Investigations
1st investigations to order
FBC
Test
Lymphocytosis with greater than 50% lymphocytes seen in 70% cases.[34] Highest in second and third week.[48]
Atypical lymphocytosis greater than 10% seen in up to 90% cases, but is not specific for Epstein-Barr virus (EBV).[34]
Anaemia and reticulocytosis can also identify patients with haemolytic anaemia secondary to EBV infection.
Haematological abnormalities can be absent in young children.
The sensitivity of this test is moderate.[39]
Result
lymphocytosis, atypical lymphocytosis
heterophile antibodies
Test
Non-specific for Epstein-Barr virus (EBV) infection. IgM antibodies agglutinate red cells from other species (sheep, horse, goat, bovine).
Commonly used Monospot test is a rapid qualitative slide agglutination test using horse or bovine red cells.
Prevalence in acute phase varies from 50% to 85% depending on age.[40] Once detected may persist for 6 to 12 months.
For 6 different commercial tests for heterophile antibodies, sensitivities ranged from 81% to 95%, and specificities ranged from 98% to 100%.[38] However, these tests can be less sensitive in early disease in adults. False-negative rates of 25% are found in the first week, and 5% to 10% in the second and third week.[37][39] Nearly 10% of adult patients with IM will be persistently heterophile antibody negative. The test may also be negative in children under 4 years of age.[40] False-positive tests are possible in patients with autoimmune diseases, cytomegalovirus, toxoplasmosis, rubella, and lymphoma. False-positive test is also possible in patients with acute retroviral syndrome from an early HIV infection.
In patients with IM symptoms and lymphocytosis, but negative heterophile antibodies, testing for EBV-specific antibodies is indicated.
Result
positive heterophile antibodies
Epstein-Barr virus (EBV)-specific antibodies
Test
This test has a high sensitivity and specificity and is more sensitive than heterophile antibody test; the sensitivity of 6 commercial tests ranged from 95% to 99% and specificity from 86% to 100%.[37][38][39] It is often positive in young children with asymptomatic disease.
The specific antigens are important for distinguishing between acute and past infection.
Viral capsid antigen-IgM (VCA-IgM) in most patients is detectable with symptom onset; peaks at 2 to 3 weeks; becomes unmeasurable by 4 months.
VCA-IgG peaks at 2 to 3 months; persists for life.
Antibodies to early antigens (EA) rise in acute stage; become undetectable by 3 to 4 months; may reappear with reactivation of EBV infection. EA antibodies are also detectable in some clinically healthy persons.
Nuclear antigen (EBNA) antibodies rise in resolution phase, and remain detectable for life.[40] These antibodies develop after 6 to 8 weeks and can be used to identify past infection, or as evidence to rule out acute EBV infection.[41]
Detection of EBV antibodies, VCA-IgG, VCA-IgM, and EBNA is possible in cerebrospinal fluid of patients with EBV encephalitis.[49]
Result
positive for EBV-specific antibodies: VCA-IgM, VCA-IgG, EA, EBV EBNA
LFTs
Test
Transaminase elevations are usually transient and mild (2-3 times the upper limit of normal), but in some patients much higher transaminase elevations (5-10 times the upper limit of normal) are observed.[46]
Result
elevated
Investigations to consider
real-time polymerase chain reaction (PCR)
Test
Real-time PCR is when the amplified DNA is detected as the reaction progresses in real time. Test has 95% sensitivity and 97% specificity for primary EBV infection.[50]A meta-analysis found that pooled sensitivity for detecting EBV DNA by PCR was 77% and pooled specificity was 98%.[51]
Is expensive and not commonly used in clinical practice.
Test can be useful for diagnosis of serologically indeterminate EBV infections.[42]
EBV nucleic acid amplification test is useful for detecting EBV in the cerebrospinal fluid of patients with EBV encephalitis.[49]
Emerging data shows that PCR has a higher diagnostic value than VCA-IgG in children aged <6 years, especially those aged <3 years.[52]
Result
EBV DNA detection
ultrasonography of abdomen
Test
This is not a routine investigation but it can help detect splenomegaly when it is not evident on clinical examination. If EBV-specific laboratory tests are negative in a patient with splenomegaly, a different diagnosis should be sought to explain the splenomegaly.
It can be used to monitor spleen size and also to check if it has returned to a normal size before allowing a patient to take part in contact sports.
Result
splenomegaly
CT of abdomen
Test
Performed on a haemodynamically stable patient when splenic rupture is suspected.
Result
splenic rupture
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