Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE4 Carriers before the Onset of Dementia.

INTRODUCTION: Lower blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) are correlated with worse cognitive functions, particularly among APOE ε4 carriers. Whether DHA supplementation in APOE ε4 carriers with limited DHA consumption and dementia risk factors can delay or slow down disease progression when started before the onset of clinical dementia is not known. METHODS: PreventE4 is a double-blind, single site, randomized, placebo-controlled trial in cognitively unimpaired individuals with limited omega-3 consumption and dementia risk factors (n=368). Its objectives are to determine (1) whether carrying the APOE ε4 allele is associated with lower delivery of DHA to the brain; and (2) whether high dose DHA supplementation affects brain imaging biomarkers of AD and cognitive function. RESULTS: 365 cognitively unimpaired individuals between 55 and 80 (mean age 66) were randomized to 2 grams of DHA per day or identically appearing placebo for a period of 2 years. Half the participants were asked to complete lumbar punctures at baseline and 6-month visits to obtain cerebrospinal fluid (CSF). The primary trial outcome measure is the change in CSF DHA to arachidonic acid ratio after 6 months of the intervention (n=181). Secondary trial outcomes include the change in functional and structural connectivity using resting state functional MRI at 24 months (n=365). Exploratory outcomes include the change in Repeatable Battery of the Assessment of Neuropsychological Status at 24 months (n=365). CONCLUSIONS: Findings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.

Simian foamy virus infection in a blood donor.

BACKGROUND: Infections with simian foamy virus (SFV) are widely prevalent in nonhuman primates. SFV infection was confirmed in a worker, occupationally exposed to nonhuman primates, who donated blood after the retrospectively documented date of infection. Human-to-human transmission of SFV through transfusion and its pathogenicity have not been studied. STUDY DESIGN AND METHODS: Recipients of blood from this donor were identified and blood samples from such recipients were tested for SFV infection by Western blot and PCR assay. RESULTS: One recipient of RBCs and another recipient of FFP had died; retroviral infections were not implicated. One platelet recipient could not be tested. Recipients of RBCs (two), a WBC-reduced RBC unit (one), and a platelet unit (one) tested SFV-negative 19 months to 7 years after transfusion. Tested recipients had transfusions 3 to 35 days after blood donation. Samples of one lot of albumin and three lots of plasma protein fraction (manufactured from recovered plasma from two donations) tested negative both for antibodies and for viral RNA. CONCLUSION: SFV transmission through transfusion was not identified among four recipients of cellular blood components from one SFV-infected donor. Derivatives containing plasma from that donor tested negative for SFV.

Seroprevalence of known and putative hepatitis markers in United States blood donors with ALT levels at least 120 IU per L.

BACKGROUND: ALT testing of blood donors was initiated as a surrogate marker for non-A, non-B hepatitis. Increased sensitivity of subsequent HBV and HCV tests used for standard donor screening make any residual value of ALT testing questionable. STUDY DESIGN AND METHODS: A prospective study was conducted in 166 of 645 eligible blood donors from three American Red Cross regions whose ALT was > or =120 IU per L and whose standard donor screening tests were negative. Of these enrolled donors, 124 (75%) completed follow-up. Samples obtained from the index donation, at enrollment (1 month), and at follow-up (6 months) underwent the standard donor screening tests, as well as those for HCV RNA and HGV RNA (RT-PCR), antibodies to the virus envelope E2 protein of GB virus type C (GBV-C E2 antibody), and IgM antibody for CMV, parvovirus B19, EBV VCA, and HAV. Participants completed a brief demographic and exposure history questionnaire at follow-up. RESULTS: All study samples were negative in standard donor-screening tests. ALT levels were variable at return visits, with 80 to 86 percent <120 IU per L. No participants were positive for HCV RNA; 4 percent were positive for HGV RNA, and 10 percent were positive for GBV-C E2 antibody. Results of CMV, parvovirus B19, EBV VCA, and HAV testing were similar to published background rates. No demographic or exposure history variables had significant correlation with ALT or other testing results. CONCLUSION: These data suggest that an ALT > or =120 IU per L in blood donors with negative standard screening tests has questionable value as a surrogate marker for seronegative HBV or HCV infection. Continued ALT testing may contribute little, if anything, to the safety of blood components or plasma for further manufacture.

