The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance.

BACKGROUND: Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer. METHODS: The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background. RESULTS: EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102. CONCLUSION: EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.

MicroRNA-106b-25 cluster expression is associated with early disease recurrence and targets caspase-7 and focal adhesion in human prostate cancer.

The miR-106b-25 microRNA (miRNA) cluster is a candidate oncogene in human prostate cancer. Here, we report that miRNAs encoded by miR-106b-25 are upregulated in both primary tumors and distant metastasis. Moreover, increased tumor miR-106b expression was associated with disease recurrence and the combination of high miR-106b and low CASP7 (caspase-7) expressions in primary tumors was an independent predictor of early disease recurrence (adjusted hazard ratio=4.1; 95% confidence interval: 1.6-12.3). To identify yet unknown oncogenic functions of miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that CASP7 is a direct target of miR-106b, which was confirmed by western blot analysis and a 3'-untranslated region reporter assay. Moreover, selected phenotypes induced by miR-106b knockdown in DU145 human prostate cancer cells did not develop when both miR-106b and CASP7 expression were inhibited. Further analyses showed that CASP7 is downregulated in primary prostate tumors and metastatic lesions across multiple data sets and is by itself associated with disease recurrence and disease-specific survival. Using bioinformatics, we also observed that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally examined using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and disease outcome and may do so by altering apoptosis- and focal adhesion-related pathways.

Purification and identification of a 7.6-kDa protein in media conditioned by superinvasive cancer cells.

BACKGROUND: Selection of the human drug sensitive and invasive cell line (MDA-MB-435S-F) with the chemotherapeutic agent paclitaxel, resulted in the development of drug resistant cell lines displaying enhanced invasion-related characteristics. MATERIALS AND METHODS: Serum-free conditioned media from the human cancer drug-sensitive and invasive cell line (MDA-MB-435S-F) and its paclitaxel-resistant superinvasive variant (MDA-MB-435S-F/Taxol10p4pSI) were analyzed using Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). RESULTS: A differentially expressed protein was observed at 7.6 kDa, which was 4-fold up-regulated in MDA-MB-435S-F/Taxol10p4pSI. The differentially expressed protein was identified using matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS), as a fragment of bovine transferrin. The transferrin receptor was also found to be overexpressed in the superinvasive cell line. CONCLUSION: Cleavage of serum proteins such as transferrin could provide a valuable source of markers for malignant tumours and could also play a role in aspects of cancer pathogenesis, such as tumour cachexia.

The RADAR repository: a resource for studies of infectious agents and their transmissibility by transfusion.

BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent. RESULTS: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus. CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.

Does prevalence of transfusion-transmissible viral infection reflect corresponding incidence in United States blood donors?

BACKGROUND: Calculation of viral residual risk is dependent on estimating incidence, which is not easily obtainable by most blood centers. Prevalence, however, is readily available. Understanding whether prevalence reflects corresponding incidence may help blood centers monitor disease risks. STUDY DESIGN AND METHODS: With data on 12 million allogeneic donations, prevalence and incidence of transfusion-transmitted viral infections (TTVIs) were calculated. Relationships between prevalence (in total, first-time, and repeat donations) and incidence were analyzed for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) relative to temporal and donor demographic stratifications, respectively. RESULTS: Overall prevalence of HIV, HBV, and HCV did not consistently reflect corresponding incidence. The relationship between prevalence and incidence varied with time and donors' age and was virus-specific. CONCLUSION: Incidence of TTVIs cannot be easily predicted from overall prevalence. Accurate assessment of TTVI risk necessitates knowledge about donation histories and person-years at risk. Establishing comprehensive frameworks for monitoring blood donations and infectious disease markers remains a key to monitoring blood safety.

Detection of West Nile virus RNA and antibody in frozen plasma components from a voluntary market withdrawal during the 2002 peak epidemic.

