Cytomegalovirus (CMV) is a common virus belonging to the herpesvirus family. Once a person is infected, the virus remains dormant in the body for life. Most healthy individuals show no symptoms or experience only a mild, mononucleosis-like illness. However, CMV can cause serious complications in specific populations, including those who are immunocompromised and developing fetuses. Diagnosing CMV requires different methods depending on the patient’s immune status and age, such as whether the patient is an adult, a pregnant woman, or a newborn.
Serological Testing for CMV Antibodies
The standard diagnostic approach for non-pregnant adults and adolescents involves serological testing for antibodies in the blood. Two main types of antibodies are measured: Immunoglobulin G (IgG) and Immunoglobulin M (IgM). The presence of IgG antibodies indicates a past infection and lifelong immunity.
IgM antibodies are produced early in the infection process, suggesting a recent or active infection. However, IgM can reappear during viral reactivation. Because IgM alone cannot definitively confirm a recent primary infection, IgG Avidity testing is often performed to measure the binding strength of the IgG antibodies to the virus.
In a primary infection, the initial IgG antibodies are “low avidity” because they bind weakly. Over three to four months, these antibodies mature and become “high avidity,” binding much more strongly. Therefore, low-avidity IgG, often with a positive IgM result, strongly indicates a primary CMV infection occurred within the past few months.
Prenatal and Fetal Diagnostic Procedures
When CMV infection is suspected in a pregnant woman, diagnosis is a sequential process because a primary infection carries the highest risk of transmission to the fetus. The initial step is maternal serology, using IgG and IgM to determine the woman’s immune status and if a recent infection has occurred. A positive IgM and low-avidity IgG result suggests a primary infection within the past few months, placing the pregnancy at risk.
Once a recent maternal infection is confirmed, the definitive diagnostic procedure for fetal infection is the polymerase chain reaction (PCR) test performed on amniotic fluid collected via amniocentesis. This procedure is typically performed no earlier than 17 to 21 weeks of gestation and ideally at least six to eight weeks after the estimated time of maternal infection. PCR detects the viral DNA in the fluid, confirming the virus has crossed the placenta and infected the fetus.
Fetal ultrasound plays a supportive role by looking for specific signs that may suggest fetal infection. These signs can include abnormalities in the brain, such as microcephaly or calcifications, or fetal growth restriction. The presence of such anomalies may indicate the need for amniocentesis.
Diagnosing Congenital CMV in Newborns
Confirming congenital CMV infection relies on detecting the virus in a newborn’s body fluids within a specific time frame. This is important because the virus can also be acquired during or shortly after birth (perinatal or postnatal infection) through contact with maternal secretions or breast milk. The preferred specimen types are urine and saliva, which typically contain high concentrations of the virus in congenital cases.
The sample must be collected within the first 21 days of life to definitively establish a congenital infection. If a saliva sample tests positive for CMV DNA using a molecular test like PCR, it is often confirmed with a urine sample to rule out a false positive from viral shedding in maternal breast milk. After the 21-day window, it becomes difficult to distinguish between congenital and acquired infection. Dried blood spot (DBS) analysis from the newborn screening card can sometimes be used retrospectively to confirm the diagnosis in older infants.
Understanding Active Infection: Viral Load Testing
For patients with known CMV infection, especially those who are immunocompromised, diagnosis shifts to assessing active viral replication. This is achieved through quantitative Polymerase Chain Reaction (PCR) testing, which measures the amount of CMV DNA present in the blood, known as the viral load. PCR directly confirms the presence of the virus’s genetic material, unlike serology which detects the immune response.
The viral load is usually reported in International Units per milliliter (IU/mL) and is used for monitoring disease activity and guiding treatment decisions. In high-risk patients, such as solid organ transplant recipients, regular monitoring is used to initiate preemptive antiviral therapy before disease develops. A change of more than 0.5 log IU/mL is typically required to represent a biologically meaningful change in the patient’s condition.