Indications for therapeutic plasma exchange at a university hospital and a regional blood center.

The AABB guidelines for therapeutic plasma exchange (TPE) are divided into four categories: I. TPE is "standard and acceptable therapy," II. "generally accepted," III. "insufficient evidence to evaluate efficacy," and IV. "data suggest no therapeutic efficacy." Since little is known about the implementation of these guidelines, and since the indications for TPE may vary, depending upon an institution's patient mix, this study reviewed the indications and their categories for two co-located institutions. A retrospective review of the indications for all patients undergoing TPE from January 1, 1994 to December 31,1997 at Emory University Hospital (EUH), a tertiary-care teaching hospital, and the American Red Cross (ARC), a regional blood center, using AABB criteria (ASFA criteria used when not rated [NR] by AABB) was conducted. Categories I/II represented 75% and 88% of cases (EUH and ARC, respectively), while Categories III/IV/NR (NR as used below is "not rated" by both AABB and ASFA criteria; n is number of patients) were 25% and 12% of indications, respectively (P =0.002). Cases at EUH (n=101) were I, 62%; II, 13%; III, 3%; IV, 13%; and NR, 9%. Cases at ARC (n=359) were I, 77%; II, 11%; III, 9%; IV, 0%; and NR, 3% (P<0.001). No Category IV patients underwent TPE at ARC (13% at EUH). Thrombotic thrombocytopenic purpura (TTP) was the most common indication for TPE at both centers. The majority of the procedures were "appropriate" (Categories III/); several disorders ( approximately 10%) for which TPE was utilized at both centers were NR by both AABB and ASFA guidelines. Indications for TPE may differ, depending on the type of requesting institution. Physicians requesting TPE for patients with disorders in Categories III/IV/NR should be more strongly encouraged to enter their patients into controlled trials to best evaluate the efficacy of TPE in inadequately-studied clinical situations. This might best be accomplished at university hospitals, where requests for Category III/IV/NR may be higher. A need exists for periodic updating of the AABB guidelines to include those diseases for which new information is available with regard to the potential therapeutic role of TPE.

Hemochromatosis probands as blood donors.

BACKGROUND: There has been no estimate of the potential eligibility of hemochromatosis probands or patients as blood donors or the suitability for transfusion of their blood that was removed by therapeutic phlebotomy. STUDY DESIGN AND METHODS: According to guidelines of the American Association of Blood Banks, a retrospective estimate of these factors in 211 adult white hemochromatosis probands diagnosed during routine medical care was performed. The findings were compared to those in volunteer white whole-blood donors. RESULTS: Before diagnosis of hemochromatosis, 49 probands had voluntarily donated 597 units of blood; 88 percent were donated by men. After diagnosis, 142 (67%) of 211 probands were potentially eligible. Data on each unit removed during iron-depletion therapy and during the first year of maintenance therapy (therapeutic phlebotomy) were available in 86 eligible probands. Of 1592 units, 1029 (65%) obtained during iron-depletion therapy in eligible probands were potentially suitable; 86 percent were from men. During maintenance therapy, 106 (88%) of 121 units from eligible probands were potentially suitable. In volunteer donors, 255,567 (94%) of 273,302 presenting donors were accepted. After testing and laboratory losses, 239,300 (94%) units were acceptable for transfusion. CONCLUSIONS: In comparison with normal volunteers, hemochromatosis probands at diagnosis are less likely to be eligible as blood donors. The percentage of units obtained from patients during iron-depletion therapy that are suitable for transfusion is also lower, although the percentage increases during maintenance therapy.

A survey of phlebotomy among persons with hemochromatosis.

