APIC: Undiscovered bugs could slip through xeno net
Lack of baboon ban questioned by others
The Association for Professionals in Infection Control and Epidemiology is warning that the measures outlined in draft federal guidelines on xenotransplants may not prevent transmission of new infectious agents, according to comments obtained by Hospital Infection Control through the Freedom of Information Act.
The comments by Washington DC-based APIC came in response to proposed guidelines by the U.S. Public Health Service (PHS) on xenografts animal-to-human transplants.1 The procedures hold great promise to relieve the chronic shortage of human organs, but also carry a real but unquantified risk of unleashing new infectious agents. (See special report in HIC, December 1996, pp. 149-159.)
While praising the general preventive approach of the guidelines, APIC reminded that the reason many allotransplant donor-associated infectious agents are known is because they have already been transmitted, sometimes with "dire consequences." The major difference with the approach suggested for xenotransplantation is in the attempt to avoid infections from the onset, rather than waiting for them to occur, APIC said.
"We applaud this thinking, but must also caution that it is much more expensive and will still not predict all infectious agents," APIC stated. "We submit as evidence of this the fact that screening of human products does not prevent transmission of novel, and as yet, undetected organisms."
APIC also questioned where the funding would come from to answer infectious disease research questions raised by the guidelines. For example, some microorganisms are known to be zoonotic and hazardous. If such microorganisms were found in specific donor species, those animals would be excluded. However, it is less clear how to deal with microbial agents that may be hazardous but have never been shown to cross into humans nor to be a danger, the association noted.
"These are only hypothetical, not known risks," APIC stated. "How much research and development is going to be required for microbial agents that fall into this category before a procedure goes forward? Where is the funding for these infectious disease research questions? The statements in this [guideline] section point to the ideal. They imply, however, that we already know which organisms are going to be a problem, and that we have tests currently available to look for these agents. Neither implication is true."
A signed cover letter by APIC president Ava D. Lancaster, RN, BSN, CIC, noted that the association’s more than 11,000 members are responsible for protocols dealing with the potential risk for infection in patients and health care workers, and thus are "very interested in the concept of infection related to xenotransplantation and how it will impact our facilities and patient populations."
The attached, unsigned APIC comments were generally favorable to the approach outlined by the PHS, calling them "an exceptionally good starting point" and strongly agreeing with the measures proposed for hospital infection control following xenotransplants.
The section regarding collection and archiving of baseline sera on all health care workers who may be exposed to xenograft recipients, however, "sounds wonderful [but] it is not very practical," APIC stated. Such an approach is quite cumbersome when consideration is given to all personnel who might come in contact with a patient, and it probably is not 100% necessary, the association noted, adding that it may be enough to have baseline blood drawn at the time of an exposure like a needlestick.
The Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health are reviewing the 123 comments received on the guidelines, and will soon begin meeting to discuss possible revisions, says Louisa Chapman, MD, medical epidemiologist in the CDC retroviruses diseases branch.
"Many of [the comments] are very thoughtful point-by-point reviews of the document," she says. "We are in the process now of reviewing that commentary, and each agency will need to assess their consensus of what is appropriate to revise in light of public commentary and any additional science that has come forth."
The monkey question
According to other documents obtained by HIC under the FOIA request, the draft guidelines sparked a broad array of comments from major medical associations, researchers, and clinicians. Several observed that the risk of introducing new infectious agents is too great to allow procedures to proceed using baboons or other non-human primates.
Implementation of the guidelines as currently written will pose "a great public health danger," warned Ronald C. Desrosiers, PhD, professor of microbiology and molecular genetics in the New England Regional Primate Research Center at Harvard Medical School in Boston.
"The guidelines do not take seriously enough the likelihood of transmission of monkey viruses to humans upon xenotransplantation," he commented. "It is more than just a theoretical risk. I feel that it is highly likely, almost a certainty, that monkey viruses will be transmitted to humans if xenotransplantations are allowed to proceed with the guidelines as currently written. The concern goes far beyond the individual human recipient. It extends to contacts of the recipient and to the entire global population."
