Absence of evidence of transfusion transmission risk of Creutzfeldt-Jakob disease in the United States: Results froma 28-year lookback study.

BACKGROUND: For many years, there has been concern about the risk of transmission of classic forms of Creutzfeldt-Jakob disease (CJD) by blood transfusion, particularly after the recognition of such transmission of variant CJD (vCJD). We report on a 28-year lookback study of recipients of blood from donors who subsequently developed CJD. METHODS: Patients with diagnosed CJD and a history of blood donation were identified. Blood centers were asked to provide information about the distribution of the donations and consignees were requested to provide information about the recipients of the donations. Vital status of each available recipient was determined and, if deceased, the reported cause(s) of death were obtained primarily from the National Death Index. All recipients included in the study database contributed person-time up to the last recorded review of vital status. RESULTS: There were 84 eligible donors who gave 3284 transfusable components, and it was possible to evaluate 1245 recipients, totaling 6495 person-years of observation. The mean observation period per recipient was 5.5 years with a maximum of 51 years. No case of CJD or prion disease was reported among the recipient population. DISCUSSION: The study suggests that CJD may not be transfusion-transmissible, a position in agreement with similar findings from two similar European reports amounting to an overall observation period of 15,500 person-years. These studies have supported the conclusion that the risk, if any, of transmission of CJD by blood products is extremely small and remains theoretical.

Changes in transfusion-transmissible infection prevalence and demographics among US blood donors during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic impacted the US blood supply. We compared blood donor demography and infectious disease prevalence before and during the pandemic using a large multicenter database. METHODS: Data were categorized as "Before COVID-19" (March 2018-February 2020) or "During COVID-19" (March 2020-February 2022). Donor demographics, donation frequency, and infectious marker prevalence of HIV, HBV, and HCV were compared for the two time periods. The odds of a donor testing positive for these infections among the two time periods were calculated using multivariable logistic regression. RESULTS: Our study assessed a total of 26,672,213 donations including 13,430,380 before and 13,241,833 during COVID-19. There were significantly more donations from donors who were female, aged 40 and older, white, and repeat, during COVID-19. Donation frequency comparison quantified the increase in donations from donors who were white, female, older, and repeat during the pandemic. The prevalence of HIV and HCV decreased significantly during COVID-19 compared to before, but not for HBV. For HIV, the adjusted odds of infection during the pandemic did not differ but for HBV, the odds were significantly more likely during the pandemic and were significantly lower for HCV. DISCUSSION: Demographics and infectious disease marker prevalence changed during the COVID-19 pandemic in the United States. Prevalence of each infection in the donor population will continue to be monitored to determine if changes were specific to the pandemic period.

Syphilis seroprevalence and incidence in US blood donors from 2020 to 2022.

BACKGROUND: HIV, HBV, and HCV infections for ~60% of the US blood supply are monitored by TTIMS with syphilis added in 2020. STUDY DESIGN AND METHODS: Data were compiled from October 2020 to September 2022. Syphilis prevalence was estimated for allogeneic and directed donors who were consensus positive (CP) and the subset of those with confirmed-active infections (AI). Prevalence and incidence were stratified by demographics for two consecutive 1-year periods, starting October 1, 2020 and for both years combined. Incidence was estimated for repeat donors. Associations between syphilis positivity and other infections were evaluated. RESULTS: Among 14.75 million donations, syphilis prevalence was 28.4/100,000 donations and significantly higher during the second year compared to the first year. Overall, syphilis incidence for the two-year period was 10.8/100,000 person-years. The adjusted odds of a CP infection were 1.18 (95% CI: 1.11, 1.26) times higher in the second year compared to the first, and for AI, 1.22 (95% CI: 1.10, 1.35) times higher in year 2. Highest rates occurred among males, first-time, Black, and younger (ages 18-39) donors, and those in the South US Census region. Syphilis CP donors were 64 (95% CI: 46, 89) times more likely to be HIV CP, and AI donors 77 (95% CI: 52, 114) times more likely to be HIV CP than non-CP donors, when controlling for confounders. SUMMARY/CONCLUSIONS: Syphilis prevalence increased over the study period mirroring national trends reported by CDC and is significantly associated with HIV CP.

