Cytomegalovirus (CMV) Inclusion Disease
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Ubiquitous and common infection impacting all ages, ethnic, socioeconomic groups, and geographic areas
- Although most cytomegalovirus (CMV) infections are asymptomatic or cause mild disease, disease can be serious in neonates and immunocompromised patients.
- CMV is a DNA virus in the Herpesvirus family (human herpesvirus-5 [HHV-5]); β-herpesvirus subfamily also includes HHV-6 and -7.
- Primary infection: often asymptomatic; may remain latent for long periods in immunocompetent patients
- Wide spectrum of disorders ranging from asymptomatic to a subclinical infection to a mononucleosis syndrome in healthy patients. Disseminated disease is more common in immunocompromised patients, and fulminant disease is more common in neonates.
- Severe disease can result from primary infection of the fetus and newborn or reactivation in immunocompromised or organ transplantation.
- Name derives from large intranuclear inclusions (“owl’s eye”) within infected cells.
- Not highly contagious
- Spread via close contact with persons shedding virus from saliva, urine, blood, breast milk, feces, semen, or organ transplantation
- Any organ can be affected.
- Categories of CMV infections
- Acute infection in a normal host
- Latent infection
- Infection in immunocompromised hosts: solid organ transplant, bone marrow transplant, AIDS
- System(s) affected: ophthalmic, pulmonary, GI, neurologic, renal, skin/exocrine, hepatic, cardiac
- Synonym(s): giant cell inclusion disease (CID); cytomegalic inclusion disease; HHV-5
- CMV infection in pregnancy may cause broad range of illness in the newborn, ranging from asymptomatic infection to severe disease or even death.
- Infection occurs in utero, intrapartum, or postnatally.
- Preexisting maternal CMV seropositivity decreases (but does not eliminate) fetal infection because reinfection with a different strain is possible.
Although breastfeeding can cause transmission to high-risk preterm infants, there is otherwise a low risk of symptomatic disease and no evidence of long-term sequelae from transmission via breastfeeding. There are no recommendations to avoid breastfeeding or treat breast milk.
- Common and frequently asymptomatic
- Prior to effective highly active antiretroviral therapy (HAART), CMV retinitis was present in approximately 30% of persons infected with HIV (1).
- CMV infection more prevalent in populations at higher risk for HIV infection (IV drug users, 75%; men who have sex with men, 90%)
- CMV reactivation frequently occurs in immunocompromised hosts.
- Occurs in patients of all ages with peaks at <3 months, 16 to 40 years, and 40 to 75 years
- Predominant sex: female > male
- Occurs worldwide; higher prevalence in underdeveloped countries
- 30–97% of the worldwide population and ~50% of the general U.S. population are seropositive (2).
- 20% of U.S. children are seropositive before puberty.
- Most common perinatally transmitted infection: 0.2–2.2% of births in the United States (3)
Etiology and Pathophysiology
- Primary infection. Virus infects epithelial cells, macrophages, and T cells causing coalescence (protects from antibody). Intact host cell–mediated immunity required for host’s defense against CMV infection; incubation approximately 1 to 2 months
- Reinfection can occur with different CMV strains.
- Reactivation of latent virus in patients who are immunosuppressed can occur.
- HIV infection with specific risks, including:
- CD4 count <50 cells/μL
- Absence of treatment or failure to respond to ART
- Previous opportunistic infections
- HIV viral load >100,000
- Organ transplantation
- Blood transfusion
- Living in closed population: daycare, nursing home, military barracks, correctional facilities
- Corticosteroid therapy
- Maternal infection during pregnancy (neonatal disease)
- Low socioeconomic status
- Critically ill immunocompetent adults in ICU settings (up to 1/3 develop CMV, 4 to 12 days after admission)
- Inflammatory bowel disease
- Hand washing/personal hygiene
- Avoid immunosuppression; maintain CD4 count >100 cells/mm3 in HIV patients.
- HAART is best prevention for high-risk HIV patients.
- Primary prophylaxis and routine screening of pregnant women are not recommended (4).
- Chronic maintenance therapy for secondary prophylaxis in HIV patients (1,3)[A] should continue until CD4 >100 cells/μL for 3 to 6 months.
- Options for secondary prophylaxis include (2)[A]:
- PO valganciclovir
- IV ganciclovir, foscarnet, or cidofovir
- Combined IV ganciclovir and foscarnet
- Severely immunosuppressed CMV antibody+ and HIV+ children require adult dosage PO valganciclovir (1,3)[C].
- Antiviral suppression of CMV reactivation in CMV+ transplant recipients or recipients of CMV+ organs
- Solid organ transplant: prophylactic or preemptive treatment with IV ganciclovir, PO valganciclovir
- Bone marrow transplant: IV ganciclovir
- CMV immunoglobulins decrease rate of severe disease after liver transplant and decrease incidence of disease after renal transplant.
Commonly Associated Conditions
AIDS, corticosteroid therapy, transplantation, or immunosuppression, congenital TORCH (toxoplasmosis; other; rubella; CMV; herpes) infections