the end of the incubation period, they are determined for no more than 2-3 months. Igl to the capsid antigen appear in the acute period of infection and persist for life. Antibodies to early antigens (IgM) appear at the height of the disease in 70-80% of patients and quickly disappear, and antibodies to Igl persist for a long time. An increase in the titer of antibodies to early antigens is characteristic of reactivation of EBV infection and for tumors caused by this virus. Antibodies against the nuclear antigen appear 6 months after infection and persist in low titers for life.

An additional confirmation of EBV infection can be a test for the detection of viral DNA in blood or saliva using the PCR method. Its use is effective for detecting EBV infection in newborns, when the determination of serological markers is ineffective due to the formed immune system, as well as in complex and questionable cases when diagnosing Epstein-Barr virus in adults.

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Indications for consultation with other specialists

All patients diagnosed with infectious mononucleosis or suspected of having it must be tested for HIV infection during the acute period of the disease, and after 1, 3, and 6 months during the recovery period.

If hematological changes persist, a consultation and examination with a hematologist is indicated; if abdominal pain occurs, a consultation with a surgeon and an ultrasound of the abdominal organs are indicated.

If neurological symptoms appear, a consultation with a neurologist is necessary.

Indications for hospitalization

Patients are hospitalized based on clinical indications. The main indications for hospitalization and inpatient treatment are: prolonged high fever, jaundice, complications, and complex diagnostics of infectious mononucleosis.

Differential diagnosis of infectious mononucleosis

Differential diagnostics of infectious mononucleosis is carried out with febrile diseases occurring with lymphadenopathy and hepatosplenic syndrome; occurring with acute tonsillitis syndrome and occurring with the presence of atypical mononuclear cells in the blood.

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