Cytomegalovirus (CMV) Inclusion Disease

Description

• 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.

Epidemiology

Incidence

• 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

Prevalence

• 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