Transplantation Associated Rabies

This week's JAMA has a paper and editorial on the recent case of transplantation associated rabies. I blogged about this a few months ago based on the report in the Washington Post. The editorial helps to put all of this in perspective by pointing out that transmission of disease from donor to recipients is a rare occurrence (0.1%) and that many patients die each year while awaiting transplantation. Both the paper and the article make recommendations on how to make the process safer, particularly with regards to how to handle donors with unexplained encephalitis. Even still, as the editorial points out, some donors with infectious encephalitis have had masking conditions (e.g., subarachnoid hemorrhage, intoxication with drugs of abuse, or head trauma). Neither paper mentions that there could be two sets of exclusion criteria for donors--those for when the organ is immediately life saving (primarily heart and liver), and those in which it is not (primarily kidney). Most patients and families would likely be willing to accept a higher level of risk when the transplant is immediately life saving. Fortunately in this case, the three other organ recipients from the rabies infected donor remain infection free. 

Transplantation associated rabies (again!)

The Washington Post is reporting today on the death of a renal transplant recipient from rabies. Interestingly, the transplant occurred 15 months prior, yet the donor and recipient rabies viruses were genetically identical. It's another case of organs being transplanted from a donor who died of encephalitis, which still strikes me as absurd. We've blogged before about this topic in cases involving rabies and Balamuthia.

Three years in this blog I wrote: It seems to me that at a minimum there should be an immediate ban on transplanting organs from donors with undiagnosed encephalitides in cases where transplantation is not immediately life-saving (e.g., cornea, kidney, intestine, pancreas, musculoskeletal grafts). And where transplantation is potentially immediately life-saving (e.g., heart, liver), full disclosure of the donor's diagnosis and its implications should be made available as part of the informed consent process.

I haven't changed my mind.

Trouble in Pittsburgh

The behemoth healthcare system, University of Pittsburgh Medical Center, had its living donor transplant program temporarily shut down after a patient was transplanted with a kidney from a hepatitis C infected donor. The details of the fateful transplant can be found in two well-written articles in the Pittsburgh Post-Gazette (here and here). It's a classic example of the swiss cheese model of complex system failure, where all the holes lined up (in this case the positive lab test was missed on 6 occasions), allowing an adverse outcome to occur. The articles note that UPMC's response was to demote the transplant surgeon and suspend the transplant nurse coordinator. A noted transplant surgeon describes that as an administrator's knee jerk reaction and another stated, "if everyone in transplants got hit for making a mistake, no one would be working." But the journalist probes to unearth how the system fostered the error, and he notes the stresses on the surgeon to increase surgical volume (as well as stressors in his personal life), problems with the electronic medical record, and alarm fatigue. 


I have been intrigued at how physicians who perform the most highly technical procedures in medicine can sometimes be uninterested in details that ultimately can unravel their programs. What infectious diseases physician hasn't been consulted to see a patient who has undergone an amazingly complex surgical procedure, who survived against all odds only due to an enormously talented surgeon, all to be undone by sloppy infection control practices down the line, such as noncompliance with hand hygiene? In the UPMC case, I have to wonder whether a simple tool, such as a checklist, could have prevented this error.

Sunday Times blogging

This report from Arizona serves as a disturbing reminder of how quickly bad health outcomes data can be turned into bad public policy. And this report from Zimbabwe provides some needed perspective on the enormous healthcare gap between the richest and poorest nations. If we had to steam-clean all disposable gloves for re-use, we'd probably find some alternatives to widespread use of contact precautions!

More cases of Balamuthia encephalitis transmitted via organ transplantation

Late last year, we blogged about the transmission of Balamuthia mandrillaris from an organ donor with an undiagnosed encephalitis in Mississippi to 2 organ recipients (liver and kidney-pancreas) who subsequently developed encephalitis. One recipient died of encephalitis and the other survived with neurologic sequelae. These cases are described in the most recent MMWR. Then there was the report in Clinical Infectious Diseases of transmission of rabies to 2 organ recipients who died. Again the donor had an undiagnosed encephalitis. Seven other cases of transplant-associated rabies had been previously described. Now the Arizona Star and MMWR are reporting another cluster of two Balamuthia encephalitis cases who received organs from a 27-year old man who died of what was thought to be a stroke (no details on brain imaging are included in either report).

Several months ago, I argued that there should be an immediate ban on transplanting organs from donors with undiagnosed encephalitides (and I would now add other neurologic diseases without a confirmed diagnosis) in cases where transplantation is not immediately life-saving (e.g., cornea, kidney, intestine, pancreas, musculoskeletal grafts). And where transplantation is potentially immediately life-saving (e.g., heart, liver), full disclosure of the donor's diagnosis and its implications should be made available as part of the informed consent process. I was surprised that CDC did not make this recommendation earlier, and even more so after additional cases have been reported.

