How Is Cytomegalovirus (CMV) Diagnosed?

Cytomegalovirus (CMV) is a highly common virus belonging to the herpes family, infecting people of all ages across the globe. For most healthy individuals, an infection is typically mild or entirely without symptoms, often resembling a common cold or mononucleosis. However, for certain populations—specifically pregnant women, newborns, and people with weakened immune systems—CMV infection can lead to severe health complications. The specific method chosen for diagnosis depends heavily on the patient’s overall health status and the clinical suspicion, aiming to determine if the virus is currently active or if the person has merely been exposed in the past.

Scenarios Where Testing is Necessary

Testing for Cytomegalovirus is not routinely recommended for the general healthy population, but it becomes a priority in three main clinical situations where the virus poses a significant health risk.

Pregnant Women

Pregnant women are often tested, particularly if they exhibit flu-like symptoms or if an ultrasound suggests potential infection in the developing baby. Determining the timing of a primary infection during pregnancy is important because it directly affects the risk of transmission and potential harm to the fetus.

Immunocompromised Patients

This group includes organ transplant recipients, stem cell transplant patients, and individuals with HIV/AIDS. In these patients, a prior, dormant CMV infection can reactivate and cause serious disease, necessitating regular monitoring.

Adults with Mononucleosis-like Symptoms

Testing may be ordered for healthy adults presenting with persistent mononucleosis-like symptoms—including prolonged fever, fatigue, and swollen glands—when other common causes like Epstein-Barr virus (EBV) have been ruled out.

Detecting Active Viral Presence (Viral Load Testing)

To confirm that Cytomegalovirus is actively replicating and causing an acute or reactivated infection, molecular testing is the preferred method. The Polymerase Chain Reaction (PCR) test is the standard for detecting CMV DNA in various body fluids, including blood, urine, or cerebrospinal fluid. PCR is highly sensitive and quantitative, providing a “viral load” measurement, often reported in International Units (IU) per milliliter.

The viral load is especially important in transplant patients, where a rising concentration of CMV DNA indicates active viral replication that may require preemptive antiviral treatment. PCR offers a much faster and more quantifiable assessment of active infection than viral culture. A detectable viral load confirms the virus is present and replicating, which is a strong indicator of current infection or reactivation.

Determining Past Exposure (Antibody Testing)

Serology, or antibody testing, is conducted to establish a person’s exposure history to CMV. This blood test measures two distinct types of antibodies: Immunoglobulin G (IgG) and Immunoglobulin M (IgM). A positive IgG result indicates that the individual was infected with CMV at some point and has developed long-term immunity.

IgM antibodies are typically the first to appear after a new infection, suggesting a recent or acute infection. However, IgM can sometimes remain detectable for months or reappear during a viral reactivation, making its presence alone an unreliable marker for the exact timing of infection. In cases where both IgG and IgM are positive, a specialized test called IgG avidity is used to differentiate between a recent primary infection and a past one. Low avidity suggests the infection occurred within the last three to four months.

Diagnosis Procedures for Congenital CMV

Diagnosing a CMV infection in a fetus or newborn requires specialized, time-sensitive procedures. For prenatal diagnosis, if a pregnant woman is suspected of having a recent primary infection, an amniocentesis may be performed. This involves testing the amniotic fluid for CMV DNA using PCR, which can confirm if the virus has passed from the mother to the baby.

For a newborn, the diagnosis of congenital CMV (infection acquired before birth) must be confirmed within the first two to three weeks of life. The preferred specimens are the infant’s saliva or urine, which are tested using PCR. Detecting CMV after this three-week window does not confirm congenital infection, as it may be a milder, postnatally acquired infection.

Understanding Your CMV Test Results

Interpreting the combination of antibody results provides a clear picture of a person’s CMV status.

  • If both IgG and IgM are negative, the person has never been infected and is susceptible to a primary infection.
  • A positive IgG and negative IgM indicates past infection and presumed immunity.
  • If both IgG and IgM are positive, the IgG avidity test is necessary to pinpoint the approximate timing of the infection.

For patients undergoing viral load testing, an undetectable CMV DNA level suggests no active viral replication is occurring. Conversely, a detectable viral load confirms active infection. The magnitude of the viral load helps physicians monitor the severity of the infection and the effectiveness of antiviral treatment. A significant increase in viral load over serial measurements, often a three-fold or 0.5 log10 change, is considered important, especially in immunocompromised patients.