CMV (Cytomegalovirus)

1. What does the test measure?

Cytomegalovirus (CMV) is a prevalent virus that often remains asymptomatic or causes only mild illness. CMV testing identifies antibodies in the blood, which the body generates in response to the infection, or directly detects CMV. The majority of individuals become infected during childhood or as young adults, yet many remain unaware of it since CMV typically manifests with no discernible symptoms or only results in mild illness in those who are otherwise healthy. In cases of mild illness, individuals might experience non-specific signs and symptoms, including a sore throat, fever, fatigue, and swollen glands. Among otherwise healthy adults, CMV infection may occasionally induce flu-like symptoms or mononucleosis (mono)-like manifestations, such as profound fatigue, fever, chills, body aches, and headaches, which typically subside within a few weeks.

2. What happens when once you are infected?

Once you are infected, CMV remains in your body for life without causing symptoms. After the initial "primary" infection resolves, CMV becomes dormant or latent, similar to other herpes family members. However, if your immune system becomes significantly weakened, the virus can reactivate and cause illness.

3. When can CMV cause notable health problems?

CMV can lead to significant health problems in the following situations:

1. A pregnant woman experiencing her first infection (primary infection) during pregnancy may transmit the virus to her developing baby through the placenta. This can result in serious physical and developmental issues for the baby. While most infected newborns (about 90%) may appear healthy at birth, they might develop complications such as hearing or vision problems, pneumonia, seizures, and delayed mental development a few months later. Some infants could be stillborn, while others may exhibit symptoms at birth, including jaundice, anemia, an enlarged spleen or liver, and microcephaly (a small head).
2. CMV can cause severe illness and even be fatal in individuals with weakened immune systems, including those with HIV/AIDS, transplant recipients, and cancer patients undergoing chemotherapy. These individuals are more likely to experience the most severe symptoms, and their CMV infection may remain active. CMV can reactivate in individuals previously exposed to the virus, affecting various body parts such as:

- Eyes, leading to retinal inflammation and potential blindness.

- Digestive tract, resulting in bloody diarrhea and abdominal pain.

- Lungs, causing pneumonia characterized by a non-productive cough and shortness of breath.

- Brain, causing encephalitis.

- Spleen and liver.

- Organ or bone marrow transplant recipients, contribute to some degree of organ rejection.

Active CMV infection can further weaken the immune system, making individuals susceptible to secondary infections such as fungal infections.

4. How is the test used?

Cytomegalovirus (CMV) testing is not performed on everyone but is utilized in specific cases, including:

1. Some pregnant women or individuals with weakened immune systems exhibit signs and symptoms.
2. People who are candidates for organ or bone marrow transplants.
3. Newborns born with specific congenital abnormalities.

Several testing methods may be employed depending on the purpose of the test:

Antibody Testing (Serology):

This test identifies antibodies produced in response to a CMV infection in the blood. It can diagnose both current and past infections by measuring two classes of CMV antibodies:

• _IgM antibodies_ are the first to be produced by the body in response to a CMV infection. They can be detected in the blood within a week or two after the initial exposure. IgM levels rise temporarily, then decline, and typically become undetectable after several months. They may rise again if latent CMV is reactivated.
• _IgG antibodies_ appear several weeks after the initial CMV infection. IgG levels increase during the active infection, stabilize as the CMV infection resolves, and the virus becomes dormant. Once exposed to CMV, individuals will have a measurable amount of CMV IgG antibodies in their blood for life, providing immunity against another primary infection.

Healthcare providers compare the presence or absence of IgG and IgM antibodies in the same sample or the amount of antibody present (titer) in samples collected at intervals (acute and convalescent samples) to differentiate between active and latent CMV infections.

Direct Detection of CMV:

Molecular techniques like polymerase chain reaction (PCR) are used to diagnose congenital infections in newborns and can detect and/or confirm active infections in other individuals. These methods identify the genetic material (DNA) of CMV (qualitative testing) and may measure the quantity of viral DNA in a sample (quantitative, or viral load). Molecular techniques offer higher sensitivity than culture methods, and results can be obtained quickly.

People with weakened immune systems experiencing active CMV infections may be monitored with various CMV tests. Healthcare providers often assess the viral load to determine a person's response to antiviral therapy.

Viral Cultures:

Although not routinely available, viral cultures may occasionally be employed to detect CMV.

