(See also Overview of Herpesvirus Infections Overview of Herpesvirus Infections Eight types of herpesviruses infect humans (see Table: Herpesviruses That Infect Humans). After initial infection, all herpesviruses remain latent within specific host cells and may subsequently... read more and Congenital and Perinatal Cytomegalovirus Infection Congenital and Perinatal Cytomegalovirus Infection (CMV) Cytomegalovirus infection may be acquired prenatally or perinatally and is the most common congenital viral infection. Signs at birth, if present, are intrauterine growth restriction, prematurity... read more .)
CMV (human herpesvirus type 5) is transmitted through blood, body fluids, or transplanted organs. Infection may be acquired transplacentally or during birth.
Prevalence increases with age; 60 to 90% of adults have CMV infection (resulting in lifelong latent infection). Lower socioeconomic groups tend to have a higher prevalence.
Congenital CMV infection Congenital and Perinatal Cytomegalovirus Infection (CMV) Cytomegalovirus infection may be acquired prenatally or perinatally and is the most common congenital viral infection. Signs at birth, if present, are intrauterine growth restriction, prematurity... read more may be asymptomatic or may cause abortion, stillbirth, or postnatal death. Complications include extensive hepatic and central nervous system (CNS) damage.
Acquired infections are often asymptomatic.
An acute febrile illness, termed CMV mononucleosis, may cause hepatitis with elevated aminotransferases (usually subclinical without jaundice), and atypical lymphocytosis similar to infectious mononucleosis Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more due to Epstein-Barr virus (EBV).
Postperfusion/posttransfusion syndrome can develop 2 to 4 weeks after transfusion with blood products containing CMV. It causes fever lasting 2 to 3 weeks and the same manifestations as CMV mononucleosis.
In immunocompromised patients, CMV is a major cause of morbidity and mortality. Disease often results from reactivation of latent virus. The lungs, gastrointestinal tract, or CNS may be involved. In the terminal phase of AIDS, CMV infection causes retinitis Herpesviruses: Cytomegalovirus A number of infectious diseases cause uveitis (see table Infectious Causes of Uveitis). The most common are toxoplasmosis, herpes simplex virus, and varicella-zoster virus. Different organisms... read more in up to 40% of patients and causes funduscopically visible retinal abnormalities. Ulcerative disease of the colon (with abdominal pain and gastrointestinal bleeding) or of the esophagus (with odynophagia) may occur.
Diagnosis of Cytomegalovirus
Detection of CMV antigen or DNA
Urine culture in infants
Often biopsy in immunocompromised patients
CMV infection is suspected in
Healthy people with mononucleosis-like syndromes
Immunocompromised patients with gastrointestinal, CNS, or retinal symptoms
Neonates with systemic disease
CMV mononucleosis can be differentiated from infectious (EBV) mononucleosis Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more by the usual lack of pharyngitis, a negative heterophile antibody test, and through CMV serologic testing. CMV infection affecting the liver can be differentiated from other viral hepatitis infections by hepatitis serologic testing Serology Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more . Laboratory confirmation of primary CMV infection is necessary only to differentiate it from other, particularly treatable, conditions or serious disease, such as primary HIV Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more .
Seroconversion can be demonstrated by development of CMV antibodies and indicates new CMV infection. However, much CMV disease results from reactivation of latent disease in the immunocompromised host. Reactivation of CMV can result in virus in the urine, other body fluids, or tissues, but the presence of CMV in body fluids and tissues does not always indicate disease and may merely represent shedding. Therefore, biopsy showing CMV-induced abnormalities is often necessary to demonstrate invasive disease. Quantitative detection of CMV antigen or DNA in the peripheral blood can also be very helpful because an elevated or rising CMV viral load is often highly suggestive of invasive disease.
Diagnosis of CMV infection in infants can be made by urine culture.
Treatment of Cytomegalovirus
For serious disease, antivirals (eg, ganciclovir, valganciclovir, foscarnet, cidofovir)
CMV retinitis, which occurs mostly in AIDS patients, is treated with systemic antivirals.
Anti-CMV drugs are used to treat severe disease other than retinitis but are less consistently effective than in retinitis.
Drugs used to treat CMV retinitis in induction and maintenance regimens include
Ganciclovir or valganciclovir
Foscarnet, with or without ganciclovir
Most patients receive induction therapy with one of the following:
Ganciclovir 5 mg/kg IV every 12 hours for 2 to 3 weeks
Valganciclovir 900 mg orally every 12 hours for 21 days
If induction fails more than once, another drug should be used.
Maintenance (suppressive) therapy with one of the following is given after induction:
Ganciclovir 5 mg/kg IV once a day
Valganciclovir 900 mg po once a day
Alternatively, foscarnet can be given with or without ganciclovir. Dosage is
Induction: Foscarnet 60 mg/kg IV every 8 hours for 2 to 3 weeks
Maintenance: Foscarnet 90 to 120 mg/kg IV once a day
Adverse effects of IV foscarnet are significant and include nephrotoxicity, symptomatic hypocalcemia, hypomagnesemia, hyperphosphatemia, hypokalemia, and CNS effects. Combination therapy with ganciclovir and foscarnet increases efficacy as well as adverse effects.
Cidofovir therapy is another alternative; it consists of
Induction: Cidofovir 5 mg/kg IV once a week for 2 weeks
Maintenance: Cidofovir 5 mg/kg IV once every other week
Efficacy of cidofovir is similar to that of ganciclovir or foscarnet. Significant adverse effects, including renal failure, limit its use. Cidofovir may cause iritis or ocular hypotony (intraocular pressure ≤ 5 mm Hg). The potential for nephrotoxicity can be reduced by giving probenecid and prehydration with each dose. However, the adverse effects of probenecid, including rash, headache, and fever, may be significant enough to prevent its use.
With any of the maintenance regimens, clinicians can consider stopping maintenance therapy after 3 months of CMV therapy in HIV-infected patients who are taking antiretroviral therapy Treatment Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more (ART) and have had a CD4 count of ≥ 100 cells/mcL for 3 months.
Intravitreal antiviral therapy should be used in combination with systemic therapy for patients with CMV retinitis that immediately threatens sight (ie, disease involving or close to the optic nerve or macula). Even patients receiving ocular injections need systemic therapy to prevent CMV in the contralateral eye and extraocular tissues.
Prevention of Cytomegalovirus
Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antiviral drugs to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease. Drugs used include ganciclovir, valganciclovir, and foscarnet. Letermovir is a newer agent with a novel mechanism of action that can be used for prophylaxis in bone marrow transplantation. CMV hyperimmune globulin can be considered to prevent CMV infection in transplant recipients but is controversial.
Sixty to 90% of adults have latent CMV infection.
Healthy children and adults can have mild, nonspecific symptoms or sometimes a mononucleosis-like syndrome when first infected with CMV.
Congenital infection may cause stillbirth or severe, sometimes fatal postnatal complications including extensive hepatic or CNS damage.
Severely immunocompromised patients may have severe disease involving the retina, lungs, gastrointestinal tract, or CNS.
Antiviral drugs may help treat retinitis but are less effective when other organs are affected.
Transplant patients at risk of CMV infection require prophylactic antivirals or close monitoring for early indications of infection.