CMV, a member of the herpes virus family of DNA viruses, is a large, membrane-enveloped virus. Like other members of the herpes virus family, CMV possesses the characteristics of latency and reactivation, which means that viral infection can reactivate repeatedly with viral shedding occurring for many years after initial infection. CMV is widely prevalent throughout the world and most infections are asymptomatic. Major manifestations are: mononucleosis, congenital CMV infection (CMV is the most common cause of virus-induced mental retardation in the Western World); graft rejection in organ transplant recipients; severe pneumonia, hepatitis and CMV retinitis in immunosuppressed individuals.
CMV retinitis, an infection that progresses to blindness, afflicts approximately 15 to 40 percent of AIDS patients. CMV retinitis usually begins as a white infiltrate within the retina, and can progress rapidly to cause destruction of retinal tissue. Retinal damage can lead to detachment of the retina, occurring in 15 to 29 percent of patients with AIDS-related CMV retinitis, and permanent loss of vision.
Each year, approximately 40,000 infants are born with congenital CMV, which is transmitted congenitally (or in the womb through the placenta) from mother to fetus. Whether due to a severe disease at birth or to long-term sequellae of a latent infection, congenital CMV infection is a leading cause of congenital deafness and mental retardation.
CMV is also a major cause of morbidity in solid organ transplant recipients. CMV can trigger acute illness and adversely affect graft survival.
The modes of CMV transmission include mother to infant (congenitally, during the birth process and through milk), sexual contact, and exposure to blood products or transplanted organs.
Diagnosis.
Diagnosis of CMV infection in children and adults requires
laboratory confirmation. Chiron is developing a branched DNA (bDNA) probe
test for use following diagnosis to quantitate CMV DNA (viral load) in
blood and plasma samples.
Treatment.
CMV is a difficult systemic virus to treat. Current treatments include antiviral agents which offer viral suppression as long as therapy is ongoing. Advancements in treatment of CMV retinitis are helping delay its progression and its devastating impact on the retina. Chiron's Vitrasert Implant, which contains the drug Cytovene, ganciclovir, is the only treatment designed to provide local, sustained release of ganciclovir directly to the eye. Release of ganciclovir, for five to eight months, results in a dramatic delay in progression of CMV retinitis. Other products for treatment of CMV retinitis include Gilead's Vistide, and Astra Pharmaceuticals' foscarnet (Foscavir).
Prevention.
The magnitude of problems arising from CMV infection are
yet to be fully recognized by the medical community. Vaccination against
CMV could be an essential strategy for helping reduce the congenital transmissions
which often result in death, or severe handicap of infants. Chiron Vaccines
is testing a genetically engineered subunit vaccine against CMV infection.
Phase 2 clinical studies are underway to test the safety and efficacy of
Chiron Vaccine's CMV glycoprotein B vaccine in seronegative adult volunteers.