Two kidneys.
Three different people with different underlying diseases.
All three had initially survived transplantation.
All three developed neurological symptoms within approximately a month.
All three deteriorated frighteningly fast.
All three died.
Now the most important question inside the hospital was no longer:
What killed this patient?
It was:
What did all three patients share?
The answer was sitting in their transplant records.
The donor.
The Medical Detective Story Begins
In an ordinary criminal investigation, detectives look for connections between victims.
Same neighborhood.
Same employer.
Same vehicle.
Same telephone number.
Same person seen near each crime scene.
In an outbreak investigation, physicians and epidemiologists do something remarkably similar.
They look for a common exposure.
A medication.
A device.
A blood product.
A hospital room.
A surgical procedure.
A contaminated solution.
A donor.
The three dead patients had received three different organs.
But all three organs had come from the same young man.
That immediately changed the investigation.
Doctors now had to consider a terrifying possibility.
Whatever had killed the donor might not have been what everyone believed.
And whatever had killed him might have traveled with his organs.
The problem was that the donor's death had seemed explainable.
He had appeared to suffer a catastrophic brain hemorrhage.
There had been imaging evidence.
The hemorrhage had expanded.
His brain had herniated.
That was a coherent medical story.
But coherent does not always mean complete.
Investigators began going backward.
Before the hemorrhage, what had happened?
What symptoms had he experienced?
What had his family noticed?
What had he told doctors?
Had he traveled?
Had he been exposed to chemicals?
Animals?
Insects?
Unusual infections?
Was there anything in his history that had looked insignificant when he was alive but suddenly mattered now?
At the same time, pathologists began examining tissue from the recipients.
The answer would come not from one dramatic test, but from a pattern hidden inside their brains.
Something Inside the Neurons
Pathologists examined central nervous system tissue from the three recipients.
They found encephalitis.
That was expected.
What they saw next was not.
Inside nerve cells were viral inclusions.
Some looked like Negri bodies.
To a pathologist, that is an alarming clue.
Negri bodies are classically associated with rabies.
Rabies.
The possibility seemed almost absurd.
These patients had not come into the hospital reporting bites from aggressive animals.
They had not been attacked by dogs.
They had not independently encountered bats.
Three people receiving three organs from one donor had somehow developed findings suggesting the same disease.
Laboratory testing intensified.
Immunohistochemical staining was performed.
Direct fluorescent antibody testing was performed on brain tissue.
The result came back positive.
Rabies virus antigen.
In all three recipients.
Electron microscopy on tissue from one kidney recipient revealed structures consistent with rhabdovirus.
Scientists even inoculated laboratory mice with brain tissue from one of the recipients.
The mice developed illness and died within days.
Under electron microscopy, researchers could see the characteristic viral particles.
The diagnosis was no longer a vague suspicion.
It was rabies.
On June 30, 2004, the Centers for Disease Control and Prevention confirmed rabies in the three transplant recipients.
Then investigators examined evidence from the donor.
He too showed evidence of rabies infection.
Suddenly the entire case inverted.
The donor had not simply been a young man with an unfortunate brain hemorrhage.
He had been carrying one of the most feared neurological viruses known to medicine.
And nobody knew it when his organs were transplanted.
The Disease Nobody Was Looking For
Rabies is almost always associated in the public mind with an animal bite.
A dog.
A raccoon.
A bat.
An infected animal's saliva enters tissue through a bite, scratch or mucous membrane.
Then comes an incubation period.
Sometimes weeks.
Sometimes months.
The virus moves through peripheral nerves toward the central nervous system.
Once clinical neurological symptoms appear, the disease is almost invariably fatal.
That fact is crucial.
Rabies can be prevented remarkably effectively when exposure is recognized early and post-exposure treatment is given before symptoms begin.
But once the virus reaches the brain and symptomatic rabies develops, options become extraordinarily limited.
That is why identifying exposure matters so much.
And that is exactly what had failed in the donor's case.
Nobody had realized that he had been exposed to rabies.
Nobody had realized that his neurological illness could be rabies.
Nobody had realized that his organs might carry the virus.
The donor screening process had done what it was designed to do.
It looked for established contraindications.
It included history, physical examination and testing for selected infectious diseases.
Rabies was not routinely tested.
The CDC later emphasized the reason: routine screening cannot practically test donated organs for every rare pathogen, especially when organs must be transplanted quickly and the disease being considered is exceptionally uncommon.
Before this event, rabies had been transmitted through corneal transplantation in other countries.
But solid organs?
Liver?
Kidneys?
This had not been documented before.
The three deaths represented the first recognized cases of rabies transmitted through solid-organ transplantation.
And once investigators understood that, another question became urgent.
Where had the donor gotten rabies?
Go Back to Arkansas
Public-health investigators began reconstructing the donor's life.
He was an Arkansas resident.
He had sought treatment at two hospitals in Texas before his death.
He had experienced severe mental-status changes.
A low-grade fever.
The brain imaging had pointed doctors toward hemorrhage.
But now that rabies had been confirmed in the recipients, every part of his history had to be reconsidered.
Symptoms that had once seemed secondary could become important.
Difficulty swallowing.
Behavioral changes.
Neurological abnormalities.
Anything that could fit encephalitis.
Investigators spoke with people who knew him.
They asked about animal exposure.
And then they found the overlooked detail.
The donor had reportedly told others that he had been bitten by a bat.
A bat.
One small encounter.
One detail that had not stopped the organ-donation process.
Now it connected everything.
Laboratory typing of the virus supported the same conclusion.
The rabies variant was associated with bats.
Suddenly the medical mystery had a chain.
Bat.