Cytomegalovirus (CMV) is a ubiquitous virus that commonly infects people across all ages, ethnic and socioeconomic groups, and geographic areas. Although most CMV infections are asymptomatic or cause mild disease, the virus can cause serious disease in neonates and immunocompromised people. Because of its ubiquity, it is often difficult to define the role of CMV in a disease process. A thorough knowledge of CMV virology, epidemiology, clinical manifestations, diagnostic testing, and indications for treatment is required to appropriately manage patients with suspected CMV infections.

• CMV is a DNA virus in the Herpesvirus family. It is a member of the β herpesvirus subfamily, which also includes HHV-6 and -7.
• Primary infection: Often asymptomatic; may remain latent throughout a person’s life if not immunocompromised
• Severe disease can result from primary infection of the fetus and newborn or reactivation in setting of immunocompromise or organ transplantation.
• Name derives from the infected cells, which are large and contain intranuclear inclusions, described as “owl’s eye” inclusions
• Not highly contagious:
  • Spread via close contact with persons shedding virus from saliva, urine, blood, breast milk, or semen
  • Also acquired via infected transplant organs
  • Any organ can be affected.
• Categories of CMV infections:
  • Congenital:
    • ∼1% (0.2–2.5%) of newborns are congenitally infected with CMV.
    • Most infected newborns appear normal and are asymptomatic.
    • As many as 15% of these children may later develop progressive hearing loss, which is most often unilateral.
    • ∼10% (5–15%) of congenitally infected newborns will be symptomatic at birth with manifestations including small size for gestational age, hepatosplenomegaly, petechial or purpuric rash, and jaundice.
  • Perinatal: Exposure to CMV in maternal cervicovaginal secretions, breast milk, or from blood product transfusions. Often asymptomatic.
  • Acute infection in a normal host: Symptomatic infection commonly presents with acute mononucleosis syndrome (1).
  • Latent infection: Higher IgG titers may contribute to development of atherosclerotic disease (4).
  • Infection in bone marrow and solid organ transplant patients:
    • Heart transplant: Early myocarditis followed by late atherosclerosis
    • Lung and bone marrow transplant: Interstitial pneumonia
    • Liver transplant: Hepatitis and colitis
    • Kidney transplant: Graft loss
  • Infection in patients with AIDS: Most commonly retinitis, second most common is colitis, followed by esophagitis and neurologic disease (3)
  • Infections in other immunocompromised patients: Pulmonary, GI, or renal disease
• System(s) affected: Ophthalmic; Pulmonary; GI; Neurologic; Renal; Skin/Exocrine
• Synonym(s): Giant cell inclusion disease; CID CMV

ALERT
Pregnancy Considerations

• CMV infection in pregnancy may cause illness in the newborn ranging from asymptomatic infection to severe disease or even death.
• Infection may occur in utero, intrapartum, or postnatally.
• Pre-existing maternal CMV seropositivity substantially decreases, but does not completely eliminate fetal infection.

Pediatric Considerations
Breastfeeding can transmit virus to high-risk preterm infants. However, there is low risk of symptomatic disease and no evidence of long-term sequelae from transmission from breastfeeding. Currently, there are no recommendations for avoidance or treated breast milk (6).

Incidence

• Common, but frequently asymptomatic
• <2–3 cases of end-organ disease per 100 person-years in HIV patients
• CMV infection is even more prevalent in populations at higher risk for HIV infection (IV drug users 75%, homosexual males 90%).
• Predominant age: All ages, peaks at <3 months, 16–40 years, and 40–75 years
• Predominant sex: Male > Female

Prevalence

• Occurs worldwide
• 40–100% of the general US population is seropositive from prior exposure during childhood or early adulthood (5).
• 20% of children in the US are seropositive before reaching puberty (5).
• Most common perinatally transmitted infection: 0.2–2.2% of births in the US (6)

• HIV infection with specific risks, including:
  • CD4 count <50 cells/μL (3)[B]
  • Absence of treatment with or failure to respond to ART (3)[B]
  • Previous opportunistic infections (3)[B]
  • HIV viral load >100,000 (3)[B]
• Organ transplantation
• Blood transfusion
• Immunocompromise
• Living in closed population
• Corticosteroid therapy
• Daycare environment, infant, or geriatric
• For congenital infection, maternal infection during pregnancy
• Low socioeconomic status (6)[C]
• Critically ill immunocompetent adults in intensive care unit settings (up to 1/3 develop CMV, primarily between days 4 and 12 after admission) (7)[A]

• Hand washing/basic hygiene
• Avoid immunosuppression.
• Highly active antiretroviral therapy (HAART) is the best method for high-risk HIV patients (5)[A].
• Chronic maintenance therapy for life in HIV patients with CMV end-organ disease unless successfully treated with ART (1)[A]
• Options include:
  • Parenteral or oral ganciclovir (1)[A]
  • Parenteral foscarnet (1)[A]
  • Combined parenteral ganciclovir and foscarnet (1)[A]
  • Parenteral cidofovir (1)[A]
  • Ganciclovir via intraocular implant or repetitive intravitreous injection of fomivirsen (1)[A]
• CMV antibody+, HIV+ children who are severely immunosuppressed require oral ganciclovir 30 mg/kg t.i.d.
• Antiviral suppression of CMV reactivation in CMV+ transplant recipients or recipients of CMV+ organs:
  • Solid organ transplant: Prophylactic or preemptive treatment with oral ganciclovir, valganciclovir (8)[A]
  • Bone marrow transplant: IV ganciclovir
• CMV immunoglobulins decrease rate of severe disease after liver transplant (9)[A] and decrease incidence of disease after renal transplant.

• Primary infection
• Reinfection with different CMV strains
• Reactivation of latent virus in patients who are immunosuppressed

AIDS, corticosteroid therapy, transplantation, or immunosuppression