Increased mortality associated with HTLV-II infection in blood donors: a prospective cohort study.

BACKGROUND: HTLV-I is associated with adult T-cell leukemia, and both HTLV-I and -II are associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Several published reports suggest that HTLV-I may lead to decreased survival, but HTLV-II has not previously been associated with mortality. RESULTS: We examined deaths among 138 HTLV-I, 358 HTLV-II, and 759 uninfected controls enrolled in a prospective cohort study of U.S. blood donors followed biannually since 1992. Proportional hazards models yielded hazard ratios (HRs) for the association between mortality and HTLV infection, controlling for sex, race/ethnicity, age, income, educational level, blood center, smoking, injection drug use history, alcohol intake, hepatitis C status and autologous donation. After a median follow-up of 8.6 years, there were 45 confirmed subject deaths. HTLV-I infection did not convey a statistically significant excess risk of mortality (unadjusted HR 1.9, 95%CI 0.8-4.4; adjusted HR 1.9, 95%CI 0.8-4.6). HTLV-II was associated with death in both the unadjusted model (HR 2.8, 95%CI 1.5-5.5) and in the adjusted model (HR 2.3, 95%CI 1.1-4.9). No single cause of death appeared responsible for the HTLV-II effect. CONCLUSIONS: After adjusting for known and potential confounders, HTLV-II infection is associated with increased mortality among healthy blood donors. If replicated in other cohorts, this finding has implications for both HTLV pathogenesis and counseling of infected persons.

Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication.

As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population.

Convenience, the bane of our existence, and other barriers to donating.

BACKGROUND: To prevent donor loss and improve retention, it is important to understand the major deterrents to blood donation and to identify factors that can be effectively addressed by blood centers. STUDY DESIGN AND METHODS: A 30-item self-administered questionnaire was completed in 2003 by 1705 first-time and 2437 repeat US donors who had not donated in 2 to 3 years. Asian, Hispanic, black, and white first-time and repeat donors rated the importance of deterrents to donation in their decision to not return with a 1 to 5 scale. Categorical analysis of variance methods were used to compare the importance of deterrents between first-time and repeat donors of different race or ethnicity. RESULTS: Not having a convenient place to donate was most commonly cited as an important or very important reason for not returning by 32 to 42 percent of first-time and 26 to 43 percent of repeat respondents. Although bad treatment and poor staff skills were less of a barrier than convenience, they were more important for minority donors. Other factors such as physical side effects, foreign travel, or length of the process appeared less important. CONCLUSION: Inconvenience is a major barrier to donating, suggesting that mobile collections and increased hours of operation might help recapture lapsed donors. The finding that lapsed minority donors were more likely to give bad treatment and poor staff skills as important reasons to not donate is disconcerting in light of the changing donor demographics and increased efforts to recruit these donors.

The impact of male-to-male sexual experience on risk profiles of blood donors.

BACKGROUND: Men who have had sex with men (MSM) since 1977 are permanently deferred from donating blood. Excluding only men who engaged in male-to-male sex within either the prior 12 months or 5 years has been proposed. Little is known about infectious disease risks of MSM who donate blood. STUDY DESIGN AND METHODS: Weighted analyses of data from an anonymous mail survey of blood donors were conducted to examine the characteristics of men reporting male-to-male sex during specified time periods. RESULTS: Of the 25,168 male respondents, 569 (2.4%) reported male-to-male sex, 280 (1.2%) since 1977. Compared to donors who did not report male-to-male sex, the prevalence of reactive screening test results was higher among donors who reported the practice within the past 5 years (< or =12 months odds ratio [OR] 5.3, 95% confidence interval [CI] 2.6-10.4; >12 months to 5 years, OR 7.1, 95% CI 1.2-41.7); however, no significant difference was found for donors who last practiced male-to-male sex more than 5 years ago (>5 years-after 1977, OR 1.4, 95% CI 0.7-2.6; 1977 or earlier, OR 1.6, 95% CI 0.7-3.7). The prevalence of unreported deferrable risks (UDRs) other than male-to-male sex was significantly higher for all donors who reported male-to-male sex with ORs ranging from 3.1 to 18.9 (p < or = 0.01). CONCLUSIONS: No evidence was found to support changing current policy to permit donations from men who practiced male-to-male sex within the past 5 years. For donors with a more remote history of male-to-male sex, the findings were equivocal. A better understanding of the association between male-to-male sex and other UDRs appears needed.

