INTRODUCTION:The US adopted an individual donor assessment (IDA) policy in 2023 to evaluate blood donor risk, potentially resulting in more eligible donors and first-time donors (FTDs). FTDs are associated with higher transfusion-transmissible infectious disease (TTID) risk. Thus, we compared FTD demographics, characteristics, and return behavior during the first 2 years of the IDA compared to the previous 2 years during the 3-month deferral (3MD) policy. METHODS:FTD donation data from the transfusion-transmissible infections monitoring system (TTIMS) during the initial 2 years of IDA were compared to the preceding 2 years (3MD). Descriptive statistics were used to assess changes in FTD demographics, donation characteristics, state of residence, and return behavior during the IDA policy compared to the 3MD policy. RESULTS:There were slightly over 4 million donations from FTDs during the entire study period, with a 6% increase overall during the IDA period, led mostly by male FTDs (14% increase). Increases were observed in most other demographic/characteristic groups except for a few (female, aged 16-24, or other procedure types). There was a higher absolute number of returning donors and subsequent donations from the FTDs during the IDA period compared to the previous period. The Northeastern US states were found to have the highest increase in FTDs. CONCLUSIONS:There were variable increases in FTDs among most demographic and characteristic groups post-implementation of the IDA policy, notably among men. Although attributability to the new policy is unclear, blood availability may increase with such policies. Continued monitoring will ensure blood safety during donor policy changes.

BACKGROUND AND OBJECTIVES:The results of a global survey on blood safety measures to prevent transfusion-transmitted infectious diseases (TTIDs) were analysed, focusing on TTID testing requirements, practices and associated donor actions (vigilance). MATERIALS AND METHODS:Responses by country/region (C/R) were categorized by World Bank income (WBI) levels: low- and lower middle-income (LLMI), upper middle-income (UMI) and high-income (HI). Consensus responses were used for C/Rs with multiple survey responses. Regions within China and India were analysed separately. Survey questions on TTID testing and donor vigilance were compared across WBI levels. RESULTS:Responses from 74 C/Rs representing 65 countries and Hong Kong were analysed. All C/Rs reported mandatory human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) screening, with a few exceptions for syphilis. Most testing standards were set by national law, using antibody and/or antigen testing for HIV, HBV and HCV; antibody testing was common for syphilis. Nucleic acid testing (NAT) was less common in LLMI than in UMI and HI C/Rs. Confirmatory testing was reported by almost all (96%) C/Rs, often using the same screening test. All C/Rs provided educational material to donors, and deferred/notified donors based on reactive/positive TTID results. Most C/Rs reported reactive/positive results to a central entity, and 89% withdrew and destroyed in-date units from previous collections. CONCLUSION:All reporting C/Rs screened for HIV, HBV and HCV, with most using confirmatory testing. Advanced tests such as NAT were less common in LLMI C/Rs. Donor vigilance was consistent across income groups, with education, notification and deferral for TTID results, and most reporting withdrawal/destruction of previous collections.

INTRODUCTION:Most US blood donations are from donors living in urban areas. Demographics and infectious disease prevalence may vary in urban versus rural areas. We assessed demographic and transfusion-transmissible infection (TTI) prevalence among donors living in urban versus rural areas. METHODS:Blood donation data from the Transfusion-Transmissible Infections Monitoring System were categorized as urban or rural based on donor residential zip code for a three-year period (October 2020-September 2023). Demographics and TTI prevalence (HBV, HCV, HIV consensus positive (CP) and recent infection (RI), and syphilis CP and active infection (ASI)) were compared between the two geographies. Regression analysis determined the odds of TTIs among donors while controlling for demographic characteristics. RESULTS:From 21,941,910 donations, 83.9% were categorized as urban and 16.1% as rural. Donations from urban versus rural donors were more likely to be from men, between the ages of 25 and 54, non-White, and first-time. HBV CP, HIV CP, syphilis CP, and ASI were more prevalent in donations from urban versus rural donors. Significantly higher seroconversion rates also occurred in donors with syphilis CP and ASI. When adjusting for differences in donor demographics and characteristics, only prevalence in HBV CP remained more likely to occur among urban donors (odds ratio (OR): 1.28, 95% CI: 1.03, 1.6) and HCV CP less likely to occur among urban donors (OR: 0.8, 95% CI: 0.71, 0.9). DISCUSSION:Blood donor demographics and TTI prevalence differ in urban areas compared to rural; however, the differences in demographics may explain some of the TTI prevalence trends.

