Risk of HLA antibody generation after receipt of Mirasol versus standard platelets in the MIPLATE randomized trial.

BACKGROUND: Human leukocyte antigen (HLA) alloimmunization can occur after platelet transfusion. These antibodies can complicate future platelet transfusions or organ transplantation. Animal data suggest that Mirasol pathogen reduction treatment (PRT) can prevent alloimmunization after transfusion. STUDY DESIGN AND METHODS: The MIPLATE trial enrolled 330 of a planned 660 participants with hematological malignancies at risk for grade 2 or greater bleeding. The study was halted early for futility after a planned interim analysis. Participants were randomized to receive PRT versus standard control platelets. Serum samples were collected from participants at baseline (pretransfusion), weekly for the first 4 weeks, then at days 42 and 56. HLA antibody levels were determined using a commercial multianalyte bead-based assay. HLA antibody levels were analyzed using low, medium, and high cutoffs based on prior studies. RESULTS: The rate of alloimmunization was low in both arms of the study, particularly at the high HLA antibody cutoff (total of 6 of 277 subjects at risk, or 2.2%). The risk of alloimmunization did not differ between study arms, nor did the risk of immune refractoriness to platelet transfusion. CONCLUSIONS: The data do not support the conclusion that Mirasol exerted a protective effect against alloimmunization after platelet transfusion in the MIPLATE trial.

Hepatitis C prevalence and key population size estimate updates in San Francisco: 2015 to 2019.

BACKGROUND: In 2017, San Francisco's initiative to locally eliminate hepatitis C virus (HCV) as a public health threat, End Hep C SF, generated an estimate of city-wide HCV prevalence in 2015, but only incorporated limited information about population HCV treatment. Using additional data and updated methods, we aimed to update the 2015 estimate to 2019 and provide a more accurate estimate of the number of people with untreated, active HCV infection overall and in key subgroups-people who inject drugs (PWID), men who have sex with men (MSM), and low socioeconomic status transgender women (low SES TW). METHODS: Our estimates are based on triangulation of data from blood bank testing records, cross-sectional and longitudinal observational studies, and published literature. We calculated subpopulation estimates based on biological sex, age and/or HCV risk group. When multiple sources of data were available for subpopulation estimates, we calculated an average using inverse variance weighting. Plausible ranges (PRs) were conservatively estimated to convey uncertainty. RESULTS: The total number of people estimated to have anti-HCV antibodies in San Francisco in 2019 was 22,585 (PR:12,014-44,152), with a citywide seroprevalence of 2.6% (PR:1.4%-5.0%)-similar to the 2015 estimate of 21,758 (PR:10,274-42,067). Of all people with evidence of past or present infection, an estimated 11,582 (PR:4,864-35,094) still had untreated, active HCV infection, representing 51.3% (PR:40.5%-79.5%) of all people with anti-HCV antibodies, and 1.3% (PR:0.6%-4.0%) of all San Franciscans. PWID comprised an estimated 2.8% of the total population of San Francisco, yet 73.1% of people with anti-HCV antibodies and 90.4% (n = 10,468, PR:4,690-17,628) of untreated, active HCV infections were among PWID. MSM comprised 7.8% of the total population, yet 11.7% of people with anti-HCV antibodies and 1.0% (n = 119, PR:0-423) of those with untreated active infections. Low SES TW comprised an estimated 0.1% of the total population, yet 1.4% of people with HCV antibodies and 1.6% (n = 183, PR:130-252) of people with untreated active infections. CONCLUSIONS: Despite the above-average number (2.6%) of people with anti-HCV antibodies, we estimate that only 1.3% (PR:0.6%-4.0%) of all San Francisco residents have untreated, active HCV infection-likely a reflection of San Francisco's robust efforts to diagnose infection among high-risk groups and initiate curative treatment with as many people as possible. While plausible ranges of infections are wide, these findings indicate that while the overall number of people with anti-HCV antibodies may have increased slightly, the number of people with active HCV infection may have decreased slightly since 2015. This estimate improves upon the 2015 calculations by directly estimating the impact of curative treatment citywide and in subgroups. However, more research is needed to better understand the burden of HCV disease among other subgroups at high risk, such as Blacks/African Americans, people with a history of injection drug use (but not injecting drugs in the last 12 months), people who are currently or formerly incarcerated, and people who are currently or formerly unhoused.