In a finding that will likely exacerbate such concerns, the CDC recently reported there have been five documented transmissions of monkey viral infections of biomedical research workers following occupational exposures such as bites or needlesticks. (See related story, p. 55.)
In other comments, Wayne Hancock, MD, PhD, and Daniel Solomon, MD, PhD, co-chairs of the xenotransplantation committee of the American Society of Transplant Physicians, raised the question of what will be done to control the infectious disease risks of xenotransplants done outside of the United States.
"It is extremely likely that xenotransplantation experiments will begin in Europe and/or Asia before or in parallel with U.S. studies," the physician society noted. "What can the PHS do to protect the U.S. from exposure to xenotransplant-related infectious risks from patients that may be exposed outside our country and then travel here?"
The transplant society suggested that international support for the PHS guidelines be developed in collaboration with groups such as the World Health Organization. As part of that effort, there should be an international agreement to discourage the potential "traffic" in xenotransplants particularly involving non-human primate donors such as baboons and chimpanzees done in an effort to profit by circumvention of PHS guidelines.
"Precedence for such international profiteering in transplantation is found in the documented cases of the exploitative use of paid living donors for kidney transplantation which is presently still in practice in Asia and South America," the society stated.
The guidelines are too lax regarding possible use of non-human primates as donor animals, the society warned, saying the draft includes a "dangerous loophole" that could allow the use of non-human primate donors without appropriate health histories or controls. The risk of introducing xenogeneic infection with "wild-caught" or recently imported primates is very real, the society warned.
"Hence, we believe that non-human primates should not be used as transplant donors in the first phases of xenotransplantation trials because of the increased risk of xenogeneic infections as compared to swine donors, and because it is extremely unlikely that our Society could ever afford the expense of developing a pool of non-human primate donors, even if it could permit these animals to be bred and raised under these conditions," the society concluded.
Taking a somewhat different tack, the American Society of Transplant Surgeons (ASTS) in comments submitted by Hans W. Sollinger, MD, PhD, ASTS president said the guidelines should be significantly revised because "they represent an unnecessary intrusion of government regulation in the performance of transplant surgery and because they fail to set standards which will protect the public health most effectively."
The ASTS argued that is unnecessary and unwarranted for the FDA to require that all forms of xenotransplantation receive approval.
"While it may be appropriate that tissues which have been biologically modified be subject to FDA regulation, we do not believe that it is appropriate for the FDA to claim regulatory authority over organ transplantation just because the donor is from a non-human species," the ASTS noted. "The transplant community has functioned for more than 40 years without such FDA oversight and has established an extraordinary record, guarding patient safety while introducing innovation and achieving ever-improving clinical outcomes."
Furthermore, the guidelines go into great detail about the housing and care of donor animals and even suggest that transplant surgeons should practice the donor surgery before performing it in a clinical setting, the ASTS stated. Yet, on the other hand, the guidelines do not indicate which particular potential pathogens should not be present in animals of different species. "Thus, it is possible for transplant groups to comply exactly with the current FDA guidelines but still end up with donor animals that are unsatisfactory from a public health point of view," the ASTS noted.
Emphasizing that is impossible to produce animals completely free of contamination that includes viruses and prions, Nancy L. Bischof, MPH, an epidemiologist in the School of Public Health at the University of Michigan in Ann Arbor, argued against allowing xenotransplant procedures to proceed lest they spur an epidemic.
"This procedure might result in far more human suffering and death than it would prevent," she warned. "We as a society cannot afford to sacrifice the greater good of the many for the potential, and in my opinion not very much potential, of the very few."
References
1. Department of Health and Human Services. Draft Public Health Service guideline on infectious disease issues in xenotransplantation. Fed Reg Sept 23, 1996; 49,920-49,932.
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