BACKGROUND:The Transfusion-Transmissible Infections Monitoring System assesses trends in ~60% of the US blood supply. Donors with high-risk behaviors, including injection drug users, men having sex with other men, or those exchanging sex for money/drugs, were deferred for 12 months (12 M) from 2016 to 2020 and 3 months (3M) from 2020 to 2023. Here we evaluate HIV, HBV, and HCV donation prevalence annually from 2015 to 2023 and in two comparison periods of pre-3M (2015-2020) and 3M (2020-2023) to identify differences between the two periods. METHODS:Annual prevalence was assessed for 8 TTIMS years (2015-2023) and compared between the pre-3M and 3M periods. HIV, HBV, and HCV prevalence/100,000 donations (phtd) was calculated based on serology and nucleic acid testing results. Negative binomial regression assessed prevalence using 1-year intervals. Fisher's exact test evaluated prevalence changes between the two periods (α = 0.05). RESULTS:Annual HIV and HBV prevalence remained stable, changing slightly from year 1 to 8 (2.5-2.1 phtd for HIV and 6.3-6.6 phtd for HBV). HCV prevalence declined (19.7-9.6 phtd; p <.01). HIV (2.5-2.0 phtd) and HCV (18.4-9.8 phtd) prevalence decreased from pre-3M to 3M (p <.01), while HBV prevalence remained stable (6.5-6.2 phtd; p = .06). CONCLUSIONS:Despite reducing donor deferral periods for many infectious risk behaviors, HIV and HBV prevalence were stable, while HCV prevalence declined over 8 years. Either slight or significant declines occurred from the pre-3M to 3M period for all agents. Thus, changes in policy did not adversely impact the current safety of the blood supply with respect to the major infectious disease agents.

BACKGROUND:Over time, changes to the deferral policy for males who had sex with other males (MSM) allowed those reporting past MSM to donate if other eligibility criteria were met. We assessed the return rate after the removal of the MSM deferral and transfusion-transmissible infectious disease (TTID) rates in MSM compared to first-time male donors and donors overall. STUDY DESIGN AND METHODS:Males presenting to donate at the American Red Cross and self-reported MSM between December 13, 2016 and December 31, 2024 were assessed. TTID rates were determined by evaluating all donors with donation results collected during defined deferral periods. Queries tracked subsequent donations/deferrals post-MSM deferral. RESULTS:Approximately, 9.1 million American Red Cross donors were screened for TTIDs; 0.04% self-identified as MSM. The overall rate of allogeneic donors who screened repeat reactive for markers for hepatits B virus (HBV), hepatits C virus (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus 1 and 2 (HTLV-1/2), and/or syphilis was 5.6%, 1.9%, and 1.8% among MSM, all donors, and first-time males, respectively. The most frequent marker detected among MSM donors was anti-Treponema pallidum, fo llowed by anti-HBc. There were no HBV, HCV, or HIV nucleic acid testing (NAT)-yield cases detected among MSM donors. Overall, only 10% of MSM donors attempted to donate after expiration/removal of their deferral. CONCLUSION:The low yield in MSM returns could be attributed to donors not being directly notified of their eligibility, knowledge of on-going deferrable risks, or other factors. Donors with a history of MSM were more likely to screen reactive for TTID marker(s), although not NAT-yield infections indicating absence of recent risk when compared to the overall donor population and first-time males.