How do we form and coordinate a national serosurvey of SARS-CoV-2 within the blood collection industry?

BACKGROUND: A national serosurvey of U.S. blood donors conducted in partnership with the Centers for Disease Control and Prevention (CDC) was initiated to estimate the prevalence of SARS-CoV-2 infections and vaccinations. METHODS: Beginning in July 2020, the Nationwide Blood Donor Seroprevalence Study collaborated with multiple blood collection organizations, testing labs, and leadership from government partners to capture, test, and analyze approximately 150,000 blood donation specimens per month in a repeated, cross-sectional seroprevalence survey. RESULTS: A CDC website (https://covid.cdc.gov/covid-data-tracker/#nationwide-blood-donor-seroprevalence) provided stratified, population-level results to public health professionals and the general public. DISCUSSION: The study adapted operations as the pandemic evolved, changing specimen flow and testing algorithms, and collecting additional data elements in response to changing policies on universal blood donation screening and administration of SARS-CoV-2 spike-based vaccines. The national serosurvey demonstrated the utility of serosurveillance testing of residual blood donations and highlighted the role of the blood collection industry in public-private partnerships during a public health emergency.

A novel high performing multiplex immunoassay Multi-HTLV for serological confirmation and typing of HTLV infections.

BACKGROUND: Human T-Cell Lymphotropic Viruses (HTLV) type 1 and type 2 account for an estimated 5 to 10 million infections worldwide and are transmitted through breast feeding, sexual contacts and contaminated cellular blood components. HTLV-associated syndromes are considered as neglected diseases for which there are no vaccines or therapies available, making it particularly important to ensure the best possible diagnosis to enable proper counselling of infected persons and avoid secondary transmission. Although high quality antibody screening assays are available, currently available confirmatory tests are costly and have variable performance, with high rates of indeterminate and non-typable results reported in many regions of the world. The objective of this project was to develop and validate a new high-performance multiplex immunoassay for confirmation and discrimination of HTLV-1 and HTLV-2 strains. METHODOLOGY/PRINCIPAL FINDINGS: The multiplex platform was used first as a tool to identify suitable antigens and in a second step for assay development. With data generated on over 400 HTLV-positive blood donors sourced from USA and French blood banks, we developed and validated a high-precision interpretation algorithm. The Multi-HTLV assay demonstrated very high performance for confirmation and strain discrimination with 100% sensitivity, 98.1% specificity and 100% of typing accuracy in validation samples. The assay can be interpreted either visually or automatically with a colorimetric image reader and custom algorithm, providing highly reliable results. CONCLUSIONS/SIGNIFICANCE: The newly developed Multi-HTLV is very competitive with currently used confirmatory assays and reduces considerably the number of indeterminate results. The multiparametric nature of the assay opens new avenues to study specific serological signatures of each patient, follow the evolution of infection, and explore utility for HTLV disease prognosis. Improving HTLV diagnostic testing will be critical to reduce transmission and to improve monitoring of seropositive patients.

Zika virus RNA and IgM persistence in blood compartments and body fluids: a prospective observational study.

