Cytomegalovirus (CMV, human herpesvirus type 5) can cause infections that have a wide range of severity. A syndrome of infectious mononucleosis that lacks severe pharyngitis is common. Severe focal disease, including retinitis, can develop in HIV-infected patients and in organ transplant recipients and other patients who are immunocompromised. Severe systemic disease can develop in neonates and patients who are immunocompromised. Laboratory diagnosis, helpful for severe disease, may involve culture, serologic testing, biopsy, or antigen or nucleic acid detection. Ganciclovir and other antiviral medications are used to treat severe disease, particularly retinitis.
(See also Overview of Herpesvirus Infections and Congenital and Perinatal Cytomegalovirus Infection.)
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; 50 to 90% of adults have CMV infection (resulting in lifelong latent infection) (1). Lower socioeconomic groups tend to have a higher prevalence.
Congenital CMV infection 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 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 patients who are immunocompromised, 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 about 30% of patients and causes funduscopically visible retinal abnormalities (2). Ulcerative disease of the colon (with abdominal pain and gastrointestinal bleeding) or of the esophagus (with odynophagia) may occur.
Довідкові матеріали загального характеру
1. Staras SA, Dollard SC, Radford KW, et al: Seroprevalence of cytomegalovirus infection in the United States, 1988-1994. Clin Infect Dis 43(9):1143-1151, 2006. doi:10.1086/508173
2. Sugar EA, Jabs DA, Ahuja A, et al: Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Am J Ophthalmol 153(6):1016-24.e5, 2012. doi:10.1016/j.ajo.2011.11.014
Diagnosis of Cytomegalovirus
Detection of CMV antigen or DNA
Urine culture in infants
Biopsy of tissue that may be infected in patients who are immunocompromised
Serologic testing
CMV infection is suspected in
Healthy people with mononucleosis-like syndromes
Patients who are immunocompromised and have gastrointestinal, lung, CNS, or retinal symptoms
Neonates with systemic disease
CMV mononucleosis can be differentiated from infectious (EBV) mononucleosis by the usual lack of pharyngitis, a negative heterophile antibody test, and positive CMV serologic testing. CMV infection affecting the liver can be differentiated from other viral hepatitis infections by hepatitis serologic testing. Laboratory confirmation of primary CMV infection is necessary only to differentiate it from other, particularly treatable, conditions or serious disease, such as primary HIV.
Seroconversion can be demonstrated by development of CMV antibodies and indicates new CMV infection. However, CMV disease can also result from reactivation of latent disease in immunocompromised hosts. 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 viral shedding. Therefore, biopsy showing CMV-induced abnormalities in infected tissue 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. Such CMV detection can be particularly helpful in patients who are severely immunocompromised with compatible clinical syndromes in whom biopsy may not be feasible.
Diagnosis of CMV infection in infants can be made by urine culture.
Treatment of Cytomegalovirus
For serious disease, antivirals (eg, ganciclovir, valganciclovir, foscarnet, cidofovir, maribavir)
CMV retinitis, which occurs mostly in AIDS patients, is treated with systemic antivirals.
Anti-CMV medications are used to treat severe disease other than retinitis but are less consistently effective than in retinitis.
ЦМВ ретиніт
Medications used to treat CMV retinitis in induction and maintenance regimens include
Ganciclovir or valganciclovir
Foscarnet, with or without ganciclovir
Cidofovir
Maribavir
Most patients receive induction therapy with IV ganciclovir or oral valganciclovir.
Maintenance (suppressive) therapy with ganciclovir or valganciclovir is given after induction.
Alternatively, IV foscarnet can be given with or without ganciclovir. 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. 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.
Maribavir is an oral medication for treatment of refractory CMV disease. Maribavir has a novel mechanism of action, targeting the viral UL97 kinase, and prevents viral maturation. It is active against CMV that is resistant to ganciclovir. Maribavir cannot be coadministered with ganciclovir or valganciclovir.
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 (ART) and have had a CD4 count of ≥ 100 cells/mL 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 antivirals 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. Medications 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 or renal transplantation. It has many important drug interactions, including with cyclosporine, tacrolimus, sirolimus, and voriconazole.
Ключові моменти
Fifty 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.
Patients who are severely immunocompromised may have severe disease involving the retina, lungs, gastrointestinal tract, or CNS.
Antivirals 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.
