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

https://doi.org/10.1016/S1473-3099(22)00425-XGet rights and content

Summary

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.

Introduction

Donor-derived tuberculosis after solid organ transplantation has been well described in high-incidence and low-incidence countries and carries a high mortality risk.1, 2 However, Mycobacterium tuberculosis transmission through tissue grafts is rare. Case reports have shown transmission via bone,3 heart valve,4 and dura mater5 grafts. Tuberculosis transmission can occur from donors with undetected tuberculosis disease or latent tuberculosis infection,1 which is estimated to affect one quarter of the world's population6 and 5% of the US population.7 Despite this high prevalence, current regulations in the USA do not require organ or tissue donors to be assessed for tuberculosis or tuberculosis risk factors, and laboratory testing for M tuberculosis is not routinely performed.8, 9

In the summer of 2021, we investigated an unprecedented outbreak of tuberculosis in the USA linked to a bone allograft product containing live cells derived from a single deceased donor. On May 25, 2021, a Delaware hospital notified public health authorities about an unusual cluster of tuberculosis cases in patients who had undergone spinal surgery, involving implantation of bone allograft material from a single product lot. On June 2, 2021, the manufacturer issued a voluntary nationwide recall of that product lot.10 The same day, a different state health department notified the US Centers for Disease Control and Prevention (CDC) about another tuberculosis case in a surgical patient exposed to the same product lot. Initial investigations in Delaware have been described previously.11 We describe nationwide efforts to sequester unused product, evaluate and treat product recipients, and identify opportunities to improve tissue transplant safety in the USA.

Research in context

Evidence before this study

Our preliminary report published in September, 2021, showed high attack rates of spinal and disseminated tuberculosis in bone allograft recipients at a single hospital. To identify previous reports of tuberculosis transmission through transplanted tissues, we searched PubMed for articles published between database inception and Nov 1, 2021, using the search terms “tuberculosis” and “transplant”, “transplantation”, “graft”, or “allograft”. We also reviewed regulatory and guidance documents from the US Food and Drug Administration, Centers for Medicare and Medicaid Services, American Association of Tissue Banks, and the Organ Transplantation and Procurement Network. We found three previous case reports of tuberculosis transmission through transplanted tissues and no current US regulations, guidelines, or professional standards that adequately address tuberculosis screening for tissue donors.

Added value of this study

We provide a detailed description of the largest recorded tissue-derived tuberculosis outbreak, including multiple lines of evidence supporting donor-derived transmission; the incidence and severity of tuberculosis disease among all product recipients in the USA; and the rapid and effective response by public health authorities. We show that standard screening was unsuccessful at detecting infection in the donor and donated tissues, and we propose measures to improve safety of tissue and organ donation. Based on our investigation, the American Association of Tissue Banks issued new recommendations for preventing tissue-derived tuberculosis transmission.

Implications of all the available evidence

All prospective tissue and organ donors should be routinely assessed for risk factors and clinical findings of tuberculosis. When these are present, laboratory testing for Mycobacterium tuberculosis should be strongly considered.

Section snippets

Study design

In this outbreak report, we describe the tuberculosis outbreak management, frequency and severity of tuberculosis among product recipients, procedures used to screen the tissue donor and donated tissues, and clinical and laboratory evidence for donor-derived transmission. To facilitate tracking of units from the recalled product lot, the product manufacturer immediately provided CDC with records of recipient health-care facilities and shipment dates. During early June, 2021, CDC worked with

Results

Bone was procured from a 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 in 18 states (figure 1; figure 2; some individuals received multiple units). After the manufacturer issued a voluntary recall of the affected product lot between June 2 and 7,

Discussion

This study found strong evidence of donor-derived transmission of M tuberculosis through the use of a bone allograft product containing live cells, resulting in spinal and disseminated tuberculosis in most (77%) product recipients residing in 15 US states. Rapid collaborative action by public health agencies, health-care facilities, and the product manufacturer enabled sequestration of 18 unused product units within 5 days of the recall and initiation of tuberculosis treatment by all 105

Data sharing

Individual participant data will not be made available.

Declaration of interests

We declare no competing interests.

References (30)

  • Latent TB infection in the United States—published estimates

  • Organ Procurement and Transplantation Network (OPTN) policies

  • Eligibility determination for donors of human cells, tissues, and cellular and tissue-based products

  • Urgent voluntary notification: FiberCel Fiber Viable Bone Matrix (“FiberCel”)—lot number: NMDS210011

  • R Li et al.

    Notes from the field: tuberculosis outbreak linked to a contaminated bone graft product used in spinal surgery—Delaware, March–June 2021

    MMWR Morb Mortal Wkly Rep

    (2021)
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