BACKGROUND: The US West Nile virus (WNV) epidemic in the summer and fall of 2002 included the first documented cases of transfusion-transmitted WNV infection. In December 2002, the FDA supported a voluntary market withdrawal by the blood banking community of frozen blood components collected in WNV high-activity areas. At the time, the prevalence of viremia and serologic markers for WNV in the blood supply was undefined. STUDY DESIGN AND METHODS: In collaboration with America's Blood Centers, 1468 frozen plasma components (of approx. 60,000 frozen units voluntarily withdrawn from the market) were selectively retrieved from the peak epidemic regions and season (June 23, 2002-September 28, 2002). These units were unlinked, subaliquoted, and tested by WNV enzyme immunoassays (EIAs; Focus Technologies and Abbott Laboratories) and nucleic acid amplification tests (NATs; Gen-Probe Inc. and Roche Molecular Systems). RESULTS: Of the 1468 EIA results from Abbott and Focus, 7 were anti-immunoglobulin M (IgM)- and anti-immunoglobulin G (IgG)-reactive by both assays, 8 and 1 were IgM-only-reactive, and 8 and 23 were IgG-only-reactive, respectively. NAT by Gen-Probe and Roche Molecular Systems yielded one RNA-positive, antibody-negative unit containing approximately 440 RNA copies per mL. An additional 10-fold replicate NAT testing by Gen-Probe on 14 of 15 IgM-reactive specimens yielded 2 additional IgM- and IgG-reactive units with low-level viremia (i.e., 7/10 and 2/10 replicates tested reactive). CONCLUSION: The prevalence of acute (RNA-positive) and recent (IgM-seroreactive) WNV infections indicates that transfusion risk in high-risk areas could have been considerable and that voluntary market withdrawal of frozen components likely averted some WNV transfusion transmissions. The existence of very-low-level viremic units raises concerns, because WNV minipool NAT screening will miss such units and individual NAT may not completely correct this situation.

First year donation patterns predict long-term commitment for first-time donors.

BACKGROUND AND OBJECTIVES: Converting first-time donors to become regular donors continues to be a challenge facing blood centres. We examined whether first-time donors with frequent return in the first 12 months were more likely to become regular donors. SUBJECTS AND METHODS: The donation histories of 179 409 community whole-blood donors, whose first-time donation in 1991 was negative on donor screening tests, were evaluated. Donors were categorized by the number of donations made in the 12 months after (and including) their first donation. The donor return pattern in the subsequent 6 years, and its association with first-year donation frequency and demographics, was evaluated by using logistic regression analysis. A 'regular donor' was defined as one who returned to donate in at least 4 of the 6 years of follow-up. RESULTS: First-year donation frequency was significantly correlated with long-term donor return (P < 0.0001). Among those giving 1, 2, 3, 4 and > or = 5 donations in the first year, 4%, 11%, 21%, 32% and 42%, respectively, became regular donors (P < 0.0001). Similar associations between donation pattern and donor return behaviour were observed after adjusting for demographic variables (P < 0.0001). CONCLUSIONS: Strategies aimed at encouraging current donors to donate more frequently during the first year may help to establish a regular donation behaviour.

A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin.

Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasion through matrigel and membrane pores, by decreased adhesion to extracellular matrix proteins and by increased motility. This may represent an in vitro model of a step in the metastatic process occurring subsequent to invasion. The paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubicin-selected variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr-10p10p, in contrast, exhibited only small increases in resistance to doxorubicin, although they were slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to paclitaxel, carboplatin and 5-fluorouracil.

Comparison of demographic and donation profiles and transfusion-transmissible disease markers and risk rates in previously transfused and nontransfused blood donors.

BACKGROUND: Increasing concern about transfusion transmission of variant Creutzfeldt-Jakob disease has resulted in indefinite deferral of transfused donors in France and the UK. Little is known, however, about the impact of indefinite deferral of transfused donors on blood safety and availability in the US. STUDY DESIGN AND METHODS: Data were collected on allogeneic donations at five US blood centers during 1991 through 2000. Donation characteristics, prevalence, and incidence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were compared between transfused and nontransfused donors. Unreported deferrable risk (UDR) and reasons to donate were evaluated with data from a mail survey. RESULTS: Transfusion history was reported by 4.2 percent of donors. Prevalence and incidence of HIV and HBV were comparable between transfused and nontransfused donors. Although HCV incidence was similar in both groups, HCV prevalence was nearly three times higher in transfused than in nontransfused first-time donors. UDR and reasons to donate were similar in the two groups, except transfused donors were less likely to donate for screening test results (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). CONCLUSION: Transfused and nontransfused donors had similar viral incidence and comparable UDR, suggesting that indefinite deferral of transfused donors would unlikely improve blood safety. Until more is known about the prevalence and transfusion transmissibility of emerging agents, indefinite deferral of previously transfused donors in the US does not appear warranted.

