Chapter 11 : Zoonosis as a Risk to the Xenograft Recipient and to Society: Theoretical Issues

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Zoonosis as a Risk to the Xenograft Recipient and to Society: Theoretical Issues, Page 1 of 2

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Scientists have proffered widely varying opinions on the extent to which xenotransplantation clinical trials threaten to introduce new infections into the human community. Observers at one extreme conclude that the risk of introducing new infections to the human community is too great, and the potential for benefit is too unclear. These observers argue that the only responsible stance is to impose a complete moratorium on clinical xenotransplantation until there is sufficient knowledge to assess these risks. Observers on the other extreme argue that in the absence of data to support these fears, restrictions that slow or halt the progress of xenotransplantation research would unnecessarily impede progress in an area that promises unmeasurable relief to human suffering. Other observers note that both the risks and the benefits associated with clinical xenotransplantation remain theoretical at present. Advocates of this approach argue that these trials can be accompanied by safeguards stringent enough to adequately protect the public. Laboratory-based studies of xenograft survivors will also increase one's ability to quantify xenotransplant-associated risks and thereby expand one's capacity to make science-based assessments of appropriate public policy. The risk that any xenograft recipient may become infected with porcine endogenous retrovirus (PERV) is likely a function of multiple factors associated with the source animal, the xenotransplantation technique, the characteristics of the human recipient, and the level of PERV expression by the transplanted cells. Reviews of historic developments in xenotransplantation coupled with critiques of developing public policy and procedures have furthered efforts at consensus development.

Citation: Chapman L. 2001. Zoonosis as a Risk to the Xenograft Recipient and to Society: Theoretical Issues, p 207-216. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch11

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Feline leukemia virus
Simian foamy virus
Simian immunodeficiency virus
Feline leukemia virus
Simian immunodeficiency virus
Feline leukemia virus
Simian immunodeficiency virus
Simian foamy virus
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1.Advisory Group on the Ethics of Xenotransplantation. 1997. Animal Tissues into Humans. Stationery Office, London, United Kingdom.
2. Akiyoshi, D. E.,, M. Denaro,, H. Zhu,, J. L. Greenstein,, P. Banerjee,, and J. A. Fishman. 1998. Identification of a full length cDNA for an endogenous retrovirus of miniature swine. J. Virol. 72:45034507.
3. Allan, G. M.,, F. McNeilly,, S. Kennedy,, B. Daft,, E. G. Clarke,, J. A. Ellis,, D. M. Haines,, B. M. Meehan,, and B. M. Adair. 1998. Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe. J. Vet. Diagn. Invest. 10:310.
4. Allan, J. S. 1996. Xenotransplantation at a crossroads: prevention vs progress. Nature Med. 2:1821.
5. Allan, J. S.,, S. R. Broussard,, M. G. Michaels,, T. E. Starzl,, K. L. Leighton,, E. M. Whitehead,, A. G. Comuzzie,, R. E. Lanford,, M. M. Leland,, W. M. Switzer,, and W. Heneine. 1998. Amplification of simian retroviral sequences from human recipients of baboon liver transplants. AIDS Res. Hum. Retroviruses 14:821824.
6. Bach, F. H.,, J. A. Fishman,, N. Daniels,, J. Proimos,, B. Anderson,, C. B. Carpenter,, L. Forrow,, S. C. Robson,, and H. V. Fineberg. 1998. Uncertainty in xenotransplantation: individual benefit versus collective risk. Nature Med. 4:141144.
7. Bailey, L. L.,, S. L. Nehlsen-Cannarella,, W. Conception,, and W. B. Jolley. 1985. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA 254:33213329.
8. Bellucci, S.,, A. Bondolfi,, B. Husing,, and A. Ruegsegger. 1998. The Swiss technology assessment (TA) project on xenotransplantation. Ann. N. Y. Acad. Sci. 862:155165.
9. Bjoersdorff, A.,, O. Korsgen,, R. Feinstein,, A. Andersson,, J. Tollemar,, A.-S. Malmborg,, A. Ehrnst,, and C. G. Groth. 1995. Microbiological characterization of porcine fetal islet-like cell clusters for intended clinical xenografting. Xenotransplantation 2:2631.
