Microbiological hazards of xenotransplantation. 1. Doubts and convictions relating to the risk of xenozoonosis.

The use of a xenogenic organ, tissue or cells for transplantation permits in theory the transmission of microbiological agents from one species to another. The risk of transmission of an unknown animal pathogen to man is assumed to be a public health issue. The genotype homology between human beings and non-human primates, theoretically, should increase the probability of transmission of microbiological agents. It is also assumed that pathogenicity is intensified in closely related species. Historically, most zoonoses come from species that are distant from man. Viruses are more often responsible for human disease than other animal microbial agents. Exposure of humans to animal viruses does not predicate infection. The pathogenicity of an animal virus for man may be immediate or delayed by a possible recombination of adaptive processes. The ultimate risk is the inter-human transmission of a highly pathogenic and fatal animal disease. The retrovirus possesses the enzyme which enables it to become inserted into chromosomal DNA. With an endogenous retrovirus, viral genomes are transmitted through heredity. Some of the retrovirally derived sequences in mammals are fossil viruses. It has been argued that the more closely the species are related, the less likely the retrovirus is to be transmitted, because of xenotropism.

Microbiological hazards of xenotransplantation. 2. Facing the risk.

The high number of xenotransplantations that have been carried out around the world since the beginning of the century, combined with the quantity of animal experiments that have exposed man to animal viruses under similar conditions, should be measured against the low incidence of known pathological consequences. The pathogenic potential of animal viruses for man, then, is unpredictable; and while the risk is acknowledged, it cannot be defined. Unless no benefit can be in xenotransplantation, the application of the precautionary principle to the extent of a moratorium seems to be excessive. The precautionary principle offers possible modes of action in the face of an unquantifiable risk. In the event of xenotransplantation, precautionary measures should be taken in advance, in order to limit risk to the maximum extent. The risk is reduced and the benefit/risk ratio becomes higher, rendering the challenge acceptable. Preventive measures should be taken as the knowledge grows about possible modes of transmission. Guidelines of good practice should be implemented at each step of the xenotransplantation process: birth of animal source by hysterotomy in a 'Specific Pathogen-Free' (SPF) centre rearing in incubator then in isolated conditions (SPF centre) transportation to and rearing in the procurement site (SPF hospital special wing) surgical procurement and xenotransplantation (hospital) post-surgical reanimation (intensive care unit) convalescence (isolated room--hospital) long-term recipient follow-up (home) All these steps should be taken in such a way as to limit the number of persons coming into contact with the recipient.