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Patient Safety Tip of the Week
Rabies
Contracted via Organ Transplant
A Michigan resident recently died from
rabies following a kidney transplant at a hospital in Ohio (Wethington
2025, Richardson
2025, Thomson
2025, Salzman
2025). Investigations showed
that the donor had the virus when they died. CDC said that the organ donor was
exposed to rabies from a wild animal in Idaho five weeks before they died and
their organ was transplanted, though the donor had not died with
"traditional rabies symptoms," and they had not sought out medical
help or notified public health officials after their exposure to the animal.
All of the patients
who had received transplants of the donor's corneal tissue have since been
given rabies post-exposure prophylaxis shots and are in good health according
to the CDC. CDC also worked with Missouri health officials to intercept a
fourth corneal graft before it could be implanted into a Missouri resident.
We have not been told what the clinical
presentation in the donor was in this case. In at least one previous case of
rabies transmission via transplant, the donor patient had been felt to have Guillain-Barre
Syndrome. In a monograph we published on Guillain-Barre Syndrome (Ropper
1991), we discussed rabies
in the differential diagnosis of GBS. So-called “paralytic rabies” may present
with an ascending paralysis that may resemble GBS. Clues that it is rabies
might be subtle asymmetry of paralysis, fact that symptoms began
in one limb, a CSF pleocytosis, and perhaps some degree of confusion. So,
caution should be exercised when considering organ or tissue donation in a
patient with suspected Guillain-Barre Syndrome.
There have been several other instances in
which rabies was transmitted via organ or tissue transplant.
In 2004 (CDC
2004, Srinivasan
2005), physicians at a
hospital in Texas diagnosed encephalitis in three recipients of a liver and two
kidneys from a common organ donor. It was later discovered that encephalitis
also developed in a fourth patient, who had received a vascular graft from the
same donor during liver transplantation. All four patients became progressively
obtunded, lapsed into coma, and died within 50 days after transplantation. CDC
reported laboratory confirmation of rabies as the cause of encephalitis in an
organ donor and three organ recipients in Texas. It was subsequently determined
that the donor had reported being bitten by a bat.
All patients had rapid neurologic
deterioration characterized by agitated delirium and seizures. Respiratory
failure requiring intubation developed within 48 hours after the onset of
neurologic symptoms. Examination of cerebrospinal fluid from the three patients
showed pleocytosis, with an average of 18 cells per cubic millimeter (range, 7
to 35), and elevated protein levels (mean, 135 mg per deciliter; range, 17 to
331). Four days before his death, the organ donor was seen twice at an
emergency department for nausea, vomiting, and difficulty swallowing. He was
subsequently admitted to another hospital with altered mental status requiring
intubation. He was febrile with fluctuating blood pressures, including systolic
measurements of more than 200 mm Hg. On admission, a urine toxicology screen
was positive for cocaine and marijuana, and computed tomography of the brain
demonstrated a subarachnoid hemorrhage. The hemorrhage progressed, and the
neurologic symptoms, including seizures and coma, worsened. Srinivasan et al. noted
it was unknown whether the shorter than average incubation period in these
patients was due to the immunosuppression, the route of transmission, or both.
Bonnert et al. (Bronnert 2007) described those same
4 American cases and noted that three Germans had recently died of rabies after
organ transplantation from a donor who experienced an animal bite. The German female
donor first went to see a doctor because of severe headache, fever, mental
changes, and aggressive behavior. A drug screen was
positive for cocaine, and she was believed to have a toxic psychosis. She soon
suffered a cardiac arrest and was pronounced brain dead and cleared as a tissue
donor. Six patients were given organs (corneas, liver, lung, kidney, and kidney/pancreas).
Three of them died during the following weeks. Interestingly, 3 other recipients
from that donor survived. One had a previous rabies vaccination and had
detectable neutralizing antibodies.
