U.S. health officials are racing to control an outbreak of tuberculosis linked to contaminated bone graft material that has killed one person and infected at least four others — the second outbreak of the rare disease in two years.
The contaminated product was used in at least 36 patients who underwent surgical or dental procedures earlier this year, according to the Centers for Disease Control and Prevention. But the outbreak did not become public until Aziyo issued a voluntary recall on July 13.
All patients are being treated as if they have tuberculosis because of the large percentage of people who develop severe forms of the disease from implanted bone material, according to Kathleen Conley, a CDC spokesperson.
TB is caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but it can attack any part of the body, such as the kidney, spine and brain. The bacteria spread through the air, from one person to another. Left untreated, tuberculosis can be fatal.
In 2021, surgeons used the contaminated material in 113 patients, sparking a wave of lawsuits and calls for tighter regulation of the product, a commonly used surgical putty that contains living cells procured from the bones of a cadaver.
CDC investigating TB cases linked to tainted bone repair product used in more than 100 patients
In the current outbreak, the bone products were derived from a single donor and sent to 13 facilities in seven states: California, Louisiana, Michigan, New York, Oregon, Texas and Virginia, between Feb. 27 and June 20, according to the CDC.
Aziyo recalled a single lot of the bone repair product, ViBone Moldable, which is made from human tissue and used primarily in orthopedic and spinal procedures, according to a July 13 company statement. Samples from the lot had tested negative for the bacteria that causes tuberculosis, the company said. The CDC said the company’s bone grafting solution, called alloOss Plus, used for dental procedures, also came from the same donor and was recalled.
The company said it has suspended shipments of all bone repair products from all donors. All patients, facilities and states involved have been contacted and remaining units of the product lot have been removed from inventory and will not be used, according to the CDC.
Aziyo, which processes the bone product, is responsible for ensuring the product is free of contamination. But current U.S. regulations do not require organ or tissue donors to be assessed for tuberculosis or tuberculosis risk factors. The Food and Drug Administration requires human tissue used for products like the bone repair material to be tested for several communicable diseases, including hepatitis, HIV and syphilis — but not tuberculosis.
Nor is laboratory testing for the tuberculosis bacteria routinely performed on donors, according to a report on the 2021 outbreak published in the Lancet Infectious Diseases. Its authors include CDC, FDA and other federal and state health officials who investigated that outbreak, the largest recorded tissue-derived tuberculosis outbreak, the report said.
Standard screening was unsuccessful at detecting infection in donated tissues as well as in the donor, an 80-year-old man who traveled frequently to an unidentified country where the annual number of new TB cases is more than eight times higher than in the United States, the report said.
In that report, federal health officials recommended that “all prospective tissues and donors should be routinely assessed for tuberculosis risk factors and clinical findings.”
In a recent statement, Aziyo said neither the FDA nor the American Association of Tissue Banks, the organization that promotes the safety and use of donated human tissue, mandate testing for the tuberculosis bacteria in cellular products.
“However, considering our experience in 2021 and with the intent to protect patients, Aziyo worked with outside experts to develop a test to screen for [the bacteria] where none was previously commercially available,” the company said. “We have used this test as part of our standard operating procedures since that time. This test exceeds guidelines set by both the AATB and the FDA.”
The company said samples from the specific lot of bone material that was related to the tuberculosis infections had tested negative for the bacteria by an independent laboratory using a nucleic acid test that is designed to specifically detect the organism. “Our investigation has involved additional testing on the donor lot in question through multiple independent labs and in each instance, [the bacteria] has not been detected in the donor samples,” the company said.
Beverly Bliss, vice president for accreditation standards and regulatory affairs at the American Association of Tissue Banks, agreed that even a more sensitive laboratory test, which would take six to eight weeks, is not guaranteed to turn up tuberculosis in bones. And that length of time might threaten the live cells in the Aziyo product.
“There simply isn’t a good test,” she said. Current tests were “all designed for living people.”
The association is preparing to release a new set of “risk factors” Monday to help companies avoid collecting tissue from the remains of people most likely to have been exposed to tuberculosis in their lifetimes. Their bodies should not be used for “any viable cell product,” she said.
Bliss said extensive investigations by both the AATB and the FDA did not turn up anything wrong in Aziyo’s processing of the bone in 2021. She declined to comment on why a single company, of the many in the United States that process tissue, is involved in both tuberculosis outbreaks.
“We have not detected anything noncompliant yet,” Bliss said.
The FDA said it is working with the CDC “to fully understand the impact of this recall,” said Carly Kempler, an FDA spokesperson.
In response to whether the agency plans to update its human tissue requirements and mandate testing for tuberculosis, Kempler said the agency routinely reviews its approaches for screening and testing of human cells, tissues and cellular and tissue-based products from donors to determine whether any changes should be made.
James Sunstrum, an infectious-disease expert in Dearborn, Mich., who treated two patients for severe tuberculosis after they underwent spinal surgery with Aziyo’s contaminated bone product in 2021, said the type of test performed by Aziyo is a quick test, but “some TB cells could certainly escape with that DNA test.” He and other clinicians say a more thorough test to detect tuberculosis would entail culturing a specimen, but that requires six to eight weeks of additional incubation for this very slow-growing bacteria.
“It’s very disturbing and distressing to hear about a second outbreak,” Sunstrum said. “We think this kind of product should be removed from the shelves.”
Chris Buri, 72, of Denver, was among the patients in the 2021 outbreak who contracted tuberculosis after spinal surgery. His 10-hour surgery was a success, he said, but the tuberculosis infection hit him with severe pain and night sweats. The months-long antibiotic treatment for TB made the pain worse. When he learned how he had become infected, “I wanted to get healthy and I wanted to get even,” Buri said in an interview this week. He filed a lawsuit but reached a settlement with the company. He is not allowed to disclose the terms.
Buri said he was eager to move on. He became active in WeAreTB.com, a TB education and support group. But the new outbreak is bringing back difficult memories. “I’m heartbroken to find out that more people have now suffered from a second outbreak,” he said.