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.

Animals

Those of you who follow our Facebook page have noted several recent stories on the zoonotic disease front. New human cases were reported of the influenza A (H3N2) variant, a swine virus that thus far appears to cause mild disease and has limited-to-no transmissibility from human-to-human (virtually all cases have been among those with direct pig contact, often at summer fairs). Meanwhile, an avian H3N8 strain was reported to be the cause of a recent fatal outbreak of pneumonia among New England harbor seals—whenever an avian strain demonstrates adaptation to a mammalian host, it is cause for concern. This development further stresses the importance of open and transparent work to understand the key features of virulent influenza strains that predict human infection and transmission (in other words, lift the “voluntary moratorium”). Finally, we have a very provocative report suggesting that rabies virus exposure, at least in remote communities in the Peruvian Amazon, may not always result in infection and death. Rabies is notorious for having a human fatality rate approaching 100%, with very few reports of survival after clinical infection. It is surprising, then, to find evidence for nonlethal rabies virus infection among those with bat exposure and no history of vaccination. Too soon, really, to determine if this finding is explained by unique genetic-immunologic characteristics of this remote population, or if there are other mechanisms of nonlethal exposure that have not yet been identified.

While we are on the topic, I’d like to plug my favorite blog about infections in animals, Worms and Germs, by Drs. Scott Weese and Maureen Anderson of the Ontario Veterinary College's Centre for Public Health and Zoonoses.

As if flying weren't miserable enough...

The CDC is urging the 50 passengers on this recent Delta flight to contact them regarding potential rabies risk from a bat flying around the plane (the flight left Madison, WI, and returned there shortly after takeoff, after the bat made several forays through the cabin and was finally trapped in the airplane bathroom).

I have only two comments. First, the rabies risk, at least from the video footage, seems close to zero. The bat didn’t interrupt its flight long enough to scratch or bite anyone. Second, that’s a pretty big bat! If the plane was domestic only, it seems most likely to have been a “big brown”. Of the 45 documented human rabies cases in the U.S. since 1995, only one was traced to a big brown bat (most are associated with silver-haired or eastern pipistrelle bats). Given the size, it’s pretty disappointing that it couldn’t be captured for testing (it was trapped in a tiny airplane lavatory!). Detaining the bat for further analysis would have simplified the contact counseling greatly.

I’m sure all affected passengers will be offered free drinks on their next Delta flight (provided they aren’t hydrophobic).

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!

I think I got a touch of the rabies, doc…..

Check out the MMWR for an amazing story of “abortive” rabies—a 17 year old girl survived rabies, apparently intact, without even requiring ICU care. She didn’t return for her follow up clinic appointment. I assume she headed off to Vegas after her physicians explained to her just how lucky she was…..