Serologic screening of United States blood donors for Babesia microti using an investigational enzyme immunoassay

Abstract

BACKGROUND The tick-borne pathogen Babesia microti has become recognized as the leading infectious risk associated with blood transfusion in the United States, yet no Food and Drug Administration–licensed screening tests are currently available to mitigate this risk. The aim of this study was to evaluate the performance of an investigational enzyme immunoassay (EIA) for B. microti as a screening test applied to endemic and nonendemic blood donor populations. STUDY DESIGN AND METHODS The study aimed to test 20,000 blood donors from areas of the United States considered endemic for B. microti and 10,000 donors from a nonendemic area with the investigational B. microti EIA. Repeat-reactive samples were retested by polymerase chain reaction (PCR), blood smear, immunofluorescent assay (IFA), and immunoblot assay. In parallel, serum samples from symptomatic patients with confirmed babesiosis were tested by EIA, IFA, and immunoblot assays. RESULTS A total of 38 of 13,757 (0.28%) of the donors from New York, 7 of 4583 (0.15%) from Minnesota, and 11 of 8363 (0.13%) from New Mexico were found repeat reactive by EIA. Nine of the 56 EIA repeat-reactive donors (eight from New York and one from Minnesota) were positive by PCR. The specificity of the assay in a nonendemic population was 99.93%. Among IFA-positive clinical babesiosis patients, the sensitivity of the assay was 91.1%. CONCLUSION The B. microti EIA detected PCR-positive, potentially infectious blood donors in an endemic population and exhibited high specificity among uninfected and unexposed individuals. The EIA promises to provide an effective tool for blood donor screening for B. microti in a format amenable to high-throughput and cost-effective screening.

Transfusion-transmitted babesiosis: is it time to screen the blood supply?

“…Secondly, people who have cleared a B. microti infection typically exhibit a measurable antibody titer lasting for months and sometimes years [6,30]. In endemic populations, the majority of seropositive individuals have been found to be PCR negative and thus are most likely to represent prior rather than active infections [34,35]. These individuals pose little or no risk to blood safety but would be subject to deferral based on detection of B. microti antibody.…”

“…Repeat reactive rates of 1.08% and 0.40% were observed in endemic and non-endemic regions, respectively, which were reduced to 0.92% and 0.16% upon application of a revised cut-off. A second study was carried out in 2013 in which approximately 27,000 donor samples were screened by ELISA, with repeat reactive samples reflexed to PCR, immunofluorescence and immunoblot assays[35]. In this study, with application of an adjusted cut-off, the rate of seropositive donors in a region of NY that combined areas of greater and lesser endemicity was 0.28%, while the rate in a non-endemic region (NM) was 0.13%.…”

“…Both assays have been positioned for FDA licensure for blood screening and according to the manufacturers have been adapted for high volume throughput [23,35]. …”

“…The sensitivity of the ELISA assay for PCR or blood smear positive patients with symptoms of babesiosis was 78.3%[35]. The two methods were statistically equivalent in sensitivity.…”

Assessing the risk of Babesia to the United States blood supply using a risk‐based decision‐making approach: Report of AABB's Ad Hoc Babesia Policy Working Group (original report)

“…‡ Risk from outside an endemic state is one per 10 million, 6 thus negligible yield from 11 million screened units. § Specificity using current cutoff and screening in a nonendemic state = 99.69% (a) (six true positives, 26 false positives of 8363 screened, or 8331/8357 = 99.69%16 ), although 99.93% was recalculated (b).Bothfigures are used (reactive rates of 0.31% or 0.07%). Sensitivity for the test = 91%.…”