BACKGROUND
The Medical Review Subcommittee (MRS) of the EBAA Medical Advisory Board was notified of a potential rabies transmission in a kidney recipient following their December 2024 transplant. The recipient was reported to have experienced “acute neurologic decline and refusal to drink water” shortly before passing away. The kidney recipient’s saliva and skin biopsies were PCR+ for rabies.
The donor was a farmer who was in his usual state of health until 2am when the patient’s wife heard him talking to himself and he seemed delirious. He was later found unconscious, and the family began CPR. Pt. remained unconscious for 5 days in the hospital and expired. The cause of death was listed as Anoxic Brain Injury; EtOH cirrhosis; Hereditary hemochromatosis. Only corneas and kidneys were recovered from the donor.
The DRAI was performed by the OPO, and the donor was noted to have been scratched by the hind leg of a skunk on his shin 6-weeks prior to death. Established follow up questions in the DRAI for this question noted: No unusual symptoms were noted, no medical intervention sought, and animal was not quarantined.
The donor had a history of alcoholism but reportedly had stopped drinking in July. The family noticed he has been stumbling and having more frequent falls, so they assumed he had been hiding continued alcohol use. The patient’s wife found an empty bottle of tequila, 1L, buried under his clothes at the time of his collapse. She reported that she was certain he was drinking earlier that night but is uncertain how long he had been drinking. Of note, the hospital ethanol level was <0.01.
Assessment by multiple medical personnel did not raise concerns for unusual symptoms or suspicion for other neurologic disease. Head CT and MRI were performed.
Both corneas were processed into DMEKs, and the resulting caps were sent out for sterilization (gamma irradiated after storage at -80C). The DMEK grafts were transplanted on 12/16/24 and one sterile graft was used for CTAK on 1/27/25.
Following CDC notification on 1/28/25, all three corneal grafts have been explanted and sent to CDC for testing. All recipients are asymptomatic to date and have received post-exposure prophylaxis. CDC interview of the family did subsequently reveal a complaint of difficulty swallowing the night before his collapse.
Aggregate lab report from CDC demonstrated a partial genome sequence from rabies virus RNA pooled from donor corneal cells that was consistent with the rabies virus variant seen in silver-haired bats in the USA, and this was a partial genome sequence match with the kidney biopsy. NOTE: These results are only intended for public health purposes only and should not be used for individual diagnosis, treatment, or assessment. The report also states that the results must
not be communicated to the patient, their care provider, or be placed in the patient’s medical chart.
Rhabdoviruses: Rabies Virus
Rabies is a fatal but preventable viral disease, which can be spread to people and pets through the bites and scratches of an infected animal. Rabies primarily affects the central nervous system, leading to severe brain disease and death if medical care is not received before symptoms start. In the U.S., rabies is mostly found in wild animals like bats, raccoons, skunks, and foxes.
The incubation period for rabies is typically 2–3 months but may vary from one week to one year, depending on factors such as the location of virus entry and the viral load. Initial symptoms of rabies include generic signs like fever, pain and unusual or unexplained tingling, pricking, or burning sensations at the wound site. As the virus moves to the central nervous system, progressive and fatal inflammation of the brain and spinal cord develops. Usually, severe disease appears within two weeks of the first symptoms, when the rabies virus causes brain dysfunction. Once clinical signs of rabies appear, the disease is nearly always fatal, and treatment is typically supportive.
According to the World Health Organization there are two presentations for rabies in humans:
- Furious rabies results in hyperactivity, excitable behavior, hallucinations, lack of coordination, hydrophobia (fear of water) and aerophobia (fear of drafts or of fresh air). Death occurs after a few days due to cardio-respiratory arrest.
- Paralytic rabies accounts for about 20% of the total number of human cases. This form of rabies runs a less dramatic and usually longer course than the furious form. Muscles gradually become paralyzed, starting from the wound site. A coma slowly develops and eventually death occurs. The paralytic form of rabies is often misdiagnosed, contributing to the under-reporting of the disease.
While extremely rare, rabies transmission through corneal transplants has been documented, with at least eight cases reported worldwide, emphasizing the importance of thorough donor screening.
In reports of rabies transmission from corneal transplants, symptoms developed an average of 26 days after transplantation, suggesting that implantation of material from infected donors may lead to a shorter incubation period. The cornea is in close contact with brain tissue via the retina and the aqueous humor, and it is well innervated with sensory neurons.
CURRENT RABIES SCREENING
EBAA Medical Standard D1.110: EBAA Contraindications to Transplant states:
- Suspected rabies and persons who, within the past six months, were bitten by an animal suspected to be infected with rabies;
The Uniform Donor Risk Assessment Interview (DRAI) question 9 asks “In the past 12 months, was she/he* bitten or scratched by any pet, stray, farm, or wild animal?” and a series of follow-up questions.
MRS RECOMMENDATION
- Suspected rabies and persons who were bitten or scratched by an animal suspected to be infected with rabies or whose condition is otherwise unknown within the last 6 months;
As this case highlights, unusual symptoms associated with an unknown animal exposure should include not only the classic signs of “Furious” rabies, but new or progressive peripheral neurologic or altered mental status changes leading up to death may represent “Dumb or Paralytic” rabies and may need to be further investigated.
This proposed change to the EBAA Medical Standards will be discussed at the June Medical Advisory Board meeting.
REFERENCES
