• Seroprevalence varies with socioeconomic status; 50% of middle and 80% of lower socioeconomic status adults are seropositive.
• Increased rates of primary infection seen in early childhood, adolescence, and child-bearing years.
• Transmission may occur via contact with infected respiratory secretions, urine, or breast milk, sexual contact, solid organ transplantation, or infusion of infective blood products.

• Occurs in 1% of newborns.
• 10% of infected infants are symptomatic at birth, with severe cytomegalic inclusion disease characterized by growth retardation, hepatosplenomegaly, thrombocytopenia, and central nervous system (CNS) involvement.
• 10% to 20% of infants who are asymptomatically infected at birth will develop long-term sequelae.
• Most common cause of congenital deafness.

• CMV can cause a mononucleosis-like syndrome similar to that caused by Epstein-Barr virus (EBV) infection.
• Pharyngitis and splenomegaly may be less severe than that associated with EBV-induced mononucleosis.

• Primarily seen in immunosuppressed children and adults.
• Usually begins with fever and non-productive cough, but may progress to dyspnea and severe hypoxia over 1 to 2 weeks.
• Mild, self-limited pneumonitis may occur in immunocompetent patients.

• Seen in approximately 30% of infants with symptomatic congenital infection.
• May complicate CMV disease in patients with severe immunodeficiency.

• Occurs in healthy individuals with primary infections and immunosuppressed patients with either primary or reactivated disease.
• Characterized by mildly elevated liver function studies, mild hepatomegaly, and fever.
• Jaundice and severe hepatitis uncommon.

• Severely immunosuppressed patients may experience esophagitis, gastritis, colitis, or pancreatitis.

• Commonly seen in infants with symptomatic congenital infection.
• Characterized by microcephaly, periventricular calcifications, seizures, developmental delay, and sensorineural hearing loss.
• Encephalitis or meningoencephalitis may occur postnatally in either healthy or immunocompromised patients.

• Congenital rubella syndrome
• Toxoplasmosis
• Syphilis
• Neonatal herpes simplex virus
• HIV
• Enteroviral infection

• EBV infection
• Toxoplasmosis
• Hepatitis A or B infection

• Respiratory syncytial virus
• Adenovirus
• Measles
• Varicella
• Pneumocystis carinii
• Chlamydia
• Mycoplasma
• Fungal
• Drug/toxin-induced

• Ocular toxoplasmosis
• Candidal retinitis
• Syphilis
• Herpes simplex virus

• EBV infection
• Hepatitis A, B, or C infection
• Enterovirus
• Adenovirus
• Herpes simplex virus
• Drug/toxin-induced

• Herpes simplex virus
• Adenovirus
• Salmonella
• Shigella
• Campylobacter
• Yersinia
• C. difficile
• Giardia
• Cryptosporidium

• Congenital disease (see Congenital infection)
• Meningoencephalitis in immunocompetent host: herpes simplex virus, EBV, varicella-zoster virus, enterovirus, arbovirus
• Meningoencephalitis in immunocompromised host: in addition to organisms listed previously, differential diagnosis should include HIV encephalitis, fungal meningitis (due to Cryptococcus, Candida, Aspergillus, Histoplasma), toxoplasmosis.

Question: Day care attendance?
Significance: Increased risk of infection

Question: Recent blood transfusion?
Significance: Transfusion-associated CMV

Question: Use of immunosuppressive medications
Significance: Increased use of serious infection

Question: Prolonged fever?
Significance: Mononucleosis-like syndrome

Question: Blurred vision?
Significance: CMV retinitis

Question: Cough, dyspnea, wheezing?
Significance: CMV pneumonitis

Question: Vomiting, abdominal pain, diarrhea (watery or bloody)?
Significance: CMV colitis

• Strabismus

Finding: Microcephaly
Significance: Congenital infection

Finding: White, perivascular retinal infiltrates and hemorrhage
Significance: Retinitis

Finding: Deafness (may require audiogram, brainstem evoked auditory responses, etc.)
Significance: Congenital infection

Finding: Photophobia, headache, nuchal rigidity
Significance: Meningitis

Finding: Tachypnea, rales
Significance: Pneumonitis

Finding: Hepatomegaly and/or splenomegaly
Significance: Mononucleosis-like syndrome

Finding: Rash
Significance: Petechiae, purpura, “blueberry muffin” lesions, rubelliform rash

Finding: Adenopathy
Significance: Mononucleosis-like syndrome

Test: Viral culture
Significance: Virus may be isolated from nasopharyngeal/oropharyngeal secretions, urine, stool, white blood cells. Isolation of virus may take up to 4 weeks.

Test: Shell-vial assay
Significance: Enhanced viral culture through the use of centrifugation. Allows detection of virus 24 to 72 hours after inoculation.

Test: Direct immunofluorescence
Significance: Detection of CMV-infected cells in specimens from biopsy or bronchoalveolar lavage.

Test: Quantitative antigenemia assay
Significance: Detection of circulating CMV-infected mononuclear cells by indirect immunofluorescence. In an immunocompromised patient, may monitor response to therapy or identify viral reactivation.

Test: DNA hybridization
Significance: Detection of viral nucleic acid in tissue or other specimens

Test: Histological examination
Significance: Presence of typical enlarged cells with intranuclear inclusions (“owl’s eye” nuclear inclusion)

Test: Serology
Significance: ELISA or indirect fluorescent antibody assay to detect the presence of CMV IgM or IgG. CMV IgM usually persists for 6 weeks following primary infection although may persist up to 6 months.

• Due to frequency of asymptomatic shedding, mere isolation of virus does not necessarily establish an etiological association.
• Severely immunocompromised patients who are actively infected with CMV may be seronegative.
• Four-fold rise in CMV IgG not diagnostic of primary infection. Increased antibody titers may occur with reactivation.
• False-positive detection of CMV IgM may occur due to production of cross-reactive antibodies.
• Congenital CMV infection should be established by viral isolation from urine or nasopharyngeal secretions within the first 2 weeks of life.

• Ganciclovir will suppress replication but not eradicate virus (virostatic agent).
  • Indications: CMV chorioretinitis in immunocompromised patients; tissue diagnosis (hepatitis, enteritis, pneumonitis) of CMV infection or isolation of CMV from buffy coat of immunocompromised patient; not indicated for symptomatic neonate with congenital CMV disease (clinical trials in progress at present)
  • Side effects: neutropenia (»50%), thrombocytopenia (»5%)
• Foscarnet—virostatic agent
  • Indications: CMV chorioretinitis, pneumonitis, hepatitis, enteritis (biopsy-proven) in an immunocompromised patient who has failed to improve on ganciclovir therapy or has experienced significant bone marrow toxicity related to ganciclovir use
  • Side effects: renal impairment (25%), headache (25%), seizures (10%)

• Drainage and secretion, and pregnant women precautions should be instituted for hospitalized patients known to be shedding CMV.
• Seriously ill CMV seronegative neonates should receive blood products from CMV-negative donors.
• CMV-seronegative solid organ or bone marrow transplantation recipients should receive organs (and all blood products) from CMV-negative donors whenever possible.
• Controversy exists over role of hyperimmune g-globulin to prevent disseminated CMV disease in CMV-negative recipient of CMV-positive transplantation.

Q: Should children with congenital CMV infection be excluded from daycare settings?
A: No. Due to the high frequency of shedding of CMV in the urine and saliva of asymptomatic children, especially under 2 years of age, exclusion from out-of-home care is not justified for any child known to be infected with CMV. Careful attention to hygienic practices, especially handwashing, is important.