BACKGROUND: One in 10 whites in the United States is a carrier for hemochromatosis and an estimated 1 in 200 is clinically affected. Early treatment with therapeutic phlebotomy to remove excess iron can prevent associated chronic diseases. However, little information is available on the amount of blood withdrawn or the rates of withdrawal from hemochromatosis patients. The patterns of therapeutic phlebotomy and the magnitude of charges in persons with hemochromatosis were surveyed. STUDY DESIGN AND METHODS: Surveys were mailed to persons with hemochromatosis identified by health care providers, blood centers, patient advocacy groups, and the Internet. There were 2362 respondents to the survey from the United States. RESULTS: Thirty-seven percent of respondents reported being voluntary blood donors prior to diagnosis. The mean rate of therapeutic phlebotomy for iron depletion was 2.6 units per month (mean duration, 13 months). The mean rate of maintenance phlebotomy was 0.5 units per month. Therapeutic phlebotomy rates varied by sex, age, reason for diagnosis, and severity of symptoms. Seventy-six percent of respondents reported full or partial insurance coverage of therapeutic phlebotomy charges. Seventy-six percent received therapeutic phlebotomy services in a hospital or physician's office and 30 percent in a blood center. Charges for therapeutic phlebotomy varied by site, with a mean cost of $90 in hospitals and $52 in blood centers. Fifty-four percent of respondents attempted to donate blood after their diagnosis but were excluded. CONCLUSION: The amount of blood withdrawn from persons with hemochromatosis is substantial. The location where patients received phlebotomy services appears to be influenced by charges and time since diagnosis.

Predictive value of past and current screening tests for syphilis in blood donors: changing from a rapid plasma reagin test to an automated specific treponemal test for screening.

BACKGROUND: This study evaluated the change from a rapid plasma reagin (RPR) test to an automated specific treponemal test (PK-TP) in screening for syphilis in blood donors. STUDY DESIGN AND METHODS: A cross-sectional seroprevalence analysis was performed on 4,878,215 allogeneic blood donations from 19 American Red Cross Blood Services regions from May 1993 through September 1995. Positive predictive values relative to the confirmatory fluorescent treponemal antibody absorption test (FTA-ABS) were calculated. Differences in seroprevalence were compared in RPR and PK-TP tests for 1) unconfirmed and confirmed tests, 2) first-time and repeat donors, and 3) "recent" versus "past" infections. Donation data from three additional Red Cross regions were evaluated for repeat donation patterns of blood donors who had a donation that was positive in a serologic screening test for syphilis. The value of RPR and PK-TP tests as surrogate markers for HIV infection was compared. RESULTS: Reactive rates were lower but the positive predictive values was higher for the PK-TP test than for the RPR test. Initially, donors screened by PK-TP were more likely to be confirmed as positive than were donors screened by RPR, but these rates became comparable. It is estimated that a single HIV window-period donation was removed by serologic testing for syphilis each year of this study period. CONCLUSIONS: The change to the PK-TP test resulted in a lower repeatedly reactive rate, better prediction that a confirmed-positive test for syphilis would occur in testing in the FTA-ABS, fewer donations lost, and comparable deferral rates. Because of the high rate of reactivity to serologic testing for syphilis among donors previously confirmed positive for syphilis, indefinite deferral after a confirmed-positive index donation may be warranted. Serologic testing for syphilis is ineffective as a marker of HIV-infectious window-period donations.

Hemochromatosis, iron, and blood donation: a short review.

Hereditary hemochromatosis (HH), an autosomal recessive disease of iron overload, is one of the most common inherited diseases. The candidate gene (HFE) for HH has been identified recently and a DNA-based test for the mutation is available. Treatment for HH patients with elevated iron stores include repeated phlebotomy. Left untreated, iron overload can lead to cirrhosis, organ failure, and a shortened life expectancy. In the past and present, blood collected for therapeutic purposes from patients with HH has been discarded. The aim of this article is to address whether blood collected from HH patients should be used for allogeneic transfusion in the future.

Assessment of motivations for return donation among deferred blood donors. American Red Cross ARCNET Study Group.

BACKGROUND: The recent addition of a computerized donor deferral registry to American Red Cross blood donation procedures has enabled blood center staffs to identify, before donation, persons who attempt to donate despite previous deferral. The current study investigated reasons that deferred donors return to donate, despite having been notified that they are ineligible. STUDY DESIGN AND METHOD: Anonymous mail surveys requesting demographic information, details of last donation or attempted donation, and assessments of incentives for donating were sent to 311 donors presenting inappropriately at blood drives and 849 matched controls in three American Red Cross regions between April and July 1996. RESULTS: Responses were received from a total of 113 deferred donors and 388 matched controls. Analysis of the 49 permanently deferred donors indicated that they were more likely than controls to donate blood to receive test results or to be awarded community service credit. Responses also revealed that some deferred donors may return to donate blood because of a misunderstanding of the deferral message or erroneous recruitment by blood center staff. CONCLUSION: There is a need before donation for the provision of educational materials regarding the window period of infection and for careful consideration of the use of incentives to attract donors to blood centers. It is also important to provide to donors a clear and consistent message regarding their test results and deferral status.