10. Borie, D. C.,, D. V. Cramer,, L. Phan-Thanh,, J. C. Vaillant,, J. L. Bequet,, L. Makowka,, and L. Hannoun. 1998. Microbiological hazards related to xenotransplantation of porcine organs into man. Infect. Control Hosp. Epidemiol. 19:355365.
11. Brown, J.,, A. L. Matthews,, P. A. Sandstrom,, and L. E. Chapman. 1998. Xenotransplantation and the risk of retroviral zoonosis. Trends Microbiol. 6:411415.
12. Chapman, L. E. 1999. Speculation, stringent reasoning, and science. Bull. W. H. O. 77:6870.
13. Chapman, L. E.,, and J. A. Fishman,. 1997. Xenotransplantation and infectious diseases, p. 736748. In D. K. C. Cooper,, E. Kemp,, J. L. Piatt,, and D. J. White (ed.). Xenotransplantation: The Transplantation of Organs and Tissues Between Species. Springer-Verlag, Berlin, Germany.
14. Chapman, L. E.,, T. M. Folks,, D. R. Salomon,, A. P. Patterson,, T. E. Eggerman,, and P. D. Noguichi. 1995. Xenotransplantation and xenogeneic infections. N. Engl. J. Med. 333:14981501.
15. Chari, R. S.,, B. H. Collins,, J. C. Magee,, J. M. DiMaio,, A. D. Kirk,, R. C. Harland,, R. L. McCann,, J. L. Platt,, and W. C. Meyers. 1994. Brief report: treatment of hepatic failure with ex vivo pig-liver perfusion followed by liver transplantation. N. Engl. J. Med. 331:234237.
16. Daar, A. S. 1998. Analysis of factors for the prediction of the response to xenotransplantation. Ann. N. Y. Acad. Sci. 862:222233.
17. Daar, A. S. 1999. Animal-to-human transplants—a solution or a new problem? Bull. W. H. O. 77:5461.
18. Deacon, X.,, J. Schumacher,, J. Dinsmore,, C. Thomas,, P. Palmer,, S. Kott,, A. Edge,, D. Penney,, S. Kassissieh,, P. Dempsey,, and O. Isacon. 1997. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nature Med 3:350353.
19.DHHS Interagency Working Group on Xenotransplantation. 1998. The draft US Public Health Service guideline on infectious disease issues in xenotransplantation. Ann. N. Y. Acad. Sci. 862:166170.
20. De Sola, C. 1998. Current developments on xenotransplantation in the Council of Europe. Ann. N. Y. Acad. Sci. 862:211213.
21. Eastlund, T. 1995. Infectious disease transmission through cell, tissue, and organ transplantation: reducing the risk through donor selection. Cell Transplant. 4:455477.
22. Galili, U.,, A. Tibell,, B. Samuelsson,, L. Rydberg,, and C. G. Groth. 1995. Increased anti-gal activity in diabetic patients transplanted with fetal porcine islet cell clusters. Transplantation 59:15491556.
23. Geo, F.,, E. Bailes,, D. L. Robertson,, Y. L. Chen,, C. M. Rodenburg,, S. F. Micheal,, L. B. Cummins,, L. O. Arthur,, M. Peeters,, G. M. Shaw,, P. M. Sharp,, and B. H. Hahn. 1999. Origin of HIV-1 in the chimpanzee Pan troglodytes. Nature 397:436441.
24. Groth, C. G.,, O. Korsgren,, A. Tibell,, J. Tollemar,, E. Moller,, J. Bolinder,, J. Ostman,, F. P. Reinholt,, C. Hellerstrom,, and A. Andersson. 1994. Transplantation of porcine fetal pancreas to diabetic patients. Lancet 344:14021404.
25. Hamel, A. L.,, L. L. Lin,, and G. P. Naylar. 1998. Nucleotide sequence of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs. J. Virol. 72:52625267.
26. Heneine, W. 1996. Strategies for diagnosis of xenotransplant-associated retroviral infections. Mol. Diagn. 1:255260.
27. Heneine, W.,, and W. M. Switzer. 1996. Highly sensitive and specific polymerase chain reaction assays for detection of baboon and pig cells following xenotransplantation in humans. Transplantation 62:13601362.