BACKGROUND:The Transfusion-Transmissible Infections Monitoring System assesses trends in ~60% of the US blood supply. Donors with high-risk behaviors, including injection drug use, men having sex with other men, or exchanging sex for money/drugs were deferred for 12 months (12M) from 2016 to 2020 and 3 months (3M) from 2020 to 2023. Here we evaluate HIV, HBV, and HCV incidence and window-period residual risk (WPRR) in two ~3-year periods of 12M (2017-2020) and 3M (2020-2023) to identify any differences. METHODS:First-time (FT), repeat (RPT), and overall weighted incidence/100,000 person-years (phtpy) for HIV, HBV, and HCV were estimated based on serology and nucleic acid test results. WPRR was calculated by multiplying respective incidence by agent-specific WP. Fisher's exact test evaluated incidence changes between the two periods (α = 0.05). RESULTS:Overall weighted incidence for HIV, HBV, and HCV was 2.22, 1.59, and 0.53 phtpy versus 1.03, 0.93, and 0.16 phtpy in 12M and 3M periods, respectively. Overall WPRR per 1,000,000 donations for HIV, HBV, and HCV was 0.45, 0.63, and 0.53 versus 0.23, 0.43, and 0.16 in 12M and 3M periods, respectively. All comparisons by agent and by period were significant (p < .01). CONCLUSIONS:Despite reducing donor deferral periods for many infectious risk behaviors, HIV, HBV, and HCV overall incidence declined from the 12M to 3M periods. WPRR also declined from 12M to 3M, remaining under 1 per 2,000,000 donations in the 3M period. Thus, changes in policy did not adversely impact the safety of the blood supply with respect to the major infectious disease agents.

BACKGROUND AND OBJECTIVES:A global survey on blood safety measures to prevent transfusion-transmitted infectious diseases (TTIDs) was performed by examining variations in current usage. This analysis focuses on participation rates and the presence of relevant laws, regulations, standards and best practices for collection/processing of whole blood/components. MATERIALS AND METHODS:Distribution occurred between October 2023 and March 2024. States, provinces or cities within China and India were analysed as separate regions. Country/region (C/R) responses were categorized by World Bank income (WBI) levels: low- and lower middle-income (LLMI), upper middle-income (UMI) and high-income (HI). Consensus responses were used for multiple survey responses. RESULTS:Responses from 131 individuals representing 74 C/Rs (65 countries, Hong Kong, counted separately, and 8 regions in China/India) were analysed. Affirmative responses for laws, regulations and standards were similar across WBI levels. Regulatory jurisdiction for blood/components was present in 96% of C/Rs (HI 100%, UMI 100%, LLMI 87%) and 94% at a national level when present (HI 100%, UMI 94%, LLMI 85%). All HI, UMI and 74% LLMI C/Rs reported routinely separating whole blood into components. HI C/Rs were more likely to screen for bacterial contamination, whereas periodic platelet quality control was more common in LLMI and UMI C/Rs. Pathogen reduction and universal leukocyte reduction were more common in HI C/Rs. CONCLUSION:Laws, regulations and standards for collection/processing of blood were consistent across WBI groups. Resource-intensive practices of blood component separation and use of advanced blood safety technologies were more variable, with less utilization in LLMI/UMI C/Rs.

BACKGROUND:US blood donors are tested for syphilis because the bacterial agent is transfusion transmissible. Here we describe trends over an 11-year period of donations positive for recent and past syphilis infections, and donations classified as syphilis false positive (FP). METHODS:Data from January 1, 2013, to December 31, 2023 (11 years) were compiled for all American Red Cross blood donations to evaluate demographics/characteristics and longitudinal trends in donors testing syphilis reactive/positive. The prevalence of recent, past, and total (combination of recent/past) infections were evaluated, along with syphilis FP donations. Classification was based on known serological methods using treponemal and non-treponemal tests. RESULTS:Approximately 53 million donations were included with 10,365 total syphilis infections (3463 recent and 6902 past; 0.02% total) and 48,719 FP (0.09%). Donor demographics, characteristics, and HBV/HCV/HIV nucleic acid testing reactivity differed among syphilis-positive and FP compared with nonreactive donations. Donors with a FP donation had high rates of subsequent donations testing syphilis positive (0.3%) and FP (7.7%). Median time from first FP to subsequent FP was observed to be 3.6 months. Recent infections increased over the 11 years, with past infections peaking in 2014 followed by increases in 2021-2023 paralleling recent infections. Repeating cycles of seasonal FP spikes occurred in the fall of 2013 and from 2017 to 2022 corresponding with vaccine administrations. CONCLUSIONS:Syphilis infections in blood donors are trending upward, paralleling US population trends. Syphilis FP donors had high rates of subsequent FP and unexplained syphilis-positive donations. Seasonal syphilis FP spikes occurred for most years but are trending downwards.