5. When should I do the CMV test?

CMV testing may be requested when a pregnant woman or an individual with a weakened immune system presents with flu- or mono-like symptoms, including:

• Fatigue and weakness
• Sore throat
• Swollen lymph nodes
• Fever
• Headache
• Muscle aches

CMV tests are also used when monitoring individuals who have received a transplant or to assess the effectiveness of antiviral therapy.

In the case of newborns or infants, CMV molecular testing may be conducted when they exhibit specific symptoms such as:

• Jaundice (yellowing of the skin and eyes)
• Low platelet count
• An enlarged spleen and/or liver
• A small head
• Hearing and vision problems
• Pneumonia
• Seizures
• Delayed mental development

When a person is being considered for an organ or bone marrow transplant, CMV antibody testing may be ordered to determine whether they have been previously exposed to CMV.

6. How can the result interpreted?

Interpreting CMV test results requires careful consideration. Healthcare practitioners evaluate the results in the context of clinical findings, including signs and symptoms. Distinguishing between latent, active, or reactivated CMV infections can sometimes be challenging due to several factors, such as:

1. In healthy individuals previously exposed to CMV, the virus may persist in the body without causing symptoms. Periodic reactivation can lead to small amounts of the virus appearing in body fluids.
2. Immune-compromised individuals may not generate a robust antibody response to CMV infection, resulting in lower IgM and IgG levels despite having an active CMV infection.
3. The virus may not be present in sufficient quantities in the specific fluid or tissue tested, making it undetectable.
4. Tests conducted in the very early stages of an acute infection may yield undetectable CMV antibody levels.

Regarding antibody testing:

• A positive result for both CMV IgG and IgM when experiencing symptoms suggests recent exposure to CMV for the first time or reactivation of a previous CMV infection. This can be confirmed by reevaluating IgG levels 1 to 3 months later. A significant increase in IgG levels (a 4-fold or greater rise) between the initial and follow-up tests indicates an active CMV infection (either primary or reactivated).
• A positive result for CMV IgM and a negative result for CMV IgG may indicate a very recent infection.
• Negative or low levels of IgG and/or IgM may suggest that your symptoms are attributable to an infection other than CMV or could indicate an abnormal immune response (insufficient antibody production even in the presence of CMV).

Interpreting viral detection results:

• A positive CMV DNA test suggests the presence of CMV, indicating an active infection in you or the tested newborn. High levels of viral DNA may signify a more severe infection with serious symptoms, while low levels may indicate a milder CMV infection, often with no or mild symptoms, or it may suggest that there's no active infection.
• Negative results on the DNA test do not definitively rule out a CMV infection. The virus may be present in very low quantities or may not be present in the tested sample.
• When the DNA test is used to monitor the effectiveness of treatment, decreasing CMV levels (viral loads) indicates a positive response to antiviral therapy. Conversely, if levels fail to drop despite treatment, it might indicate that the virus is resistant to the therapy.
• A positive CMV culture suggests an active infection. This determination can typically be made within 1 to 2 days. Negative cultures should be held for 3 weeks to confirm the absence of CMV, as the virus might be present in very low numbers in the original sample, or the CMV strain may be slow-growing.

7. What are other important points about the CMV test?

The CMV test is one of the components in a TORCH testing panel. This panel of tests is designed to screen for a group of infectious diseases that can lead to illness in pregnant women and potentially cause birth defects in their newborns. TORCH is an abbreviation representing: Toxoplasmosis, Rubella, Cytomegalovirus, and Herpes simplex virus. Additionally, it may include screening for other infections.

In situations requiring blood transfusions, specific patients, such as CMV-negative individuals with HIV/AIDS or CMV-negative candidates for heart/lung transplants, should be provided with blood components that have been confirmed as negative for CMV antibodies (referred to as CMV seronegative blood products) or blood products that have been subjected to leukocyte reduction.

8. can I transmit the CMV infection to others?

If you are infected with CMV, either recently or in the past, you can potentially transmit the virus to others, even if you are not displaying any symptoms. Symptoms can manifest within 9 to 60 days after the initial infection. However, close contact with others is typically required for transmission. CMV can be transmitted through various body fluids, including saliva, breast milk, vaginal fluids, semen, urine, and blood.

9. How can I prevent getting CMV?

At present, there is no vaccine for CMV. Practicing diligent hygiene measures can aid in preventing the transmission of the virus. However, because CMV is highly prevalent, found in various body fluids, and is typically transmitted through close contact, most individuals become infected early in life. It has been estimated that up to 70% of children in daycare settings have been exposed to CMV, and each year, approximately 8% to 20% of childcare providers contract CMV.