Donor/Recipient Health & Epidemiology

U.S. Centers for Disease Control and Prevention funded research contract investigating the possibility of non-variant CJD transmission by blood. This project utilizes donor lookback to trace recipient outcomes.

Crowder LA, Schonberger LB, Dodd RY, Steele WR. Creutzfeldt-Jakob disease lookback study: 21 years of surveillance for transfusion transmission risk. Transfusion 2017;57: 1875-8.
 

The American Red Cross is a participant in the FDA, NHLBI and HHS-OASH funded Transfusion-Transmissible Infections Monitoring System (TTIMS) project. TTIMS consists of two coordinating centers: The Donation Database Coordinating Center (DDCC) and the Laboratory and Risk Factor Database Coordinating Center (LRCC). The American Red Cross acts as the DDCC and Vitalant Research Institute acts as the LRCC for the study. TTIMS brings together donation and test data acquired during routine blood donation collections at four major US blood systems (American Red Cross, New York Blood Center, OneBlood and Vitalant) with data collected from specialty research studies. Together this data provides critical blood safety and monitoring information on more than 50% of the US blood supply.

The DDCC is responsible for acquiring and validating donor demographic data from the four participating blood systems plus testing results from Creative Testing Solutions, ensuring that the data available from each system are harmonized, and that appropriate consensus positive definitions are consistently applied across sites. The DDCC then analyzes and reports on the prevalence and incidence of HIV, HBV and HCV in US blood donors and donations, with special attention paid to temporal and demographic changes and trends. The DDCC also reports positive and false positive donors to the LRCC. The LRCC coordinates the Risk Factor Questionnaire study. The LRCC provides each blood center lists from which donors are interviewed by each center’s donor counselors. LRCC compiles and analyses this data. The LRCC also acts as the repository for positive samples and conducts follow-up molecular sequencing, recency and other testing of interest. The American Red Cross participates in both the DDCC and the LRCC activities.

Steele WR, Dodd RY, Notari EP, et al. Prevalence of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in United States blood donations, 2015 to 2019: The Transfusion-Transmissible Infections Monitoring System (TTIMS) [published online ahead of print, 2020 Aug 31]. Transfusion. 2020;10.1111/trf.16005. doi:10.1111/trf.16005

Custer B, Stramer SL, Glynn S, Williams AE, Anderson SA. Transfusion-transmissible infection monitoring system: a tool to monitor changes in blood safety. Transfusion 2016;56: 1499-502.

Dodd RY, Notari EP, Nelson D, Foster GA, Krysztof DE, Kaidarova Z, Milan-Benson L, Kessler DA, Shaz BH, Vahidnia F, Custer B, Stramer SL, NHLBI REDSI. Development of a multisystem surveillance database for transfusion-transmitted infections among blood donors in the United States. Transfusion 2016;56: 2781-9.

Vahidnia F, Stramer SL, Kessler D, Shaz B, Leparc G, Krysztof DE, Glynn SA, Custer B. Recent viral infection in US blood donors and health-related quality of life (HRQOL). Qual Life Res 2017;26: 349-57.

Vahidnia F, Stramer SL, Kessler D, Goncalez TT, Shaz BH, Leparc G, Krysztof DE, Dodd RY, Glynn SA, Custer B, Nhlbi Retrovirus Epidemiology Donor Study I. Motivations for donating and attitudes toward screening policies in US blood donors with viral infection. Transfusion 2016.

Custer B, Kessler D, Vahidnia F, Leparc G, Krysztof DE, Shaz B, Kamel H, Glynn S, Dodd RY, Stramer SL, Nhlbi Retrovirus Epidemiology Donor Study I. Risk factors for retrovirus and hepatitis virus infections in accepted blood donors. Transfusion 2015;55: 1098-107.

ARCNET is a database containing information on every donation and deferral to the American Red Cross since 1995 including demographics, procedure information, infectious disease testing data and deferral information, as applicable. Blood donors can be followed longitudinally giving the ability to track an individual Red Cross donor’s donation-deferral history or to examine temporal trends in donor demographics or transfusion-transmissible diseases for the entire population. ARCNET is frequently used to provide estimates for the FDA, WHO, CDC and other interested parties.

Zou S, Eder AF, Musavi F, Notari EP, Fang CT, Dodd RY, Group AS. Implementation of the Uniform Donor History Questionnaire across the American Red Cross Blood Services: increased deferral among repeat presenters but no measurable impact on blood safety. Transfusion 2007;47: 1990-8.

Zou S, Notari EP, Stramer SL, Wahab F, Musavi F, Dodd RY, ARCNET Research Group. Patterns of age- and sex-specific prevalence of major blood-borne infections in United States blood donors, 1995 to 2002: American Red Cross blood donor study. Transfusion 2004;44: 1640-7.

Orton SL, Liu H, Dodd RY, Williams AE, ARCNET Epidemiology Group. Prevalence of circulating Treponema pallidum DNA and RNA in blood donors with confirmed-positive syphilis tests. Transfusion 2002;42: 94-9.

The ARC is at the leading edge of investigations into iron depletion in blood donors. Recently, this has included studies of prevalence of and risk factors for iron depletion, and current efforts are oriented more to adverse consequences resulting from iron depletion and potential mitigation options. Current studies are collecting information on the practice of and motivations for iron supplementation and simulations of different iron depletion mitigation strategies to assess likely efficacy and impact on blood availability.