A prospective study of sexual transmission of human T lymphotropic virus (HTLV)-I and HTLV-II.

BACKGROUND: Cross-sectional studies support sexual transmission of human T lymphotropic virus (HTLV)-I/II; however, prospective incidence data, particularly for HTLV-II, are limited. METHODS: A cohort of 85 HTLV-positive (30 with HTLV-I and 55 with HTLV-II) blood donors and their stable (>or=6 months) heterosexual sex partners were followed biannually over the course of a 10-year period. RESULTS: Four of 85 initially seronegative sex partners of HTLV-I and -II carriers seroconverted, for an incidence rate (IR) of 0.6 transmissions/100 person-years (py) (95% confidence interval [CI], 0.2-1.6). This includes 2 HTLV-I transmissions/219 py (IR, 0.9 transmissions/100 py [95% CI, 0.1-3.3]) and 2 HTLV-II transmissions/411 py (IR, 0.5 transmissions/100 py [95% CI, 0.06-1.8]), with no significant difference by HTLV type. There were 2 male-to-female (IR, 1.2 transmissions/100 py [95% CI, 0.1-4.3]) and 2 female-to-male (IR, 0.4 transmissions/100 py [95% CI, 0.05-1.6) transmissions. HTLV-I or -II proviral load was 2 log10 lower in newly infected partners than in index positive partners who transmitted HTLV (P=.007). CONCLUSIONS: The incidence of sexual transmission of HTLV-II may be similar to that of HTLV-I, and female-to-male transmission may play a more important role than previously thought. HTLV-I and -II proviral load may be lower in sexually acquired infection, because of a small infectious dose.

Mammalian brain consumption by blood donors in the United States: brains today, deferred tomorrow?

BACKGROUND: Theoretical concerns of possible variant CJD (vCJD) transmission by transfusion have led to deferral of US donors potentially exposed to the bovine spongiform encephalopathy agent. Although the efficacy of these policies is unknown, impact on blood collections has been substantial. Under the precautionary principle, deferral of donors consuming bovine (or other mam-malian) brains, possibly contaminated with the vCJD agent, might be considered. Blood donors were surveyed to determine lifetime mammalian brain consumption. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study (REDS) conducted an anonymous mail survey of 92,581 donors from eight US blood centers. RESULTS: Responses were received from 52,650 donors (57%). Of these, 6.4 percent reported lifetime brain consumption; bovine (3.6%) and hog brains (1.7%) were the most common. Bovine brain consumption varied fourfold by center (1.7-7.0%) and was highest among male (4.5%), older (age 55+, 6.5%), foreign-born (9.2%), Asian (7.2%), and Hispanic (8.6%) donors. Among bovine brain consumers, 67 percent engaged in the practice 4 times or less, 79 percent were repeat donors, and 61 percent reported giving at least 11 donations in the past 10 years. CONCLUSION: Following the precautionary principle, further steps to reduce the theoretical vCJD risk could include deferring donors who eat bovine (or other mammalian) brains. The impact of such a policy would not be trivial, especially in areas with older, foreign-born, Asian, or Hispanic donors. Cautious implementation and periodic evaluation of deferral policies is warranted.

Higher human T lymphotropic virus (HTLV) provirus load is associated with HTLV-I versus HTLV-II, with HTLV-II subtype A versus B, and with male sex and a history of blood transfusion.