BACKGROUND: Characterisation of the dynamics of Zika virus persistence following acute infection is needed to inform blood donor and diagnostic testing policies and understand the natural history of Zika virus infection. We aimed to characterise the natural history, persistence, and clinical outcomes of Zika virus infection through a prospective study in initially asymptomatic Zika virus RNA-positive blood donors. METHODS: Zika virus-infected blood donors identified through Zika virus nucleic acid amplification test (NAAT) screening at three blood collection organisations in the USA were enrolled into a 1-year follow-up study, with blood and body fluid samples and detailed symptom data collected at up to seven visits. All samples were tested for Zika virus RNA by real-time PCR (rtPCR); follow-up plasma, whole blood, and urine were also tested by replicate NAAT. Plasma was tested for flavivirus-specific IgM and IgG by ELISA. Zika virus RNA persistence for each assay or sample type and plasma antibody persistence from estimated date of plasma NAAT-detectable infection were calculated from follow-up data using survival statistical methods. FINDINGS: Between July 6, 2016 and March 7, 2017, we enrolled 53 participants. From the estimated date of plasma NAAT-detectable infection, Zika virus RNA was detectable in plasma for 9·9 days (95% CI 8·1-12·0), in red blood cells for 95·4 days (62·8-129·1), and in whole blood for 73·5 days (39·8-107·5). Replicate NAATs (one or more of eight replicates positive) extended detection of Zika virus RNA in plasma to 34·8 days (19·9-56·2) and in whole blood (at least one of two tests positive) to 104·8 days (76·7-129·9). Urine was rtPCR reactive up to 14·5 days (10·5-20·3) and saliva up to 26·4 days (19·7-38·7). Zika virus IgM persisted for 237·7 days (128·7-459·5) from estimated time since plasma NAAT-detectable infection. Zika virus RNA fell below detectable limits more rapidly in the saliva of participants with pre-existing dengue virus IgG than in those without. Of 25 donors identified pre-seroconversion with symptom data at the first or second study visit, 16 (64%) developed multiple Zika virus-related symptoms after asymptomatic index donations, compared with nine (36%) of 25 donors detected after seroconversion. INTERPRETATION: Determination of viral marker persistence is enhanced by follow-up of blood donors who are pre-symptomatic or asymptomatic, Zika virus RNA-positive, and antibody negative. Zika virus RNA persists in red blood cells for several months following clearance from plasma and body fluids, and replicate, highly sensitive NAATs extend RNA detection in all compartments. Whole blood testing can extend detection of acute infection for diagnostics and monitoring of pregnant women, sexual partners, and travellers. FUNDING: National Heart, Lung, and Blood Institute, Biomedical Advanced Research and Development Authority.

Early and sustained improvement in fatigue-related quality of life following red blood cell transfusion in outpatients.

PURPOSE: Outpatients with hematologic disease often receive red cell transfusion to treat anemia and fatigue. The effect of transfusion on fatigue-related quality of life and how well this effect is sustained has not been quantified. The study aim was to describe the early and sustained impact over 4 weeks of red cells on patient-reported fatigue in outpatients age ≥ 50 receiving transfusion as routine clinical care. METHODS: FACIT-Fatigue scale scores were measured pre-transfusion and at visits targeting 3, 7, and 28 days post-transfusion. Group-based trajectory modeling of patient fatigue scores by study day was used to identify the number of distinct trajectories (Groups), then longitudinal mixed effects modeling of fatigue scores was used to estimate group-specific mean improvements early after transfusion and between days 3 and 28 post-transfusion. RESULTS: Four distinct fatigue score trajectory groups were identified and were found to be correlated with baseline fatigue scores (means 12, 26, 34, and 47 points). In the three groups with the lowest fatigue trajectories (indicating greater fatigue), improvements in fatigue early after transfusion achieved the established minimum clinically important difference (≥ 3 points, Group p = 0.0039). In all trajectory groups, mean fatigue levels did not change significantly between 3 and 28 days (± 1 point, Group p = 0.60). CONCLUSION: Patient-reported fatigue varies widely among older adult outpatients with hematologic disorders. Nonetheless, trajectory modeling suggests that most anemic patients can expect a noticeable improvement in fatigue in the first few days after transfusion that generally is sustained up to 4 weeks.

Proficiency Testing of Viral Marker Screening in African Blood Centers - Seven African Countries, 2017.

A 2014 report evaluating accuracy of serologic testing for transfusion-transmissible viruses at African blood center laboratories found sensitivities of 92%, 87%, and 90% for detecting infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), respectively (1). Following substantial investments in national blood transfusion service (NBTS) laboratories, in 2017 investigators tested proficiency at 84 blood center laboratories (29 NBTS and 55 non-NBTS) in seven African countries. A blinded panel of 25 plasma samples was shipped to each participating laboratory for testing with their usual protocols based on rapid diagnostic tests (RDTs) (2) and third and fourth generation enzyme immunoassays (EIA-3 and EIA-4). Sensitivity and specificity were estimated using separate regression models that clustered assays by laboratory and adjusted for assay type and NBTS laboratory status. Mean specificities were ≥95% for all three viruses; however, mean sensitivities were 97% for HIV-positive, 76% for HBV-positive, and 80% for HCV-positive samples. Testing sensitivities for all viruses were high when EIA-3 assays were used (≥97%). Lower sensitivities for HBV-positive samples and HCV-positive samples were associated with assay types other than EIA-3, used primarily by non-NBTS laboratories. Proficiency for HIV testing has improved following international investments, but proficiency remains suboptimal for HBV and HCV testing. In sub-Saharan African blood centers, the quality of rapid tests used for HBV and HCV screening needs to be improved or their use discouraged in favor of EIA-3 tests.