Trajectory and Demographic Correlates of Antibodies to SARS-CoV-2 Nucleocapsid in Recently Infected Blood Donors, United States.

We evaluated antibodies to the nucleocapsid protein of SARS-CoV-2 in a large cohort of blood donors in the United States who were recently infected with the virus. Antibodies to the nucleocapsid protein of SARS-CoV-2 indicate previous infection but are subject to waning, potentially affecting epidemiologic studies. We longitudinally evaluated a cohort of 19,323 blood donors who had evidence of recent infection by using a widely available serologic test to determine the dynamics of such waning. We analyzed overall signal-to-cutoff values for 48,330 donations (average 2.5 donations/person) that had an average observation period of 102 days. The observed peak signal-to-cutoff value varied widely, but the waning rate was consistent across the range, with a half-life of 122 days. Within the cohort, only 0.75% of persons became seronegative. Factors predictive of higher peak values and longer time to seroreversion included increasing age, male sex, higher body mass index, and non-Caucasian race.

A Longitudinal Study of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response in a Subset of United States Blood Donors.

Background: Blood donors were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); resulting antibody levels were monitored over time. Methods: Donors reactive to anti-SARS-CoV-2 spike protein (S1-total antibodies) participated in a follow-up study of 18 months. Testing for nucleocapsid antibodies distinguished between vaccination and infection. Vaccination and symptom information were collected for anti-S1-reactive donors by completing a survey. Results: The majority of 249 followed donors were over 60 years old (54%), White (90%), and female (58%); 83% had not been vaccinated at enrollment, but by study completion, only 29% remained nonvaccinated. Of the 210 (84%) anti-N-reactive donors, 138 (66%) reported vaccination, whereas 37 (95%) of donors vaccinated and anti-N negative at enrollment remained uninfected. Vaccinated (2 doses) and infected donors showed a steady increase in anti-S1 that increased markedly for vaccinated donors after a booster and infected donors after vaccination (slightly higher for those with hybrid immunity), whereas anti-N levels declined. Most surveyed nonvaccinated donors (65%) reported symptoms, whereas 85% of vaccinated donors were asymptomatic. A coronavirus disease 2019 (COVID-19) diagnosis was reported by 48 (31%) nonvaccinated and 3 (8%) vaccinated donors. Of asymptomatic donors, 38% never tested diagnostically for COVID-19, and 35% tested negative, suggesting an absence of knowledge of the infection. Conclusions: Healthy blood donors were vaccinated at high rates and remained mostly asymptomatic and noninfected, whereas approximately two thirds of infected donors reported symptoms. Anti-S1 levels increased while anti-N decreased over 18 months but remained comparable between vaccinated and hybrid immune individuals with dramatic anti-S1 increases after vaccination or boosting.

Low risk of human T-lymphotropic virus infection in U.S. blood donors; Is it time to consider a one-time selective testing approach?