Multicenter comparison of serologic assays and estimation of human herpesvirus 8 seroprevalence among US blood donors.

BACKGROUND: As part of assessing the possibility of transfusion transmission of human herpesvirus 8 (HHV-8 or Kaposi's sarcoma-associated herpesvirus), HHV-8 seroprevalence was estimated among US blood donors, the performance of HHV-8 serologic tests was compared, and the presence of HHV-8 DNA was tested for in donated blood. STUDY DESIGN AND METHODS: Replicate panels of 1040 plasma specimens prepared from 1000 US blood donors (collected in 1994 and 1995) and 21 Kaposi's sarcoma patients were tested for antibodies to HHV-8 in six laboratories. HHV-8 PCR was performed on blood samples from 138 donors, including all 33 who tested seropositive in at least two laboratories and 22 who tested positive in at least one. RESULTS: The estimated HHV-8 seroprevalence among US blood donors was 3.5 percent (95% CI, 1.2%-9.8%) by a conditional dependence latent-class model, 3.0 percent (95% CI, 2.0%-4.6%) by a conditional independence latent-class model, and 3.3 percent (95% CI, 2.3%-4.6%) by use of a consensus-derived gold standard (specimens positive in two or more laboratories); the conditional dependence model best fit the data. In this model, laboratory specificities ranged from 96.6 to 100 percent. Sensitivities ranged widely, but with overlapping 95 percent CIs. HHV-8 DNA was detected in blood from none of 138 donors evaluated. CONCLUSIONS: Medical and behavioral screening does not eliminate HHV-8-seropositive persons from the US blood donor pool, but no viral DNA was found in donor blood. Further studies of much larger numbers of seropositive individuals will be required to more completely assess the rate of viremia and possibility of HHV-8 transfusion transmission. Current data do not indicate a need to screen US blood donors for HHV-8.

Do blood donors read and understand screening educational materials?

BACKGROUND: Blood donors with high-risk behaviors may not self-defer because they failed to read or understand the screening educational materials. STUDY DESIGN AND METHODS: In 1993, a total of 34,726 allogeneic donors responded to an anonymous mail survey of 50,162 donors that inquired about demographics, donor status, amount of the donor educational materials read, new HIV knowledge gained, and donors' opinions on the length and difficulty of materials. RESULTS: Although 78 percent reported reading all materials, only 32 percent indicated reading carefully; 34 percent learned new information about HIV and 95 percent perceived the materials as easy to understand. First-time donors were more likely to read carefully (OR, 7.9) and gain more HIV knowledge from the materials (OR, 1.9) than repeat donors. Minority, less educated, screening test-reactive, and HIV test-seeking donors reported reading the materials more carefully and learning more about HIV than their respective counterparts. Donors with less education, those with reactive screening tests, those seeking HIV test results, and those not reporting a risk behavior were more likely to find the materials difficult to understand. CONCLUSION: Most donors reported skimming and not having difficulty understanding the educational materials. Some donors may be aware that they should not donate or are failing to assimilate the information in the materials. Methods to present information more clearly and concisely are clearly needed. However, some high-risk donors may still continue donating no matter how improved the educational materials are.

Prevalence of transfusion-transmissible viral infections in first-time US blood donors by donation site.

BACKGROUND: Understanding the donor base, infectious disease prevalence, and donation loss at various blood donation sites will help maximize blood collection efforts and blood availability. STUDY DESIGN AND METHODS: Using donation data collected at five US blood centers, the prevalence of HIV, HTLV, HBsAg, and HCV in first-time whole-blood donations at 10 donation sites was evaluated: military, education, religious, professional, industry, services, community, health care, government, and fixed sites. Donation loss from screening test reactivity at each donation site was also evaluated. RESULTS: During the study, 1.2 million first-time whole-blood donations were collected. Military and education sites had a low prevalence of all viral markers, except for HBsAg, which was highest at education sites. Variations in viral marker prevalence among donation sites were partially explained by donor demographic differences. Donation loss varied by donation site, ranging from 3.3 percent at education sites to 6.4 percent at industry sites, indicating differential efficiency of blood collection efforts. CONCLUSION: Different rates of positive viral test results and donation loss in first-time whole-blood donors were observed at various types of donation sites. This information may be useful in estimating the yield of usable units from specific blood drives and in allocating resources to meet blood center collection goals.