The prevalence of human T-lymphotropic virus type 1 & 2 (HTLV-1/2) in South African blood donors.

BACKGROUND AND OBJECTIVES: Donated blood is not currently screened for human T-cell lymphotropic virus (HTLV) in South Africa. Several small studies have detected HTLV-1 in South Africa, but prevalence by geographic region or population group is unavailable. MATERIALS AND METHODS: We performed a large seroprevalence study of South African blood donors during 3 months in 2013. All geographic regions except the Western Cape were included, and Black and Coloured (local term for mixed race) donors were oversampled. Identity-unlinked plasma samples were screened with the Abbott Prism HTLV-1/2 assay, and repeatedly reactive samples were tested by the Inno-LIA HTLV-1/2 Score confirmatory assay. Odds ratios were calculated with multivariable logistic regression. RESULTS: Of 46 752 donors tested, 133 (0·28%) were initially reactive, 111 (0·24%) repeatedly reactive and 57 (0·12%) confirmed positive for HTLV-1; none were HTLV-2 positive. Prevalence was 0·062% weighted to annual blood donations but highly concentrated in the Black population group (OR = 20·24 CI: 2·77-147·88); higher in females than males (OR = 1·81 CI: 1·06-3·08); and in donors aged >50 years compared to ages 16-19 (OR = 6·4 CI: 2·95-13·86). After controlling for age, sex and population group, there was no difference in prevalence between new and repeat blood donors or among geographic regions within South Africa. CONCLUSIONS: We conclude that HTLV-1 infection is widespread among the Black population of South Africa and its epidemiology is similar to other endemic areas. Because South Africa is increasing its recruitment of Black blood donors, the implications for blood screening require further consideration.

Implementation of a script for predonation interviews: impact on human immunodeficiency virus risk in South African blood donors.

BACKGROUND: The way in which the donor history questionnaire is conducted plays a crucial role in the self-disclosure of behavioral risk factors for human immunodeficiency virus (HIV) infection by prospective donors. The South African National Blood Service changed its policy on the process of donor assessment in May 2015 by implementing a compulsory interviewer script used to assess donor eligibility. STUDY DESIGN AND METHODS: A pre- and postevaluation study to determine the impact of scripted interviews on high-risk deferrals and recently acquired HIV infections. We used historical data to compare 18 months before and after the implementation of the script. RESULTS: We recorded a total of 3,169,656 donor presentations during the two 18-months periods, of which 52.2% (1,655,352) were made during the scripted period. A multivariable logistic regression analysis adjusting for donor and demographic characteristics found the odds of high-risk deferral to be slightly greater (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.05-1.07) during the scripted period. A separate multivariate logistic regression model, also adjusting for donor and demographic characteristics, showed that the odds of recently acquired HIV infection were significantly lower (OR, 0.88; 95% CI, 0.79-0.97) during the scripted period. CONCLUSION: This study showed that implementation of a scripted interview was associated with increased HIV risk deferral and decreased recent HIV infection. This study indicates potential improvement in blood safety with the implementation of a scripted donor interview and has relevance to blood safety in other sub-Saharan African countries.

Does deferral for high-risk behaviors improve the safety of the blood supply?