Kuehn (Kuehn
2013) noted a patient in
Maryland died after contracting rabies from an organ transplant. No details
were available, but it was noted that the infection occurred more than a year
after the patient received the transplant.
Zhou et al. (Zhou
2015) reported that physicians
at a hospital in Beijing, China, in 2015 diagnosed rabies in 2 patients who had
each received a kidney from a common organ donor who had died from acute
progressive encephalitis of unknown cause. The patients had rabies incubation
periods of 42 and 48 days. Altered mental status developed in both patients and
progressively worsened to deep coma within 80 days after transplantation; both
patients died. Two other transplant recipients received corneas but remained
well after receiving timely rabies prophylaxis. The donor was a 6-year-old boy
who lived in an area of China that had the highest number of cumulative
reported rabies cases during 2004–2014. The boy had a fever and refused to eat,
drink, or sleep. He subsequently
developed extreme irritability, screaming, and slurred speech, followed by dysphagia
and hypersalivation. He was suspected of having viral encephalitis. His
neurologic condition continued to decline, progressing to coma and died, and
his kidneys and corneas were collected for transplantation.
Bassam
(Bassam 2020) reported a case of rabies transmission via
transplant in a child. The child was a 5-year-old girl who was admitted to the
pediatric intensive care unit with encephalitis of unexplained cause 3.5 months
after she received a kidney transplant from a deceased donor. The laboratory
and imaging studies did not reveal any explanation for her rapidly declining
clinical and neurologic condition, which ended with death 4 days after
admission. Death of another recipient from the same donor led to an
investigation that revealed rabies as the cause. Polymerase chain reaction
sequence analysis of the corneas was consistent with a rabies virus from the
same donor’s state of residence. Bassam concluded that rabies transmission,
although rare, should be suspected when a donor comes from or has visited
endemic countries and that donors with unclear causes of death should be
rejected.
Lu et al. (Lu
2021) described a case of
rabies case caused by organ transplantation in China in 2019. They note that
this was the fourth rabies case caused by organ transplantation in China over a
4-year period.
Rabies is contracted via contact with saliva,
usually through bites,
scratches, or direct contact with mucosa (e.g. eyes, mouth, or open wounds) of
infected animals. In the US, bites from skunks, raccoons, bats and a few other
animals (eg. fox, bobcat) are the most common causes,
now that canine rabies has become rarer. The incubation period for rabies is
typically 2-3 months but may vary from one week to one year (the incubations
period may depend on factors such as the location of virus entry and the viral
load). Note that long incubation periods may cause patients (or their families)
to forget past possible exposures. Tingling, prickly sensations, or burning
sensations at the wound site may be early symptoms. As the virus moves to the
central nervous system, progressive and fatal inflammation of the brain and
spinal cord develops. Symptoms of the latter include fever, hyperactivity,
excitability, hallucinations, lack of coordination, dysphagia, hydrophobia, aerophobia,
cardiac arrest and death. But, as we noted earlier, about 20% of cases follow a
paralytic course. That usually begins with weakness in the limb where the bite
occurred, followed by spread to other limbs before CNS
symptoms appear. So, it might resemble Guillain-Barre Syndrome or an acute myelitis. (Note also that so-called “dumb rabies”
in animals may be suspected by an animal limping on one limb.) Once signs of
rabies have developed, there is almost 100% mortality (there have been very
rare cases of patients surviving rabies in recent years). That’s why
post-exposure prophylaxis is so important in preventing rabies. The
cerebrospinal fluid in rabies often shows a modest pleocytosis
(mainly lymphocytic) and mild protein elevation, with normal glucose levels.
That often leads clinicians to suspect a viral
encephalitis. A CSF pleocytosis would also be a feature that should point one
away from Guillain-Barre syndrome in patients with the paralytic progression.