Knowledge of HIV/AIDS transmission and screening in United States blood donors.

BACKGROUND: Increased knowledge of HIV transmission and behavioral and test screening may encourage high-risk blood donors to self-defer. STUDY DESIGN AND METHODS: Knowledge of HIV transmission and screening and the association with demographics, screening test reactivity, and unreported deferrable risks (UDRs) was assessed by a 1998 anonymous mail survey sent to 92,581 blood donors, of whom 57 percent responded. Groups were compared by using weighted chi-square tests and logistic regression analysis. RESULTS: Four percent of the donors thought that it was very likely or somewhat likely for a person to contract HIV from donating blood, and 20 percent perceived a similar risk from blood transfusion. Only 60 percent of the donors knew that the available screening tests may not detect a recent infection. Thirty-seven percent either did not know or felt it was acceptable to donate blood to obtain HIV testing. Those most likely to answer knowledge questions incorrectly were more likely to have a higher prevalence of test reactivity or UDRs and to be

Prevalence, donation practices, and risk assessment of blood donors with hemochromatosis.

CONTEXT: Despite changes in eligibility policies, practical barriers limit blood donations from individuals with hemochromatosis. Increased knowledge of hemochromatosis donor characteristics may help foster further changes that will promote more donations. OBJECTIVES: To estimate the prevalence of donors diagnosed as having hemochromatosis and to compare rates of unreported deferrable risks for transfusion-transmissible viral infections (TTVIs), positive screening test results for TTVIs, and donation patterns between hemochromatosis patient donors and donors reporting no medical conditions necessitating phlebotomy (non-health-related donors). DESIGN: An anonymous mail survey conducted in 1998 as part of the ongoing Retrovirus Epidemiology Donor Study. SETTING AND PARTICIPANTS: Among a stratified probability sample of 92 581 blood donors from 8 geographically diverse US blood centers, 52 650 (57%) responded. MAIN OUTCOME MEASURES: Prevalence of hemochromatosis among blood donors; prevalence of unreported deferrable risks and positive screening test results for TTVIs among hemochromatosis patient donors vs non-health-related donors. RESULTS: One hundred ninety-seven respondents (0.4%) identified themselves as hemochromatosis patients and 50 079 (95.1%) as non-health-related donors. An estimated 0.8% of all donations were from hemochromatosis patients, 45.8% of whom reported that they had donated blood to treat their illness. The proportion of repeat donors was higher in hemochromatosis patients than in non-health-related donors (83.5% vs 76.5%; P =.03). Among repeat donors, 68.7% of hemochromatosis patients reported donating at least 3 times in the past year compared with 49.1% of non-health-related donors (P<.001). The prevalence of unreported deferrable risks for TTVIs was similar in hemochromatosis patients (2.0%) and non-health-related donors(3.1%) as was the overall prevalence of positive screening test results (1.3% of hemochromatosis patients vs 1.6% of non-health-related donors). CONCLUSIONS: Although significant numbers of hemochromatosis patients reported donating blood for therapeutic reasons, our findings suggest that this population does not present a greater risk to blood safety than other donors.

Incidence rates of viral infections among repeat donors:are frequent donors safer?

BACKGROUND: Incidence rates (IRs) for viral infections may vary with the frequency of donation among repeat, community, whole-blood (WB) donors, with IRs thought to be lower among donors with higher frequency of donation. STUDY DESIGN AND METHODS: IRs for HIV, HTLV, HCV, and HBV infection were stratified by frequency of donation among 868,403 repeat WB donors who gave approximately 4 million donations at five United States blood centers from 1991 through 96. All donors had given at least 2 donations during those years, with the first donation being nonreactive on confirmatory testing. Frequency of donation was measured in three ways: by the number of donations per year; at the time of donation, by the number of donations given within the preceding 2-year period; and by the number of donations given from 1991 through 1993. RESULTS: The IRs for HIV, HCV, and HBV infection did not appear to differ among donors with lower or higher numbers of donation per year. However, the IR for HTLV infection decreased as the number of donations per year increased (p = 0.0004). IRs for all viral markers remained stable, regardless of the number of donations given within the 2-year period before the donation. Although IRs for HIV, HTLV, and HCV infection did not vary by the number of donations given in 1991 through 1993, the IR for HBV infection appeared to be lower in donors who gave more donations in that period (p = 0.01). CONCLUSION: These findings do not provide evidence of a lower IR for transfusion-transmissible viral infections among repeat WB donors who give more frequently. Abbreviated screening histories for frequent repeat donors might not be advisable.

