Protecting Patients
Infection Control Topics
About Tissue Transplants
Updated:September 1, 2006
Released:February 2006
- What is a bone or tissue allograft?
- Where do allograft bones and tissues come from?
- What laws and regulations govern the recovery, processing and distribution of tissues in the United States?
- How common is the use of bone and tissue allografts?
- What are allografts used for?
- Why would an allograft be used instead of a person’s own tissue or a synthetic material?
- Can allograft tissues transmit infections?
- What measures are in place to ensure that donors of allograft tissues do not have infections that could be transmitted to recipients?
- Who removes tissues from donors?
- Where are tissues sent once they are removed (recovered)?
- What is done with tissues from eligible donors once they are removed?
- What testing is done on the tissues themselves?
- What should I do if I am worried that I may have contracted an infection from a bone or tissue allograft?
- On October 26, 2005, Centers for Disease Control and Prevention and Food and Drug Administration recommended that recipients of tissues recovered by Biomedical Tissue Services (BTS) be tested for evidence of infection with HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis. On August 30, 2006, CDC and FDA made the same recommendation for testing of recipients of tissues recovered by Donor Referral Services. What tests should be performed and how often?
- How were these infectious diseases selected?
- If a patient had a negative result with a non-treponemal test for syphilis more than six months after the tissue was implanted, do they also need to have a treponemal test?
- What if one of the screening tests is positive?
- Should nucleic acid tests (direct virus tests) for HIV, HBV, and HCV be used as initial, screening tests for recipients of BTS tissues?
What is a bone or tissue allograft?
The bones or tissues that transplanted from the body of one person to another person are called allografts. Tissue allografts can include: bones, heart valves, blood vessels, skin and tendons.
Where do allograft bones and tissues come from?
Most allograft bones and tissues are obtained from deceased donors. Family members give consent to donate the tissues of their loved ones.
Human tissues intended for transplantation have been regulated by Food and Drug Administration (FDA) since 1993. In May of 2005, three new, comprehensive regulations went into effect that address manufacturing activities associated with human cells, tissues and cellular and tissue- based products (HCT/Ps). The first requires that companies that produce and distribute HCT/Ps register with the FDA. The second provides criteria that must be met for donors to be eligible to donate tissues and is referred to as the “Donor Eligibility” rule. The third rule governs the processing and distribution of the tissues and is often referred to as the “Current Good Tissue Practices” rule. Together they are designed to ensure that sound, high quality practices are followed to reduce the risk of tissue contamination and of communicable disease transmission to recipients. These rules are available at: www.fda.gov/cber/tissue/docs.htm.
How common is the use of bone and tissue allografts?
According to data from the American Association of Tissue Banks (AATB), a voluntary accreditation organization that sets standards for tissue banking, approximately 1.5 million bone and tissue allografts are distributed each year by AATB-accredited tissue banks in the United States.
Bone and tissue allografts are used for a variety of reasons. For example, they are used to replace damaged heart valves and skin. They are also frequently used in orthopedic surgery to replace tendons or bones damaged by trauma, tumors or other conditions. Bone and tissue allografts are used in a variety of procedures that can save lives, repair limbs, relieve pain or enhance a patient’s quality of life.
Why would an allograft be used instead of a person’s own tissue or a synthetic material?
Sometimes, there is not enough of the person’s own tissue to use in an operation. Synthetic materials have different properties from human tissue and may not be suitable for some patients or purposes.
Can allograft tissues transmit infections?
There have been rare instances where allograft tissues have transmitted infections to recipients. In most instances the infection was present in the donor at the time of death but was not detected. In some cases, tissues have been contaminated during removal, transport, processing, or storage. It is important to note that many of these instances have been investigated carefully and resulted in improvements to methods for screening and testing donors for infections, for processing to prevent contamination, and for removing or inactivating organisms that may be present in allografts. The Donor Eligibility rule requires up-to-date and appropriate donor screening and testing. The Current Good Tissue Practices rule requires methods be put in place to reduce risks during the production of the tissues.
Potential donors of allograft tissues are screened for possible infections in a variety of ways. First, detailed information regarding the potential donor’s medical history is reviewed for evidence of diseases that might be transmissible to a tissue recipient. In addition, someone who knew the donor completes a detailed questionnaire to review a number of potential risks for and any symptoms of infections that might have been present when the donor died. The Food and Drug Administration (FDA) has set forth a number of criteria that include risk factors, clinical evidence, and other findings that might be an indication of a transmissible disease in the donor. Presence of these factors or symptoms would make a donor ineligible to donate tissues. These factors are very similar to those examined for blood donors.