BACKGROUND: U.S. blood donors are tested at each donation for human T-lymphotropic virus (HTLV) antibodies. Depending on donor incidence and other mitigation/removal technologies, a strategy of one-time selective donor testing should be considered. METHODS: Antibody seroprevalence was calculated for HTLV-confirmed-positive American Red Cross allogeneic blood donors from 2008 to 2021. Incidence was estimated for seven 2-year time periods using confirmed-positive repeat donors having seroconverted in 730 days. Leukoreduction failure rates were obtained from internal data from July 1, 2008-June 30, 2021. Residual risks were calculated using a 51-day window period. RESULTS: Between 2008 and 2021, >75 million donations (>18 million donors) yielded 1550 HTLV seropositives. HTLV seroprevalence was 2.05 antibody-positives per 100,000 donations (0.77 HTLV-1, 1.03 HTLV-2, 0.24 HTLV-1/2), and 10.32 per 100,000 among >13.9 million first-time donors. Seroprevalence differed significantly by virus type, sex, age, race/ethnicity, donor status, and U.S. census region. Over 14 years and 24.8 million person-years of observation, 57 incident donors were identified (25 HTLV-1, 23 HTLV-2, and 9 HTLV-1/2). Incidence decreased from 0.30 (13 cases) in 2008-2009 to 0.25 (7 cases) in 2020-2021. Female donors accounted for most incident cases (47 vs. 10 males). In the last 2-year reporting period, the residual risk was 1 per 2.8 million donations and 1 per 3.3 billion donations when coupled with successful leukoreduction (0.085% failure rate). CONCLUSIONS: HTLV donation seroprevalence for the years 2008-2021 varied by virus type and donor characteristics. Low HTLV residual risk and use of leukoreduction processes support the conclusion that a selective one-time donor testing strategy should be considered.

How do we forecast tomorrow's transfusion: Infectious safety?

Continuous improvement has led to a very high degree of microbial safety of transfusion. Four issues are likely to impact the future of this safety. There will be further advances in the efficacy and efficiency of donation testing and pathogen reduction, increasing safety and hopefully eliminating unnecessary procedures. While system failures have been essentially eliminated, there will be ongoing, unpredictable issues that are inevitable. Emerging infections are likely the greatest concern and will continue, although advances in science and technology will permit increasingly rapid responses to outbreaks. Finally, the practice of transfusion may eventually impact safety as usage of blood is reduced and perhaps as alternatives to conventional blood components are developed.

Genotype Distribution and Demographic Characteristics of Hepatitis C Virus Nucleic Acid Testing Yield Cases Among US Blood Donors.

BACKGROUND: Hepatitis C virus (HCV) infection rates among US blood donors have been well characterized; however, few studies evaluated HCV genotypes among blood donors. Monitoring trends in disease and demographic patterns contributes to understanding the safety of the blood supply. We examined the demographic characteristics and distribution of HCV genotypes/subgenotypes for nearly a 16-year period among blood donors confirmed positive for HCV RNA but antibody negative (defined as nucleic acid testing [NAT] yield). METHODS: A retrospective assessment of demographic characteristics and testing data was used to determine temporal trends and geographical distribution of HCV genotypes/subgenotypes among American Red Cross blood donors confirmed positive as HCV-NAT yield. RESULTS: From 2003-2018, 343 donors (0.38/100 000 donations; 95% CI, .35-.43) were confirmed positive as HCV-NAT-yield cases. Temporal analysis revealed a significant increase in HCV-NAT-yield cases of 54.1% between 2009 and 2014 (P = .014), followed by a significant decline of 31.4% between 2015 and 2018 (P = .002). Significantly more HCV-NAT-yield cases were detected among first-time donors, non-Hispanic Whites, donors aged 20-29 years, equally likely to be males as females, with the highest frequency in the South (0.52/100 000 donations). Subgenotype 1a (49.6%) was most frequent, followed by 3a (18.7%), 2b (12.5%), 1b (8.5%), and 2a (1.7%). CONCLUSIONS: Voluntary nonremunerated blood donors are at low risk for HCV infection. Since 2015, the frequency of HCV-NAT-yield cases decreased despite an increase in acute HCV infection in the general population. HCV subgenotypes 1a and 3a continue to remain predominant among US blood donors with recent HCV infection.

Patterns of Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 Among 1.6 Million Blood Donors: Impact of Vaccination, United States, December 2020-June 2021.