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.

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.

Background The first coronavirus disease 2019 (COVID-19) case in the United States was recognized on 19 January 2020, but the time of introduction of the virus into the United States is unknown. An existing sample cohort was examined for serologic evidence of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.Methods A repository of 46 120 samples from healthy routine blood donors, representing 46 states and the District of Columbia, was tested for total antibodies to SARS-CoV-2 nucleocapsid (anti-N) using a commercial test. All reactive samples were further tested using an experimental receptor-binding domain (RBD)-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Further testing was also conducted for anti-spike (anti-S) antibodies by commercial tests, experimental anti-S immunologic blocking, and for antibodies to the 4 human cold coronaviruses.Results Anti-N reactivity was observed in 92 tested samples (0.2%), 91 of which had adequate volume for further testing; of these, 55 were confirmed positive by anti-RBD. None of these reactive findings were attributable to the other human coronaviruses tested. The confirmed-positive frequency increased over time paralleling patterns observed for COVID-19 cases reported in the United States (in contrast to stable patterns over time for the cold coronaviruses). Nine confirmed positive samples (0.07%) were identified among the 13 364 donations collected between 13 December 2019 and 22 January 2020. None of these early confirmed-positive samples were reactive by commercial anti-S tests suggesting very recent infection.Conclusions The samples tested in this study were broadly representative of the United States, and all were from individuals who had successfully donated blood. The antibody-reactive results of this study suggest that SARS-CoV-2 was likely present in the United States before 19 January 2020. SARS-CoV-2 infections in the US likely occurred before clinical COVID-19 disease cases. SARS-CoV-2 anti-nucleocapsid reactivity was low during the first 3 months (December 2019-March 2020), increased 10-fold in the following 3 months, and unrelated to the common cold coronaviruses.

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.

Background: Transfusion-transmissible infection (TTI) prevalence among US blood donors has been widely documented. Here we estimate the prevalence of donors presenting with >= 2 TTIs (multiple infections past or present referred to as coinfections) and describe their demographics and associations. Methods: Data from the Transfusion-Transmissible Infections Monitoring System were compiled for October 2020-September 2023 (3 years). Prevalence per million donations (pmd) was calculated for each TTI coinfection combination with demographic characteristics summarized. The odds of each TTI coinfection combination were estimated using logistic regression. Reactivity by NAT and/or serology (HIV, HBV, and HCV) defined donors as consensus positive (CP) for each infection while serology-based algorithms defined syphilis CP and the subset with active syphilis infections (ASIs). Results: About 22 million donations were included, with 212 coinfections (9.7 pmd). Around 2% of donations positive for any TTI (n = 10,516) were coinfections. Coinfection prevalence per TTI combination ranged from 0.3 pmd for HIV CP and HCV CP, to 4.3 pmd for HIV CP and syphilis CP. There were high proportions of coinfections from donors who were male, aged 25-54 years, white or black, first time, and residing in the southern US Census Region. The odds of a second TTI occurring in an individual donor with a TTI ranged from 23 (95% CI: 13, 41) times more likely for HBV CP and ASI to 395 (95% CI: 298, 524) times more likely for HIV CP and ASI. Conclusions: Coinfections are relatively uncommon among blood donors in the United States; however, associations exist among HIV, HBV, HCV, and syphilis infections.

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.

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.

