Cytomegalovirus infection

Infection with the cytomegalovirus (CMV or human herpes virus 5) is generally asymptomatic in immunocompetent hosts, but can cause mild mononucleosis-like symptoms. Like all Herpesviridae infections, CMV persists for the lifetime of its host; reactivation may therefore occur. Immunocompromised individuals (e.g., AIDS, post-transplantation) are especially at risk of illness following reactivation or initial infection, which can include severe manifestations such as CMV retinitis (risk of blindness) or life-threatening CMV pneumonia. Treatment with ganciclovir or valganciclovir should therefore begin promptly on clinical suspicion of a CMV infection.

Congenital CMV infection is discussed in another article.

• Prevalence of CMV infection in the general population: 40–100%
• Seroprevalence increases with age with more than 90% in individuals > 80 years

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: cytomegalovirus (CMV, human herpes virus 5, HHV-5)
• Transmission
  • Blood transfusions
  • Sexual transmission
  • Transplacentally (highest risk during the first trimester of pregnancy)
  • Perinatal transmission (e.g., contact with contaminated blood/vaginal secretions during delivery or breastfeeding)
  • Body fluids (e.g., respiratory droplets, saliva, urine, genital secretions)
  • Transplant-transmitted infection (e.g., bone marrow, lungs, kidneys) ^[1]

References:^[2][3]

• CMV binds to integrins →; activation of integrins → induction of cellular morphological changes → activation of signal transduction pathways; such as FAK (focal adhesion kinase) and apoptotic pathways → cell damage → clinical manifestations depending on the organ/tissue affected. ^[4][5]
• After primary infection resolves, CMV remains latent in mononuclear cells (e.g., myeloid cells). Reactivation can occur if the patient becomes immunocompromised. ^[6]

CMV infection is usually asymptomatic. Severe manifestations occur in immunocompromised states (e.g., following organ transplantation, AIDS).

For information about congenital CMV infection, see the corresponding article.

In immunocompetent patients

• > 90%: asymptomatic course ^[2][3][7]
• < 10%: CMV mononucleosis ^[8]
  • Fever, malaise, myalgia/arthralgia, fatigue, headache
  • Less common: sore throat, cervical lymphadenopathy, hepatomegaly, splenomegaly ^[7]
  • Differential diagnosis: infectious mononucleosis caused by EBV (in the case of CMV, heterophile antibody test would be negative)

In immunocompromised patients

One or more of the following clinical manifestations may be present:

• CMV mononucleosis
• CMV pneumonia: interstitial pneumonitis ;.
  • Etiology: immunocompromised patients (e.g., following bone marrow transplant or in HIV/AIDS patients with CD4 ≤ 50 cells/mm³)
  • Clinical findings: fever, nonproductive cough, dyspnea
  • Diagnostics
    • Chest x-ray: diffuse bilateral interstitial infiltrates
    • Detection of CMV in bronchoalveolar lavage fluid or lung tissue samples following biopsy ^[9]
  • Differential diagnoses: pneumocystis pneumonia and other viral respiratory infections ^[7]
• CMV retinitis: floaters, photopsia, visual field defects ; ^[10]
  • Fundoscopy: “pizza-pie” appearance (retinal hemorrhages, fluffy/granular white opacities around retinal vessels resembling cotton-wool spots, retinal detachment)
  • Differential diagnoses: HIV retinopathy, herpes simplex retinitis, varicella zoster retinitis, toxoplasmosis
• CMV esophagitis and/or CMV colitis
  • Most commonly occurs in patients with HIV.
  • Manifests with odynophagia, abdominal pain, bloody diarrhea
  • Endoscopic examination of the GI tract typically shows linear ulcers ^[11]
• Adrenal insufficiency^[12]
• CMV encephalitis: impaired cognitive function, neurological deficits ^[11]

Among HIV-positive patients, manifestations of CMV disease usually occur when the CD4 count is ≤ 50!

• CBC: relative lymphocytosis with > 10% atypical lymphocytes ^[3] and sometimes pancytopenia
• Tissue biopsy: large atypical lymphocytes with intranuclear inclusion bodies that have an owl-eye appearance
• Monospot (heterophile antibody) test: negative ^[3]
• Serological tests ^[2]
  • Active disease
    • IgM antibodies
    • A four-fold increase in the levels of IgG antibodies ^[7][8]
  • Inactive disease: IgG antibodies in the absence of IgM antibodies ^[2]
• Direct evidence of viremia: especially useful in immunosuppressed patients ^[7]
  • PCR to detect CMV DNA in bodily fluids
  • Indirect immunofluorescence assay: pp-65 CMV antigens
• Fundoscopy: retinal hemorrhages and cotton-wool spots (“pizza-pie” appearance) in CMV retinitis

In immunocompetent patients, CMV infection may present similarly to EBV infection. However, in CMV infection the monospot test will be negative!

Serological tests may be unreliable in immunosuppressed patients!

• In immunocompetent patients: No specific treatment is needed. ^[2][3]
• In immunosuppressed patients ^[11]
  • Optimize antiretroviral therapy regimen to increase CD₄ count above 100 cells/mm³