From December 2020 to June 2021, 1654487 blood donors were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein, and 1028547 (62.17%) were reactive. A rapid increase in prevalence was due to vaccination. Among a subset of 1567446 donors, 729771 (46.56%) reported SARS-CoV-2 vaccination, of whom 633769 (86.84%) were S1-antibody reactive only in response to vaccination and 68269 (9.35%) were reactive to both S1 and nucleocapsid in response to prior infection; the remainder were not reactive to either antibody. Among the 837675 (53.44%) donors who did not report vaccination, 210022 (25.07%) had reactivity to both antibodies and 29446 (3.52%) to S1 only.

Babesia blood testing: the first-year experience.

BACKGROUND: Babesia is an intraerythrocytic parasite responsible for hundreds of cases of transfusion-transmitted babesiosis in the past 50 years. In May of 2020, blood testing for Babesia was implemented at the American Red Cross (ARC) for all donations in endemic areas of the northeastern and midwestern regions of the United States. METHODS: Between May 2020 and May 2021, 1,816,669 donations from 13 states and DC were tested for Babesia by the ARC. Testing was performed in pools of 16 whole blood lysates using a licensed nucleic acid test (NAT) targeting Babesia 18S rRNA. Reactive donations were tested for B. microti antibody by immunoglobulin G immunofluorescence. Suspected cases of transfusion-transmitted babesiosis (TTB) were investigated if reported. RESULTS: The first 13 months of Babesia screening identified 365 NAT-reactive donations. Antibodies for B. microti were detected in 79% (287) of reactive donations; negative serology samples were prevalent between May and July. Follow-up donations were collected from 142 donors, and 86% (122), collected up to 74 days after index, remained NAT reactive. Reactive donations were mainly collected in MA (77), CT (68), NY (49), NJ (47), and PA (44), but were identified in all states except Delaware. Most reactive blood donors were male (65%) aged between 40 and 80 years. Since the beginning of Babesia testing, no case of TTB was identified. CONCLUSIONS: The absence of TTB cases since implementation of Babesia screening for blood donations collected in endemic areas suggests testing is an effective strategy to eliminate TTB.

Characteristics of US Blood Donors Testing Reactive for Antibodies to SARS-CoV-2 Prior to the Availability of Authorized Vaccines.

In the United States, many blood collection organizations initiated programs to test all blood donors for antibodies to SARS-CoV-2, as a measure to increase donations and to assist in the identification of potential donors of COVID-19 convalescent plasma (CCP). As a result, it was possible to investigate the characteristics of healthy blood donors who had previously been infected with SARS-CoV-2. We report the findings from all blood donations collected by the American Red Cross, representing 40% of the national blood supply covering 44 States, in order to characterize the seroepidemiology of SARS-CoV-2 infection among blood donors in the United States, prior to authorized vaccine availability. We performed an observational cohort study from June 15th to November 30th, 2020 on a population of 1.531 million blood donors tested for antibodies to the S1 spike antigen of SARS-CoV-2 by person, place, time, ABO group and dynamics of test reactivity, with additional information from a survey of a subset of those with reactive test results. The overall seroreactivity was 4.22% increasing from 1.18 to 9.67% (June 2020 - November 2020); estimated incidence was 11.6 per hundred person-years, 1.86-times higher than that based upon reported cases in the general population over the same period. In multivariable analyses, seroreactivity was highest in the Midwest (5.21%), followed by the South (4.43%), West (3.43%) and Northeast (2.90%). Seroreactivity was highest among donors aged 18-24 (Odds Ratio 3.02 [95% Confidence Interval 2.80-3.26] vs age >55), African-Americans and Hispanics (1.50 [1.24-1.80] and 2.12 [1.89-2.36], respectively, vs Caucasian). Group O frequency was 51.5% among nonreactive, but 46.1% among seroreactive donors (P< .0001). Of surveyed donors, 45% reported no COVID-19-related symptoms, but 73% among those unaware of testing. Signal levels of antibody tests were stable over 120 days or more and there was little evidence of reinfection. Evaluation of a large population of healthy, voluntary blood donors provided evidence of widespread and increasing SARS-CoV-2 seroprevalence and demonstrated that at least 45% of those previously infected were asymptomatic. Epidemiologic findings were similar to those among clinically reported cases.

