Frequently Asked Questions (FAQs) regarding AATB Bulletin 23-6 about MTB

On August 7, 2023, AATB released Bulletin 23-6, which contains mandatory requirements and recommendations for accredited establishments designed to reduce the risk of tuberculosis (TB) transmission through tissues. This FAQ is intended to provide additional clarification of those requirements and will be updated as needed to provide the most current information to accredited institutions. Please submit additional questions to standards@aatb.org. All questions received will be considered for inclusion in future updates of this FAQ.

Frequently asked questions (FAQ) regarding AATB Bulletin 23-6 about MTB last updated August 18, 2023.

 

Physicians Council MTB Working Group: Interim Mycobacterium tuberculosis (MTB) Donor Screening Requirements (webinar recording) - August 21, 2023

 

A. Tissues Containing Viable Cells

A1: Why did AATB make the decision that donors of tissues that will be processed into grafts containing viable cells over 65 years of age were ineligible? What information was this decision based on? 

The decision regarding age of the donors being ineligible to donate tissues that will be used for tissue grafts containing viable cells is related both to the risk of MTB exposure (the incidence of MTB was much higher in the United States in the past) and the risk of latent TB infection reactivation in people aged 65 and older (due to factors including immune senescence, atypical presentation including extrapulmonary disease, and more frequent co-morbidities, which can increase the chances of TB reactivation).  

References 17-21 listed in Bulletin 23-6 are among the references reviewed by the Physicians Council MTB working group to inform that decision.  

 

A2: Will AATB define “exposure” as used in “Exposure to an individual with tuberculosis disease in the last 2 years”? In previous bulletins, “exposure” (COVID and Monkeypox) has been defined.

Exposure is not defined for TB because the CDC doesn’t define “exposure.”  Any time spent with someone with TB disease could result in TB transmission—there is no reliable way to narrow that down to a more specific exposure type, e.g., household contacts, a quantified period of time spent, etc. 

 

A3: Can AATB provide clarification or additional detail regarding what constitutes “tissues containing viable cells”? Is decellularization required for the tissue not to be considered “tissues containing viable cells”?

In AATB Bulletin 23-6, for purposes of the bulletin, it was stated that “tissues containing viable cells” are “…all products comprising or containing tissues that are processed in a manner to retain live cells—including reproductive cells.” It is up to the manufacturer to determine and document whether they process their tissues in a manner to retain live cells. Many manufacturers of tissues containing viable cells make statements about cell viability, including in the Instructions for Use (IFU), research papers, white papers, or advertisements to end users that make it clear that the tissue comprises or contains living cells.  

Tissues that are considered “cryopreserved” and where the degree of preservation of living cells may be less clear, require the manufacturer to conduct and document a risk assessment. Issues to consider in making such a risk assessment include but are not limited to, the following:

• Reasons for the “cryopreservation” – such as maintaining structural characteristics of the tissue vs. maintaining cell viability.
• Information related to the presence of viable cells provided in IFU, published research, advertising matter, or oral or written statements.
• Processing methods.
• Method of freezing used, e.g., use of cryoprotectants and freezing rate as compared with data on how Mycobacterium tuberculosis (MTB) is (intentionally) cryopreserved—references noted at end of FAQ.
• Do you have data indicating the presence of living cells for your tissues? Did you document why that assessment was or was not performed and did you use that data to inform your end users as a claim or attribute of the tissue? 
• Whether there is any possibility of living bone marrow cells or white blood cells being retained in any part of the tissue.

The available information should be considered in total. The tissue establishment must determine whether tissues have sufficient numbers of viable cells to transmit MTB based on their assessment and understanding of any risk that may be present. It is not required that tissues be decellularized to conclude they do not contain viable cells. The tissue establishment can make that determination based on their own assessment of the tissues. 

The following are examples of tissue types that may or may not be subject to the new donor screening criteria and recommendations. Please note that the examples below are not all-inclusive.   

Examples of tissue types that are subject to MTB screening criteria and recommendations: 

• Cellular bone matrix tissue, osteochondral allografts, and birth tissue processed or advertised to preserve viable cells. 

Examples of tissues that should be evaluated against the MTB screening criteria and recommendations: 

• Bone, tendon, ligaments, cartilage, skin, nerve, cardiovascular tissues, saphenous veins, birth tissues and, dermal tissue that undergo processes to remove or destroy living cells through exposure to detergents, chemical disinfectant or terminal sterilization, lyophilization, cryopreservation, or low temperature freezing. 

It is the responsibility of each tissue establishment to document an evaluation of their tissues and a rationale for why the tissues are not subject to the MTB criteria and recommendations in the bulletin. 

 

A4: What does AATB mean by “chronic renal failure on dialysis”?  

Anyone who is on dialysis for chronic renal failure and is anticipated to continue to need dialysis or an organ transplant. This is in comparison to someone who receives dialysis support for an acute condition that is anticipated to resolve. 

 

B. Current Inventory

B1: Does AATB have a recommendation or requirement regarding how affected accredited tissue banks should or must handle those tissues containing viable cells that are in distributable inventory, in process, or waiting to be processed? 

AATB Bulletin 23-6 states that the requirements go into effect no later than September 4, 2023. At a minimum, the criteria apply to any tissue collected on or after September 4, 2023. The AATB Bulletin 23-6 does not require tissue establishments to retroactively apply those criteria to all tissue in inventory, and therefore it is up to each tissue establishment to determine their risk tolerance in assessing tissue in inventory, in process, or waiting to be processed. 