28. Heneine, W.,, W. M. Switzer,, P. Sandstrom,, J. Brown,, S. Vedapuri,, C. A. Schable,, A. S. Khan,, N. W. Lerche,, M. Schweizer,, D. Neumann-Haefelin,, L. E. Chapman,, and T. M. Folks. 1998. Identification of a human population infected with simian foamy viruses. Nature Med. 4:391392.
29. Heneine, W.,, A. Tibell,, W. M. Switzer,, P. A. Sandstrom,, G. Vazaquez-Rosales,, A. Mathews,, O. Korsgren,, L. E. Chapman,, T. M. Folks,, and C. G. Groth. 1998. No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet 352:695699.
30.Institute of Medicine. 1996. Xenotransplantation: Science, Ethics, and Public Policy. National Academy Press, Washington, D.C.
31. Ito, T.,, J. N. S. S. Couceiro,, S. Kelm,, L. G. Baum,, S. Krauss,, M. R. Castrucci,, I. Donatelli,, H. Kida,, J. C. Paulson,, R. G. Webster,, and Y. Kawaoka. 1998. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J. Virol. 72:73677373.
32. Khabbaz, R. F.,, W. Heneine,, J. R. George,, B. Parekh,, T. Rowe,, T. Woods,, W. M. Switzer,, H. M. McClure,, M. Murphey-Corb,, and T. M. Folks. 1994. Brief report: infection of a laboratory worker with simian immunodeficiency virus. N. Engl. J. Med. 330:172177.
33. La Prairie, A. J. P.,, and D. R. Brodie. 1998. Public confidence and government regulation. Ann. N. Y. Acad. Sci. 862:171176.
34. Le Tissier, P.,, J. P. Stoye,, Y. Yasuhiro,, C. Patience,, and R. A. Weiss. 1997. Two sets of human-tropic pig retrovirus. Nature 389:681682.
35. Martin, U.,, V. Kiessig,, J. H. Blusch,, A. Haverich,, K. von der Helm,, T. Herden,, and G. Steinhoff. 1998. Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells. Lancet 352:692694.
36. Matthews, A. L.,, J. Brown,, W. Switzer,, T. M. Folks,, W. Heneine,, and P. A. Sandstrom. 1999. Development and validation of a Western immunoblot assay for detection of antibodies to porcine endogenous retrovirus. Transplantation 67:939943.
37. Meng, X. J.,, P. G. Halbur,, M. S. Shapiro,, S. Govindarajan,, J. D. Bruna,, I. K. Mushahwar,, R. H. Purcell,, and S. U. Emerson. 1998. Genetic and experimental evidence for cross-species infection by swine hepatitis E. virus. J. Virol. 72:97149721.
38. Meng, X. J.,, R. H. Purcell,, P. G. Halbur,, J. R. Lehman,, D. M. Webb,, T. S. Tsareva,, J. S. Haynes,, B. J. Thacker,, and S. U. Emerson. 1997. A novel virus in swine is closely related to the human hepatitis E. virus. Proc. Natl. Acad. Sci. USA 94:98609865.
39. Michaels, M. G. 1997. Infectious concerns of cross-species transplantation: xenozoonoses. World J. Surg. 21:968974.
40. Michaels, M.,, J. Hilliard,, S. Deeks,, P. Gupta,, W. Heneine,, D. Pardi,, C. Kaufman,, C. Rinaldo,, K. St. George,, L. Chapman,, T. Folks,, Y. Colson,, P. Volberding,, and S. Ildstat. 1996. Baboon bone marrow xenotransplant in a patient with advanced HIV: a model for the evaluation of potential xenozoonoses. Institute of Human Virology Abstract #11. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 14:S3.
41. Michler, R. 1996. Xenotransplantation: risks, clinical potential, and future prospects. Emerg. Infect. Dis. 2:6470.
42. Morgan, F. 1997. Babe the magnificent organ donor? The perils and promises surrounding xenotransplantation. J. Contemp. Health Law Policy 14:127160.
43. Naylar, G. P.,, A. Hamel,, and L. Lin. 1997. Detection and characterization of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs. Canad. Vet. J. 38:385386.
