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By Gary Evans, Medical Writer
Consider two separate tales of transplant and transfusion gone horribly awry by the narrowest of margins. Each represents a conspiracy of unlikely events that enabled deadly pathogens to find a path to frail patients. Four people died in the two clusters, which share a strange menagerie of mosquitoes, birds, dogs, and horses. We begin with an event that is all too human — suicide.
“The organ donor experienced a self-inflicted gunshot wound,” says William Walker, DVM, PhD, an investigator at the Centers for Disease Control and Prevention.
The victim’s family proceeded with her wish for organ donation, not realizing she had an apparently subacute infection with eastern equine encephalitis virus (EEEV). The “triple E” virus outbreak was recently reported in Atlanta at the annual conference of the CDC’s Epidemic Intelligence Service (EIS).1 Transmitted by mosquitoes, the virus can cause a rare but often fatal encephalitis.
In October 2017, three cases of EEEV were identified in recipients who received the donor’s heart and other solid organs.
“Two of the organ recipients died,” he said. “The surviving recipient continues to have residual tremors.”
It is not known whether the donor’s suicide was related to symptomatic EEEV, but there was enough of the virus in the patient’s organs to transmit the deadly virus.
“There was some question that [the suicide] was possibly related to triple E infection,” Walker says. “There is really no way to know. Most infections with triple E are asymptomatic or may cause mild illness.”
As part of the organ procurement organization’s process, the suicide victim’s family was interviewed, he says. There was no indication that the donor had any neurologic symptoms suggestive of EEEV.
Before her death, the organ donor received blood products from eight people, but all were negative for EEEV infection.
“While the investigation is ongoing, the available evidence suggests the organ donor was likely infected through mosquito exposure rather than transfusion transmission of EEEV,” Walker reports.
No EEEV human disease cases were reported near the organ donor’s residence. However, equine cases and a positive mosquito pool were reported in nearby counties. Adding to the mystery, the donor’s blood tested negative for EEEV.
“We were able to test at least one blood sample from the donor and we had no positive results,” he says.
The natural reservoir for EEEV is in birds, with mosquitoes serving as the vector to transmit to humans and horses, from which it gets the “equine” name.
“Triple E is in the environment in endemic places where there are freshwater hardwood swamps,” Walker says.
“It is transmitted among birds in those locations. There are bridge-vector mosquitoes that like to bite both people and horses.”
However, both humans and horses are considered “dead-end hosts,” meaning they do not serve as a reservoir for transmission to others via mosquitoes.
“It’s a rather unfortunate name, but it basically indicates that the presence of virus in their blood is not sufficient to infect mosquitoes to perpetuate transmission,” he says.
Though EEEV was detected in horses in the area, the most likely scenario is that a mosquito bit the organ donor after feeding on a bird with the virus.
“It is kind of an accidental spillover — a rare occurrence,” he says.
Rarer still is the resulting sequence of events, wherein an organ donor transmits EEEV to transplant recipients. Indeed, this is the first documented case of that happening.
“I’ll tell you, people liken this to having lightning strike,” he says.
If blood products are not routinely screened for EEEV, is it possible some cases of transmission are being missed?
“It is not routinely screened for triple E, but collection agencies do ask a number of questions to make sure blood donors don’t have an illness,” he says. “Typically, most of the infections with triple E are believed to be asymptomatic or just cause a mild clinical illness.”
Thus, most of those go unrecognized, with only about eight human cases a year being severe enough to be picked up in CDC surveillance.
“For organ donor screening, we are not suggesting a change in policies and procedures,” Walker says. “This is rare. If you tested, you would expect to find a pretty low yield. The test itself is not readily available and it takes time [for results]. It could delay organ procurement and transplants as well. If you look at our test results for the organ donor, the specimen that we tested was negative.”