Repeat whole-blood and plateletpheresis donors:unreported deferrable risks, reactive screening tests, andresponse to incentive programs.

BACKGROUND: Evaluating plateletpheresis (PPH) and repeat community whole-blood (RWB) donors' responses to donation incentive programs is essential for developing effective donor retention programs. STUDY DESIGN AND METHODS: Using data from a 1998 anonymous questionnaire sent to 92,581 US blood donors, the prevalence of unreported deferrable risks, screening test reactivity, and response to incentives were compared in RWB and PPH donors by the use of weighted chi-square tests and logistic regression analyses. RESULTS: From 52,650 respondents, 38,884 RWB and 2,028 PPH donors were identified. Levels of screening test reactivity (1%) and unreported deferrable risks (UDRs, 2-3%) were similar in RWB and PPH donors. RWB and PPH donors were strongly encouraged or discouraged by similar incentives. Of the incentives that would encourage a higher proportion of UDR-free RWB donors to return, cholesterol screening and earning a blood credit appealed to >50 percent. Similar results were obtained for cholesterol screening in PPH donors. Community service or education credits, premarital screening, and cash had limited appeal for PPH and RWB donors, respectively, and would be more likely to differentially encourage donors with a UDR to return. CONCLUSION: Incentives that were associated with the greatest donor appeal and that minimized the potential recruitment of more risky donors were identified.

First-time blood donors: demographic trends.

BACKGROUND: With changing demographics of the United States population and the continuous need to recruit new donors, it is important to monitor the demographic profile of first-time donors and to evaluate changes in the donor pool to improve recruitment targeting. STUDY DESIGN AND METHODS: First-time whole blood (n = 901,862) donors at five United States blood centers between 1991 and 1996 were analyzed. RESULTS: The total number of first-time donors appears to be decreasing. Over the 6-year period, there was an overall increase in the proportion of Hispanic and other minority first-time donors and a concurrent decrease in the proportion of white donors at Retrovirus Epidemiology Donor Study centers. Other variables, including age, sex, and education, did not show a consistent trend. CONCLUSION: The demographic profile of first-time donors is changing. These data highlight the importance for blood centers to continuously monitor the donor population. A better understanding of the donor population may help blood centers adjust their donor outreach, recruitment, and retention programs. New recruitment efforts appear needed to counter general apathy toward donating blood, and minority groups appear to be receptive to becoming blood donors.

Trends in incidence and prevalence of major transfusion-transmissible viral infections in US blood donors, 1991 to 1996. Retrovirus Epidemiology Donor Study (REDS)

CONTEXT: Evaluating trends in blood donor infectious disease rates is essential for monitoring blood supply safety and donor screening effectiveness. OBJECTIVE: To determine changes over time in blood donor population infection rates of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV). DESIGN: Cross-sectional survey data from the National Heart, Lung, and Blood Institute-sponsored Retrovirus Epidemiology Donor Study. SETTING: Five blood centers in different regions of the United States. PARTICIPANTS: A total of 1.9 million volunteer blood donors with 1 or more nonautologous donations from January 1991 to December 1996. MAIN OUTCOME MEASURES: Changes in rates of HIV, HTLV, HCV, and HBV infections were evaluated by comparing yearly prevalence estimates (per 100,000 donations) for first-time allogeneic donors and period-specific incidence rates (IRs) (per 100,000 person-years) for repeat allogeneic donors between 1991 and 1996 (for HCV, from about March 1992 to June 1996). RESULTS: Prevalence of HIV decreased in first-time donors from 0.030% to 0.015% (P=.006) and HCV prevalence decreased from 0.63% to 0.40% (P<.001). Trends were not statistically significant for the proportion of first-time donors with hepatitis B surface antigen (HBsAg) or HTLV. For repeat donors, IRs did not change significantly, indicating a stable but low level of seroconversion. The overall IRs (95% confidence intervals) per 100,000 person-years were 2.92 (2.26-3.70) for HIV, 1.59 (1.12-2.19) for HTLV, 3.25 (2.36-4.36) for HCV, and an estimated 10.43 (7.99-13. 37) for HBV (based on an HBsAg rate of 2.66 [2.04-3.41] with presumed false-positive results considered negative). The HBV IR estimate with presumed false-positive results considered positive (for comparability to previous analyses) was 17.83 (14.60-21.56). CONCLUSION: The decrease in HIV and HCV prevalence rates, combined with the previously documented lower rates of infection in first-time donors compared with the general population, suggests the continued benefit of behavioral risk factor screening. JAMA. 2000;284:229-235

