IMPORTANCE OF SIMULTANEOUS ACTIVE CYTOMEGALOVIRUS AND EPSTEIN-BARR-VIRUS INFECTION IN RENAL-TRANSPLANTATION

Background: Although being the most common infective complication afte r transplantation, cytomegalovirus (CMV) infection does not always pro duce disease symptoms in immunosuppressed patients. Development of CMV disease may depend on different factors such as virulence of particul ar CMV strains and impairment of CMV-specific immune reactions. Object ive: Demonstration of the importance of simultaneous Epstein-Barr viru s (EBV) activation for development of symptomatic CMV infections. Stud y design: 208 renal transplantation patients were monitored for 3 year s with respect to (i) CMV and EBV replications, and (ii) clinical symp toms associated with combined and single infections, respectively. Res ults: CMV and EBV replications were observed in 22% and 19% of the pat ients, respectively. Many of these active virus infections were found to overlap in time (59% and 74% of all active CMV and EBV infections, respectively). The increased detection of combined CMV and EBV infecti ons probably does not result from higher initial immunosuppression in these patients, since the percentage of patients receiving OKT3 or ATG was almost identical in the groups of single and combined infections. In 18 cases of combined infections, CMV replication preceeded EBV rep lication, while EBV replication prior to CMV replication was observed in one case only, indicating that activation of latent EBV infection m ay be induced during active CMV infection. Conclusions: Simultaneous r eplication of both viruses seems to be clinically important, since sev ere clinical symptoms were observed only in the group of combined CMV and EBV infections. Symptoms were similar to the clinical pictures of CMV disease. Thus, simultaneous EBV replication may be an important co -factor for the development of CMV disease, possibly by further decrea sing the number of functional CD4 T cells or enhancing the CD8-positiv e cytolytic/suppressor T-cell subset as reflected by the comparatively stronger decrease of CD4/CD8 ratio during simultaneous CMV and EBV re plication, particularly in the case of symptomatic infections.