Donor-transmitted-infection issues still haunted by HIV
We can never say never’
Though increasingly rare due to improving donor organ screening efforts, allograft transplant recipients remain at risk of acquiring a host of pathogens from the donor organ including cytomegalovirus (CMV), Epstein-Barr Virus (EBV), and hepatitis B and C virus.
But amid the prolonged evaluation and educational process transplants patients undergo to be listed as a possible organ recipient and in the weeks and months of waiting that can follow one pathogen tends to dominate infectious disease concerns, says Robert Michler, MD, associate professor of surgery and director of the cardiac transplantation service and the cardiac transplantation research laboratory at Columbia University in New York City.
"In that litany of things that are discussed and admittedly it’s overwhelming there is the issue that, although unlikely, it is possible that they could receive an HIV-positive organ," he says. "Which is the thing that scares everybody. Very few people get worked up about HCV, CMV, or EBV. People tend to respond more with a visceral reaction to the word AIDS.’"
Indeed, the most highly publicized incident of donor-transmitted infection following allografts involved transmission of HIV to four recipients of organs and tissues from an accident victim in North Carolina who was HIV seronegative at the time of donation in 1991.1 Following that case, the CDC issued guidelines to test all whole organ transplant recipients for HIV three months after procedures in case other patients receive organs from donors in a window period prior to seroconversion.2 While such a case could occur again with HIV or presumably another viral pathogen like HCV it remains something of an anomaly that should not be given undue weight in discussions of allograft infection risks, clinicians argue.
"That was really an unusual case in that it was an accident victim who had been multiply transfused, was seronegative for HIV when tested, but in fact had HIV replicating," says Jay Fishman, MD, clinical director of transplantation infectious disease at Massachusetts General Hospital in Boston. "We know that can occur, but that really is a rare animal. There is always the risk that someone has been infected but has not seroconverted and has low [viral] levels that we might not detect. So we can never say never."
Yet the rapidity and accuracy of tests continues to improve for such pathogens as HIV, HCV, HBV, and CMV, Fishman notes. While the chronic shortage of human organs is one of the frequently cited reasons for increasing interest in xenograft procedures with animal organs, Fishman says that pressure does not undermine efforts to screen human donor organs for infections.
Imperfect assays permit some risk
"The pressure that is brought to bear is not only providing organs, but providing high-quality organs, because infection in these individuals is such a disaster," he says. "We have enough trouble with the [non-donor-related] infections that occur after transplantation. We don’t have to put any in."
Still, donor-transmitted infection remains a risk factor for human allografts due to imperfect assays and the aforementioned threat of virus replicating at undetected levels. For example, the CDC has noted that a small percentage of current HCV tests can be expected to yield inaccurate results, less so if polymerase chain reaction (PCR) is used.3 Similarly, PCR could provide greater accuracy in a few rare situations where a donor organ may be HIV-negative by conventional tests but prove HIV-positive by PCR, notes Marian Michaels, MD, MPH, transplant infectious disease physician at the Childrens Hospital of Pittsburgh. However, adopting PCR for all organ screening would be impractical, expensive, and time-consuming, she adds.
"I’m not advocating changing to PCR for HIV, but we have to recognize there’s always a limitation to any screening that we do," she says. "With allografts as with xenotransplantation we have to reassess our screening as new insights into infections are learned. As we recognized hepatitis C and had the means to identify HCV in donors, it then became incumbent upon us to look for it. As Toxoplasma gondii was recognized as a substantial risk factor in heart transplants in particular, then we needed to modify our screening protocols."
Although the elaborate preventive measures recently proposed for xenotransplants are viewed in part as evidence of lessons learned from past infections in allografts, Michaels notes that much of the debate surrounding animal transplants seemed to suggest that procedures using human organs were comparatively risk-free.
"In my mind, any time you use any biologic, whether it be human or animal, there is a true infectious risk," she says. "One must always be thinking about the risk/benefit when you give biologic agents. [Current screening] is pretty good. I don’t think too much is getting through. Now, is there ever a chance? Yes. Would I tell a person who is undergoing a transplant that there is no risk of getting an infection from one of the organisms we have screened for? I would never say that."
While emphasizing the importance of rigorous pre-transplant screening of donor organs and patient follow-up protocols, Michler expressed concern that the renewed debate regarding infectious disease risk in transplantation threatens to overshadow the critical mission of saving patient lives.
"Science is science, and there are going to be cases that slip through the cracks," Michler says. "Are we going to have patients who 10 years from now still wind up getting HIV because of a transplanted organ? I think the answer is yes, but it is going to be even rarer. These are the realities of dealing with life-and-death situations."
With a clinical research protocol currently under consideration by the Food and Drug Administration to do baboon and pig heart xenotransplants, Michler also questioned the emphasis in the draft federal xenograft guidelines on the unquantified risk of unleashing new infectious agents.
"I get very worked up about people who live their lives writing doctrine and making strong statements that pertain to the what-ifs,’ when these things are potentially not quantifiable," he says "If you were to ask me or a hundred other heart surgeons or transplant directors what the likelihood is of someone dying on a transplant waiting list I can tell you that."
1. Simonds RJ, Holmberg SD, Hurwitz RL, et al. Transmission of human immunodeficiency virus type 1 from a seronegative organ and tissue donor. N Engl J Med 1992; 326:726-732.
2. Centers for Disease Control and Prevention. Guidelines for preventing transmission of human immunodeficiency virus through transplantation of human tissue and organs. MMWR 1994; 43(No.RR-8)1-17.
3. Centers for Disease Control and Prevention. Issues and Answers: What is the risk of acquiring hepatitis C for health care workers and what are the recommendations for prophylaxis and follow-up after occupational exposure to hepatitis C virus? Hepatitis Surveillance Report No. 56. Atlanta; 1996.