Cytomegalovirus (CMV) is a common infection. In the United States, nearly one in three children is infected by 5 years of age, and more than 50% of adults have been infected by 40 years of age. CMV can be transmitted in several ways: congenitally, by blood transfusion or organ transplantation, and through direct contact with urine or saliva. The virus is generally asymptomatic in immunocompetent children and adults but can lead to serious complications in neonates, pregnant women, immunocompromised individuals, and those receiving transplants. Polymerase chain reaction (PCR) testing is commonly used to detect and quantify viral load. Serology is most useful in immunocompetent individuals, in pregnant women with possible active infection, and during pretransplant analysis.
Quick Answers for Clinicians
- Immunocompromised patients who present with febrile illness, hepatitis, and colitis
- Pregnant women with possible cytomegalovirus (CMV) infection
- Neonates with congenital syndromes suggestive of CMV
- Patients receiving organ transplants
Cytomegalovirus by quantitative polymerase chain reaction (PCR) is preferred for posttransplant surveillance and determining antiviral treatment response. Refer to Monitoring.
Interpreting serologic test results can be challenging. A positive cytomegalovirus (CMV) immunoglobulin G (IgG) result suggests a past infection, but only in persons older than 1 year. A positive CMV IgM result cannot be used alone to diagnose primary CMV infection. See the CDC’s suggested interpretive guidance.
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:
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 positive | Suggests past infection
Only applicable for persons ≥12 mos of age (when maternal antibodies are no longer present) |
Paired CMV IgG samples (taken 1-3 mos apart) | Can be used to diagnose primary infection
Seroconversion (initial IgG-negative sample followed by positive second sample) offers clear evidence for recent primary infection |
CMV IgM positive | In isolation, not helpful in diagnosing primary CMV infection because IgM can also be present during recurrent CMV infection |
Source: CDC, 2016 |
CMV IgG avidity testing aids in distinguishing between primary and recurrent CMV infection in pregnant women after initial serologic testing.
Low IgG avidity | Suggests primary CMV infection occurred within the last 2-4 mos
During first trimester, patients should seek consultation with obstetrician experienced with congenital CMV infections; further invasive testing may be warranted |
Intermediate IgG avidity | Clinical relevance undetermined
Lower risk of intrauterine transmission |
High IgG avidity | Suggests past infection |
Note: Because not all avidity assays have been validated, they should be interpreted with caution.
Source: CDC, 2016 |
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.
ARUP Laboratory Tests
Preferred test to detect, quantify, and monitor CMV infection
Quantitative Polymerase Chain Reaction
Determine antiviral drug resistance
Quantitative Polymerase Chain Reaction/Sequencing
Polymerase Chain Reaction/Sequencing
Does not quantify viral load; potentially useful for specimens other than blood
Qualitative Polymerase Chain Reaction
Primary means of discriminating between current and past CMV infection in immunocompetent individuals
Semi-Quantitative Chemiluminescent Immunoassay
Semi-Quantitative Chemiluminescent Immunoassay
Distinguish between primary and recurrent CMV infection in pregnant women after initial serologic testing
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Cell Culture/Immunofluorescence
Medical Experts
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References
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CDC - Cytomegalovirus (CMV) and Congenital CMV Infection
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Cytomegalovirus (CMV) and congenital CMV infection. [Last reviewed: May 2019; Accessed: Nov 2019]
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SMFM - Diagnosis and antenatal management of congenital cytomegalovirus infection
Hughes BL, Gyamfi-Bannerman C. Diagnosis and antenatal management of congenital cytomegalovirus infection. 39 Society for Maternal-Fetal Medicine (SMFM). [ Accessed: Nov 2019]Online -
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Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009; 9 Suppl 3 S1-155.PubMed -
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Tomblyn M, Chiller T, Einsele H , et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15 (10): 1143-238.PubMed
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