BACKGROUND: Predonation donor deferral is used to select donors with presumed lower risk for transfused transmitted infections. The contribution to blood safety from this practice has not been reported previously for Brazil. STUDY DESIGN AND METHODS: At four large Brazilian blood centers from September 2010 to March 2011, donors who were deferred due to responses on eligibility questions were invited to provide a blood sample to test for HIV, hepatitis C virus, hepatitis B virus, human T-lymphotropic virus, syphilis, and Trypanosoma cruzi and complete an audio computer-assisted structured interview on risk behaviors. RESULTS: Of 299,848 potential donors during the study period, 66,870 were deferred with 10,453 (15.6%) for high-risk behaviors. Of those, 4860 (46.5%) were consecutively approached and 4013 (82.5%) participated. Disclosed risk behaviors by audio computer-assisted structured interview included 4 or more sexual partners in the past 12 months (15.0% of females [F] and 34.5% of males [M]), unprotected sex (62.0% F and 44.0% M), other high-risk sexual exposure (85.0% F and 73.0% M), being a person who injects drugs (3.0% F and 10.0% M), and test-seeking (17.0% F and 22.0% M). Eleven percent of deferred males reported male-to-male sex. Individuals who reported other high-risk sexual exposure, sexual partner risk, or male-to-male sex had the highest frequency of confirmed HIV: 1.2, 0.7, and 0.7%, respectively. Individuals who reported male-to-male sex, sexual partner risk, test seeking, and unprotected sex had the highest frequency of confirmed syphilis: 3.8, 3.3, 2.4, and 2.0%, respectively. CONCLUSION: Donor deferral deters donation by individuals with risk behaviors and elevated rates of infectious disease markers.

Ultraviolet light-based pathogen inactivation and alloimmunization after platelet transfusion: results from a randomized trial.

BACKGROUND: The current study explored whether pathogen-reduction treatment of platelet components before transfusion would decrease the risk of alloimmunization. STUDY DESIGN AND METHODS: Study participants were patients with hematologic cancer who were included in two parallel, randomized clinical trials testing pathogen-reduction treatment versus conventional platelets using the Mirasol or Intercept pathogen-reduction systems. Patients who had a baseline, pretransfusion sample and a follow-up, posttransfusion sample were included in the study (n = 179 patients in each study arm). Human leukocyte antigen antibody levels were determined using a commercial multianalyte, bead-based assay. RESULTS: The rate of human leukocyte antigen Class I alloimmunization at the clinical sites in recipients of conventional platelets was low at the highest assay cutoff (range, 1.2%-5.9%). Consistent with prior studies, human leukocyte antigen antibodies were first detected from 3 to 35 days after transfusion. There were no statistically significant differences between alloimmunization rates in patients who received pathogen-reduction treatment versus conventional platelet transfusions. Although he difference was not statistically significant, the effect size for protection from alloimmunization was greatest for high-level human leukocyte antigen Class I antibodies (approximately threefold) in the Intercept-treated patients compared with those who received conventional platelets. In the Mirasol study, only two patients and one patient in the control group developed medium-level or high-level antibodies, respectively, so it was impossible to determine an effect size for potential protection. CONCLUSIONS: The current study was not sufficiently powered to determine whether pathogen-reduction treatment provides protection from human leukocyte antigen alloimmunization in platelet transfusion recipients. The data presented will be useful in the design of future trials and endpoints powered to detect a protective effect.

Cytokines Elevated in HIV Elite Controllers Reduce HIV Replication In Vitro and Modulate HIV Restriction Factor Expression.

A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4+ T cells, and individually SDF-1ß, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1ß, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4+ T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies.IMPORTANCE Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the exact mechanisms of how their immune responses control infection are not known. In this study, we identified five soluble immune signaling molecules (cytokines) in the blood that were higher in ECs than in subjects with typical chronic HIV infection. We demonstrated that these cytokines can activate CD4+ T cells, the target cells for HIV infection. Furthermore, these five EC-associated cytokines could change expression levels of intrinsic resistance factors, or molecules inside the target cell that fight HIV infection. This study is significant in that it identified cytokines elevated in subjects with a good immune response against HIV and defined potential mechanisms as to how these cytokines could induce resistance to the virus in target cells.

Correlation of West Nile Virus Incidence in Donated Blood with West Nile Neuroinvasive Disease Rates, United States, 2010-2012.