In another unusual outbreak reported at EIS, two fatal cases of Clostridium perfringens infection were traced back to the skin of a blood platelet donor. Investigators suspect the donor had recurrent colonization due to contact with her two dogs. The fact that they were able to detect the pathogen on her skin two weeks after transmission suggested a repeated source of exposure. She reported her dogs had been sick, raising a suspicion that they were the source that could not be confirmed.
“We were unable to do any environmental testing of the home,” says Roberta Horth, PhD, MPH, an EIS officer in Salt Lake City. “The donor did consent to getting the samples from the skin, but she did not allow anyone to come to her home or to collect samples from her home.”
The investigation began in August 2017 when two immunocompromised patients developed sepsis and died shortly after receiving blood platelet units donated by the same donor. The genetic sequencing identified three isolates from the donor’s skin that matched isolates from one patient’s blood and the other’s platelet infusion bag. One platelet recipient died within a few hours and the other five days later.
“They were immunocompromised,” she says. “Because the patients had complex medical histories and this bacterial contamination is so rare, it wasn’t actually considered the source of sepsis.”
Whole genome sequencing linked C. perfringens colonization on the donor’s skin to the platelet product and to the recipients, she explains. A cousin of notorious C. difficile, C. perfringens also is a spore former that can be difficult to remove from the skin and can produce powerful toxins once in the blood system.
“It is extremely uncommon in terms of contamination of blood and platelet products,” she says. “There are only two or three other times in the literature it has been cited as having been a source of sepsis from platelet products.”
In contrast, C. perfringens is the most common source of food poisoning in the U.S., as it can transmit from improperly cooked beef and poultry.
Horth and colleagues reviewed the blood collection facility, hospital records, and infection prevention practices. Healthcare professionals at the hospital and blood collection facility as well as the donor were interviewed.
No blood collection or transfusion-related infection control breaches were identified, and the platelet center facility confirmed the donor’s initial platelet screening culture was negative.
The donor reported no recent exposures to farm animals or travel, known risk factors for C. perfringens. However, she did disclose that her two household dogs had been sick with diarrheal illness. The donor was permanently deferred from donating, and since there was no ongoing risk, her refusal to let investigators inspect her domicile and test her dogs was not challenged.
“We were surprised that we were actually able to detect C. perfringens on her skin because it was two weeks after she donated,” she says. “It points more to her being colonized or having some constant exposure in her house. It is common in farm animals, and she doesn’t live too far from a farm. It most likely was from the dogs, but we can’t say that for sure. It’s speculation.”
The blood collection center followed standard practice in cleaning the skin insertion site with chlorhexidine.
“Even with standard practice, spores are pretty difficult to kill with the antiseptics that are used for skin cleansing,” she says. “So, there is a chance that some bacteria can get in even after skin is cleaned.”
They also performed another common safeguard, diverting the first 25 mls of blood to avoid just this type of skin contamination of blood products.
“Those procedures were followed, but some remnant stayed in the product,” she says. “Small enough that even with quality control testing, it was not detected.”
Overall bacterial contamination during blood and platelet donation remains rare, with approximately seven deaths linked to it annually.
The FDA drafted guidelines3 to address the problem in 2016 that include pathogen inactivation technology and rapid detection at point of use. Currently, there are no CDC recommendations endorsing these practices.
“These [guidelines] have been adopted in several European countries — France, Belgium, and Switzerland — and there has been a reduction in the number of septic transfusions associated with bacterial contaminated platelets,” she said.
“There are some blood suppliers that have started to adopt this, but it is not nationwide yet and it is not mandatory.”
Financial Disclosure: Peer Reviewer Patrick Joseph, MD, reports that he is a consultant for Genomic Health Reference Laboratory, Siemens Clinical Laboratory, and CareDx Clinical Laboratory. Senior Writer Gary Evans, Editor Jesse Saffron, Editor Jill Drachenberg, Nurse Planner Patti Grant, RN, BSN, MS, CIC, and Editorial Group Manager Terrey L. Hatcher report no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.