Infection in Xenotransplantation: Organ-Source Health and Patient Safety

Fishman, Jay A.

Posttransplant infections are common in allograft recipients, largely due to the immunosuppressive therapy required to maintain graft function. Infection is derived from the environment, the recipient, and the transplanted organ. Procedures have been developed to minimize the risk of posttransplant infection, including organ donor screening, prophylactic antimicrobial therapies, and monitoring of recipients for common infections. These approaches have dramatically increased the success of clinical transplantation. The requirement for immunosuppressive therapy in xenotransplantation from swine, or from other species, necessitates similar safeguards. In addition, xenotransplantation poses the added challenge of more limited data on the microbiology of swine used for commercial purposes and, specifically, with the impact of immunosuppression of swine or humans carrying viable swine tissues. Significant advances in knowledge have been achieved which allow procedures that enhance the safety of allotransplantation to be applied in xenotransplantation. This includes screening of source animals and organs for potential human pathogens, antimicrobial prophylaxis, and monitoring of recipients for infections – both of xenogeneic origin and from the host and the environment. Monitoring for specific pathogens in donors or organs may allow the exclusion of common organisms comparable to those causing infection in allograft recipients, such as porcine cytomegalovirus and porcine lymphotropic herpesvirus, mycobacteria, molds, and parasites. Pig-specific pathogens, such as porcine endogenous retroviruses or circoviruses, may be excluded from donors or monitored in recipients. Novel monitoring strategies may supplement these pathogen-specific assays using advanced sequencing modalities, including broad-range molecular probes, microarrays, and high-throughput pyrosequencing. Xenotransplantation provides the unique opportunity to examine approaches to microbiological safety in transplantation while providing a supply of organs for clinical application.