Tuberculosis from a Bone Graft, Again: The Second Nationwide Outbreak, 2023

In July 2023, two doctors in different states noticed something familiar. One patient had developed tuberculous meningitis five weeks after spinal fusion surgery; another had a surgical wound that wouldn't heal after a laminectomy and tested positive for Mycobacterium tuberculosis. Both had received bone grafts containing live cells. Both doctors remembered the 2021 outbreak in which a contaminated bone graft product infected 113 patients in 18 states — and asked CDC to investigate. They were right: it was happening again.

A fast response

CDC recommended quarantining unused units, starting every recipient on multidrug treatment for TB disease whether or not they had symptoms, and using TB infection control precautions at their follow-up visits.

The toll

As of December 20, 2023:

• 5 of 36 recipients had laboratory-confirmed TB disease, four confirmed by culture, and at least 10 others had signs or symptoms consistent with it.
• 2 died of TB — the two patients first reported.
• 27 of 34 tested (79%) had positive blood tests for TB infection.
• Genome sequencing showed the bacteria from patients in four states and from unused graft material differed by at most one single-nucleotide change, confirming the grafts as the source.

The response prevented as many as 53 more surgeries with the contaminated material.

How it slipped through

The donor was a U.S.-born person whose next of kin reported no TB risk factors. But a chest X-ray before death showed lung infiltrates and a nodule in the right upper lobe, and the causes of death were pneumonia and sepsis. Both the 2021 and 2023 donors had signs of sepsis in their final hospital stay, with no TB testing documented — and people with sepsis should be ineligible to donate tissue.

After 2021, this manufacturer voluntarily began testing grafts with a nucleic acid amplification test, and this lot tested negative. Such tests are excellent for diagnosing TB but less sensitive than slower culture-based testing, which can take up to 8 weeks: in this outbreak, the donor specimen didn't grow TB in liquid culture until day 40. Low levels of bacteria in the grafts may explain both the negative test and why fewer recipients became ill than in 2021; prompt treatment may also have helped. Before 2021, the last reported bone-graft TB transmission was in the United Kingdom in 1953.

What needs to change

About 58,000 donors provide tissue for 2.5 million transplants in the United States each year. The authors call for:

• Culture-based testing of donor tissue before distribution — live-cell grafts are stored frozen for months or years, so there is time;
• Strict donor screening, rejecting donors with sepsis as current recommendations require;
• Informed consent that covers infection risks and alternatives, especially for live-cell grafts;
• Tissue tracking like that required for organs and blood, and routine monitoring and prompt reporting of problems in recipients.

TB is not gone from the United States, where up to 13 million people have untreated, often undiagnosed latent TB infection.

Sources

Based on Jonathan M. Wortham, Maryam B. Haddad, Rebekah J. Stewart, et al., "Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells — United States, 2023," Morbidity and Mortality Weekly Report, volume 72, Centers for Disease Control and Prevention; a work of the United States government in the public domain.