The federal Centers for Disease Control and Prevention is trying to understand why three of the four people who got organs from a rabies-infected donor in 2011 didn’t develop the disease, the agency’s top rabies expert said Wednesday.
Investigators have been puzzled because four recipients in a similar 2004 case all died of rabies within weeks. The answer could lie in the strain of rabies involved, the amount of virus in the transplanted organs, the medical history of the recipients or their genetic makeup, CDC veterinarian Richard Franka said in a telephone interview.
“It’s surprising. In all previous transplant cases of solid organs, all the recipients developed rabies in a very short time,” Franka said. “We are looking into it, trying to understand what mechanism was behind it.”
The fourth recipient of the 2011 transplants, a Maryland man who got a kidney, died of rabies in late February. His death prompted a public health investigation that found that other organs from same Florida donor went to recipients in Florida, Georgia and Illinois. They are “very likely” out of danger, having begun post-exposure treatment before developing symptoms, Franka said.
Those three patients have completed the conventional preventive course of four vaccine shots, he said. In the next week, they will get a fifth dose, prescribed for patients with suppressed immune systems, including transplant recipients.
In the only other such U.S. case, in 2004, patients who received the kidneys, liver and an artery from a rabies-infected Texas donor died of rabies within seven weeks.
Franka said the strain of rabies in the 2011 case — a type found in raccoons — might have a longer incubation period in humans than the bat strain involved in the 2004 case.
A second theory is that the transplanted kidneys, heart and liver from the 2011 donor contained varying concentrations of virus depending on their distance from the central nervous system, where the rabies virus resides. Franka said numerous published studies have suggested or proven that in some rabies patients, virus indicators weren’t present in all organs.
“This could be potentially one of the hypotheses in this case — that maybe there was no virus present in the organ, or the dose was not sufficient for infection,” he said.
It’s also possible that the surviving recipients were on medication that inhibited the disease, or that they were simply not susceptible due to their genetic makeup, he said.
“Not everybody has to die if infected with rabies virus. Once symptoms develop, it’s almost 100 percent fatal. But the path from infection to development of symptoms depends on many variables,” Franka said.
Another puzzle is the long incubation period — nearly 17 months — in the Maryland patient. Franka said 99 percent of people bitten by a rabid animal develop rabies symptoms within a year, but in rare cases it can take up to eight years for the disease to appear. In the 2004 transplant patients, the incubation period was much shorter because their immune systems were weakened by anti-rejection drugs. It’s a mystery why that didn’t happen in this case.
Franka said the CDC plans to study how different strains of rabies virus behave in transplant recipients, but any findings are months or years away.
“Today, we do not have an answer why this incubation period was so long,” he said.
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