 

C. Donor History of Tuberculosis

C1: Is the recommendation that any positive test for tuberculosis, even if a pursuant blood test or chest x-ray are negative, will render the donation ineligible? For example, if a PPD skin test is positive, but follow-up testing is negative, as might be caused by historical administration of Bacille Calmette-Guérin (BCG) vaccine?

Yes, if someone has a tuberculosis infection (a positive TB test result), they are ineligible to donate tissues containing viable cells. If the positive TB test result was within the past two years, they are ineligible to donate any tissues. Information about individuals who had BCG vaccine previously can be found at https://www.cdc.gov/tb/topic/testing/testingbcgvaccinated.htm. 

 

D. Testing

D1: Can AATB provide a list of FDA-licensed tests for MTB? What type of test was used on tissues associated with the latest transmission episode? 

There are no FDA licensed/cleared/approved tests for tuberculosis for deceased tissue donors. The 2 approved tests for clinical/diagnostic purposes are QuantiFERON-TB Gold Plus and T-SPOT TB test. These interferon gamma release assays (IGRA) rely on the ability of white blood cells to release interferon gamma in response to TB antigen, and therefore require living cells. As a result, testing must be completed in a very short timeframe that is not possible with deceased tissue donors. Furthermore, poor immune function will negatively impact the ability to obtain positive test results. More information about IGRA testing can be found at https://www.cdc.gov/tb/publications/factsheets/testing/igra.htm.

For the 2023 tuberculosis transmission event, the viable bone matrix tissue was tested for MTB using polymerase chain reaction (PCR) methodology. 

 

E. Additional Risk Factors

E1: How does AATB define “homelessness” as a risk factor for TB? 

People are considered to be experiencing homelessness if they stay in a shelter, live in transitional housing, or sleep in a place not meant for human habitation, such as a car or outdoors. See https://www.cdc.gov/orr/science/homelessness/about.html and 
https://www.cdc.gov/tb/publications/factsheets/statistics/tbtrends.htm.

 

E2: Why are there some risk factors included in the list of risk factors for MTB exposure or reactivation (i.e., occupational exposures and residence in a long-term care facility), but no recommended donor screening questions were provided to gather that information?

At this time, the AATB Physicians Council MTB Working Group has not made a determination regarding the degree of risk that may be present for occupational exposure in the same types of facilities where residents would be at increased risk of MTB exposure and/or residence in a long-term care facility. The list of additional risk factors was provided so that the membership is aware of what is still under consideration, and to provide a comprehensive list of risk factors for medical director review. 

We know that during the interview with the donor family, information may be offered that is not specifically asked by the coordinator, and it is possible for such information to include these additional TB risk factors. This can be any type of additional information that, in context, might lead the donor screener to request additional information, as some of that information may help inform medical directors when making the donor-eligibility determination. As with all donor evaluations using the DRAI, the interviewer needs to utilize their knowledge and experience to evaluate the responses to the questions and determine if more information should be obtained from the interviewee. The MTB Working Group will continue to state the recommendations for establishments to consider when evaluating donors for risk of MTB.

Once a final decision is made regarding how to manage the occupational risk factors and residence in a long-term care facility, donor screening questions may be added as appropriate. 

 

F. UDRAI

F1: Why are the new donor screening questions related to MTB provided as an addendum rather than making changes to the UDRAI? Some questions in the MTB Addendum are similar to those currently in the UDRAI. 

While it is true that some of the information being requested in the MTB Addendum (e.g., incarceration history, history of positive test results for TB, history of TB disease) may be part of the current UDRAI, the timeframes are different. There was no way to go through the process to permanently change the UDRAI in the timeframe necessary to be responsive to the need for definitive requirements around MTB screening, and the MTB Working Group wishes to minimize the number of times that the UDRAI itself is amended. The decision was therefore made to add the questions in the form of an addendum until decisions are made regarding how to handle all the MTB risk factors and any permanent changes to the UDRAI can go through the usual process. 

 

References:  

1. Shu Z, Weigel KM, Soelberg SD, Lakey A, Cangelosi GA, Lee KH, Chung JH, Gao D. Cryopreservation of Mycobacterium tuberculosis complex cells. J Clin Microbiol. 2012 Nov;50(11):3575-80. doi: 10.1128/JCM.00896-12. Epub 2012 Aug 29. PMID: 22933596; PMCID: PMC3486236.
2. Huang T-S, Chen Y-S, Lee S S-J, Tu H-Z, and Liu Y-C. Preservation of Clinical Isolates of Mycobacterium tuberculosis Complex Directly from MGIT Culture Tubes. Ann Clin Lab Sci. Autumn 2005; 35(4): 455-458.
3. Giampaglia CMS and colleagues. Maintenance of Mycobacterium tuberculosis on Glass Beads. Ann Clin Lab Sci. Winer 2009; 39(1): 51-54. 
4. Shu Z and colleagues. C-2017: Cryopreservation of Mycobacterium tuberculosis (MTB) complex cells and sputum specimens for MTB diagnosis. Cryobiology. 2014; 69(3): 520.
5. Kremer K, van der Laan T, van Soolingen D. Storage of mycobacterial strains. National Institute of Public Health and the Environment, Bilthove, The Netherlands. 
6. Ikuta CY and colleagues. Cryopreservation of Mycobacterium bovis isolates. 
7. Gheorghiu M, Lagranderie M, Balazuc AM. Stabilisation of BCG vaccines. Dev Biol Stand. 1996;87:251-61. PMID: 8854025.

 

Version History

August 11, 2023 – initial release
August 18, 2023 – Modified question numbering. Revised A1 (formerly Q1); added A4, E1, E2, and F1