Thursday, November 25, 2010

Allografts and the risks of infection and disease transmission

Here is some valuable information on the risks associated with implantation of allografts [i.e. cadaver grafts in nose surgery]

 AAOS 2004: All About Allografts -- Select Highlights of the 71st Annual Meeting of the American Academy of Orthopaedic Surgeons

 Controlling Infection is Crucial

In limiting infection during allograft procedures, it is important to determine whether the tissue bank that you or your hospital is using is a member of the American Association of Tissue Banks (AATB). This organization requires that its members perform full screening that meets US Food and Drug Administration requirements; however, secondary sterilization of the grafts is still optional. Not all tissue banks are members of AATB, and not all tissue banks are inspected. The review by Vangsness and colleagues[2] describes the process of procurement, processing, and storage, and should be required reading for anyone who is using allograft tissue. Be sure that you know your tissue bank and its procedures.
Infection of tissue can be controlled by screening the tissue donor and through secondary sterilization of the tissue. At this time, we can screen for both hepatitis B and C, which should prevent infection by these entities. There have only been 2 cases of HIV infection through allograft tissue, and both of these incidents occurred in the 1980s. These reported infections occurred with frozen bone as the vector, but none of the freeze dried grafts from the same donor transmitted the disease. The AATB has formulated guidelines for their members; these guidelines recommend donor screening.

There are a number of methods and federal guidelines for storing tissue after procurement. The methods of storing the tissue are: fresh frozen, deep frozen, freeze dried, demineralized, and proprietary treatments, such as CryoLife (CryoLife Inc., Kennesaw, Georgia

Factoring Relative Risk
The risk of hepatitis B after blood transfusion is 1/63,000. The risk of hepatitis C is 1/100,000, and the risk of HIV is 1/1,000,000. The risk of HIV after bone transplantation is 1/1,500,000. The risk of HIV after soft tissue transplantation is 1/1,600,000 with secondary sterilization.
To put this in the proper perspective, one should remember that the risk of death due to pregnancy is 1/10,000, the risk of death from administration of penicillin is 1/30,000, and the risk of death with oral contraceptives is 1/50,000. In fact, it may be more dangerous driving to the hospital than receiving a bone graft at the hospital.
In summary, allografts are a valuable treatment option for today's orthopaedic practice. The academy believes allografts to be safe if used within the guidelines, when they are supplied by an accredited tissue bank, and if the appropriate surgical techniques are employed.

How safe are soft-tissue allografts?

By C. Thomas Vangsness Jr., MD

 Although several cases of viral infection—specifically human immunodeficiency virus (HIV), viral hepatitis, and human T-lymphotropic virus (HTLV)—have been reported, these transmissions occurred before the guidelines for donor screening for viruses and bacteria were implemented and before the availability of currently validated serologic tests.

Sterility is expressed as a mathematic probability of relative risk. According to the FDA, a sterility assurance level (SAL) of 10-3 means there is a 1 in 1,000 chance that a nonviral viable microbe exists in or on the implanted material. The Association for the Advancement of Medical Instrumentation (AAMI) states that an SAL of 10-6 (one in a million chance) in organisms is more desirable. The American Association of Tissue Banks (AATB) requires an SAL of 10-6 for tissue bank allografts.

Contamination of the graft can also occur during the final handling and packaging of tissue. Gamma irradiation is commonly used to terminally sterilize allograft tissue with lower doses of radiation.

Freeze drying (lyophilization) is a preservation process that allows tissues to be stored at room temperature. Lyophilization freezes the tissue and reduces the water content to less than 6 percent of initial weight through a primary drying process (sublimation) and a secondary drying process (desorption). Although freeze-dried allografts (lyophilized grafts) are not commonly used for sports medicine applications in the United States, this process is commonly used with soft-tissue patches.

With improved donor screening techniques, such as nucleic acid testing (NAT), the current risk of transplanting tissue from an HIV-infected donor is reported to be between 1 in 1 million and 4 in 1 million.

According to a recent AATB survey covering data from 2003 to 2004, the current risk of an allograft infection to the average patient appears to be much less than the risk of infections surrounding the surgery itself. According to the report, there were 192 reports of suspected allograft-related infections in 2003-2004; 42 percent involved soft-tissue grafts and 37 percent involved bone grafts, with an overall incidence of 0.014 percent. Currently, better reporting of infections is actively under investigation to improve the accuracy of these numbers.

Do not do routine culturing of allograft tissue in the operating room immediately prior to implantation. These cultures are documented to be inaccurate and may reflect the native airborne or backtable contamination.

Musculoskeletal tissue regeneration: biological materials and methods  By William S. Pietrzak, Charles A. Vacanti

Although the risk is low, bacteria, hepatitis, HIV, and syphilis can be transmitted from donor to recipient. There is also the theoretical possibility of transmitting slow viruses (prions) with allograft use.
Irradiation of the soft tissue allografts with high dose (>3Mrad) radiation can sterilize allograft tissue, destroying bacteria and viruses including HIV and hepatitis. Bone plug allografts may still be capable of transmitting hepatitis despite treatment with 3 Mrad irradiation. Although, allograft irradiation will reduce the risk of disease transmission, it does so at the expense of diminishing the biomechanical properties of the tissue. Newer screening tests such as polymerase chain reaction (PCR) and nucleic acid testing (NAT) improve the detection of viral and bacterial DNA and RNA, and many increase the accuracy of identifying infected donor tissue and minimizing false-negatives. By improving the sensitivity and specificity of infected donor  tissue identification, the risk of bacterial and viral disease transmission should be less, thereby increasing the safety of allograft use. These newer techniques could potentially decrease the need for graft irradiation and other sterilization techniques that many affect allograft properties.

Surgeons can minimize complications associated with infected allograft tissue by only using tissue processed from a tissue bank accredited by the American Association of Tissue Banks (AATB). It is imperative that surgeons know the source of their allograft tissue, particularly if they rely on the hospital or a surgery center to obtain the allograft tissue for their patients.

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