Human immunodeficiency virus infection among health care workers who donate blood.

OBJECTIVE: To estimate the prevalence of human immunodeficiency virus (HIV) infection among health care workers who donate blood. DESIGN: Point prevalence survey of blood donors. SETTING: 20 U.S. blood centers that participate in an ongoing interview study of HIV-seropositive blood donors. MEASUREMENTS: Prevalence rates for HIV in persons who reported being health care workers were measured directly for 6 of the 20 blood centers. For the other 14 centers, we derived the numerator from the interview study in the same manner used for the 6 centers; we estimated the denominator using blood collection logs at those centers and extrapolations from the survey completed at the 6 blood centers. RESULTS: Between March 1990 and August 1991, 8519 health care workers donated blood at 6 hospitals and other medical facilities. Three persons were HIV seropositive: Two reported being health care workers and having nonoccupational risk factors for HIV infection; the occupation and other possible risk factors of the third seropositive donor could not be determined. Therefore, the highest overall prevalence of HIV infection among health care worker donors at these 6 centers was 0.04% (3 of 8519; upper limit of 95% CI, 0.1%). We estimated that during the same period, approximately 36,329 health care workers were tested for HIV at all 20 centers. Twenty-seven persons infected with HIV who donated at hospitals were identified; 7 did not return for interviews, so their health care occupations could not be verified. Thus, the highest estimated overall prevalence of HIV infection among health care worker donors at the 20 centers was 0.07% (27 of 36,329; upper limit of CI, 0.1%). Of the 20 known health care worker donors, 11 reported nonoccupational risks for HIV infection; 3 of the remaining 9 health care workers described occupational blood exposures that could have resulted in transmission of HIV. CONCLUSIONS: Blood donors can serve as a sentinel cohort when evaluating the risk for occupationally acquired HIV infection. These findings suggest that among the many health care worker donors in this study, HIV infection attributable to occupational exposure was uncommon.

Duration of time from onset of human immunodeficiency virus type 1 infectiousness to development of detectable antibody. The HIV Seroconversion Study Group.

BACKGROUND: For persons newly infected with the human immunodeficiency virus type 1 (HIV-1), the time from the onset of infectivity to the development of detectable HIV-1 antibody is unknown. Persons who donate blood during this period account for nearly all instances of HIV-1 transmission from HIV-1 antibody-screened blood transfusions. STUDY DESIGN AND METHODS: To estimate the window period from infectivity to HIV-1 antibody positivity, 701 HIV-1-seropositive blood donors who made a previous seronegative donation at 40 United States blood centers were studied. The HIV-1 antibody status was determined for at least one recipient of blood from the seronegative donation preceding the seropositive donation made by 182 of the 701 donors. RESULTS: There were 39 seropositive recipients of blood from these 182 donors. Three donors were excluded from further analysis because the seropositive recipients of their blood had other HIV-1 risk factors or had HIV-1 infection before transfusion. The final study population comprised the remaining 179 donors, of whom 36 (20%) transmitted HIV-1 infection to recipients. When the interval between the seropositive donation and the preceding seronegative donation was less than 180 days, 46 percent of the donors transmitted HIV-1. In contrast, when that interval exceeded 540 days, only 2 percent transmitted HIV-1. A mathematical model was developed to explain the relationship between the probability that the previous seronegative donation occurred during the donor's window period of infectiousness, and hence transmitted HIV-1, as a function of both the window period and the duration between the seropositive and previous seronegative donations. This model indicated that the transmission data were most consistent with an average window period of 45 days. Assuming a log-normal window period distribution, it was estimated with 95 percent certainty that at least 90 percent of persons had a window period of less than 141 days. CONCLUSION: The window period averages 45 days, with few, if any, donors remaining infectious and seronegative for longer than 6 months.

Indeterminate HTLV serologic results in U.S. blood donors: are they due to HTLV-I or HTLV-II?