HIV, HCV, and HBV incidence and residual risk in US blood donors before and after implementation of the 12-month deferral policy for men who have sex with men.

BACKGROUND: In December 2015, the men who have sex with men (MSM) deferral was reduced to 12 months in the United States. We compared human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) incidence and residual risk before and after this policy change using data from >50% of the US blood supply. STUDY DESIGN AND METHODS: Three estimation intervals from the Transfusion-Transmissible Infections Monitoring System were compared: 15-months pre- and two consecutive, nonoverlapping 15-month post-MSM deferral implementation. Repeat, first-time, and weighted all-donor incidences were estimated. Residual risk was calculated for all incidence estimates using the incidence/window-period method. RESULTS: HIV repeat donor incidence was 1.57 per 100 000 person-years (phtpy) in the second 15-month post change and not significantly different from pre-MSM incidence of 2.19 phtpy. Similar values were seen for HCV (1.49 phtpy vs 1.46 phtpy) and HBV (1.14 phtpy vs 0.97 phtpy). In some cases, higher estimated incidence, but without significant change from pre-MSM to the second post change period occurred for males and first-time donors (eg, first-time donors, second post change period: 6.12 phtpy HIV, 6.41 phtpy HCV and 5.34 phtpy HBV). Estimated per donation residual risk was 1:1.6 million for HIV, 1:2.0 million for HCV and 1:1.0 million for HBV based on weighted incidence for all donors. CONCLUSIONS: Repeat, first-time, and overall donor incidence did not vary significantly comparing pre-MSM to either of the post-MSM estimation intervals. Residual risk estimates vary by study, but all yield residual risks in the United States of ≤1 per million, and thus far have not shown increasing risk with the 12-month MSM policy change.

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).

BACKGROUND: The Transfusion-Transmissible Infections Monitoring System (TTIMS) combines data from four US blood collection organizations including approximately 60% of all donations to monitor demographic and temporal trends in infectious disease markers and policy impacts. STUDY DESIGN AND METHODS: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) consensus-positive definitions combined serology and nucleic acid testing results. These along with donor and donation characteristics were assembled into a single data set. Overall donation prevalence and demographic subsets were compared pre- and post-implementation of the 2015 change in men who have sex with men (MSM) deferral policy, among other prevalence comparisons. RESULTS: From October 2015 to September 2019, there were 712 HIV-, 1735 HBV-, and 5217 HCV-positive samples identified from approximately 27.5 million donations (>9.4 million donors). Prevalences per 100 000 donations were 2.6 (HIV), 6.3 (HBV), and 19.0 (HCV), and the highest for all three agents were in donations from first-time male donors. Two slight but significant increases in HIV prevalence were observed, both for comparisons of Year 1 (pre-MSM policy change) versus Year 4 (post-MSM policy change) for first-time males and first-time females; in contrast, similar comparisons demonstrated decreases in HCV prevalence (all donors and general trends for males and females). Except for HIV, prevalence increased with age; for all agents, prevalence was markedly higher in the south. CONCLUSIONS: No major trends were observed over 4 years covering the MSM policy change from indefinite to a 12-month deferral, but ongoing monitoring is warranted. Demographic trends are consistent with those observed in other donor studies and community trends.

Use of a rapid electronic survey methodology to estimate blood donors' potential exposure to emerging infectious diseases: Application of a statistically representative sampling methodology to assess risk in US blood centers.

