Developing Xenostandards for Microbiological Safety: New Zealand Experience

Human patients have the potential to become infected with animal viruses following xenotransplantation. Concerns have also been raised that in a worst case scenario, pathogens originating from pig donors may adapt and then propagate to the wider public resulting in a new epidemic (Fiane, Mollnes, & Degre, 2000; Fishman, 2001a; Onions et al., 2000; Patience, Wilkinson, & Weiss, 1997; Weiss, 2003). The likelihood that cross-species infection may occur is enhanced in a xenotransplantation setting because normal host defences such as skin and mucosal surfaces are bypassed and direct contact between donor and recipient cells is maintained for extended periods of time (O’Rourke, 2000). Similarly for applications that use immunosuppression to prevent xenograft rejection, host complementmediated immunity is circumvented (Takeuchi, Magre & Patience, 2005). Currently pigs are recognised as the most popular choice as donor animals due in part to their ostensibly lower infectious risk (compared with non-human primates), excellent breeding potential, comparable organ size, physiological similarity, amenability to genetic modification, non contentious public perception and the relatively moderate costs associated with their maintenance (Sachs, Sykes, Robson, & Cooper, 2001). In terms of pig pathogens it has been determined that the preponderance of fungi, bacteria and parasites can be excluded as major risk factors simply by the use of good animal husbandry practices in Specific Pathogen Free (SPF) herds (Ye, Niekrasz, Kosanke, Welsh, Jordan et al, 1994). Consequently viruses are recognised as the predominant infectious agent for zoonosis owing to their rapid rate of evolution and excellent adaptive competence within new hosts. Precedents for cross-species infection of viruses and adaptation in humans are numerous and include several notorious examples, notably AIDS (Gao, Bailes, Robertson, Chen, Rodenburg et al, 1999) and avian influenza [reviewed in (Alexander & Brown, 2000)]. Although pigs are not always a natural reservoir for exogenous viruses, it has been hypothesised that swine may act as “mixing vessels” for adaptation to human hosts, as is certainly the case for avian viruses such as Severe Acute Respiratory Syndrome (SARS) (Bush, 2004).