Over the past decade, West Nile virus (WNV) has spread across the United States. We aggregated blood donor data from 2010-2012 and then calculated the incidence of WNV RNA-positive donations and compared the incidence with neuroinvasive disease (NID) case data from the ArboNET surveillance system. Of 10,107,853 donations, 640 were confirmed positive. The seasonal WNV incidence rate per 100,000 persons was 33.4 (95% CI 22-45) in 2010, 25.7 (95% CI 15-34) in 2011, and 119.9 (95% CI 98-141) in 2012. NID to blood donor ratios were 1 in 164 (95% CI 152-178) in 2010, 1 in 158 (95% CI 145-174) in 2011, and 1 in 131 (95% CI 127-136) in 2012. We updated estimates of the ratio of NID to WNV infection rates, demonstrating stable disease penetrance over the study period. Blood donor WNV RNA screening is a valuable public health tool for WNV surveillance.

Development of a multisystem surveillance database for transfusion-transmitted infections among blood donors in the United States.

BACKGROUND: The frequency of positive test results for transfusion-transmitted infections (TTIs) among blood donors is an important index of safety; thus, appropriate monitoring is critical, particularly when there are changes in policies affecting donor suitability. STUDY DESIGN AND METHODS: Testing algorithms from three large blood systems were reviewed and consensus definitions for a surveillance-positive result for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) established. In addition, information on each donation, including donor demographics and location, was collected. Combined data were analyzed to characterize the epidemiology of TTIs by person, place, and time. RESULTS: Data from 14.8 million donations were collected for 2011 to 2012, representing more than 50% of the US blood supply. Surveillance-positive rates per 10,000 donations were as follows: HBV, 0.76; HCV, 2.0; HIV, 0.28; and HTLV 0.34. Rates did not vary between the 2 years, although there was variation within a year. With the exception of HTLV, rates were higher among males, and all rates were higher among first-time donations. Window-period donations (those positive only in nucleic acid tests) were infrequent (HBV, 13; HCV, 60; HIV, 14) during the 2-year period. Frequencies of surveillance-positive results varied by donor age and residence location. CONCLUSIONS: We demonstrated that standardized data from multiple major US blood systems can be combined and analyzed for change. However, TTI frequencies are low, impacting their sensitivity to change. Furthermore, observed fluctuations in TTI frequencies may be secondary to changes in blood donor demographics rather than necessarily reflecting the immediate impact of policy modification.

Characterization of Simian Immunodeficiency Virus Variants Anatomically Compartmentalized in Plasma and Milk in Chronically Infected African Green Monkeys.

UNLABELLED: Unlike human immunodeficiency virus type 1 (HIV-1)-infected humans, African-origin, natural simian immunodeficiency virus (SIV) hosts, such as African green monkeys (AGMs), sustain nonpathogenic SIV infections and rarely vertically transmit SIV to their infants. Interestingly, chronically SIV-infected AGMs have anatomically compartmentalized SIV variants in plasma and milk, whereas humans and SIV-infected rhesus monkeys (RMs), Asian-origin nonnatural SIV hosts, do not exhibit this compartmentalization. Thus, it is possible that AGM SIV populations in milk have unique phenotypic features that contribute to the low postnatal transmission rates observed in this natural host species. In this study, we explored this possibility by characterizing the infectivity, tropism, and neutralization susceptibility of plasma and milk SIVsab env variants isolated from chronically SIVsab92018ivTF-infected AGMs. AGM plasma and milk SIVsab env pseudovirus variants exhibited similar infectivities, neutralization susceptibilities to autologous and heterologous plasma, and chemokine coreceptor usages for cell entry, suggesting similar abilities to initiate infection in a new host. We also assessed the cytokine milieu in SIV-infected AGM milk and compared it to that of SIV-infected RMs. MIP-1ß, granulocyte colony-stimulating factor (G-CSF), interleukin-12/23 (IL-12/23), and IL-13 trended significantly higher in SIV-infected AGM milk than in that of RMs, while IL-18 and IL-6 trended significantly higher in SIV-infected RM milk than in that of AGMs. Taken together, our findings imply that nonviral maternal factors, such as the cytokine milieu, rather than unique characteristics of SIV populations in the milk contribute to the low postnatal transmission rates observed in AGMs. IMPORTANCE: Due to the ongoing global incidence of pediatric HIV-1 infections, including many that occur via breastfeeding, development of effective vaccine strategies capable of preventing vertical HIV transmission through breastfeeding remains an important goal. Unlike HIV-1-infected humans, African green monkeys (AGMs), the natural SIV host species, sustain nonpathogenic SIV infections, rarely transmit the virus postnatally to their infants, and exhibit anatomically compartmentalized SIV populations in milk and plasma. Identifying unique features of the anatomically compartmentalized milk SIV populations could enhance our understanding of how AGMs may have evolved to avoid transmission through breastfeeding. While this study identified limited phenotypic distinctions between AGM plasma and milk SIV populations, potential differences in milk cytokine profiles of natural and nonnatural SIV hosts were observed. These findings imply the potential importance of nonviral factors in natural SIV host species, such as innate SIV/HIV immune factors in milk, as a means of naturally preventing vertical transmission.