44.Organization for Economic Co-operation and Development 1998. Policy consideration on international issues in transplantation biotechnology including the use of non-human cells, tissues, and organs. Report by Elettra Ronchi, Organization for Economic Co-operation and Development, Paris, France.
45. Onions, D.,, D. Galbraith,, D. Hart,, C. Mahoney,, and K. Smith. 1998. Endogenous retroviruses and the safety of porcine xenotransplantation. Trends Microbiol. 6:430431.
46. Patience, C.,, G. S. Patton,, Y. Takeuchi,, R. A. Weiss,, M. O. McClure,, L. Rydberg,, and M. E. Breimer. 1998. No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys. Lancet 352:699701.
47. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nature Med. 3:282286.
48. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1998. Zoonosis in xenotransplantation. Curr. Opin. Immunol. 10:539542.
49. Patterson, A. P.,, E. Bloom,, and L. E. Chapman. 1999. Clinical trials in xenotransplantation: the public health promises and challenges of an emerging technology. J. Irish Coll. Phys. Surg. 28:222227.
50. Sandstrom, P. A.,, and L. E. Chapman. 1998. Author's response, [letter]. Trends Microbiol. 6:432.
51. Satake, M., et al. 1994. Kinetics and character of xenoantibody formation in diabetic patients transplanted with fetal porcine islet cells clusters. Xenotransplantation 1:24.
52. Sharp, P. M.,, D. L. Robertson,, and B. H. Hahn. 1995. Cross species transmission and recombination of 'AIDS' viruses. Phil. Trans. R. Soc. London-Series B: Biol. Sci. 349:4147.
53. Starzl, T. E.,, J. Fung,, A. Tzakis,, S. Todo,, A. J. Demetris,, I. R. Marino,, H. Doyle,, A. Seevi,, V. Warty,, M., Michaels, et al. 1993 Baboon-to-human liver transplantation. Lancet 341:6571.
54. Stoye, J. 1998. No clear answers on safety of pigs as tissue donor source. Lancet 352:666667.
55. Switzer, W. M.,, V. Shanmugan,, and W. Heneine. 1999. Polymerase chain reaction assays for the diagnosis of infection with the porcine endogenous retrovirus and the detection of pig cells in human and nonhuman recipients of pig xenografts. Transplantation 68:183188.
56. Takeuchi, Y. 1998. Retroviral time travel. Trends Microbiol. 6:430.
57. Tibell, A.,, F. P. Reinholt,, O. Korsgren,, A. Andersson,, C. Hellerstrom,, E. Moller,, and C. G. Groth. 1994. Morphological identification of porcine islet cells three weeks after transplantation to a diabetic patient. Transplant. Proc. 26:1121.
58.United Network for Organ Sharing. 1997. Data Highlights from the 1997Annual Report: the U.S. Scientific Registry of Transplant Recipients and the Organ Procurement and Transplantation Network—Transplant Data: 1988-1996. U. S. Department of Health and Human Services, Rockville, Md.
59.U. S. Public Health Service. 1996. Draft guideline on infectious disease issues in xenotransplantation. Fed. Reg. 61:4992049932.
60. Van der Kuyl, A. C.,, and J. Goudsmit 1998. Xenotransplantation: about baboon hearts and pig livers. Trends Microbiol. 6:431432.
61. VanRongen, E. 1998. Xenotransplantation: perspective for the Netherlands. Ann. N. Y.Acad. Sci. 862:177183.
62. Webster, R. G.,, G. B. Sharp,, and E. C. Claas. 1995. Interspecies transmission of influenza viruses. Am. J. Respir. Crit. Care. Med. 152:S25S30.
63. Weiss, R. 1998. Commentary: transgenic pigs and virus adaptation. Nature 391:327328.
64. Whitehead, J.,, A. P. Patterson,, and A. Moulton. 1998. Development of databases and registries: international issues. Ann. N. Y. Acad. Sci. 862:217221.
65. Wilson, C. A.,, S. Wong,, J. Muller,, C. E. Davidson,, T. M. Rose,, and P. Burd. 1998. Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. J. Virol. 72:30823087.
66.World Health Organization. 1998. Xenotransplantation: Guidance on Infectious Disease Prevention and Management. World Health Organization, Geneva, Switzerland.

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