Human babesiosis is a malaria-like illness caused by infection of red blood cells by the protozoan parasite Babesia microti or related species, primarily transmitted to humans through the bite of infected deer ticks. Babesiosis can also be transmitted by blood transfusion, and is currently acknowledged as the foremost unaddressed infectious risk to the US blood supply. Blood donations from B. microti-endemic areas in the USA can exhibit up to 1% seropositivity, and the distribution of seropositivity is expanding rapidly into adjacent states. Babesiosis has a wide spectrum of clinical presentation with serious to fatal outcome in immunocompromised individuals which includes many transfusion recipients. Undetected Babesia infection in blood donors has been recognized as a serious threat to transfusion safety, with transfusion responsible for over 150 cases since 1979 and a dozen fatalities since 2005. Babesiosis is a rare disease by numbers, but with potentially serious to fatal impact on those who acquire it, which significantly contributes to the health burden of this disease. In the absence of other interventions, the only viable strategy to prevent the transfusion of B. microti-contaminated blood units is to screen blood donors for the presence of the parasite. However, no test for Babesia is currently licensed for blood screening and commercially available. Hence there is an urgent and unmet need for blood donor screening to interdict B. microti - contaminated blood donations. This Phase IIb grant will support the development of a Babesia assay based on antigen detection, which will supplement the antibody detection ELISA previously developed under the Applicants' prior Phase II grant. Babesia parasites secrete antigens into the extracellular medium which may be detected in serum or plasma, thus providing a sensitive marker for detection of active infection. In collaboration with consortium partner Tufts University, applicants have identified immunodominant protein antigens which meet these criteria and have generated specific antibodies suitable for antigen capture immunoassay. The antigen capture assay will enable detection of potentially infectious blood donors in the window stage, when antibodies are not yet measurable. Furthermore, it will clear individuals with persistent antibody response due to a previous, resolved Babesia infection to donate blood, eliminating unnecessary and undesirable donor deferrals. The assay will be evaluated on gold standard babesiosis patient samples through collaboration with Yale University, and on 30,000 blood donors through a donor study carried out under IND with consortium partners Blood Systems Research Institute, Creative Testing Solutions and New York Blood Center. The donor study will support a licensure application to FDA for the Babesia test for blood screening. The overall goal is to provide an assay for Babesia microti suitable for high throughput donor screening which will offer the first cost-effective intervention to reduce or eliminate the risk of transfusion-transmitted babesiosis.
This project will result in the development, clinical trial and FDA submission of the first high throughput screening test for Babesia infection in blood donors, which is currently one of the greatest infectious risks of transfusion. No test for Babesia is currently licensed by the FDA and commercially available. The test to be developed in this project is based on detection of specific Babesia antigens in human plasma samples and will detect donors with asymptomatic window phase Babesia infections, mitigating this risk but avoiding false positive results in convalescent individuals which would lead to unnecessary donor deferrals.
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