Cytomegalovirus Infections

Excerpt

Cytomegalovirus (CMV) is a double-stranded DNA virus that belongs to the family of Herpesviridae and is also known as human herpesvirus 5. The CMV genome is the largest among human viruses, measuring approximately 230 kb and containing 200 genes that encode proteins. Infection with CMV is common in both children and adults, with a worldwide seroprevalence ranging from 24% to 100%, which increases with age. CMV is transmitted through the exchange of bodily fluids, including saliva, fomites, blood transfusions, and sexual contact. CMV can also be transmitted through solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). As with other herpesviruses, it establishes lifelong latency, remaining dormant in monocytes through specific mechanisms of transcriptional silencing. CMV is a globally widespread virus that becomes latent after primary infection and can become reactivated in the setting of severe immunosuppression.

In immunocompetent patients, primary CMV typically causes asymptomatic disease or mild-to-moderate mononucleosis-like or flu-like syndromes, characterized by symptoms such as malaise, fever, lymphadenopathy, and arthralgia. Infection with CMV is a leading cause of morbidity in immunosuppressed individuals, eg, due to HIV/AIDS, after receiving SOT and HSCT. In the latter population, CMV can cause severe organ damage and even cause rejection of the transplanted organ. Additionally, mothers who become infected while they are pregnant may pass the virus to the embryo, and in some cases, this can cause congenital CMV.

CMV infection is defined by the detection of active CMV replication in tissue specimens, peripheral blood, or other body fluids, irrespective of clinical manifestations. CMV disease refers to the presence of CMV infection in conjunction with clinically attributable symptoms and signs. CMV disease is subclassified into CMV syndrome, characterized by nonspecific constitutional symptoms, such as fever, malaise, and lymphadenopathy, which are often accompanied by hematologic abnormalities, including leukopenia or thrombocytopenia, as well as tissue-invasive or end-organ CMV disease. CMV syndrome involves direct viral-mediated injury to specific organs, including, but not limited to, the gastrointestinal (GI) tract, lungs, hepatobiliary system, renal parenchyma, myocardium, pancreas, central nervous system, and retina.

Primary, but mostly reactivated, CMV can cause viremia, infecting various organs, including the eyes, stomach, esophagus, and colon, especially in patients with profound immunosuppression. The 2 most common GI tract manifestations of CMV disease include CMV colitis and CMV esophagitis.

Prevention of CMV viremia and CMV end-organ disease is critical, particularly in immunosuppressed patients. Key strategies include assessing CMV serostatus in both donor and recipient, along with regular monitoring for the emergence of viremia via frequent CMV DNA quantification. In high-risk populations, prophylactic strategies may include universal antiviral administration for all at-risk individuals, targeted prophylaxis for those at highest risk, or a pre-emptive approach. The pre-emptive strategy involves initiating antiviral therapy upon early detection of CMV DNAemia, before the onset of clinical disease.