Current screening tests to detect human T-lymphotropic virus type I (HTLV-I) in volunteer blood donors commonly yield indeterminate HTLV serologic results (mostly isolated gag reactors). To assess the significance of indeterminate HTLV serologic results in U.S. blood donors, we compared 56 persons who had such serologic patterns with 30 HTLV seropositive blood donors and with HTLV seronegative controls. Polymerase chain reaction assays showed that none of the 56 individuals with indeterminate HTLV serologic results were infected with HTLV-I or HTLV-II, while all 30 HTLV seropositive blood donors were infected with either HTLV-I (in 15) or HTLV-II (in the other 15). The seroindeterminate blood donors were also different from the HTLV seropositive blood donors and more like HTLV seronegative controls in their demographic characteristics and the presence of HTLV risk factors. These results are evidence that volunteer blood donors with isolated and persistent gag seroreactivity in the United States are unlikely to be infected with HTLV-I or HTLV-II.

Sepsis associated with transfusion of red cells contaminated with Yersinia enterocolitica.

Between April 1987 and May 1989, the Centers for Disease Control investigated seven cases of transfusion-associated Yersinia enterocolitica sepsis; four were caused by organisms of serotype O:3, and one each was caused by organisms of serotype O:1,2,3; O:5,27; and O:20. All seven recipients developed septic shock after receiving units of red cells (RBCs) contaminated with Y. enterocolitica; five recipients died. The cases occurred in seven states and were unrelated. There was no evidence for contamination of the RBC units during processing. Six of the seven donors had serologic evidence of recent Y. enterocolitica infection, and it is hypothesized that these donors had asymptomatic bacteremia when they donated the implicated blood. Four of the seven donors reported gastrointestinal illness in the 4 weeks before blood donation, and one donor became ill on the day he donated blood. Y. enterocolitica grows well at 4 degrees C and in the presence of dextrose and iron. If blood is contaminated at the time of collection, storage of the RBCs at 4 degrees C provides an ideal environment for bacterial growth and endotoxin production. These cases demonstrate the need for careful evaluation of patients with transfusion reactions for possible sepsis and suggest a need to screen prospective blood donors for mild gastrointestinal illness, including those illnesses not requiring physician evaluation or medication.

Risk of HIV infection in recipients of untested blood from donors now anti-HIV-positive.

Recipients of untested blood from donors who at a subsequent donation were positive for HIV antibody by enzyme immunoassay (EIA) were evaluated, whether the result on Western blot (WB) assay was negative (EIA+/WB-) or positive (EIA+/WB+). For 109 EIA+/WB- donors, 78 recipients were tested for HIV antibody, and 3 (4%) were positive. Two of the three anti-HIV-positive recipients had clotting disorders, and the other had been massively transfused; in each of these three cases, subsequent test data exonerated the EIA+/WB- donor. For 101 current EIA+/WB+ donors, 35 recipients were tested for HIV antibody, and 13 (37%) were positive. For donors subsequently found to be EIA+/WB+, the rate of isolation of HIV was the same whether the recipients were anti-HIV-positive or anti-HIV-negative (each, 5/6). While recipients of blood from donors subsequently found to be EIA+/WB+ were at substantial risk for HIV infection, regardless of the donor's subsequent HIV culture result, risk of HIV infection was not demonstrated for recipients of blood from donors later found to be EIA+/WB-.

Epidemiologic characteristics of blood donors with antibody to human immunodeficiency virus.

From March 1985 through July 1986, blood donors who were positive for antibody to human immunodeficiency virus (HIV) were evaluated at three major blood centers in the United States. Of 818,629 donations, 450 (0.05%) were HIV antibody-positive. The seroprevalence decreased from 0.07 to 0.04 percent during the study period, due perhaps to a decline in repeat donors. HIV-seropositive donors tended to be 20 to 29 years old (52%) and male (88%). HIV seroprevalence among white donors (2/10,000 donations) was less than that among Hispanic (9/10,000; p less than 0.0001) and black donors (31/10,000; p less than 0.0001). Of 152 seropositive men interviewed, 77 percent reported sexual contact with men; of this latter group, 53 percent were bisexual. Fifteen (44%) of 34 seropositive women had apparently acquired infection from heterosexual contact, and an equal number denied having any known risk factors for HIV infection. Educational efforts must address women and bisexual men who do not perceive themselves to be at risk for HIV infection and should be specifically designed for the mores of different racial and ethnic groups.