By Gary Evans, Medical Writer
“There is an urgent need to establish adequate screening and testing protocols for tuberculosis among donated tissues,” said EIS officer Alfonso Hernández-Romieu, MD, MPH. “This outbreak, although rare, had devastating consequences, and, without appropriate measures in place, this may happen again.”
The outbreak began on May 25, 2021, when the Delaware Division of Public Health found an unusual cluster of seven patients with suspected TB after spinal surgery during March and April 2021. “Hospital staff members identified a single common exposure: implantation of bone allograph product from a single product lot — ‘lot A,’” he said.
Bone allograph products most frequently are used in spinal surgery, although one patient was infected after receiving the contaminated product in a foot operation.
“Bone allograph product is manufactured from tissue donated by deceased donors, and each lot of product includes bone from a single deceased donor,” Hernández-Romieu said. “Donated bone is processed to retain live cells from the bone marrow, and this is important because M. tuberculosis can disseminate to the bone marrow.”
Following industry practice, the tissue manufacturer performs bioburden testing on samples collected during processing and from the final product. “The testing includes select fungi and bacteria, but testing does not include M. tuberculosis,” he said.
As a result of the outbreak, TB should be added to testing of donors, if feasible, Hernández-Romieu said, adding, “There’s a 5% prevalence of latent TB, so I think adding tuberculosis testing to this panel would make everyone safer.”
Although the CDC identified cases through sophisticated diagnostics, currently there is no approved TB test for deceased donors. In light of the outbreak, the American Association of Tissue Banks (AATB) issued recommendations to screen donors for tuberculosis risk factors.
“There are no assays suitable for deceased donor testing, so adequate medical and social history is required,” the association recommended.2 The AATB listed the following TB risk factors for donors:
- a reported history of TB or TB exposure;
- taking immunosuppressive medications;
- chronic kidney disease, on hemodialysis or peritoneal dialysis;
- chronic liver disease;
- uncontrolled diabetes;
- born in an area with a high prevalence for TB, particularly if they have one of the conditions listed previously.
In addition, the risk-benefit equation is not the same for tissue donation, while organ transplants often are lifesaving. That means there should be more time to screen for risk factors in a non-emergency situation.
“For tissues, there should be zero to minimal risk of having disseminated tuberculosis if you have an orthopedic procedure, whereas someone who receives a liver or lungs or heart is in a very different type of risk scenario,” Hernández-Romieu said.
High Attack Rate
CDC investigators determined 154 units of lot A were distributed to 37 facilities in 20 states during March and April 2021. Only this manufacturer and lot were involved, with the contaminated product made from a femur bone of the deceased patient.
“Out of 113 recipients, 77% (87) had microbiologic or imaging evidence of tuberculosis, and, for context, the secondary attack rate for tuberculosis after traditional exposure is 1%,” Hernández-Romieu said.
Overall, 49 patients underwent surgery for product-related complications and the others received drug therapy. The extraordinary attack rate is not completely understood, but the TB strain was drug-susceptible, and no healthcare workers developed active infection.
“We have several hypotheses, [including] how high the mycobacterial load was in the product itself,” he said. “Normally, any clinical specimen positive culture will take up to six to eight weeks, whereas, in this particular product, it took about two weeks to grow. There was a very high burden of mycobacteria there.”
Another factor is that TB essentially was placed directly into the spine, which may have undermined immune reactivity and facilitated the pathogen’s spread. “Of those with TB, in 25% of patients, it had disseminated to other body sites, including the lungs and the central nervous system,” he said.
Ten of the bone recipients died, with three of the deaths attributed to TB. However, there may have been more deaths linked to the transplants, since details were incomplete for some patients.
“It is very challenging to attribute a death to tuberculosis in such a short time period, because [some] patients had other comorbidities,” Hernández-Romieu said. “Five deaths we were unable to attribute to tuberculosis, and for two deaths, we did not have any additional information. In some cases, there wasn’t an autopsy performed, so we could not determine the true cause of death.”
The transplant patients who survived have faced a difficult course of treatment to clear the TB infection.
“It can be a very debilitating condition to have spinal tuberculosis,” he said. “It may take six to 12 or more months to treat it, and it can cause significant impairment of function and quality of life for recipients.”
No patient contacts were found to have latent TB other than the 73 healthcare workers, who represented 2% of 4,884 contacts tested.
“The healthcare personnel who had conversions were all people who had either had a [prior] negative test or had not been tested for tuberculosis,” he said.
Most of the healthcare workers were identified through use of a CDC definition of an exposure that included those present during graft implantation or other activities that could aerosolize TB or those who had contact with patients who had either draining tuberculous lesions or pulmonary TB in the absence of airborne precautions.3
Donor Risk Factors Missed
A donor screening questionnaire with the tissue donor’s available next of kin indicated the donor had no known history of TB disease, no positive TB test, nor exposure to TB in the previous 12 months, Hernández-Romieu said.
However, the donor had TB risk factors, including prior residence and frequent travel to a country with elevated tuberculosis incidence — 8.5 times higher than that of the United States, Hernández-Romieu said. Other risk factors included being 80 years old, having type 2 diabetes, and receiving hemodialysis for end-stage renal disease.
“The tissue donor had symptoms consistent with active tuberculosis disease, including a weight loss of 70 to 80 pounds in the last two years, and two to three weeks of cough and shortness of breath before admission to the hospital,” he said.
These symptoms were attributed to a history of congestive heart failure and end-stage renal disease.
“The donor’s cause of death was thought to be cardiogenic shock,” he said. “Public health officials’ review of the donor’s medical record revealed a negative tuberculosis skin test four months prior to hospitalization and concluded the donor likely died of unidentified disseminated tuberculosis.”
Donor screening questionnaires collect data on epidemiological and clinical tuberculosis risk factors; however, their presence does not necessarily trigger additional evaluation in the absence of a reported history of TB or a TB exposure, he added.
“The bone graft market is projected to grow substantially in the next 10 years, as the world population ages, and recovery of tissues and use of bone allographs will expand to countries with donor pools with a higher incidence and prevalence of tuberculosis, which may increase the probability of a repeat outbreak,” he said. “[The] CDC is working with regulators and industry partners to raise awareness of transmission of M. tuberculosis through donated tissue and implement additional measures to prevent future outbreaks.”
Several actions already have been taken, including the AATB’s recommendations and the tissue manufacturer’s decision to refuse donations from people with prior residence in countries with a high incidence of TB.
REFERENCES
- Hernandez-Romieu, Schwartz N, Wilson W, et al. Spinal and disseminated tuberculosis caused by surgical implantation of a bone tissue product — 20 U.S. states, 2021. Presented at the Centers for Disease Control and Prevention Epidemic Intelligence Service conference, May 2022.
- American Association of Tissue Banks. Recommendation issued to tissue banks regarding the risk of Mtb transmission. Published March 22, 2022. https://www.aatb.org/bulletin-22-2
- Li R, Deutsch-Feldman M, Hernandez-Romieu A, et al. Unusual healthcare personnel exposures to Mycobacterium tuberculosis related to a contaminated surgical product — United States, 2021. Presented at the Centers for Disease Control and Prevention Epidemic Intelligence Service conference, May 2022.
A massive Mycobacterium tuberculosis outbreak spread to 81 bone tissue recipients in 20 states, leading to multiple patient deaths and 73 latent infections in healthcare workers, investigators with the Centers for Disease Control and Prevention (CDC) report.
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