The Buzz on Mycobacterium Tuberculosis (Mtb)

Welcome back! If you’ve been following the Food and Drug Administration (FDA), one of the guidance documents released for a delayed implementation on May 4, 2025, (and remains subject to comment), was the “Recommendations to Reduce the Risk of Transmission of

Mycobacterium tuberculosis (Mtb) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)”. Mtb is identified as an RCDAD (relevant communicable disease agent or disease) that may cause Tuberculosis (TB), a global health problem that is one of the top 10 causes of death. Based on the safety concern from recipients who developed Mtb infections from bone products, this has prompted the FDA to release this guidance for screening donors for evidence of, and risk factors for, infection of this organism and additional steps to take to reduce the risk of transmission.

Latent tuberculosis infection (LTBI) is when Mtb bacteria lies dormant in a person’s body and shows no clinical evidence of the disease (asymptomatic). The person does not display any symptoms and may not feel sick but is infected with Mtb, (but they may not have TB disease).Per the FDA, most of the TB cases in the U.S. are due to the reactivation of LTBI in persons who were born in or lived in countries where TB is endemic, and the disease burden is moderate to high. Mtb transmission occurs through inhalation of aerosol droplet nuclei containing the bacteria, so infectious people can transmit this through coughing, sneezing, speaking, and singing. Other ways those can contract TB infections, for example healthcare workers, are through aerosol generating procedures or handling contaminated HCT/Ps, medical wastes, or surgical instruments.

FDA continues listing areas where Mtb transmission has been reported (e.g., bone, heart valves, hematopoietic progenitor/stem cells, dura mater, etc.) and those areas that have not been reported but remain a potential risk (e.g., skin and dermal allograft recipients, ocular tissue, etc.). Currently, there have not been any reported cases of Mtb transmission through blood or blood component transfusions nor gestational cells and tissues (e.g., amniotic membrane, umbilical cord tissue, umbilical cord blood), or cells and tissue for reproductive use. However, there have been reports of Mtb transmission between sexual partners detected in ovaries and semen. Mtb has been reported in placenta in cases of chorioamnionitis and congenital TB.

Currently, there are no FDA-licensed, cleared, or approved screening tests for use in testing HCT/P donors for evidence of Mtb infection, and so screening and reviewing a donor’s medical history, records, and test results are crucial for evaluating evidence of infection. Furthermore, there are FDA-approved diagnostic products that can detect an immune response to TB antigens, purified protein derivative (PPD) of tuberculin antigens that are injected intradermally for the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) blood tests (T-SPOT.TB test and QuantiFERON-TB Gold Plus test). These tests should be used in adjunct with a clinical risk assessment and other medical and diagnostic evaluations, with considerations for donors where viable intact immune cells can produce an accurate result (so this would not work for cadaveric/non-heart beating donors).

Recommendations by FDA include reviewing relevant medical records and screening the donor’s medial history and relevant social behavior including risk factors for RCDADs, including birth mothers where infant donors are less than one (1) month of age.

Ineligible Donors would be:

• Those who have a positive test for TB infection or ever have had a medical diagnosis of TB disease, TB infection, or LTBI.

• Those who have ever had a positive test for TB infection or TB disease (e.g., positive blood test IGRA, positive T-SPOT.TB, QuantiFERON- TB Gold Plus, QuantiFERON-TB Gold In-Tube, positive TST – also known as PPD, Mantoux, or tine test, positive TB infection on any specimen such as mycobacterial culture, NAAT or PCR for Mtb DNA).

• Physical evidence of generalized lymphadenopathy with TB infection.

• Physical evidence of unexplained cutaneous lesions that may be consistent with tuberculosis.

Donors who fall into the categories below, might still be eligible if there’s no clinical or physical evidence or suspicion of LTBI or TB disease, and no communicable disease risks have been identified with review of the relevant medical records including the medical history interview:

• Persons who were born in, have ever lived in, or ever traveled to areas of the world where TB is common (e.g., most countries in Latin America, the Caribbean, Africa, Asia, Eastern Europe, and Russia);

• Persons who have ever lived in, or worked in, high-risk congregate settings (e.g., jails, prisons, correctional facilities, long-term care facilities, homeless shelters);

• Persons who ever lived with, or have been in close contact with, another person who has TB; or

• Persons who have certain medical conditions (e.g., diabetes, chronic kidney disease/end stage renal disease with or without dialysis), or are on medication, that can impair immune function

Signs or symptoms that can mimic or overlap with other medical conditions where a person with TB disease may have and should be documented and followed up with their primary treating doctor for more information (unless TB has already been ruled out by their doctor):

• Cough lasting three (3) weeks or longer

• Chest pain

• Coughing up blood (hemoptysis) or sputum (pulmonary TB)

• Weakness or fatigue

• Unexplained weight loss or muscle wasting (cachexia or consumption)

• Loss of appetite

• Fever, chills, night sweats

• Generalized or localized lymphadenopathy or lymphadenitis

• Blood in the urine (renal TB)

• Headache or confusion (TB meningitis)

• Back pain (TB of the spine)

• Hoarseness (TB of the larynx)

• Radiographic imaging (x-ray or CT scan) that suggests TB disease

Establishments may use FDA-cleared diagnostic tests if they choose to test living donors (or donors where the heart is still beating) but must consider clinical and physical evidence and risk factors for Mtb infection when determining donor eligibility, even if the tests have negative ornonreactive test results. Once donor screening tests are available, FDA expects establishments to use the appropriate licensed, approved, or cleared Mtb donor screening tests. Specific guidance was provided for those establishments processing bone, heart valves, and dura mater.