Babesiosis is a tick-borne, intraerythrocytic protozoan infection, caused by members of the Babesia genus. Transfusion-transmitted babesiosis (TTB) is well described: 162 cases of TTB have been reported in the US alone, the overwhelming majority caused by Babesia microti, which is widely endemic in the Northeastern and upper Midwestern US. An increase in naturally-acquired and TTB, has resulted in B. microti's designation as the foremost infectious risk to blood safety in the US for which an effective screening strategy is currently unavailable. Uncertainty surrounding the epidemiology, transmissibility and immunopathogenesis of B. microti remains an obstacle to development of a viable mitigation strategy. Recent evidence suggests that transfusion transmission may be caused disproportionately by a subset of chronically parasitemic blood donors. This has prompted our aims: 1) to determine the proportions of B. microti seropositive donors that develop chronic versus transient/resolved infections, and 2) to build a specimen repository composed of longitudinal samples obtained from B. microti sero- and or PCR-positive blood donors for future characterization in order to further our understanding of the mechanisms underlying chronic infection. We plan to leverage two independently funded, planned studies which will screen 20,000 blood donations in New York from July to September in 2012 (SBIR) and 2013 (IND), using a prototype highly sensitive and specific ELISA to detect antibodies against B. microti. Seroreactive samples will be subjected to supplementary testing using a novel, highly sensitive real- time PCR-based assay in addition to IFA and peripheral blood smear examination (PBS). Under the R21, we plan to enroll these seroreactive donors (n=100) and to conduct serial blood sampling and clinical symptom/risk factor questionnaire administration over 1 year of follow-up. At each follow-up visit, we will perform ELISA, PCR, IFA and PBS testing, in addition to repeated administration of the clinical questionnaire. We will also enroll donors that have previously been implicated in cases of TTB (n=10) and donors that have been deferred following their self-reporting a history of babesiosis. After testing, residual whole blood and plasma from each follow-up visit will be frozen and archived in a repository for future characterization. Correlation of the index and follow-up results (ELISA and PCR) will enable infectious-risk categorization into: chronic infection (ELISA+/PCR+), transient infection (index PCR+/follow-up PCR -) and remote exposure (index and follow-up PCR-). This categorization informs choice of screening methodology (serology vs. PCR) and policy of deferral and reinstatement. We intend to use the sample repository for a future submission to determine the genetic and immunologic determinants of chronic vs. transient infection.

Public Health Relevance

Babesia microti, a parasite that is found widely in parts of the United States, has the ability to cause severe disease and even death when transmitted to patients through infected blood transfusion. As a result it is considered a major threat to blood safety in the US. We wish to study what proportion of blood donors that have been exposed to B. microti, go on to develop chronic infection (rather than infection that resolves on its own) as we think that these chronically infected donors may account for the majority of cases of infections obtained from blood transfusion. This is important because knowing which donors are most infectious to patients can guide which screening test for blood is best, thereby preventing new infections from blood transfusion. Furthermore, this study helps us understand the behavior of the parasite and specifically how some infected donors are able to contain the infection by themselves, while others fail to clear the parasite.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL117140-02
Application #
8700503
Study Section
Special Emphasis Panel (ZRG1-VH-F (50))
Program Officer
Zou, Shimian
Project Start
2013-07-15
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
$201,775
Indirect Cost
$34,352
Name
Blood Systems Research Institute
Department
Type
DUNS #
006902498
City
San Francisco
State
CA
Country
United States
Zip Code
94118