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.

中文翻译：

---

美国全国范围内的结核病暴发与骨移植产品有关：暴发报告

背景

结核分枝杆菌通过实体器官移植传播已得到充分描述，但通过移植组织传播的情况很少见。我们调查了美国爆发的结核病疫情，该疫情与一种骨移植产品有关，该骨移植产品含有来自一位已故捐献者的活细胞。

方法

在这份疫情报告中，我们描述了疫情的管理和严重程度，并确定了提高美国组织移植安全性的机会。2021 年 6 月初，美国疾病控制与预防中心 (CDC) 与州和地方卫生部门以及医疗保健机构合作，从召回批次中找到并隔离未使用的产品，并通知、评估和治疗所有已确定的产品接收者. CDC 和美国食品和药物管理局 (FDA) 的调查人员审查了捐献者筛查和组织处理。使用实时 PCR (rt PCR) 检测和培养对召回和其他捐赠批次中未使用的产品单元进行了结核分枝杆菌的检测。结核分枝杆菌使用系统发育分析比较未使用产品和接受者的分离物。

发现

组织供体（一名 80 岁的男性）有未被识别的与肺结核一致的危险因素、症状和体征。2021年3月1日至4月2日期间，从已故捐献者处采集骨骼，加工成154单位含有活细胞的同种异体骨移植产品，分发至美国20个州的37家医院和门诊手术中心。3月3日至6月1日， 2021 年，136 个 (88%) 单位被植入 18 个州的 113 名年龄在 24-87 岁之间的接受者（有些人接受了多个单位）。其余 18 个单位 (12%) 已找到并被隔离。113 名确定的产品接受者中有 87 名 (77%) 有结核病的微生物学或影像学证据。八名产品接受者在产品植入后 8-99 天死亡（三名死亡是在发现疫情后死于结核病）。在召回的捐赠者批次中测试的所有八个隔离未使用单位中都检测到结核分枝杆菌，但在其他捐赠者的批次中未检测到。从未使用的产品和接受者中分离出的结核分枝杆菌在基因上的一致性超过 99·99%。

解释

结核分枝杆菌通过骨同种异体移植物的供体传播导致了大量的发病率和死亡率。应定期评估所有预期的组织和器官捐献者的结核病危险因素和临床表现。当存在这些情况时，应强烈考虑结核分枝杆菌的实验室检测。

资金

没有任何。