Babesia is a red blood cell parasite and the agent of babesiosis. Ticks naturally transmit it to humans; however, the parasite can also be transmitted through blood transfusion. Healthy individuals can be infected without knowing it or may experience mild, flu-like symptoms; however, the disease can be severe and cause death in 5% of infected individuals with underlying conditions. The mortality rate for immunocompromised patients is 21%. In the past 50 years, hundreds of transfusion-transmitted Babesia (TTB) cases have occurred; from 2010 to 2020, the Red Cross investigated an average of 18 TTB cases per year and identified positive donors in about 60% of the cases.
Testing for Babesia is now part of routine blood screening in endemic areas of the United States. While this is a success story, the history of the implementation of Babesia screening is a long and complicated story.
Several cases of transfusion-transmitted babesiosis (TTB) in highly endemic areas were reported in the literature between 1980 and 1986. The first published data concerning the antibody prevalence indicative of parasitic exposure in blood donors showed positive rates that were alarmingly high (3.7 to 4.7%) 1,2 As this was still considered a relatively rare event, the only recommendation provided at this time to physicians was to include babesiosis in the differential diagnosis for a blood recipient experiencing a febrile response.
Babesia microti, the species responsible for most of the human infections in the US, has emerged as a public health issue, as did the recognition of TTB. A report published in 2011 described 159 US cases of TTB occurring between 1979 and 2009, 122 of which were reported between 2000 and 2009.3 At the same time, several publications reported on B. microti seroprevalence in blood donors residing in endemic areas of the Northeastern United States, with rates between 0.9% and 1.4% in Connecticut and on the offshore islands of Massachusetts. 4,5
By 2010 it was clear that an intervention was needed to reduce transmission of B. microti to US blood recipients. So, why did it take so long for a screening test to be implemented? Several factors have contributed to this "perfect storm," starting with the geographically restricted distribution of the parasite. B. microti was primarily found in the Northeast and the upper Midwest. Testing blood donors residing in non-endemic states was deemed costly and unnecessary, and the prospect of developing a blood screening assay that would not be used nationwide seemed less than appealing for most test-manufacturers. However, shortly after 2010, various blood centers partnered with research companies to incorporate screening tests under FDA approved investigational new drug (IND) protocols. Although B. microti blood donation screening under IND had focused only on a limited geographic area, the impact was significant.6 The accompanying reduction of TTB cases in blood recipients from donors that live in endemic areas demonstrated that testing is a successful strategy. However, the initial investigational screening relied heavily, if not exclusively, on antibody testing, which can be positive years after the infection has resolved.
Without a donor re-entry policy in place, donors who tested positive by any single test (antibody or molecular) were permanently deferred, a costly price to pay for the blood establishments and patients. Some of the tests used under an Investigational New Drug protocol (IND) were abandoned along the way, but the combination of antibody and nucleic acid testing (NAT) performed by PCR tests developed by IMUGEN received FDA licensure in July 2018, and in the same year, the FDA released draft guidance with recommendations for reducing the risk of TTB by using the licensed two-test system. However, shortly after, and for financial reasons, IMUGEN discontinued B.microti blood donation screening. By then, a new generation of NAT-only, more sensitive assays, were available and in use under IND protocols7 . Their better performance is due to their methodology which amplifies ribosomal RNA templates as well as DNA templates. These tests are used with today’s blood screening platforms, pooling several donor samples in a single test and therefore providing a significant financial advantages when screening a larger number of samples. Also, these new tests detect all four of the strains of Babesia known to infect humans. With implementation of these new testing strategies no case of TTB has been identified from a screened American Red Cross unit of blood.
As the new assays received FDA licensure in 2019, new recommendations for reducing the risk of TTB were released. The new guidance includes Babesia screening for all donation types collected in endemic areas and areas contiguous to endemic areas, which includes 14 states in the USA plus the District of Columbia. The exception is if pathogen inactivation is performed on a blood product, then Babesia testing is not required. The deferral for reactive donors was reduced to two years.
With the implementation of Babesia screening, the expectation is that the number of TTB cases will be reduced almost to zero. Travelers to endemic areas from non-endemic, non-screened states may still offer a risk, but these cases represent less than 2% of the total reported TTB cases. We are finally on the right path but should always remember to check for ticks!
By Laura Tonnetti, PhD and Sue Stramer, PhD
Links to Additional Resources/Information:
Tonnetti L et al. Babesia blood testing: the first-year experience Transfusion 2022. 62:135–142.
Popovsky MA, et al.. Prevalence of Babesia antibody in a selected blood donor population. Transfusion 1988;28: 59-61.
Linden JV, et al. Transfusion-associated transmission of babesiosis in New York State. Transfusion 2000;40: 285-9.
Herwaldt BL, et al. Transfusion-associated babesiosis in the United States: a description of cases. Ann Intern Med 2011;155: 509-19.
Leiby DA, et al. Demonstrable parasitemia among Connecticut blood donors with antibodies to Babesia microti. Transfusion 2005;45: 1804-10.
Johnson ST, et al. Seroprevalence of Babesia microti in blood donors from Babesia-endemic areas of the northeastern United States: 2000 through 2007. Transfusion 2009;49: 2574-82.
Tonnetti L, et al.The impact of Babesia microti blood donation screening. Transfusion 2019;59: 593-600.
Tonnetti L et al. Detection of Babesia ribosomal RNA reveald a longer duration of parasitemia in infected blood donors. Transfusion 2019;59: 10A.