An antibody test for Trypanosoma cruzi was FDA licensed in December 2006 following clinical trials showing yield of positive donors in the west and southwestern areas of the US (CDC; Morb Mortal Wkly Rep, 2007;51:210-211). Voluntary implementation of the licensed test occurred starting in January 2007. Through the end of 2008 (22-month experience) approximately 75-90% of blood centers have implemented the licensed test. In 2006, in the absence of FDA guidance, AABB Association Bulletin 06-08 was released to provide assistance for how to manage donors/components for those centers that chose to implement the test. To date only one test has been licensed and FDA has not issued guidance for use of the test.
The algorithm being used by most collection facilities includes the Ortho T. cruzi ELISA test system followed by a more specific RIPA (an unlicensed radioimmunoprecipitation assay, commercially available through Quest Diagnostics). During the 22-month period from the implementation of testing in January 2007 through the end of November 2008, for which US blood centers have reported data at today’s meeting, there have been 2989 EIA-repeat reactive donors of which 735, from 41 states, have confirmed positive (AABB website).
The performance of the screening assay has been excellent, with a repeat reactive rate of 0.015% and a positive predictive value of 20-30% which is comparable to other screening/confirmatory tests. However, even with the use of a licensed screening test with excellent specificity and a research RIPA as a supplemental test for donor counseling, there still is the need for an FDA licensed supplemental test that may be used for reentry of donors with false-positive screening reactivity.
During the screening experience with the Ortho ELISA, we have learned that:
US autochthonous (insect derived) cases of T. cruzi infection have occurred, primarily associated with rural outdoor activities in states where infected insect vectors and animal reservoirs are present.
No overt seroconversion in a donor has been documented after approximately 3 million person-years of observation in the ARC and BSI experiences. RIPA-positive donors have been identified with Ortho ELISA reactivity close to the assay cutoff, with ELISA results from these donors varying between reactive and nonreactive on sequential donations, but these do not represent incident cases of infection. In fact, there is no evidence of an incident infection (i.e., an unequivocal seroconversion, or results from serial testing of index donation and follow-up specimens consistent with recent seroconversion) in any US blood donor in this, or any other dataset, past or present.
Lookback data published in the literature and ongoing investigations triggered from the use of the licensed screening test suggest that infectivity of components from RIPA-confirmed US blood donors is probably not greater than 10%. It is difficult to calculate a more precise percentage because of the uncertainty of some recipient test results and because the majority of recipients were not available for testing. For example, in the Red Cross studies, only 22 percent of the total recipients were available for testing, and although 80% of living recipients were tested, deceased recipients could not be tested to confirm if transfusion transmission had occurred. Confirmed/probable transmissions have only been observed from either whole blood or platelets (including leukoreduced and/or irradiated whole-blood-derived platelets and apheresis platelets); no confirmed transmissions have resulted from packed red cells or from any frozen product. Low infectivity is likely due to limited survival of the parasite under contemporary blood banking conditions and the use of manipulated (leukoreduced) blood components that are transfused beyond the survival time of the organism. Perhaps more important is that not all units contain parasites. This low risk should be taken into account in FDA’s deliberation of testing strategies and mandates.
Based on the above, continued universal testing (i.e., testing every donor at every donation) is not medically appropriate and we know that blood collectors who did voluntarily initiate universal testing in 2007 are now looking at various other options. We should focus on selective testing strategies that adequately protect recipient safety and have been used successfully for multiple agents, including T. cruzi, outside of the US. A precedent for selective testing is particularly important as we consider other emerging infectious diseases for which it may be impractical or unnecessary to perform universal testing. Examples include babesiosis and dengue. The blood community must invest substantially in the IT systems required to support a selective strategy in a cGMP environment, and FDA endorsement of a selective testing option for T. cruzi, for which ample data support such a policy, will incentivize blood centers to invest in this IT capacity.
Of the selective testing measures reviewed, data from BSI suggest that donor interviewing to identify risk based on birth/residence/maternal birth/residence or donor travel to an endemic area cannot be recommended due to inadequate sensitivity and reproducibility of responses to endemic country exposure questions administered during the routine donation process.
We recommend that if the FDA requires testing of donors for antibodies to T. cruzi, that a selective, donor-based testing approach and the IT systems to support such testing be used. Our favored strategy for selective testing for this agent at this time is donor qualification using a single negative licensed screening test result. The excellent performance characteristics of the current licensed screening test, the lack of observed incident donor infections, and the rarity of transfusion transmission demonstrated by lookback, support the conclusion that this approach is acceptable with respect to recipient safety. One time donor screening to qualify donors as T. cruzi antibody negative is also practical from IT and operational perspectives. Two-time testing is a less desirable alternative, as is testing only donations from which platelets (apheresis or whole-blood-derived) will be manufactured.
We would like to re-emphasize to the Committee the importance of taking this opportunity to shift the testing paradigm so that we can achieve maximum safety while avoiding unnecessary testing and be able to focus on other issues related to donor and patient safety.
AABB is an international association dedicated to advancing transfusion and cellular therapies worldwide. Our members include more than 1,800 hospital and community blood centers and transfusion and transplantation services as well as approximately 8,000 individuals involved in activities related to transfusion, cellular therapies and transplantation medicine. For more than 50 years, AABB has established voluntary standards for, and accredited institutions involved in, these activities. AABB is focused on improving health through the advancement of science and the practice of transfusion medicine and related biological therapies, and developing and delivering programs and services to optimize patient and donor care and safety.
The Red Cross is committed to the safety of donors and patients, and to meet the best interests of the public we serve. The Red Cross, through its 35 Blood Services regions, supplies approximately 40% of the nation's blood for transfusion needs.