Additional Case of Rabies Transmission Linked to Solid Organ Transplantation: A Newsmaker Interview With Goran Klintmalm, MD

Laurie Barclay, MD

August 13, 2004

Aug. 13, 2004 -- Editor's Note: Last month, the Centers for Disease Control and Prevention (CDC) confirmed the first reported cases of rabies transmission through solid organ transplantation from a single donor. Although the recipients were diagnosed at autopsy, the donor was never autopsied. After examining all other autopsy cases from transplant recipients that occurred during this time, pathologists at Baylor University Medical Center in Dallas, Texas, discovered another case of rabies in a fourth patient. This transplant took place the day after the three recipients who subsequently died from rabies received organs from the Arkansas donor. The donor of the transplanted liver was not the one implicated in the earlier cases identified by CDC, but banked iliac arteries were thought to be the culprit. Because the vessels were inadequate during the procedure, the transplant surgeon used stored iliac arteries to make a conduit for the hepatic artery anastomosis.

To find out more about the role of the autopsy in these cases and the implications for organ donation policy, Medscape's Laurie Barclay interviewed Goran Klintmalm, MD, director of liver transplantation at Baylor.

Medscape: Please describe the fourth, most recently diagnosed case of rabies in a transplant patient who received banked blood vessels.

Dr. Klintmalm: The patient received a liver transplant on May 5, 2004, from a donor who was in their 70s and whose vessels were arteriosclerotic. The recipient was also arteriosclerotic, requiring advanced arterial reconstruction. This was completed using banked vessels from a Texarkana donor, who also had donated four solid organs. The use of vessels in this manner is routine during transplantation in the United States. The patient remained hospitalized with transplant-related complications related to end-stage liver disease until death in early June. At the time of this transplant, there was no indication that the Texarkana donor or any other individual who received solid organs from this same donor had been infected with the rabies virus.

Medscape: How was this case diagnosed, and why were all four known cases of rabies in transplant patients difficult to diagnose?

Dr. Klintmalm: Rabies is so exceptionally unusual that no one expects to see it, especially if there is no acute history of an individual being bitten -- or even scratched -- by a dog or cat. Bat bites are so extremely rare that it is difficult to find any verifiable histories of such cases. In addition, rabies is not supposed to infect by means other than saliva to open wounds or airborne spit that is inhaled, that might occur in bat caverns. Recognition that rabies virus could infect following solid organ transplantation was not known by the CDC or anyone else.

This particular case was detected as part of an ongoing review of transplant-patient autopsies. Once the CDC identified and reported that the specimens of the first three recipients were found to have serologic evidence of rabies infection, pathologists immediately began to review all autopsies conducted during the same time period. Within days, they identified intracytoplasmic inclusions, suggestive of rabies, in the neurons of the fourth patient. Specimens were immediately couriered to CDC and confirmation was received within hours.

Staff immediately reviewed surgical procedures, medical records, and conducted interviews and determined that a segment of vessels recovered from the Texarkana organ donor had been stored and used in this patient's liver transplant. Because the fourth patient had many transplant-related complications that explained [the patient's] death, the neurological symptoms experienced by the previous three recipients masked similarities in this patient.

Medscape: How do the symptoms of rabies or other viral diseases differ when infection isvia a solid organ transplant rather than from a bite wound or inhalation?

Dr. Klintmalm: Again, that rabies could infect via solid organs was not known by the CDC or anyone else. In either case, the rabies virus symptoms are initially the same, although one could expect a more rapid presentation and progression in immune-compromised patients.

Medscape: Do you suspect that these cases represent an isolated incident or the "tip of the iceberg" in terms of undiagnosed infections in transplant patients?

Dr. Klintmalm: Most certainly, this is an isolated incident -- rabies in solid organ transplantation is unparalleled. Most physicians will never see a case of rabies in their lifetime: only one to three people are diagnosed with rabies in the United States each year. There are only eight cases in medical history of human-to-human transfer of the rabies virus. These occurred in cornea transplants -- not solid organs like kidneys or livers -- and only one in the United States in 1978. As transplantation approaches its 50th anniversary, there had never before been a single case of rabies transmitted through solid organ transplantation.

The probability that a donated organ is infected with the rabies virus is so small it's nearly impossible to calculate. Clearly these cases could easily have been missed had they not been done in a large institution where data about all organ recipients from one single donor could be collected.

Medscape: What testing is now done routinely on donors?

Dr. Klintmalm: Nationally standardized tests include those for HIV, hepatitis B and hepatitis C, human t-lymphotropic virus, cytomegalovirus, and syphilis. The testing has not changed and will not change.

Medscape: What information is needed from donors that might affect the success of the transplanted organ, and how should this information be gathered?

Dr. Klintmalm: The information from donors of organs for transplantation is obtained from the donor's medical records, personal physician, and family members, who are the main source of information. While organ procurement agencies collect all medical and social history information available from family and friends, the answers to the extensive list of questions are only as good as what the family reports.

Medscape: Should the donor screening protocol include testing for rabies or other infectious diseases that are not currently included?

Dr. Klintmalm: Testing for rabies cannot be done in a timely fashion. Moreover, to get a positive diagnosis you must have fresh brain tissue, which is not available until after the organs have been removed. Also, since the testing takes many hours, if not days, this is simply impossible to do while maintaining the viability of donor organs. No organ procurement agency screens potential donor organs for rabies virus. Testing for rabies is not realistic at the present time, chiefly because screening takes days, not hours, and the organs would not remain viable for transplant.

We also have to be cognizant of the fact that if a test has, as an example, a 4% false-positive rate -- that is, 4% of the donors are incorrectly found to be positive for rabies -- that would mean that 200 organ donors would be ruled out annually because of false testing. Subsequently, this may mean 600 to 800 organ recipients would not be transplanted and the mortality among those patients would be immensely high.

Medscape: How can we best balance the need to quickly match, harvest, and transplant organs with the need to learn as much as possible about the donor?

Dr. Klintmalm: I believe we are already doing an excellent job, by screening donors for common transmissible diseases. We can always improve, but we must make sure that the improvements do not injure those we are trying to help by removing potential donors that would otherwise be perfect due to overblown fears of extremely rare diseases.

Medscape: In your opinion, what would be an optimal protocol for testing to obtain the most crucial information before the six-hour window for solid organs expires?

Dr. Klintmalm: All testing must be done and completed before the organs are retrieved.

Medscape: Should testing continue after transplantation so that the team can be aware of and help avert potential complications?

Dr. Klintmalm: This is purely a hypothetical issue at this point and we must really look at the potential benefits and compare it to the cost. To diagnose rabies is not an inexpensive or easy matter. The benefit of testing all recipients after transplantation will have minimal, if any, discernible impact on either public health or the protection of the recipients.

Medscape: What do you think should be the take-home lesson from this experience with regard to future policy for organ and blood vessel donation?

Dr. Klintmalm: These cases have added significantly to the scientific knowledge about rabies and the modes of transmission. As mentioned before, rabies was not thought to be transmissible this way. We have learned much about how rabies develops in the immunosuppressed patient and how the disease can be transmitted. It is quite realistic to expect that one day after we gather more information about this unique disease that we will be able to find ways to prevent and treat patients with this virus.

Reviewed by Gary D. Vogin, MD