Tuberculosis outbreak linked to a bone graft product

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Record number: 
Adverse Occurrence type: 
MPHO Type: 
Estimated frequency: 
Infrequent in counties with a low burden of disease. This is the first case reported in bone since the 1950s, and otherwise Mycobacterium tuberculosis (MTB) has been reported to be transmitted via heart valves and dura mater. In the 2021 US bone transmission case, it is notable that the bone product contained living cells (processing was minimal, and the bone was cryopreserved to maintain cell viability), and transmission of MTB via bone products has happened rarely in the past - In the 1950s, the banking of ribs removed during thoracoplasties for pulmonary TB, and subsequent application in orthopaedic procedures, became frequent. The ribs were frozen at “- 15 degrees Centigrade to -20 degrees Centigrade in a solution containing penicillin and streptomycin,” however, this did not prevent TB transmission in recipients. James et al. (1953) reported 4 cases of TB transmitted through bone in orthopedic procedures; patients presented with TB abscesses and following the “removal of the infected bone chips and curettage, the wounds have healed without further incident.” Khanna et al. (1981) reported on 165 patients that underwent aortic valve replacements with antibiotic-treated homograft, of which one case of miliary TB was reported that developed 8 months after the procedure due to “a cold abscess in relation to the donor valve.” In the six months to seven years follow-up, this patient died due to TB. Anyanwu et al. (1976) reported 7 cases of miliary TB and subsequent death in a majority of the cases following the performance of homograft valve replacements in the five years following August 1969. Sanus (2009) reported a case of TB transmission via dura mater. It is notable that 1.5% of healthcare workers investigated as part of the 2021 US transmission case were determined to also have been infected with MTB as a result of patient care for recipients
Time to detection: 
Will depend on the burden of disease and most likely impacted by whether the donor had (active) TB disease rather than (latent) TB infection. In the 2022 US case (Schwartz et al.), it took about 23 days for the first recipient to develop post-operative infection, and 42 days to identify that infection as MTB. Healthcare workers were also evaluated by the US CDC as part of the investigation, so there is little information known about when they would have presented without the recognition of transmission via the bone grafts, but within about two months after the first MTB case was identified, all living recipients had been notified of exposure. Because MTB is not detectable on standard micro cultures, there has to be an index of suspicion for MTB cultures to be drawn, and results from MTB culture can take 2-6 weeks for standard cultures to grow. In the dura mater transmission, symptoms developed four months after surgery, the recipient was followed clinically another 2 months, when MRI revealed lesions leading to more aggressive evaluation and eventual diagnosis.
Alerting signals, symptoms, evidence of occurrence: 
In 2021 investigation in the US: 75% had surgical site infection, 67% had constitutional symptoms, 39% had neurological symptoms (most of the allograft was used for spinal surgery), 33% had pulmonary symptoms, 22% had other symptoms, while 11% had no documented symptoms. Site of TB disease included 75% at the surgical site (spine/paraspinal soft tissues and 1 in a foot), 25% at other sites (lungs 24%, CNS 3%, blood 3%, bone marrow 1% and liver 1%). Recipient of dura mater had CNS symptoms, headache, and constitutional symptoms.
Demonstration of imputability or root cause: 
In the 2021 US case: US CDC tested MTB from recipients (60 were positive by AFB smear, NAT, or culture) and 8 unused units from the same donor were genetically sequenced. All isolates were >99·99% genetically identical (0 to 1 single nucleotide polymorphism differences).
Imputability grade: 
3 Definite/Certain/Proven
Suggest new keywords: 
Bone allograft
Tissue allograft
Mycobacterium tuberculosis
Post-operative wound infection
Suggest references: 
1) Schwartz NG, et al. Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report. Lancet Infect Dis. 2022 Aug 4;S1473-3099(22)00425-X 2) Ruoran Li, et al. Transmission of Mycobacterium Tuberculosis to Healthcare Personnel Resulting From Contaminated Bone Graft Material, United States, June 2021–August 2022. Clin Infect Dis. 2023 Jan 20;ciad029 3) Marshall KE, Free RJ, Filardo TD, Schwartz NG, Hernandez-Romieu AC, Thacker TC, Lehman KA, Annambhotla P, Dupree PB, Glowicz JB, Scarpita AM, Brubaker SA, Czaja CA, Basavaraju SV. Incomplete tissue product tracing during an investigation of a tissue-derived tuberculosis outbreak. Am J Transplant. 2023 Sep 15:S1600-6135(23)00693-7. doi: 10.1016/j.ajt.2023.09.005. Epub ahead of print. PMID: 37717630.
Hi all - I created a "meta" summary of the cases, and uploaded past case reports that I already had. If any of the other references I uploaded have their own reports, I suggest linking those reports to this case. This record will be cloned for the following MPHO: heart valves, dura mater - Done (EP)
Expert comments for publication: 
An unusual cluster of tuberculosis cases in patients who had undergone the implantation of bone allograft material from a single donation triggered product recall and US nationwide activities to sequester unused products and evaluate and treat product recipients. The investigation showed that the presence of factors, symptoms, and signs consistent with tuberculosis was not recognised in an 80-year-old deceased male donor from whom bone tissue was procured, processed into 154 units of a living cell-containing allogeneic bone product and distributed. Most units 136 (88%) were implanted and the remaining 18 units (12%) were located and sequestered. The evidence of tuberculosis was obtained in 87 recipients. Eight recipients of the product died, three of which were attributed to tuberculosis. All living recipients were treated for tuberculosis. Mycobacterium tuberculosis isolates from unused products and recipients were more than 99·99% genetically identical. MTB is a rare organism to transmit via tissues, and tissues involved in documented transmission cases were not irradiated. MTB is fairly susceptible to irradiation and is much less likely to be transmitted from irradiated tissues. Improvements in donor screening criteria are warranted and discussions are underway in the US to balance safety and availability in donor screening practices, particularly considering tissues that are processed and distributed in a manner to maintain living cells. Extreme caution should be considered when selecting donors for tissues containing living cells, and particularly elderly, ill patients with unclear causes of systemic inflammatory response syndrome or sepsis should be avoided for unprocessed tissues. There is a second TB transmission case being investigated by the CDC beginning in August 2023 - again bone allograft with bone marrow that is minimally processed and contains viable cells. American Association of Tissue Banks (AATB) has issued interim donor screening requirements in September 2023 (AATB Bulletin 23-6) (