Figure 1021

The lifecycle of cytomegalovirus (CMV). The envelope binds with the cell membrane, and the DNA is uncoated and transferred into the nucleus, where cell protein synthesis machinery is used to manufacture new DNA and capsid. The DNA is packaged into the cap-sid and returns to the cytoplasm, where the tegument and envelope are assembled around the capsid and the whole virus transported to the cellular surface and released.

CMV is a double-stranded DNA virus that causes disease following transplantation after primary infection, reinfection, or reactivation of latent infections. CMV disease is seen most frequently within the first 4 to 6 months of transplantation if no antiviral prophylaxis is used; however, in the presence of antiviral prophylaxis and new immunosuppressive agents, the onset of CMV disease may be shifted to longer intervals from transplantation. There also may be a slight increase in the occurrence of CMV enteritis with the use of some of the newer combinations of immunosup-pressive agents. When the recipient is CMV positive and receives an organ from a CMV-positive donor, reactivation of the latent infection in the recipient is responsible for 15% to 30% of the infections seen, and reinfection with the virus from the donor is responsible for 70%.

CMV disease prevention may be accomplished by administering prophylactic antiviral agents or by the use of routine surveillance testing. Variables to be considered in an individual's risk of CMV disease development are the use of antilymphocyte medications, and the donor and recipient, CMV serostatus. The highest risk group for CMV disease is the group at risk for primary CMV exposure and those given antilymphocyte preparations. Specifically, increased CMV disease is seen during situations that trigger viral replication. High levels of tumor necrosis factor alpha, such as levels occurring during infections or after OKT3 administration, activate the CMV promoter, thus stimulating the conversion from the latent to the reactivated state.

All of the prophylactic strategies for the prevention of CMV disease have shown some benefit in different studies; currently, however, the most effective approach is oral ganciclovir. A more bioavailable oral ganciclovir may even increase the effectiveness and is now under investigation. Oral ganciclovir is started when the patient is able to take oral medications within the first week following transplantation and is administered at a dose of 1 g 3 times a day for 3 months following transplantation adjusted for renal function. The protective effect is also seen in those who have received antilymphocyte preparations. The most desirable solution would be a vaccine that induced natural immunity mechanisms. Vaccines targeted against the structural glycoproteins of CMV are currently continuing under development but are not yet available; their ultimate effectiveness is not known at this time. As patients who already have had natural infections are not immune to reinfection or reactivation, a vaccine solution may not be possible.

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