The US Centres for Disease Control & Prevention (CDC) says there is an urgent need to improve donor screening and product testing, after contaminated bone allograft material from a single manufacturer had led to five diagnosed cases of TB and two deaths so far.
In July last year, clinicians in two states rapidly diagnosed and reported two cases of TB in patients who had undergone spinal surgical procedures using bone allografts, wrote Jonathan Wortham, MD, from the CDC in Atlanta, and colleagues in the Morbidity and Mortality Weekly Report (MMWR).
Both clinicians alerted the CDC because the cases looked similar to an outbreak in 2021, involving the same manufacturer.
The manufacturer issued a voluntary recall on 14 July.
MedPage Today reports that the 2021 outbreak involved 113 patients in 18 states who had received contaminated bone allografts.
The bone allografts in this most recent outbreak were from a single deceased donor and were used in 36 recipients. Whole genome sequencing in infected recipients and positive cultures from unused product confirmed that the bone allograft material was the source of the bacteria.
By 20 December 2023, five recipients had tested positive for TB. An additional 10 had signs or symptoms consistent with TB and 79% had positive interferon-gamma release assay results.
Eight hospitals and five dental offices in seven states received the bone allograft product in question, but the product was rapidly removed from further distribution, the authors wrote, preventing as many as 53 additional procedures with the TB-contaminated material.
The CDC also instructed the affected healthcare facilities to quarantine any unused product and implement TB prevention and control measures with affected patients. Patients who received the material were started on multidrug treatment for TB.
The donors from both the 2021 and 2023 outbreaks had evidence of sepsis, which should have made them ineligible for tissue donation, Wortham and investigators said in their study. The donor from the 2023 outbreak also had pneumonia and radiographic changes consistent with a TB diagnosis. Neither donor was tested for TB.
“This second outbreak of bone allograft-related TB in recent years underscores the urgent need to implement improved donor screening and culture-based testing to prevent tissue-derived Mycobacterium tuberculosis transmission,” the authors wrote.
Frozen live-cell tissue allografts have expiration dates of months to years after manufacturing, allowing for ample time for both culture-based testing and additional scrutiny of donor medical records, they noted.
The manufacturer involved in both outbreaks had tested for M. tuberculosis using nucleic acid amplification before distribution, but this method did not detect the organism, possibly due to low levels of the bacteria.
Although nucleic acid amplification tests give more rapid results than culture-based testing, they are less sensitive. Culture-based testing, however, can also yield false-negative results and can take as long as two months. In this instance, liquid cultures did not grow M. tuberculosis until 40 days after inoculation, although cultures will usually deliver a positive result in 14 to 21 days, the authors said.
The authors pointed out that M. tuberculosis transmission from bone allografts is rare. Before the 2021 outbreak, the last reported transmission from bone allografts occurred in 1953 in the UK.
Study details
Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells — US, 2023
Jonathan Wortham, Maryam Haddad, Rebekah Stewart, Philip LoBue, et al.
Published in Morbidity & Mortality Weekly Report on 5 January 2024
Abstract
During July 7–11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis after spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognised. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed.
MedPage Today article – Another outbreak of TB linked to contaminated bone grafts (Open access)
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