Diagnostic Use
Background
CMV infections are common and usually asymptomatic; however disease more often occurs in newborns and other immunocompromised hosts. CMV infections may be acquired before birth (congenital), at the time of delivery (perinatal) or later in life (postnatal). Like other herpes viruses, primary infection with CMV results in the establishment of a persistent or latent infection. Reactivation may occur.
Congenital Infection:
CMV has been detected in 0.2-2.5% of newborns and is the most common identified cause of congenital infection. Complications, most commonly deafness, occur in approx 10-15% of all infants of women with primary infection during pregnancy. Less than 5% of congenitally infected infants develop symptoms during the newborn period; severe manifestations include intrauterine growth retardation, jaundice, hepatosplenomegaly, petechiae, CNS abnormalities and chorioretinitis. Reactivation or re-infection during pregnancy can also cause foetal infection in about 1% of infants, but sequelae are uncommon and usually mild.
Perinatal Infection:
Newborns may acquire infection at the time of delivery by contact with virus in the birth canal. These infants start to excrete virus at ~3-12 weeks of age but usually remain asymptomatic
Postnatal Infection:
Most postnatal infections are acquired by close contact with individuals who are shedding virus. CMV can also be transmitted by organ and blood transfusion. The majority of children and adults who acquire CMV postnatally remain asymptomatic. An infectious mononucleosis-like syndrome may develop in young adults. CMV infections may be severe in children or adults with congenital or acquired cell-mediated immunity defects e.g. patients with AIDS, patients with cancer especially lymphoma and leukemia, recipients of organ transplants. Disease in these patients may be due to primary infection, re-infection or reactivation of latent virus. Symptoms include fever, leukopenia, thrombocytopenia, pneumonitis, hepatitis, retinitis, encephalitis and gastrointestinal infections.
Laboratory Investigation.
CMV nucleic acid may be detected by PCR or the antibody response to infection detected by serology.
Congenital infection:
Detection of CMV DNA from urine within the first week of life is the preferred method of confirming congenital infection. Using PCR, attempts to isolate and/or detect CMV from blood, neonatal or foetal tissue, and amniotic fluid can also be made. Serological tests are less useful because of transplacental passage of maternal antibody and technical difficulties with detection of anti-CMV IgM. Absence of IgG in the mother and baby excludes congenital infection. Infants not previously tested but found to be excreting CMV after 3 weeks of age may have either congenital or postnatal infection.
Postnatal infection:
The humoral response to CMV infection includes the production of IgM and IgG. IgM antibodies are the first to appear following a primary CMV infection and may be detectable for a long period of time. Their production can reoccur following reactivation of latent virus or re-infection with additional strains of CMV. Detection of CMV IgM is not diagnostic of a primary or even recent infection. Patients with Epstein-Barr virus-induced infectious mononucleosis may produce heterotypic IgM responses, resulting in false-positive CMV IgM results. IgG antibodies appear 6-8 weeks after primary infection and persist indefinitely. The detection of CMV IgG confirms previous exposure to CMV and implies the presence of latent infection. Serology is generally not recommended for immunocompromised patients, because they may be unable to mount a detectable humoral response or may have circulating IgG antibodies from transfusions or immunotherapy. Before transplantation, testing the serostatus of the recipient and donor is useful.
Antibody avidity assays are used to help distinguish primary from non-primary infections e.g. in pregnant women with detectable IgM. Avidity is a measure of the strength of antibody binding. High avidity IgG is associated with non-primary infections. Low avidity IgG usually means recent primary infection, however development of high-avidity IgG may be delayed in the immunosuppressed.
PCR is used to detect CMV DNA in white blood cells, biopsies and aspirates from infected patients. Qualitative PCR is useful for detection of CMV in e.g. CSF from patients with encephalitis or myelitis, aqueous or vitreous humor from patients with retinitis, amniotic fluid for detection of congenital infection.
In the immunocompromised host, virologic or serologic detection of CMV indicates infection but does not establish whether the infection is responsible for symptomatic illness. The use of quantitative methods (viral load) is used to predict which patients may progress to severe CMV disease.
For further information about CMV serology contact:
Waitemata DHB
Dr Dragana Drinkovic, Clinical Microbiologist 021 784 612
Dr Matt Rogers, Clinical Microbiologist 021 524 605