The tragedy of transfusion-associated hepatitis and HIV spurred a decades-long overhaul of the regulatory oversight and practice of blood transfusion. Consequent to improved donor selection, testing, process control, clinical transfusion practice and post-transfusion surveillance, transfusion in the United States and other high-income countries is now a very safe medical procedure. Nonetheless, pathogens continue to emerge and threaten the blood supply, highlighting the need for a proactive approach to blood transfusion safety. Blood donor populations and the global transfusion infrastructure are under-utilized resources for the study of infectious diseases. Blood donors are large, demographically diverse subsets of general populations for whom cross-sectional and longitudinal samples are readily accessible for serological and molecular testing. Blood donor collection networks span diverse geographies, including in low- and middle-income countries, where agents, especially zoonotic pathogens, are able to emerge and spread, given limited tools for recognition, surveillance and control. Routine laboratory storage and transportation, coupled with data capture, afford access to rich epidemiological data to assess the epidemiology and pathogenesis of established and emerging infections. Subsequent to the State of the Science in Transfusion Medicine symposium in 2022, our working group (WG), "Emerging Infections: Impact on Blood Science, the Blood Supply, Blood Safety, and Public Health" elected to focus on "leveraging donor populations to study the epidemiology and pathogenesis of transfusion-transmitted and emerging infectious diseases." The 5 landmark studies span (1) the implication of hepatitis C virus in post-transfusion hepatitis, (2) longitudinal evaluation of plasma donors with incident infections, thus informing the development of a widely used staging system for acute HIV infection, (3) explication of the dynamics of early West Nile Virus infection, (4) the deployment of combined molecular and serological donor screening for Babesia microti, to characterize its epidemiology and infectivity and facilitate routine donor screening, and (5) national serosurveillance for SARS-CoV-2 during the COVID-19 pandemic. The studies highlight the interplay between infectious diseases and transfusion medicine, including the imperative to ensure blood transfusion safety and the broader application of blood donor populations to the study of infectious diseases.

The Transfusion Transmissible Infections Monitoring System (TTIMS) monitors HIV, HBV, and HCV infections along with adding syphilis infections in October 2020. TTIMS includes ~60% of the US blood supply combining all data from four of the largest US blood collection organizations (BCO) to track demographic and infectious disease trends. We present blood donation syphilis prevalence and incidence based on antibody results for the first 2 years of study. Data were compiled from October 2020 to September 2022. Allogeneic, directed, and COVID-19 convalescent plasma donations were included. Syphilis prevalence estimates were calculated for consensus positive (CP) infections (which include screen reactive, confirmed-positive infections based on total antibodies) and active infections (AI; a subset of CPs that are also rapid plasma reagin [RPR] positive). Donations from one BCO were excluded from AI analyses as RPR was not used during the first year of the study. Incidence was calculated for the 2-year period using repeat incident (seroconverting) donors/total person-years (PY). Prevalence and incidence were stratified by sex, age group, race/ethnicity, first-time donation status, blood type, and US Census region overall and by year. Lastly, the odds of having an HIV infection within syphilis CP and AI were compared to those without syphilis. Nearly 14.75 million donations were divided into 7,576,645 from the first year and 7,170,844 from the second (405,801 less). Overall, syphilis prevalence was 28.4/100,000 (PHT) donations. Significantly higher prevalence occurred during the second versus the first year in most demographic groups. The unadjusted odds of a donor having a CP infection were 1.25 (95% confidence interval [CI]: 1.18, 1.33) times higher in the second year compared to the first, and for AI, 1.31 (95% CI: 1.18, 1.44) times higher in the second year compared to the first. Donations from donors who were male, first-time, black, younger (ages 18–39), and in the South Census region had the highest rates. By quarter, both CP and AI prevalence increased from 24.9 PHT to 35.8 PHT donations for CP, and from 8.9 PHT to 17.4 PHT donations for AI (Figure A). CP donors were 520 (95% CI: 391, 691) times more likely to also be HIV CP compared to non-CP donors, and AI donors were 722 (95% CI: 508, >999) times more likely to also be HIV CP compared to non-AI donors. Overall, incidence was 14.8/100,000 PY, with the highest stratified rates observed in male and black donors. There was a marked increase in syphilis prevalence in donations to the TTIMS program from October 2021 to September 2022 versus the same period in 2020. Continued monitoring is necessary to determine if the upward trend continues to mirror increasing national trends in the general population; that is, from 15.9 syphilis infections PHT in 2012 to 51.5 PHT in 2021 (cdc.gov).