Rabies Infections in Organ Donor and Transplant Recipients

Abstract & Commentary

Synopsis: The Centers for Disease Control (CDC) has confirmed the diagnosis of rabies in 4 recipients of transplanted organs and their common donor. All 4 transplant recipients presented with rapidly progressive encephalitis within 21 to 27 days after receiving their transplant and all subsequently died. What are the implications for solid organ transplant recipients worldwide, particularly when the sources of transplanted organs are not always carefully regulated.

Source: Investigation of Rabies Infections in Organ Donor and Transplant Recipients-Alabama, Arkansas, Oklahoma, and Texas, 2004. MMWR. Dispatch 2004;53:586-589.

Update: investigation of rabies infections in Organ Donor and Transplant Recipients-Alabama, Arkansas, Oklahoma, and Texas, 2004 53 (Dispatch).

On June 30, 2004 the CDC confirmed the diagnosis of rabies in 3 transplant recipients, all of whom died with a diagnosis of encephalitis of unknown etiology. The common organ donor was an Arkansas resident who presented in Texas with severe mental status changes and low grade fever. A diagnosis of subarachnoid hemorrhage was suggested following neurologic imaging. The hemorrhage expanded resulting in cerebral herniation and death. The patient’s family agreed to donation of his organs, and there appeared to be no contraindication to donation based on standard screening and testing. On May 4, the liver and kidneys were transplanted into 3 recipients at a transplant center in Texas.

The patient who received the donor liver was a man who, 5 days after uncomplicated transplant surgery, was discharged to home. However, 21 days after transplant, he was readmitted to the hospital with tremors, lethargy and anorexia, but without a fever. His neurologic status worsened rapidly; a lumbar puncture showed a lymphocytic pleocytosis and mildly elevated protein. Magnetic resonance imaging (MRI) of the brain initially showed increased signal in the cerebrospinal fluid and a second MRI 6 days after admission showed progression to diffuse encephalitis. His neurologic status continued to worsen and he subsequently died.

The first kidney recipient was a woman who presented 25 days after transplant with right-sided flank pain and underwent an appendectomy. Two days post-operative, she began having diffuse muscle twitching and mental status changes. Initial computed tomography (CT) and MRI studies were normal, yet she continued to deteriorate with seizures, hypotension, and respiratory failure. Repeat CT imaging, 14 days after admission, indicated severe cerebral edema, and she subsequently died.

The last organ recipient, who received the second kidney, presented 27 days after transplant with a change in mental status and myoclonic jerks. He was also afebrile. An initial MRI was normal. The lumbar puncture had a lymphocytic pleocytosis and mildly elevated protein. A second MRI 10 days after admission showed diffuse edema. He continued to deteriorate neurologically, and subsequently died.

The diagnosis of rabies was confirmed in all 3 cases at the CDC by immunohistochemical testing, and by the detection of rabies virus antigen in fixed brain tissue by direct fluorescent antibody tests. Pathology of the brain tissues of all 3 patients showed encephalitis with viral inclusions suggestive of Negri bodies. In addition, rabies virus antibodies were demonstrated in the blood from 2 of the 3 recipients, as well as the donor. Detecting anti-rabies antibodies in the donor suggests that he was the likely source of rabies transmission to the transplant recipients. Additional investigation and testing of the donor specimens is ongoing.

However, it has now been determined by Dr. Frank Wilson at the Arkansas Department of Health, that the donor had reported being bitten by a bat. In addition, a fourth case of rabies appears to be related to this outbreak in that an additional liver transplant recipient died of rabies encephalitis. In this fourth case, the source was not his liver donor, but appears to have been a stored segment of iliac artery recovered from the donor who had been determined to have had rabies. It had been stored at the facility for potential use in future liver transplants.

Comment by Mary-Louise Scully, MD

Rabies is an acute, fatal encephalitis caused by neurotropic viruses in the genus Lyssavirus, family Rhabdoviridae. Bites of rabid mammals cause the majority of rabies cases.1 It is very rare for nonbite exposures, such as scratches, contamination of open wounds, or direct mucous membrane contact with rabies infected material to cause rabies. Human-to-human transmission of rabies is extremely rare, but documented cases have been reported in 8 recipients of transplanted corneas in 5 countries.2 However, this is the first documented occurrence of rabies transmission among solid organ transplants. It is likely that infection occurred via infected neuronal tissue in the transplant organs, since rabies is not spread hematogenously.

This report has generated a wave of appropriate questions and concerns regarding rabies postexposure prophylaxis (PEP) in both domestic and healthcare contacts of rabies infected patients, as well as hospital personnel who may have had contact with the rabies infected organs. In the domestic setting, rabies can be transmitted when infectious material, such as saliva, enters a wound, a break in the skin, or mucous membranes, (eg, eyes, nose, or mouth). Therefore, domestic exposures to rabies patients that includes bites, sexual activity, exchanging kisses on the mouth, sharing, eating, or drinking utensils, or cigarettes, warrant rabies PEP.

There are no documented cases of rabies transmission to healthcare workers caring for patients with rabies.3 Adherence to Standard Precautions for contact with blood or body fluids (eg, gloves, gown, mask goggles, or face shield, as indicated for the type of patient contact) prevents rabies transmission.4 However, rabies PEP is recommended for health care workers who have been exposed to saliva, nerve tissue, or cerebral spinal fluid of a rabies patient. In addition, rabies PEP is recommended to healthcare workers after percutaneous injuries (needlesticks or scalpel cuts) because potentially infectious nerve material could be contained in the bore of the needle following tissue penetration in a rabies patient. Therefore, the recommendation is related to the possibility of exposure to infected nerve tissue not just blood exposure. Exposure to feces and urine are not considered a risk for rabies transmission.

Despite over 20,000 transplants being performed every year, no human rabies cases associated with solid organ transplants have previously been reported. Donor eligibility is determined through donor physical examination, laboratory data for organ dysfunction, and testing for selected bloodborne viral pathogens and syphilis. In addition, a series of questions are posed to the family and contacts of the donor. Presently, no testing for rabies is performed. In this case, the donor’s death was attributed to a noninfectious cause since imaging studies showed a subarachnoid hemorrhage and subsequent cerebral herniation. Clearly, the challenge ahead is striking a balance between the need for donor testing to minimize the risk of such infectious disease transmissions without adversely affecting the access and availability of organs for transplantation. Currently, the CDC is working with federal and organ procurement agencies to review donor screening practices. More information regarding rabies in transplant organ recipients, and the indications for rabies PEP in healthcare and domestic contacts is available from the CDC at http://www.cdc.gov/ncidod/dvrd/rabies.

References

1. Warrell MJ, et al. Rabies and Other Lyssavirus Diseases. Lancet. 2004;363:959-969.

2. CDC. Human Rabies Prevention-United States, 1999: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR. 1999;44(No. RR-1).

3. Helmick CG, et al. Is There a Risk to Contacts of Patients With Rabies? Rev Infect Dis. 1987;9:511-518.

4. Garner JS. Hospital Infection Control Practices Advisory Committee. Guideline for Isolation Precautions in Hospitals. Infect Contr Hosp Epidemiol. 1996;17:53-80.

Mary-Louise Scully, MD, Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, Calif, and Associate Editor of Travel Medicine Advisor.