AABB is an international, not-for-profit association representing individuals and institutions involved in the field of transfusion medicine and cellular therapies. The association is committed to improving health by developing and delivering standards, accreditation and educational programs that focus on optimizing patient and donor care and safety. AABB membership consists of nearly 2,000 institutions and 8,000 individuals, including physicians, nurses, scientists, researchers, administrators, medical technologists and other health care providers. Members are located in more than 80 countries.
AABB has taken steps to address the issue of transfusion-transmitted Babesia beginning in July, 1989 with a recommendation to indefinitely defer donors who give a history of babesiosis and to recall and destroy associated components. This recommendation was followed in 1991 by a standard in the 14th edition of the Standards for Blood Banks and Transfusion Services that remains in effect today. The current AABB Donor History Questionnaire contains the related question, but limited data available to date indicate this question is only marginally effective at preventing cases of transfusion-transmitted Babesia (TTB). In 2008 the AABB Board of Directors established the Babesia Work Group to provide leadership with the goal of analyzing risks to the US blood supply and developing scenarios to mitigate the risk. The work group reports through the Transfusion Transmitted Diseases Committee and is composed of representatives from blood collecting facilities in Babesia endemic areas of the US as well as members of public health and liaisons from the FDA and CDC.
The initial focus of the Babesia Work Group was to draft an Association Bulletin to address current blood safety issues posed by Babesia. In August, 2009 AABB released Association Bulletin #09-06 Transfusion-Transmitted Babesiosis to provide 1) information about the potential for TTB, 2) educational materials for clinicians about the epidemiology of Babesia, along with descriptions of the signs, symptoms, diagnosis, and treatment of babesiosis, 3) information on the processes that have been used by blood centers in endemic areas for investigating TTB cases, and 4) a summary of the development of interventions to reduce transfusion transmission of Babesia. The experience of blood centers operating in highly endemic areas was included to provide insight into management of patients, donors, and blood components in the event of known or suspected cases of TTB.
The current project of the Babesia Work Group is to develop a system to tabulate ongoing clinical cases of TTB by requesting and reviewing case reports that have been forwarded from transfusion services. Much time has been spent developing the data parameters; developing and funding the database and a mapping system are the next steps.
Today, the BPAC is asked whether the available data support development of a regionally selective donor testing strategy to reduce the risk of TTB. Additionally, the Committee is asked to comment on the suitability of donor screening either by a nucleic acid-based test (NAT), an antibody test, or both, given the current technology limitations. AABB would like to restate and update some of the information provided in the August 2009 association bulletin prepared by the task force.
The increased prevalence of TTB has provided impetus for the development, evaluation, approval, and implementation of interventions to reduce or eliminate TTB. Currently, there is no FDA-approved blood donor screening test available. Pathogen reduction methods are under investigation, but feasibility in red cell products remains to be demonstrated.
In the absence of FDA-approved blood donor screening tests, one American Red Cross center in a highly endemic area, using serologic testing (i.e., IFA) performed within a research protocol not currently under IND, has implemented interventions consisting of selective testing based on geographic areas and season of the year. This center has policies that require the deferral of donors with reactive or positive test results and when appropriate, withdrawal of other identified components by the same donor. Some blood establishments restrict collection during tick season from geographic areas known to be highly endemic for B. microti, but the efficacy of this approach has not been rigorously established.
Research studies should be continued and expanded, investigational tests should be developed, and associated protocols should be designed to prevent or reduce TTB. Ideally, testing strategies should focus on the detection of infectious donations. It is necessary to determine donor prevalence and incidence of Babesia infection in areas with reported cases of TTB, prior to the consideration of an intervention. In areas found to be highly endemic by research prevalence and incidence studies, testing under IND protocols should be considered prior to the availability of an FDA licensed test. Potential testing strategies that should be considered by manufacturers, FDA, and blood centers in such highly endemic areas include: 1) testing annually or seasonally, or 2) the screening of components designated for selected groups of patients who are at risk for severe clinical outcomes if infected with Babesia.
Of note, the Rhode Island Blood Center implemented this second approach under IND on July 8, 2010 using both IFA and NAT through IMUGEN, Inc. on a limited number of collections.
AABB continues to believe that a selective testing approach to Babesia is warranted. While it is difficult to determine which geographic areas have sufficient risk to warrant testing, we are not convinced that the inclusion of 20 states representing 60% of the blood supply is the appropriate catchment area in which to begin testing. In part the FDA proposes testing in several non-endemic states (e.g., FL, TX) based solely on isolated cases of TTB. Such cases are usually found to be associated with imported blood or recent donor travel to a highly endemic area. AABB feels strongly that regionalized testing should be defined by Babesia highly endemic areas identified through sound scientific studies of seroprevalence or locally acquired incident infections.
AABB also believes that there are insufficient data to establish whether NAT screening would be a superior approach to antibody testing and that this issue requires careful evaluation before a conclusion is reached. Longitudinal studies presented today by the American Red Cross suggest that chronic carriers need to be considered as important contributors to TTB, in addition to acutely infected donors. In most instances, these chronic carriers cannot be detected by NAT, but can be identified through serologic testing, which is almost exclusively performed using IFA. While generally considered highly sensitive, NAT is limited by its ability to detect low levels of infection, sample volume issues, and in the case of blood screening, difficulties in adapting NAT to whole blood. Consensus opinion is that NAT would not be effective in screening for Plasmodium, the causative agent of malaria, and this should be taken into account when projecting whether NAT would be effective for Babesia screening. Antibody testing by IFA has been established as the gold standard for Babesia, and has been used in virtually all seroprevalence and transfusion case investigations published to date. Accumulated data suggest that donor screening using IFA would capture most infectious donors, with the exception of acute, window-period infections that could be detected through seasonally administered NAT during the tick season. For example, in one endemic area, recent evidence shows that approximately 1% of donors were IFA positive with less than half of these donors being identified as positive by NAT. Certainly antibody screening may unnecessarily defer non-infectious, antibody-positive donors, but as discussed today, many of these donors resolve infection and could be re-entered upon development of an appropriate protocol.
The issue of TTB is a critical blood safety issue and AABB applauds the FDA’s willingness to address the issue in today’s Committee meeting. It must be recognized that the IFA methods used in previous research studies are not suitable for large scale donor screening. We think it is crucial for companies to develop assays that can be used to screen the blood supply in highly endemic areas; these assays must use methodologies that are compatible with the high throughput and cGMP required of a donor screening test. Further, AABB urges that testing begin in the most highly endemic areas rather than in more widespread locations and that the debate about the merits of antibody versus NAT should continue following the collection of additional data.