BACKGROUND: High human T lymphotropic virus (HTLV)-I provirus load (VL) has been associated with an increased risk of HTLV-associated myelopathy, but little is known about variation in HTLV-I or -II VLs by demographic characteristics and risk behaviors. METHODS: We measured HTLV-I and HTLV-II VLs in a large cohort of 127 HTLV-I-seropositive and 328 HTLV-II-seropositive former blood donors, by use of real-time polymerase chain reaction using tax primers. Multivariable linear regression was used to control for confounding by relevant covariates. RESULTS: The mean VLs were 3.28 log(10) copies/10(6) peripheral blood mononuclear cells (PBMCs) (range, 0.5-5.3 log(10) copies/10(6) PBMCs) for HTLV-I and 2.60 log(10) copies/10(6) PBMCs (range, 0.05-5.95 log(10) copies/10(6) PBMCs) for HTLV-II (P<.0001). HTLV-II VLs were higher in those subjects with subtype A infection (mean, 2.82 log(10) copies/10(6) PBMCs) than in those with subtype B infection (mean, 2.29 log(10) copies/10(6) PBMCs) (P=.005). Higher HTLV-I VL was associated with previous receipt of a blood transfusion (P=.04), and lower HTLV-II VL was associated with female sex (P=.007). These associations persisted in virus-specific multivariate linear regression models controlling for potential confounding variables. CONCLUSIONS: VL was significantly higher in HTLV-I than in HTLV-II infection and was higher in HTLV-II subtype A than in HTLV-II subtype B infection. Chronic HTLV VLs may be related to the infectious dose acquired at the time of infection, with higher VLs following acquisition by blood transfusion and lower VLs following sexual acquisition.

Attitudes toward blood donation incentives in the United States: implications for donor recruitment.

BACKGROUND: The potential effectiveness of various donation incentive programs may vary by demographics, first-time or repeat status, and collection site. STUDY DESIGN AND METHODS: Attitudes toward future incentives were obtained from a 1998 anonymous survey sent to 92,581 US blood donors. Responses (encouraged, discouraged, no difference) to incentives were compared within demographic groups, donations sites, and between first-time and repeat community whole-blood (WB) donors using chi-square tests and logistic regressions adjusted for sample design. RESULTS: Incentives most likely to encourage donation return among all 45,588 WB respondents were blood credits (61%), cholesterol screening (61%), and prostate-specific antigen (PSA) screening (73% of men). Younger donors (< or = 25 years old) were 4 to 5 times more likely to be encouraged to donate if offered compensatory incentives (tickets to events, discounts or lottery and/or raffle tickets), gifts, or a token of appreciation than were those donors older than 55. This age effect influenced positive attitudes toward incentives in first-time donors and in donors giving at schools, universities, or military sites. Among all donors, up to 7 to 9 percent reported they would be discouraged to return if offered compensatory incentives. CONCLUSIONS: Blood credits and cholesterol and PSA screening would be well received at all donation sites. Gifts, compensatory incentives, and tokens of appreciation appeal more to younger donors. These data may allow blood centers to optimize recruitment by tailoring limited incentive resources more effectively.

Respiratory and urinary tract infections, arthritis, and asthma associated with HTLV-I and HTLV-II infection.

Human T-lymphotropic virus types I and II (HTLV-I and -II) cause myelopathy; HTLV-I, but not HTLV-II, causes adult T-cell leukemia. Whether HTLV-II is associated with other diseases is unknown. Using survival analysis, we studied medical history data from a prospective cohort of HTLV-I- and HTLV-II-infected and -uninfected blood donors, all HIV seronegative. A total of 152 HTLV-I, 387 HTLV-II, and 799 uninfected donors were enrolled and followed for a median of 4.4, 4.3, and 4.4 years, respectively. HTLV-II participants had significantly increased incidences of acute bronchitis (incidence ratio [IR] = 1.68), bladder or kidney infection (IR = 1.55), arthritis (IR = 2.66), and asthma (IR = 3.28), and a borderline increase in pneumonia (IR = 1.82, 95% confidence interval [CI] 0.98 to 3.38). HTLV-I participants had significantly increased incidences of bladder or kidney infection (IR = 1.82), and arthritis (IR = 2.84). We conclude that HTLV-II infection may inhibit immunologic responses to respiratory infections and that both HTLV-I and -II may induce inflammatory or autoimmune reactions.