Transplantation associated rabies

There's an interesting and disturbing report in Clinical Infectious Diseases that describes the transplantation of organs to six recipients from a donor with undiagnosed rabies. The donor was a 26-year old woman who presented with an encephalitis-like picture and negative testing for the usual causes of encephalitis. Approximately six weeks post-transplant, it was noted that three of the recipients began to exhibit symptoms similar to the donor. Review of archived brain samples from the donor revealed characteristic histopathologic and electron microscopy findings of rabies. Further investigation about the donor revealed that she had traveled to India where she sustained a dog bite. All of the recipients were treated with rabies immune globulin and vaccine. The two cornea recipients underwent explantation of the corneas, did not become ill, never exhibited any virologic evidence of infection, and survived. The liver recipient also remained healthy and had no virologic evidence of infection; however, it is important to note that he had received rabies vaccine 20 years earlier. The other three recipients (lung, kidney, kidney/pancreas) all died of rabies despite aggressive treatment with the Milwaukee protocol.

A few months ago we blogged about two cases of Balamuthia encephalitis transmitted by an organ donor in Mississippi. Since then, at least one of the infected recipients has died. The common theme here is that both the rabies and Balamuthia infected donors died with undiagnosed encephalitides. While I agree with Eli that a complete analysis of the problem is warranted, I don't agree that actions should wait for the conclusions of such analysis. Interim actions should be taken. It seems to me that at a minimum there should be an immediate ban on transplanting organs from donors with undiagnosed encephalitides in cases where transplantation is not immediately life-saving (e.g., cornea, kidney, intestine, pancreas, musculoskeletal grafts). And where transplantation is potentially immediately life-saving (e.g., heart, liver), full disclosure of the donor's diagnosis and its implications should be made available as part of the informed consent process. I suspect that donors with undiagnosed encephalitides comprise a small fraction of the donor pool anyway, though I appreciate the scarcity of organs for transplantation.

Primum non nocere!

Media and the Public Health Response

Recently, I have become interested in how the media influences the public health response and watched with fascination as the H1N1 saga unfolded. As Mike pointed out earlier, the New York Times has written about the recent transplant-related transmission of Balamuthia mandrillaris and whether this one-off event should change overall transplantation guidelines nationwide. I hope the NY Times' assertion that patients with undiagnosed neurological conditions should be barred from donating organs is analyzed and public health officials don't make a knee-jerk decision based on immediate/transitory media attention or political pressure.

Decisions like these are quite complicated and proper analysis can turn-up unexpected findings. Two years ago, I co-authored an article in the American Journal of Transplantation with Eugene Schweizer and others at the University of Maryland that analyzed what would happen if kidneys were transplanted from donors considered high-risk for HIV or Hepatitis C, yet had tested negative. The current practice is to discard these valuable organs. Our most surprising finding was that the total number of viral infections in recipients was actually LOWER with the policy of transplanting these organs. The reason? It turns out that discarding kidneys from high-risk donors led to more time on hemodialysis which resulted in a higher Hepatitis C incidence in recipients. The transplant policy also resulted in higher quality of life and lower cost of care.

Now, the NY Times article is quite balanced, but this won't necessarily stop public health officials from making decisions before a proper analysis is completed. Let's hope cooler heads prevail before a "national policy on whether to bar people with poorly defined neurological disorders as donors" is decided by officials and not scientists. The one thing that is certain is that there is nothing harder to define than a neurological condition.

More on infections transmitted by donor organs

Over a week ago I noted the two cases of Balamuthia mandrillaris infections transmitted to two organ transplant recipients from a donor in Mississippi. Until today, the media attention had only been local. This morning's New York Times is covering this story and raises the question of whether patients with undiagnosed neurologic conditions, such as the donor in these cases, are acceptable donors or whether they should be excluded from the transplantation process.

In the news

Just about every day, I take a look at what's appearing in the mainstream media so that readers of this blog can link to the latest, hottest happenings in the world of infectious diseases and infection prevention. Today's foray yielded a treasure trove:

• First it was Christmas decorations. Then aquariums. Now British hospitals are banning flowers on wards in the name of infection prevention. I suggest they next ban food, water, and air, since none of those are sterile either.
• Two of four patients who received organs from a patient who died at the University of Mississippi Medical Center last month have been diagnosed with infections due to Balamuthia mandrillaris, a free-living amoeba that can cause encephalitis. Both patients are critically ill. Infections with these organisms are rare, and these are the first to be transmitted via transplanted organs.
• Dr. Sidney Wolfe, the well known patient advocate at Public Citizen, has added Tamiflu to his list of worst pills. The title of the press release says it all--"Tamiflu? More like Scamiflu."
• In Scotland, three injection drug users have developed cutaneous anthrax, one of whom has died of the infection.
• Lastly, if you are planning on having plastic surgery anytime soon in Connecticut, be careful! A plastic surgeon there has been cited because inspectors found mouse poop on her surgical instruments. I didn't make this up, really! See the link here.