Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report

Abstract

Background: Mycobacterium tuberculosis transmission through solid organ transplantation has been well described, but transmission through transplanted tissues is rare. We investigated a tuberculosis outbreak in the USA linked to a bone graft product containing live cells derived from a single deceased donor.

Methods: In this outbreak report, we describe the management and severity of the outbreak and identify opportunities to improve tissue transplant safety in the USA. During early June, 2021, the US Centers for Disease Control and Prevention (CDC) worked with state and local health departments and health-care facilities to locate and sequester unused units from the recalled lot and notify, evaluate, and treat all identified product recipients. Investigators from CDC and the US Food and Drug Administration (FDA) reviewed donor screening and tissue processing. Unused product units from the recalled and other donor lots were tested for the presence of M tuberculosis using real-time PCR (rt PCR) assays and culture. M tuberculosis isolates from unused product and recipients were compared using phylogenetic analysis.

Findings: The tissue donor (a man aged 80 years) had unrecognised risk factors, symptoms, and signs consistent with tuberculosis. Bone was procured from the deceased donor and processed into 154 units of bone allograft product containing live cells, which were distributed to 37 hospitals and ambulatory surgical centres in 20 US states between March 1 and April 2, 2021. From March 3 to June 1, 2021, 136 (88%) units were implanted into 113 recipients aged 24-87 years in 18 states (some individuals received multiple units). The remaining 18 units (12%) were located and sequestered. 87 (77%) of 113 identified product recipients had microbiological or imaging evidence of tuberculosis disease. Eight product recipients died 8-99 days after product implantation (three deaths were attributed to tuberculosis after recognition of the outbreak). All 105 living recipients started treatment for tuberculosis disease at a median of 69 days (IQR 56-81) after product implantation. M tuberculosis was detected in all eight sequestered unused units tested from the recalled donor lot, but not in lots from other donors. M tuberculosis isolates from unused product and recipients were more than 99·99% genetically identical.

Interpretation: Donor-derived transmission of M tuberculosis via bone allograft resulted in substantial morbidity and mortality. All prospective tissue and organ donors should be routinely assessed for tuberculosis risk factors and clinical findings. When these are present, laboratory testing for M tuberculosis should be strongly considered.

Funding: None.

Figure 1

Timeline of use or sequestration of 154 bone allograft units containing Mycobacterium tuberculosis in 20 US states from March to June, 2021 CDC=US Centers for Disease Control and Prevention.

Figure 2

Mycobacterium tuberculosis testing of bone allograft recipients and sequestered units from the recalled product lot *Eight product recipients died in total (five were not tested and three were tested for M tuberculosis). †Includes the three deceased recipients who were tested.

Figure 3

Phylogenetic tree of Mycobacterium tuberculosis isolates from bone allograft recipients and sequestered units Constructed with BioNumerics (version 7.6) using the neighbor-joining method. M tuberculosis strain H37Rv was used as the outgroup and the phylogenetic tree was rooted at the midpoint of the longest branch. The horizontal branch lengths represent genetic divergence on a logarithmic scale, and the number of single nucleotide polymorphisms is shown on each branch.