Blood group A and D negativity are associated with symptomatic West Nile virus infection.

BACKGROUND: West Nile virus (WNV) infection is mostly asymptomatic (AS) but 20% of subjects report WNV fever and 1% of patients experience neurologic diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic (S) infections, it is essential to understand prognostic factors influencing S disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. This study investigates the association between the ABO and D blood group status and WNV disease outcome. STUDY DESIGN AND METHODS: The distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 AS and 130 S WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O, and D blood groups and WNV clinical disease outcome. RESULTS: S WNV+ donors exhibited increased frequencies of blood group A (S 47.6%, AS 36.8%, p = 0.04; odds ratio [OR], 1.56; 95% confidence interval [CI], 1.01-2.40) and D- individuals (S 21.5%, AS 13.1%, p = 0.03; OR, 1.82; 95% CI, 1.04-3.18). CONCLUSION: The findings suggest a genetic susceptibility placing blood group A and D- individuals at risk for the development of S disease outcome after WNV infection.

A retrospective analysis of false-positive infectious screening results in blood donors.

BACKGROUND: False-positive infectious transfusion screening results remain a challenge with continued loss of both donors and blood products. We sought to identify associations between donor demographic characteristics (age, race, sex, education, first-time donor status) and testing false positive for viruses during routine blood donation screening. In addition the study assessed the prevalence of high-risk behaviors in false-positive donors. STUDY DESIGN AND METHODS: Blood Systems, Inc. donors with allogeneic donations between January 1, 2011, and December 31, 2012, were compared in a case-control study. Those with a false-positive donation for one of four viruses (human immunodeficiency virus [HIV], human T-lymphotropic virus [HTLV], hepatitis B virus [HBV], and hepatitis C virus [HCV]) were included as cases. Those with negative test results were controls. For a subset of cases, infectious risk factors were evaluated. RESULTS: Black race and Hispanic ethnicity were associated with HCV and HTLV false-positive results. Male sex and lower education were associated with HCV false positivity, and age 25 to 44 was associated with HTLV false positivity. First-time donors were more likely to be HCV false positive although less likely to be HBV and HTLV false positive. No significant associations between donor demographics and HIV false positivity were observed. A questionnaire for false-positive donors showed low levels of high-risk behaviors. CONCLUSION: Demographic associations with HCV and HTLV false-positive results overlap with those of true infection. While true infection is unlikely given current testing algorithms and risk factor evaluation, the findings suggest nonrandom association. Further investigation into biologic mechanisms is warranted.

Demographic determinants of syphilis seroprevalence among U.S. blood donors, 2011-2012.

