Cytomegalovirus - CMV

Indications for Testing

CMV is a common virus. Most people with this infection have no symptoms. However, the following populations warrant consideration for laboratory testing :

• Immunocompetent patients who present with mononucleosislike illness after testing negative for Epstein-Barr virus (EBV)
• Immunocompromised patients who present with febrile illness, hepatitis, and colitis
• Pregnant women with possible active CMV infection (infection immediately before or during the first trimester of pregnancy increases the risk of cytomegalic inclusion disease in the fetus)
• Neonates with congenital syndromes (eg, hepatosplenomegaly, microcephaly, sensorineural deafness) suggestive of CMV
• Patients receiving organ transplants

Laboratory Testing

Diagnosis

Immunocompromised Individuals

Molecular testing (eg, quantitative PCR) for viral DNA is the preferred test for detecting CMV infection because it:

• Quantifies viral load
• Provides rapid and early detection
• Offers higher sensitivity than culture 

PCR quantitative testing is used for both pre- and posttransplant testing for CMV status.  Serology is not recommended for diagnosis in this population.

Pregnant Women

Serologic assays are the primary tools for assessing primary CMV infections during pregnancy. Testing for maternal CMV infection generally occurs after concerning ultrasound findings.  For women with possible primary CMV infections during pregnancy, diagnosis should be based on either immunoglobulin G (IgG) seroconversion or positive CMV IgM and IgG and low IgG avidity. 

CMV IgG avidity testing aids in distinguishing between primary and recurrent CMV infection in pregnant women after initial serologic testing.

CMV can be detected in the amniotic fluid of infected fetuses by either culture or PCR.  PCR testing of amniotic fluid is most sensitive at >21 weeks gestation. The detection of CMV in amniotic fluid does not predict the severity of congenital CMV infection. 

Neonates

PCR testing of saliva can also identify CMV infection. Following positive results, PCR testing of urine is used for confirmation (most seropositive mothers shed CMV in breast milk, which can lead to a false-positive saliva test result in a recently breastfed infant).  Refer to the CDC website for information on testing for congenital CMV infection in newborns. 

Immunocompetent Individuals

Most healthy individuals who acquire CMV after birth experience few disease symptoms and no long-term health consequences. Infected individuals may present with mononucleosislike symptoms.  CMV-induced mononucleosis can be symptomatically indistinguishable from EBV-induced mononucleosis.  EBV is most often the causative agent, but CMV might be considered in the differential diagnosis if a negative heterophil antibody test rules out EBV mononucleosis.  In most patients, CMV IgM antibodies will be positive during the symptomatic phase of the disease.  However, IgM antibodies may not peak until 4-7 weeks into the infection and may remain elevated for up to 1 year or longer. IgG antibodies should continue to increase at least fourfold during active infection.  Therefore, in an otherwise healthy patient in whom EBV has been ruled out, it is not necessary to repeat a CMV IgM test if a previous IgM test result was positive.

Monitoring

PCR quantitative testing is used to monitor individuals at risk of developing CMV after solid organ or hematopoietic stem cell transplant.    Quantitation of CMV viral load in plasma correlates with progression of disease. Monitor according to site-specific transplant protocols.