Friday, March 15, 2013

Going batty over organ risk assessment

Here's a case that will have the risk management folks debating for a while.  A man in Maryland recently died from rabies.  It turns out that the cause may have been rabies from the donor of his new kidney.  Lots of screening is done before kidneys are transplanted, but not for this disease.  Should there be, or is it just too rare?  Here are some excerpt from the Washington Post story:

A Maryland man who two weeks ago became the state’s first fatal case of rabies in nearly 40 years contracted the infection from a kidney transplant, according to two people familiar with the case.

The Centers for Disease Control and Prevention compared rabies virus obtained from the recipient and determined that it was genetically identical to the virus recovered from the organ’s donor, said the two people involved in the case.  

In general, fewer than five cases of rabies are diagnosed each year in the United States. Most often the virus is acquired by contact with a bat. Bites from infected raccoons and dogs, or contact with their saliva, account for most of the rest.   

Transmission of rabies through organ or tissue transplant is extremely rare. Four people in Texas died in 2004 from rabies contracted from a single donor’s tissue. There have been at least eight cases around the world contracted through cornea transplants.

Potential organ donors are screened for a standard battery of infectious diseases before their organs are offered. Rabies is not one of them, however.

“You balance the probability of infectious complications with the cost of not undergoing the transplant,” said Dorry Segev, a transplant surgeon and epidemiologist at Johns Hopkins University who had no involvement in the case. “The risk of death on dialysis is anywhere between 5 to 15 percent per year, and sometimes higher.”

Segev said that transplanting an organ from someone who died of an infection whose cause was not known would be “incredibly rare” but that it occasionally happens.

I wonder if it would be practical to conduct rabies tests on organ donors.  Look at what the CDC says:

Several tests are necessary to diagnose rabies ante-mortem (before death) in humans; no single test is sufficient. Tests are performed on samples of saliva, serum, spinal fluid, and skin biopsies of hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and spinal fluid are tested for antibodies to rabies virus. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles.


Douglas Hanto said...

I am not familiar with the details of this case and whether there were any missed parts of the donor’s history (exposure to bats, skunks, or other potential carriers of rabies), exam, symptoms, cause of death, or lab tests that would have tipped off the physicians caring for the donor that the donor might have rabies and would have led to further testing and exclusion of the patient as a donor. There were alleged missed items in the donor’s history and symptoms in the Texas case that might have tipped off the physicians to do further testing including rabies that if true might have prevented the deaths of the four recipients.

These cases point out the high sensitivity on the part of the public and medical community for any transmitted disease from a deceased organ donor. And there should be great concern with transmitted diseases because they can be catastrophic to the recipient and their family as in this recent case. These are rare events and I’m sure we would all agree that in an ideal world they should be “never events”.

But as Dr. Segev points out, there is an organ shortage and patients are dying on the list daily waiting for life-saving organs. There is a risk: benefit equation that transplant physicians and surgeons and patients must consider when deciding to accept an organ from any deceased donor all of whom are currently carefully screened for potentially transmitted diseases. But what is the threshold? In 2009 there was a formal recommendation by the Public Health Service that HHS consolidate national biovigilance efforts for blood, cells, tissues, and organs. If we used the same criteria that are used for screening blood donors and disease avoidance is the dominant principle guiding organ donor testing, we would eliminate many donors in the name of preventing ALL disease transmission that would lead to a decrease in the already fragile organ donation rate and an increase in deaths on the waiting list. The overall benefit for organ transplant recipients should be balanced by an informed wait listed patient who is aware of the limited organ availability and the processes in place to minimize the risk of disease transmission. But please let’s not throw the baby out with the bath water.

If you are interested in reading more about biovigilance please read: Pruett TL, Blumberg EA, Cohen DJ, Crippin JS, Freeman RB, Hanto DW, Mulligan DC, Green MD. A consolidated biovigilance system for blood, tissue, organs: One size does not fit all. Am J Transplant 2012;12:1099-1101.

Douglas W. Hanto, M.D., Ph.D.
Associate Dean for Continuing Medical Education
Washington University School of Medicine

Lewis Thomas Professor of Surgery Emeritus
Harvard Medical School

Anonymous said...

I think one thing often overlooked is that we make these risk-benefit decisions every day, both on the part of individuals (crossing the street), corporations (Boeing certainly didn't want to kill people but thought it had covered the risk with the lithium batteries) and elsewhere in health care. Merely setting the number at which a given laboratory test is deemed 'positive' instead of 'negative', is not a black and white decision, and not the same world-wide.
It is when catastrophic events like this occur that we engage in the cognitive misconception that 'they' sh/could have eliminated this particular risk. But 'we' take bigger risks every day based on our own decisions.

nonlocal MD

Anonymous said...

A close friend received a kidney transplant from a donor later determined to have had the West Nile virus. Unfortunately the virus thrived in his immune-compromised system and he was brought to the very edge of death. His subsequent recovery has taken many years and is still progressing.

As a layperson, the first question that comes to mind is: Isn't there a tension between the time available to transplant organs from a recently deceased donor and the time that various tests take? I would imagine any tests that involve doing things like cultures might take too long.

So even assuming cost was no issue (obviously not a real world assumption), are there time limits that just prevent certain types of tests on deceased donors?

PJ Geraghty said...

(Disclaimer: I am the clinical director for an organ procurement organization, and while the ideas and opinions expressed are strictly my own, they are based on my 19 years' experience in the field of organ donation and transplantation. I am not involved in any way, shape or form with the donor/recipients in this case, and I have no knowledge beyond what has appeared in publicly-available reports. Lastly, I am also a longtime reader of Paul's blog.)

Dr. Hanto does an excellent job of summarizing the issues surrounding testing for infectious diseases in the deceased organ donor population. In any assessment of risk from an organ donor, the transplant center (usually the transplant surgen, with the advice of his/her colleagues) must make a decision on the ris vs. benefit for the recipient involved. In all organ transplant scenarios, there is an inherent (and not entirely quantifiable) risk in declining an organ offered and thus waiting for the next organ. In the end, every organ transplant carries a certain degree of risk. We could increase some screening of donors, but that would lead to some loss of transplantable organs, and result in some deaths on the waiting list. As we encounter these events, we must keep in mind that they are exceedingly rare, and consider the risk of such a disease transmission against the risk of candidate death while waiting for a transplantable organ.