[Posted 09/12/2023]

AUDIENCE: Patient, Health Professional, Infectious Disease, Surgery, Transplantation

ISSUE: FDA is working closely with the Centers for Disease Control and Prevention (CDC) to investigate recent reports of a tuberculosis (TB) outbreak caused by Mycobacterium tuberculosis (Mtb) that appears to be linked to a bone matrix product. We are issuing this communication to increase your awareness regarding the risk of transmission of Mtb through use of HCT/Ps in the United States.

BACKGROUND: Decades ago, Mtb transmission from transplantation of human bone, heart valves, and a dura mater allograft were reported in other countries.  In 2021, a multi-state outbreak of Mtb in the United States was linked to transplantation of a bone allograft product and resulted in significant morbidity and mortality. A new, similar outbreak is currently under investigation. Latent tuberculosis infection (LTBI) is estimated to affect one quarter of the world’s population and approximately 4% of the U.S. population. Because Mtb transmission can occur from HCT/P donors with unrecognized and undiagnosed TB infection, these circumstances demand heightened awareness when screening donors of HCT/Ps.  

RECOMMENDATIONS: Routine screening measures are in place for evaluating clinical evidence of infection in HCT/P donors. FDA has provided recommendations in guidance to reduce the risk of transmission of infections, including due to sepsis (which may be caused by Mtb); however, the following risk mitigation strategies concerning Mtb are important for public health safety.

Risk Mitigation Strategies

Responsible person

• The HCT/P establishment’s responsible person (21 CFR 1271.3(t)) must determine and document the eligibility of a cell or tissue donor (21 CFR 1271.50).  The responsible person(s) who is(are) authorized to perform designated functions related to the donor eligibility determination, should have appropriate medical training and be qualified to review clinical evidence consistent with risks for sepsis and TB infection.
• A responsible person must verify and document that, on the basis of record review, release criteria have been met and they have determined that an HCT/P is available for distribution (21 CFR 1271.265(c)(1)).
• Maintaining knowledge and awareness of these outbreaks and seeking additional training and/or re-training will help enable responsible persons to identify risk factors, conditions, clinical evidence, and physical evidence that can be associated with an increased risk for TB (including active TB and LTBI) and/or an increased risk of sepsis.

Donor screening

• TB may be underdiagnosed due to the lack of clinical suspicion, inherent diagnostic difficulty, and/or attribution of a group of symptoms to alternate causes. Although a donor with LTBI may be asymptomatic, a person with TB disease may have a number of symptoms or signs that can mimic or overlap with other medical conditions.
• Clinical evidence of TB may include one or more of the following: a prolonged cough lasting 3 weeks or longer, coughing up blood (hemoptysis) or sputum, weakness or fatigue, unexplained weight loss, fever, night sweats, back pain, meningoencephalitis, headache or confusion, local or generalized lymphadenopathy or lymphadenitis, and/or radiographic findings suggestive of TB disease.

Based on our emerging awareness of Mtb transmission risks, establishments may wish to consider whether an HCT/P donor has:

• ever had a diagnosis of TB, treatment for suspected TB, or a positive test for TB (i.e., a skin test, blood test, or sputum test).
• an increased risk for TB infection due to any of the following:
  • was born in, has lived in, or ever traveled to areas of the world where TB is endemic (refer to https://worldhealthorg.shinyapps.io/tb_profiles).
  • ever lived with another person who has TB or is currently or has been a close contact of a person with TB.
  • ever worked or resided in congregate settings (e.g., correctional facility, long-term care facility, homeless shelter).
  • has certain medical conditions, or is on medication, that can impair immune function.

Refer to CDC’s website for more information: https://www.cdc.gov/tb/default.htm

Donor testing

• Although there are currently no FDA-licensed, cleared, or approved donor screening tests available with an indication to screen HCT/P donors for evidence of active TB or LTBI, FDA is evaluating the risks and appropriate mitigation strategies including testing.

The FDA is committed to protecting public health, and patient safety is a top priority. The agency is committed to continuing to work with the CDC to assess the most recent outbreak and to look for ways to prevent transmission of Mtb from HCT/Ps going forward. We will communicate as additional information becomes available.

Health professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report online.
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on form, or submit by fax to 1-800-FDA-0178.

[09/06/2023 - FDA Safety Communication - FDA]