Laboratory abnormalities in former blood donors seropositive for human T-lymphotropic virus types 1 and 2: a prospective analysis.

CONTEXT: The human T-lymphotropic viruses types 1 and 2 (HTLV-1 and HTLV-2) are highly prevalent among injection drug users in the United States. However, the clinical course of infection has not been well characterized. OBJECTIVE: To understand HTLV-1-and HTLV-2-associated laboratory abnormalities, which may provide insights into their underlying pathophysiology. DESIGN: Cohort study. SETTING: Five US blood centers. PARTICIPANTS: A total of 133 HTLV-1-and 332 HTLV-2-seropositive former blood donors and 717 HTLV-seronegative donors followed up prospectively since 1991. MAIN OUTCOME MEASURES: Selected serum chemistry tests and complete blood cell counts were analyzed at enrollment and approximately 2 years later in participants. Repeated-measures analyses were conducted to evaluate the effect of HTLV infection on laboratory measures. RESULTS: Compared with seronegative subjects, HTLV-1-seropositive subjects had 13% higher creatine kinase (P =.02) and slightly elevated lactate dehydrogenase (P =.03) levels at follow-up. The HTLV-2-seropositive participants had 11% higher absolute lymphocyte counts than seronegative subjects (P =.0001). Infection with HTLV-2 also appeared to be associated with slightly higher hemoglobin levels (P =.03) and hematocrit (P =.03) and with lower albumin levels (P =.01). CONCLUSIONS: These results further our understanding of the biological mechanisms underlying HTLV and suggest that HTLV-associated laboratory changes are unlikely to alter clinical evaluation or counseling of otherwise healthy HTLV-infected subjects.

Risk factors for hepatitis C virus infection in United States blood donors. NHLBI Retrovirus Epidemiology Donor Study (REDS)

Injection drug use (IDU) is a known risk factor for hepatitis C virus (HCV) infection, but the strength of other parenteral and sexual risk factors is unclear. In 1997, we performed a case-control study of 2,316 HCV-seropositive blood donors and 2,316 seronegative donors matched on age, sex, race/ethnicity, blood center, and first-time versus repeat-donor status. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Questionnaires were returned by 758 (33%) HCV(+) and 1,039 (45%) control subjects (P =.001). The final multivariate model included only the following independent HCV risk factors: IDU (OR = 49.6; 95% CI: 20.3-121.1), blood transfusion in non-IDU (OR = 10.9; 95% CI: 6.5-18.2), sex with an IDU (OR = 6.3; 95% CI: 3.3-12.0), having been in jail more than 3 days (OR = 2.9; 95% CI: 1.3-6.6), religious scarification (OR = 2.8; 95% CI: 1.2-7. 0), having been stuck or cut with a bloody object (OR = 2.1; 95% CI: 1.1-4.1), pierced ears or body parts (OR = 2.0; 95% CI: 1.1-3.7), and immunoglobulin injection (OR = 1.6; 95% CI: 1.0-2.6). Although drug inhalation and a high number of lifetime sex partners were significantly more common among HCV seropositives, they were not associated with HCV after controlling for IDU and other risk factors. IDU, blood transfusion among non-IDU, and sex with an IDU are strong risk factors for HCV among United States blood donors. Weaker associations with incarceration, religious scarification, being stuck or cut with a bloody object, pierced ears or body parts, and immunoglobulin injection must be interpreted with caution.