Risk assessments of transfusion-transmitted emerging infectious diseases (EIDs) are complicated by the fact that blood donors' demographics and behaviors can be different from the general population. Therefore, when assessing potential blood donor exposure to EIDs, the use of general population characteristics, such as U.S. travel statistics, may invoke uncertainties that result in inaccurate estimates of blood donor exposure. This may, in turn, lead to the creation of donor deferral policies that do not match actual risk. STUDY DESIGN AND METHODS: This article reports on the development of a system to rapidly assess EID risks for a nationally representative portion of the U.S. blood donor population. To assess the effectiveness of this system, a test survey was developed and deployed to a statistically representative sample frame of blood donors from five blood collecting organizations. Donors were directed to an online survey to ascertain their recent travel and potential exposure to Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: A total of 7128 responses were received from 54 256 invitations. The age-adjusted estimated total number of blood donors potentially exposed to MERS-CoV was approximately 15 640 blood donors compared to a lower U.S. general population-based estimate of 9610 blood donors. CONCLUSION: The structured donor demographic sample-based data provided an assessment of blood donors' potential exposure to an emerging pathogen that was 63% larger than the U.S. population-based estimate. This illustrates the need for tailored blood donor-based EID risk assessments that provide more specific demographic risk intelligence and can inform appropriate regulatory decision making.

Screening Blood Donors for HIV, HCV, and HBV at the American Red Cross: 10-Year Trends in Prevalence, Incidence, and Residual Risk, 2007 to 2016.

Prevalence, incidence and residual risk of HIV, HCV and HBV are critical indicators of the safety of the blood supply. The American Red Cross routinely monitors these markers. Herein the results of testing over 58 million donations from 2007 to 2016 are reported. The prevalence and incidence of these infections has declined or remained essentially stable over the 7.5 to 10-year period. In 2015 to 2016, the prevalence of HIV, HCV and HBV were respectively: 1.65, 11.47 and 5.85 per hundred thousand (pht) donations with a significant decrease over the 10-year study only for HCV. Weighted incidence rates for all positives were 1.98 pht person years (py) for HIV, 2.20 pht py for HCV and 1.25 pht py for HBV. Estimates of residual risk using these incidence rates were: HIV, 1:2.3 million; HCV, 1:2.6 million; and HBV, 1:1.5 million donations, reflecting very low risk to recipients. There have been increases in the safety of the blood supply compared to prior published estimates. Demographic factors were shown to be associated with variations in infection prevalence and incidence. Continuing changes in the structure of the donor population or changes in policy could impact these measures of safety.

West Nile virus activity in United States blood donors and optimizing detection strategies: 2014-2018.

BACKGROUND: Rare transfusion-transmitted West Nile virus (WNV) cases usually occur due to gaps in testing involving converting to more sensitive nucleic acid testing (NAT) formats (referred to as triggering). Using data from 2014 to 2018, we investigated a strategy used to increase detection early in the triggering period and reviewed its yield as the individual donation (ID)-NAT geographic area was decreased. METHODS: Mini-pool-NAT transitioned to ID-NAT following triggering based on one WNV NAT-reactive donation (having an elevated signal, repeat reactive, or in an area with WNV ongoing activity). ID-NAT-triggered geographic areas included an entire state (2014-2017) or collections within a 50-mile radius of the triggering donor's residential zip code (2018). During the MP- to ID-NAT transition, donation samples were retrieved and tested by ID-NAT for those with results not yet released (referred to as in-process testing). Reactive sample confirmation was performed by repeat NAT of an independent sample or antibody testing. RESULTS: ID-NAT included 3.2 million donations of more than 25 million tested year-round, resulting in 684 confirmed positives; all confirmed-positive donations occurred from June to December (0.64/10,000). Overall, 52% (358/684) required ID-NAT for detection, including 68 (19%) antibody negatives. Ten of 19 (53%) identified in-process were ID-NAT-only detectable, including four antibody negatives, or approximately 1 per year (2.8% of ID-NAT-only detectable). With reduced triggering geography, 12 of 19 (63%) were not identified (including 6/10 ID-NAT-only detectable, and 2/4 ID-NAT-only detectable/antibody negative). CONCLUSION: WNV NAT's utility is between June-December; however, abandoning testing outside of this time may increase risk. While in-process testing identified approximately one ID-NAT-only detectable (antibody-negative) donation per year, reducing the geographic triggered area decreased its effectiveness.