Cytomegalovirus (CMV) Inclusion Disease


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
    • Congenital
    • Perinatal
    • 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

Pregnancy Considerations

  • 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.

Pediatric Considerations
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.

Risk Factors

  • 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
  • Immunocompromised
  • 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

General Prevention

  • 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

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