Cytomegalovirus (CMV) Infection Overview

Cytomegalovirus (CMV) Infection

• CMV is a human herpesvirus, infecting various cells (monocytes, neutrophils, renal cells, etc.).
• Its cytopathic effect is characterized by "owl's eye" appearance of infected cells.
• Immunocompetent individuals may experience mild or asymptomatic infection similar to infectious mononucleosis.
• Reactivation in immunocompromised individuals can severely affect organs (liver, lungs, brain, etc.).
• CMV infection is widespread, with over 50% of adults in developed countries and nearly 100% in developing countries exhibiting anti-CMV IgG antibodies, indicating prior infection.
• Primary infection often occurs in childhood/adolescence/young adulthood, with possible reinfection.
• Sources of infection include infected individuals (clinical or inapparent), saliva, urine, sexual contact, blood transfusions, bone marrow/organ transplantation, and mother-to-fetus transmission (most often transplacental).
• Transmission can occur through breast milk.
• Women of reproductive age during pregnancy are at risk of transmitting CMV to the fetus.
• Immune response involves both humoral (IgM, IgG antibodies) and cellular (T lymphocytes).

Pathogenesis

• Following infection, CMV replicates in leukocytes, salivary glands, kidneys, and vascular endothelium.
• Characteristic cytopathic changes include giant cells with large eosinophilic intranuclear inclusions and a peripheral halo (typical "owl's eye").
• Immunosuppression (post-transplant, hematological malignancies, HIV) significantly increases risk of reactivation of latent CMV infection.
• Congenital CMV infection frequently arises from primary maternal infection during pregnancy, less commonly from reactivation.

Clinical Presentation

• Primary CMV infection in immunocompetent individuals can be asymptomatic or present as infectious mononucleosis-like syndrome (heterophile antibody negative).
• Clinical picture might include prolonged fever (2-3 weeks), lymphadenopathy, hepatosplenomegaly, pharyngitis (occasionally exudative), rash, and fatigue.
• Complications in immunocompetent individuals include meningoencephalitis, polyradiculoneuritis, myelitis, pneumonia, hemolytic anemia, pancytopenia, macrophage activation syndrome, splenic rupture, myocarditis, and pericarditis.
• CMV infection in immunocompromised individuals generally has severe manifestations.
• In HIV-positive individuals, CMV retinitis (potentially leading to blindness), colitis, esophagitis, and other complications are common.
• Congenital CMV infection can cause miscarriage, premature birth, intrauterine growth restriction; manifestations in newborns can include microcephaly, intracerebral calcifications, chorioretinitis, hearing loss, jaundice, and anemia.

Diagnosis

• Serologic testing: detecting IgM, IgG, and antibody avidity to determine infection timeline, with IgM in absence of IgG indicating acute infection. IgG in absence of IgM suggests prior or chronic infection. Both IgM and IgG indicate recent infection, reinfection, or reactivation of chronic infection
• Amniocentesis and PCR for CMV-DNA in amniotic fluid are used to diagnose congenital CMV infection.
• Detection of CMV-DNA in saliva or urine samples is used to diagnose congenital CMV infection in newborns.

###Treatment

• Immunocompetent individuals typically do not require specific treatment, but support care is given.
• Immunosuppressed individuals receive ganciclovir, foscarnet, or cidofovir depending on strain resistance and other factors.
• Intravitreal ganciclovir can treat CMV retinitis.
• Treatment does not eliminate chronic infection but controls its progression.

Prophylaxis

• No effective CMV vaccine exists.
• Prophylaxis measures include strict hygiene, avoidance of contact with infected individuals, protected sexual practices, screening of blood transfusions/transplant donors, and pre-emptive therapy with ganciclovir or valganciclovir for immunocompromised individuals.
• Immunosuppressed patients may require prophylaxis (3-6 months of valganciclovir after CMV positive donors)