Chapter 15 : Prevention of Infection in Xenotransplantation

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The central hypothesis for this chapter is that some of the infectious risks associated with xenotransplantation can be assessed before the broad application of this emerging technology. Epidemiologic exposures in the transplant recipient take two forms: those occurring within the hospital or the community, and those exposures carried with the transplanted organ. On the basis of experience with human allograft recipients and with immunosuppressed miniature swine, common infections in the first month after xenotransplantation are likely to be due to bacteria and fungi common to swine and to primates: staphylococci, streptococci, spp., spp., spp., and spp., which are routinely isolated from swine and from non-human primates. With prolonged xenograft survival, the susceptibility of the xenograft recipient to infection reflects the individual's epidemiologic exposures and the immune suppression and manipulations of donor and host needed to prevent graft rejection. While breeding strategies may enhance the safety of xenotransplantation, the greatest potential risk to the recipient and to the general community by xenograft-derived organisms may be due to infection by unknown pathogens that cause minimal or novel clinical syndromes and for which clinical laboratory testing is not available. Chimerism and False Positive Assays for Infection of the Host and Routine Monitoring for Xenogeneic Infection are among the issues discussed for maintaining safety in clinical trials of xenotransplantation. Further research is essential regarding the behavior of organisms known to be present in prospective donor species in xenograft recipients and on the detection of novel potential pathogens.

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Figure 1

Porcine endogenous retrovirus replicating in human 293 kidney cells (x60,000). Provided by Drs. K. Boiler, R. R. Tonjes, J. Denner, Paul-Ehrlich Institute, Langen, Germany.

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Figure 2

Northern analysis of the expression of PERV-MSL (PERV C) in various tissues. A probe for the region of PERV was hybridized to poly-A+ RNA (0.5 g) from each tissue indicated and from normal peripheral blood lymphocytes (PBL, lane 1) and PHA-activated lymphocytes (PHA PBL, lane 2), PK15 cells (0.04 lanes 3 and 11). Expression of PERV was detected in all porcine cells and tissues analyzed (including kidney and heart with longer exposures). The expression of PERV is increased by stimulation with the mitogen PHA (reprinted from reference 1, with permission).

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Figure 3

Strategy for the evaluation of xenograft recipients with signs or symptoms of infection.

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Table 1

Nonrecognition of infection associated with xenograft transplantation

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Table 2

Infectious considerations for non-human primates in xenotransplantation

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Table 3

Microbial agents of swine known to cause infection in humans

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Table 4

Categories of potential pathogens resulting from xenotransplantation

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
Generic image for table
Table 5

Screening xenograft source animals: microbiologic exclusion criteria

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
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Table 6

Designated-pathogen-free miniature swine for xenotransplantation

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15
Generic image for table
Table 7

Microbiologic screening of animal handlers

Citation: Fishman J. 2001. Prevention of Infection in Xenotransplantation, p 261-290. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch15

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