If there are no risk factors, symptoms, or other findings of infection in the donor, the next step is to test the donor for infectious diseases. Blood samples from all potential tissue donors are tested for HIV, Hepatitis B, Hepatitis C, and syphilis. If any of these tests are positive, the potential donor is ineligible to donate tissues.
Who removes tissues from donors?
Tissues are removed by personnel working for tissue recovery agencies. Under federal law, these agencies must be registered with the Food and Drug Administration and must adhere to applicable FDA regulations that govern tissue recovery. These regulations are found in the Current Good Tissue Practices rule.
Where are tissues sent once they are removed (recovered)?
Tissues are sent to tissue banks for processing and distribution. Tissue banks are establishments that are regulated by the Food and Drug Administration (FDA). By law, any company that wishes to receive, process, or distribute tissues must register with FDA and must adhere to all FDA regulations governing tissue banking. These establishments are subject to regular inspection by the FDA.
What is done with tissues from eligible donors once they are removed?
After they are removed, tissues are subjected to one or more disinfection processes that are designed to kill or remove any bacteria, fungi or viruses that might be present. Different companies use different methods to accomplish this goal, including rinsing with antimicrobial chemicals, sometimes under pressure, as well as irradiation. In some instances, multiple methods might be used. Various methods have different levels of effectiveness in killing or removing infectious organisms.
What testing is done on the tissues themselves?
Individual tissues from eligible donors are tested for the presence of bacteria, mold and fungi when they are removed from the donor. This testing is repeated after the tissues have been subjected to the procedures designed to remove organisms.
You should discuss your concerns with your healthcare provider. Cases of suspected transmission of infections by bone and tissue allografts should be reported to MedWatch, FDA's voluntary reporting program at http://www.fda.gov/Medwatch/report.htm; by telephone, 1-800-FDA-1088; by fax, 1-800-FDA-0178; or by mail, MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20852-9787. These cases should also be reported to the tissue bank who distributed the tissues.
There are no set guidelines on how this testing should be done for tissue recipients. CDC thus recommends that clinicians follow the post-exposure follow-up testing recommendations that are used for occupational exposures to HIV, HBV or HCV, as described in the “Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis” (available at: www.cdc.gov/ncidod/dhqp/gl_occupational.html). The recommendations below can be used for all recipients who have normal immune systems. For those who have very weakened immune systems because of immune system suppressing medications, other tests might be indicated.
Patients who had tissue implanted more than six months ago should be offered the following tests: HIV antibody, antibody to hepatitis B core antigen, antibody to hepatitis C virus, a non-treponemal syphilis test (e.g. RPR or VDRL), and a treponemal syphilis test (TP-PA or any ELISA test). If all of these tests are negative it is very unlikely that the recipient will contract any of these diseases from an implanted tissue that was potentially contaminated and no further follow-up testing is necessary.
Patients who had tissue implanted less than six months ago can be offered the same series of tests as above immediately, but should also be re-tested six months after the tissue was implanted. If earlier diagnosis of HBV and HCV infection is desired, testing for hepatitis B surface antigen (HBsAg) and HCV RNA may be performed. If negative, testing for anti-HBc and anti-HCV should be performed at leastsix months after the tissue was implanted. Again, if all of these tests are negative six months after the tissue was implanted, it is very unlikely that the recipient will contract any of these diseases from an implanted tissue that was potentially contaminated and no further follow up testing is necessary.
How were these infectious diseases selected?
HIV, hepatitis B and C and syphilis are the infectious diseases for which potential tissue donors must be tested.
No. A negative non-treponemal performed six months or more after the tissue was implanted would indicate that it is very unlikely that the recipient contracted syphilis from an implanted tissue.
What if one of the screening tests is positive?
It is important to remember that these initial tests are screening tests and hence positive results do not always mean that the patient has been infected. Patients who have a positive result for any of these tests should undergo confirmatory or supplemental testing. Clinicians who have questions about confirmatory or supplemental testing should contact a clinician with expertise in infectious diseases.
No. Most nucleic acid tests (e.g. PCR assays) that are used by clinical laboratories are not intended to screen patients for disease, but are FDA-approved to confirm the results of screening tests or to monitor virus activity in patients who are known to have the disease. These tests should not be used in place of the antibody tests recommended here.
Content source:
Division of Healthcare Quality Promotion (DHQP)
National Center for Preparedness, Detection, and Control of Infectious Diseases