By Stan Deresinski, MD, FACP, FIDSA

Synopsis: The Centers for Disease Control and Prevention describes the fourth donor-organ rabies transmission event in the United States.

Source: Earnest R, Carter KK, Margrey SF, et al. Human-to-human rabies transmission via solid organ transplantation from a donor with undiagnosed rabies — United States, October 2024-February 2025. MMWR Morb Mortal Wkly Rep. 2025;74(39):600-605.

Five weeks after left kidney transplantation, an adult male recipient developed tremors, lower extremity weakness, confusion, and urinary incontinence. He was hospitalized seven days later, at which time he had fever, hydrophobia, dysphagia, and autonomic instability. The following day, mechanical ventilation was initiated. Because of suspicion of rabies, the Ohio Department of Health and the Centers for Disease Control and Prevention (CDC) were consulted on hospital day 4, three days before the patient died. Rabies virus ribonucleic acid (RNA) was detected in saliva, nuchal skin, and in brain tissue obtained postmortem. The virus proved to be consistent with the variant associated with the silver-haired bat.

The patient, a resident of Michigan, underwent transplantation in Ohio, but the donor resided in Idaho. The Idaho Department of Health initiated an investigation of the donor who had died of a presumed cardiac arrest at home in early December 2024. The death occurred several days after the onset of symptoms, including difficulty in swallowing and walking, hallucinations, and a stiff neck. After hospitalization, he was determined to have undergone brain death and, after removal from life support, his heart, lungs, left kidney, and both corneas were harvested. Upon questioning, the family recalled that approximately five weeks before his death, he had been scratched on the shin by a skunk sufficiently severely to cause some bleeding. Testing of available tissue from the donor detected the silver-haired bat rabies variant in the right kidney (there was insufficient material available to test the left kidney).

Three patients had received corneal grafts. All were asymptomatic, but the grafts were removed as a preventive measure and the virus was detected in one of the explanted grafts. All three patients were given postexposure prophylaxis (PEP) with human rabies immunogobulin and four doses of vaccine. The donor’s heart and lungs were not transplanted.

A search for contacts was undertaken. No others were known to have been exposed to the skunk. Eighty potentially exposed healthcare workers with donor contact were identified, and PEP was recommended for 17 (20%) of them. Fourteen community contacts and 269 healthcare worker contacts of the kidney recipient were identified, and PEP was recommended to be given to six (43%) and 16 (6%), respectively. Overall, PEP was recommended for 46/357 (13%) contacts.

Commentary

Although specific animals serve as significant reservoirs for rabies in the United States, any mammal can be infected. Although skunks are not considered to constitute a rabies reservoir in Idaho, bats, including silver-haired bats, are. Presumably, in this case the implicated skunk had been infected by contact with such a bat.

The authors point out that the instance described was the fourth transplant-transmitted rabies event in the United States since 1978. These instances involved a total of 13 recipients, six of whom received PEP and survived while all seven who did not receive PEP died. They point out that, globally, PEP failure has occurred in 2/21 organ recipients, but at least one of the failures failed to complete PEP.

Pre-transplant evaluations of donors and recipients are extensive, but, because of its rarity, they do not include rabies. Certainly no one would think to ask about a skunk scratch.

When rabies occurs in a transplant recipient, a deep and intensive investigation is critical. The primary aim is the identification of others who received organs from the same donor, as well as identifying associated contacts. Those identified are provided PEP.

The first step to effective intervention is early identification of rabies cases. Only fewer than 10 cases of rabies are identified each year in the United States, but the actual number is larger as a result of missed diagnoses, as was the case with the donor in the report reviewed here with resultant fatal infection of the organ recipient.¹ For antemortem diagnosis, testing of brain tissue is not practical or possible in most cases; testing of saliva, nuchal skin tissue, serum, and cerebrospinal fluid is recommended. In a study of 69 U.S. human rabies cases with 382 antemortem samples collected over 34 years, Swedberg and colleagues reported that, when all four samples were available for testing, the combined diagnostic sensitivity was 100%, with ≤ 2% false-negative results.¹ When only a single sample was tested, the sensitivity was < 65%.

Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.

Reference

1. Swedberg C, Cash-Goldwasser S, Ross Y, et al. Maximizing human rabies case detection: Understanding the diagnostic sensitivity of antemortem testing from 35 years of U.S. data. Clin Infect Dis. 2025;Dec 4:ciaf666. doi: 10.1093/cid/ciaf666. [Online ahead of print].