Spencer BR, Guo Y, Cable RG, Kiss JE, Busch MP, Page GP, Endres-Dighe SM, Kleinman S, Glynn SA, Mast AE, National Heart L, Blood Institute Recipient E, Donor Evaluation S, III. Iron status and risk factors for iron depletion in a racially/ethnically diverse blood donor population. Transfusion 2019;59: 3146-56.

Spencer BR, Bialkowski W, Creel DV, Cable RG, Kiss JE, Stone M, McClure C, Kleinman S, Glynn SA, Mast AE, National Heart L, Blood Institute Recipient E, Donor Evaluation Study IIIP. Elevated risk for iron depletion in high-school age blood donors. Transfusion 2019;59: 1706-16.

The Red Cross work on infectious risks of transfusion has focused primarily on vector-borne diseases, especially parasitic diseases including malaria and babesiosis. Of particular interest is the relationship between human mobility (such as travel and migration) and risk for transfusion-transmissible infections, and how these relationships and the attendant risk-mitigation alternatives might differ markedly by infectious agent.

• Transfusion-transmitted parasitic infections in the United States are almost exclusively due to Babesia microti, the tick-borne intraerythrocytic protozoan agent of babesiosis, naturally transmitted to humans through the bite of infected deer tick. Hospital-reported transfusion-transmitted babesiosis (TTB) are investigated by the American Red Cross’s Hemovigilance program.
• The ARC has been screening blood collected in endemic areas for B. microti under investigational protocols since 2010, performing clinical trials that lead to the Food and Drugs Administration (FDA) licensure of multiple screening tests. In May 2020, Babesia screening has  been implemented in 14 endemic states plus Washington DC, as recommended by the FDA guidance released in May 2019. The screening is performed with the Procleix Babesia assay, an FDA licensed nucleic acid amplification test for the detection of RNA from Babesia species from Grifols. 
• In the absence of an FDA licensed babesia confirmatory test, a research indirect immunefluorescenceassay (IFA) for the detection of antibody against B. microti is performed in our laboratory.
• During a collaboration between the ARC and Canadian blood centers, the Procleix Babesia assay and B. microti IFA were used to assess the risk of Babesia infection in blood donors resident in geographic areas of Canada bordering the Northeastern and Upper Midwest United States, where B. microti is endemic.  
  

On June 15, 2020 the American Red Cross initiated screening allogeneic blood donations for antibodies to the SARS coronavirus-2 (SARS-CoV-2), which is the virus that causes COVID-19. Reactive donations were tested by a second COVID-19 antibody test using a different molecular target to confirm reactivity. To see how long the antibodies are present, the Scientific Support Office (SSO) contacted donors who tested reactive by the two assays and asked them to give follow-up samples. The follow-up samples were tested for antibodies to COVID-19 using the same assays as the initial donation. The initial follow-up sample was collected about a month after the reactive index donation and then approximately every other month. The results of this additional testing were provided to the donors by letter. With the rollout of COVID-19 vaccines in the US, the American Red Cross also invited donors who have been vaccinated, independently of prior SARS-CoV-2 infection, to participate in this follow-up study. Following vaccinated donors over time helps determine the duration of the antibody response to vaccines and potential reinfections and vaccine breakthrough infections; that is, people who get reinfected with SARS-CoV-2 following prior natural infection or infected following vaccination, respectively. Additionally, these donors received a link to a survey asking questions about any COVID-19 symptoms they may have experienced before their reactive index donation. The survey also inquired about testing, vaccination status, and potential exposures to the coronavirus. This research survey, along with the testing, will help provide the American Red Cross with additional information regarding the value of coronavirus antibody testing, the duration of the antibody response following exposure to SARS-CoV-2, and the donor experience during the pandemic.

Currently, there are no Food and Drug Administration (FDA) approved tests for screening donated blood for Plasmodium, the agent that causes malaria. Therefore, donor screening in the U.S. occurs by questionnaire. The estimated incidence of Transfusion-Transmitted Malaria in the U.S. is less than one per million units of collected blood, but about 72,000 donors are deferred yearly due to malaria risks. 

The American Red Cross Scientific Support Office (SSO) is conducting two research studies on testing for Plasmodium nucleic acid (DNA and RNA) in blood donors, one in collaboration with Grifols and Grifols Diagnostics, Inc. and the other in collaboration with Roche Diagnostics Solutions. Both studies aim to evaluate new research assays and learn more about the prevalence of Plasmodium infection in donors deferred for malaria risk. What we learn will help us know how many deferred donors are indeed infected with the malaria parasite. Implementation of universal donation screening for malaria would aid in reducing the number of deferred donors for malaria risks.

Enrollment is Complete - THANK YOU! 

A heartfelt thank you to our LGBTQ+ community partners, study participants, and all those who supported the groundbreaking ADVANCE Study as we all seek to make blood donation a more inclusive process while maintaining the safety of the blood supply. Together, the LGBTQ+ community, blood centers and the FDA are collaborating to determine if a blood donor history questionnaire based on individual risk would be an acceptable alternative to a time-based deferral in reducing the risk of HIV among gay and bisexual men who present to donate blood.

This could potentially lead to changes to the FDA’s current three-month deferral policy for men who have sex with men or MSM. 

ADVANCE Study enrollment concluded on September 30, 2022. Researchers from the participating blood centers – Vitalant, OneBlood and the American Red Cross – will complete their final work by the end of 2022, which includes completing follow-up visits with participants into the fall, and then forward the information to the FDA. The FDA will determine the next steps after the analysis is complete and the results will be made public. We look forward to learning what comes next from the FDA in the months to come.

For more information, please email Lauren.Crowder@redcross.org