Cytomegalovirus (CMV) Infection

Most CMV infections are asymptomatic

CMV seroprevalence increases with

• Age

• Lower socioeconomic status

• Number of sexual partners

• History of prior sexually transmitted infections

• Employment in child day care centers

Acute acquired CMV infection is similar to infectious mononucleosis, except pharyngeal symptoms unusual

Virus can be isolated from a variety of tissues under nonpathogenic conditions

Serious disease occurs primarily in immunocompromised persons

Perinatal disease and CMV inclusion disease

• Jaundice, hepatosplenomegaly, thrombocytopenia, purpura, microcephaly, periventricular CNS calcifications, mental retardation, and motor disability

• Hearing loss develops in greater than 50% of infants who are symptomatic at birth

• Most infected neonates are asymptomatic, but neurologic deficits may ensue later in life, including hearing loss in 15% and mental retardation in 10–20%

• Perinatal infection acquired through breast-feeding or blood products typically shows a benign clinical course

CMV infection in immunocompetent persons

• Mononucleosis-like syndrome with negative heterophil antibodies

• The mononucleosis-like syndrome can also occur post-splenectomy, often years later

• Fever, malaise, myalgias and arthralgias, splenomegaly, atypical lymphocytes, and abnormal liver function tests

• Cutaneous rashes are common

• Typically, leukopenia is followed by leukocytosis

• Complications

  • Mucosal gastrointestinal damage

  • Encephalitis

  • Severe hepatitis

  • Thrombocytopenia (on occasion, refractory)

  • Guillain–Barré syndrome

  • Pericarditis

  • Myocarditis

CMV infection in immunocompromised persons

• CMV retinitis, with neovascular and proliferative retinal lesions, occurs primarily in advanced AIDS

• GI and hepatobiliary CMV, with esophagitis, small bowel inflammation, colitis, or cholangiopathy, occurs in AIDS or with high-dose chemotherapy

• Pneumonitis occurs in transplant recipients and AIDS

• Neurologic manifestations include polyneuropathy, transverse myelitis, encephalitis

Characteristic clinical symptoms in immunosuppressed patients

Tzanck smear, CMV antibodies, and polymerase chain reaction (PCR) helpful in the proper clinical context

Tissue biopsy showing characteristic histology is used to document invasive disease

Pregnant women should be tested for CMV viremia every 3 months if an assay during the first trimester is seropositive

An ELISPOT assay is superior to Quantiferon assays in reports from China and may show potential for both diagnosis and monitoring disease in transplant recipients

In immunocompetent persons, CMV infection is usually self-limited and no specific antiviral therapy is needed

In immunocompromised persons, treatment of CMV disease is necessary

• Intravenous ganciclovir: recommended dose is 5 mg/kg every 12 hours (although this needs to be adjusted for kidney function) until two CMV PCRs 1 week apart are negative (usually 14–21 days)

• Oral valganciclovir dose: 900 mg every 12 hours (also needs to be adjusted for kidney function) is an acceptable alternative in patients with non–life-threatening disease

• Pneumonia due to CMV in hematopoietic stem cell transplant recipients is treated even more aggressively

  • 5 mg/kg of ganciclovir intravenously every 12 hours for 21 days followed by 5 mg/kg daily for 3–4 weeks plus CMV immunoglobulin (500 mg/kg)

  • CMV immunoglobulin (150 mg/kg) twice per week for 2 weeks and then once weekly for an additional 4 weeks

Foscarnet and cidofovir are reserved for treatment of resistant infections

Other agents that may be useful in resistant CMV infections include

• CMV immunoglobulin

• Leflunomide

• Sirolimus-based therapy

• Artesunate

• Adoptive immunotherapy