Antemortem diagnosis can be made via rabies antigen fluorescence on neck skin
biopsy or corneal scrapings or by PCR (polymerase chain reaction) testing of saliva
or CSF. Viral cultures are generally low yield and results are often not available prior
to death. Examination of brain tissue (usually postmortem) shows typical Negri
bodies in cytoplasm of infected cells.
Rabies is not currently
one of the potential pathogens screened for in potential tissue or organ donors,
nor would it be practical to add such screening routinely, given the rare
occurrence of both rabies and transmission of rabies via transplant. Adding a question
about possible epidemiological exposure to rabies in donor risk assessment makes
sense, but most potential donors like those above would not be able to provide
answers. Nevertheless, screening for rabies should be considered in potential
donors with presentations suggesting Guillain-Barre Syndrome, transverse
myelitis, or any meningoencephalitis, or such patients should not be considered
donors. Also note that in at least 2 of the cases noted above, neurological
symptoms may have been attributed to cocaine use because of positive drug
screens. We need to be particularly careful not to assume that symptoms are
attributable to substances found on screening.
Fortunately, transmission of rabies via transplant
is an extremely rare occurrence. However, we need to be aware of that remote
possibility when we are screening potential donors. We don’t want to turn a
potential life-saving procedure into a death sentence.
References:
Wethington P. Michigan resident dies from
rabies after contracting virus from transplanted organ, health officials say.
CBS News Detroit 2025; March 29, 2025
https://www.cbsnews.com/detroit/news/michigan-resident-dies-rabies-organ-transplant-toledo-ohio/
Richardson R. After Michigan patient dies of rabies from a transplanted kidney, donor's
other recipients get preventive shots. NBC News 2025; March 26, 2025
https://www.nbcnews.com/health/health-news/rabies-organ-transplant-death-michigan-rcna198265
Thomson J. In 'extremely
rare' case, Michigan resident dies from rabies after receiving transplanted kidney
carrying the virus. Live Science 2025; March 31, 2025
Salzman S, Kekatos
M. Michigan resident dies of rabies after undergoing organ transplant in Ohio:
Officials. An investigation confirmed the patient
contracted rabies through the organ. ABC News 2025; March 28, 2025
Ropper AH, Wijdicks
EFM, Truax BT: Guillain-Barre Syndrome. FA Davis: Philadelphia 1991
CDC. Update: Investigation of Rabies
Infections in Organ Donor and Transplant Recipients --- Alabama, Arkansas,
Oklahoma, and Texas, 2004. CDC MMWR 2004; 53(27): 615-616 July 16, 2004
https://beta.cdc.gov/mmwr/preview/mmwrhtml/mm5327a5.htm
Srinivasan A, Burton EC, Kuehnert MJ et al. for
the Rabies in Transplant Recipients Investigation Team. Transmission of Rabies
Virus from an Organ Donor to Four Transplant Recipients. N Engl J Med 2005; 352(11):
1103-1111
https://www.nejm.org/doi/full/10.1056/NEJMoa043018
Bronnert J, Wilde
H, Tepsumethanon V, et al. Organ Transplantations and
Rabies Transmission. Journal of Travel Medicine 2007; 14(3): 177-180
Kuehn BM. Transplant-Related Rabies. JAMA
2013; 309(16): 1674
https://jamanetwork.com/journals/jama/article-abstract/1681387
Zhou H, Zhu W, Zeng J, et al. Probable
Rabies Virus Transmission through Organ Transplantation, China, 2015. Emerging
Infectious Diseases 2016; 22(8): August 2016
https://wwwnc.cdc.gov/eid/article/22/8/15-1993_article
Bassam
S. Rabies Acquired Through Kidney Transplantation In A Child: A Case Report. Transplantation 2020; 104(S3): S378,
September 2020.
Lu X, Cai L, Gao X, et al. The fourth case
of rabies caused by organ transplantation in China. Biosafety and Health 2021;
(3)1: 8-10
https://www.sciencedirect.com/science/article/pii/S2590053620301336
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