BACKGROUND: No cases of transfusion-transmitted syphilis have been described for over four decades. While there is mandatory transfusion screening for syphilis, the absence of transmission is in part ascribed to a low prevalence of syphilis in the blood donor population, the concomitant use of antibiotics in a high proportion of transfusion recipients, allied with poor survival of T. pallidum during refrigerated storage of blood products. METHODS: A cross-sectional retrospective data analysis was conducted to ascertain the prevalence of Treponema pallidum antibodies in U.S. blood donors by demography and geography. Routine blood donation testing data and demographics were extracted from the data warehouse of a large network of U.S. blood centers. Crude and adjusted prevalence of T. pallidum antibodies and active syphilis infection were calculated, and GIS mapping was used to illustrate geographic distribution. RESULTS: The prevalence of T. pallidum seropositivity and active syphilis in first time donors was 162.6 (95% CI 145.5-181.2) per 100,000 donors and 15.8 (95% CI 10.8-22.3) per 100,000 donors, respectively. The odds of T. pallidum seropositivity were significantly elevated in African American (OR = 18.9, 95% CI 14.2-25.2), and Hispanic (OR = 2.8, 95% CI 2.0-3.8) as compared to Caucasian donors. Similarly, the odds of active T. pallidum infections were significantly higher in African American (OR 15.0, 95% CI 7.0-32.3) and Hispanic (OR = 5.8, 95% CI 2.9-11.6) as compared to Caucasian donors. Syphilis seropositivity was associated with first time blood donation, increasing age, lower education, birth outside the US, and positive tests for HIV and HCV. Geographically, T. pallidum seropositivity was increased in southern and western regions of the US. CONCLUSIONS: Given the low seroprevalence of syphilis in blood donors, continued screening remains debatable; however it may provide a public health benefit through surveillance of at-risk populations.

West Nile virus nucleic acid persistence in whole blood months after clearance in plasma: implication for transfusion and transplantation safety.

BACKGROUND: Previous reports of West Nile virus (WNV) RNA persistence in blood compartments have raised concerns around the remaining risk of WNV transfusion transmission. This study characterized the dynamics of WNV viremia in blood compartments in a longitudinal cohort of 54 WNV-infected blood donors. STUDY DESIGN AND METHODS: Blood samples were collected throughout the year after WNV RNA-positive blood donation (index) and characterized for WNV immunoglobulin (Ig)M and IgG antibodies and for WNV RNA by real-time reverse transcription-polymerase chain reaction. WNV viral loads were compared in plasma and whole blood samples and correlated with blood groups and clinical outcomes. RESULTS: WNV RNA persisted in the red blood cell (RBC) compartment up to 3 months postindex in 42% of the donors. Donors with the highest WNV RNA levels in plasma at index maintained the highest WNV RNA levels in whole blood over the 3 months postindex. Blood group A donors maintained higher postindex WNV viral load in whole blood than blood group O individuals (p = 0.027). Despite a trend for WNV RNA to persist longer in whole blood from symptomatic subjects, no significant association was found between WNV RNA levels in whole blood and disease outcome. CONCLUSION: This study confirmed that WNV RNA persists in the RBC fraction in whole blood and further suggested that the level of persistence in whole blood may be a reflection of initial viral burden in plasma. The association with blood groups suggests that WNV adherence to RBCs may be mediated by molecules overrepresented at the surface of blood group A RBCs.

Seroprevalence and demographic determinants of human T-lymphotropic virus type 1 and 2 infections among first-time blood donors--United States, 2000-2009.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 are prevalent at low levels among US blood donors, but recent data on their prevalence is lacking. METHODS. Data on all first-time blood donors in a large network of US blood centers were examined during 2000-2009. HTLV-1 and HTLV-2 antibodies were measured by enzyme immunoassay (EIA) with confirmation by immunofluorescence or recombinant immunoblot. Prevalence rates were calculated, and odds ratios were assessed using multivariable logistic regression. RESULTS: Among 2 047 740 first-time donors, 104 were seropositive for HTLV-1 (prevalence, 5.1 cases/per 100 000; 95% confidence interval [CI], 4.1-6.1), and 300 were seropositive for HTLV-2 (prevalence, 14.7 cases/per 100 000; 95% CI, 13.0-16.3). The prevalence was lower than reported in the 1990s but stable from 2000 to 2009. HTLV-1 seropositivity was associated with female sex, older age, and black and Asian race/ethnicity. HTLV-2 seropositivity was associated with female sex, older age, nonwhite race/ethnicity, lower educational level, and residence in the western and southwestern United States. CONCLUSIONS: The HTLV-1 and HTLV-2 prevalences among US blood donors has declined since the early 1990s. A higher prevalence of HTLV-2 in the west and southwest may be attributed to endemic foci among Amerindians.