Steve Kleinman

A method for estimating hepatitis B virus incidence rates in volunteer blood donors. National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study

BACKGROUND: Calculations of the incidence of hepatitis B virus (HBV) infections in the blood donor setting that are based solely on data for seroconversion to hepatitis B surface antigen (HBsAg) will underestimate the incidence due to the transient nature of antigenemia. Estimates based on antibody to hepatitis B core antigen will overestimate the incidence due to false‐positive results caused by the nonspecificity of the test. STUDY DESIGN AND METHODS: Serologic test results were obtained from multiple‐time volunteer donors at five United States blood centers from January 1991 through December 1993. The observed HBsAg seroconversion rate was multiplied by an adjustment factor, derived from the weighted average probability of a positive HBsAg test for HBV‐infected donors who become chronic carriers, for donors with a primary antibody response without detectable antigenemia, and for donors who develop transient antigenemia. RESULTS: Among 586,507 multiple‐time donors giving 2,318,356 donations and observed for 822,426 person‐years, the HBsAg incidence rate was 4.01 per 100,000 person‐years. On the basis of prior reports of the duration of HBsAg positivity and the observed distribution of interdonation intervals among the study group, there was an estimated 53‐percent chance that an HBV‐infected donor with transient antigenemia would have a positive HBsAg test result. If 70 percent of newly HBV‐infected adults have transient antigenemia, 25 percent have a primary antibody response without primary antigenemia, and 5 percent become chronic carriers, the overall chance of being detected by the HBsAg test was 42 percent, for an adjustment factor of 2.38. The total HBV incidence rate, therefore, was estimated to be 9.54 per 100,000 person‐years. CONCLUSION: The crude HBV incidence rate observed from HBsAg test results will underestimate the true rate. The adjusted HBV incidence rate should be used in applications such as estimations of residual HBV risk to the blood supply and projections of the benefits of screening for HBV DNA.

Demographic characteristics, unreported risk behaviors, and the prevalence and incidence of viral infections: a comparison of apheresis and whole‐blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: The demographics, deferrable risk behaviors, and the prevalence and incidence of viral infections of apheresis (PH) and whole‐blood (WB) donors were compared, to characterize these two populations and to evaluate the relative safety of PH and WB donors in terms of transfusion‐transmitted viral infections.

Transfusion-Transmitted Dengue and Associated Clinical Symptoms During the 2012 Epidemic in Brazil

BACKGROUND A linked donor-recipient study was conducted during epidemics in 2 cities in Brazil to investigate transfusion-transmitted (TT) dengue virus (DENV) by DENV RNA-positive donations. METHODS During February-June 2012, samples were collected from donors and recipients and retrospectively tested for DENV RNA by transcription-mediated amplification. Recipient chart review, using a case (DENV positive)-control (DENV negative and not known to be exposed) design, was conducted to assess symptoms. RESULTS Of 39 134 recruited blood donors, DENV-4 viremia was confirmed in 0.51% of donations from subjects in Rio de Janeiro and 0.80% of subjects in Recife. Overall, 42 DENV RNA-positive units were transfused into 35 recipients. Of these, 16 RNA-positive units transfused into 16 susceptible recipients were identified as informative: 5 cases were considered probable TT cases, 1 possible TT case, and 10 nontransmissions. The TT rate was 37.5% (95% confidence interval [CI], 15.2%-64.6%), significantly higher than the viremia rate of 0.93% (95% CI, .11%-3.34%) in nonexposed recipients (P < .0001). Chart review did not find significant differences between cases and controls in symptoms or mortality. CONCLUSIONS During a large epidemic of DENV-4 infection in Brazil, >0.5% of donations were RNA positive, and approximately one third of components resulted in TT. However, no significant clinical differences were evident between RNA-positive and RNA-negative recipients.

Loss of volunteer blood donors because of unconfirmed enzyme immunoassay screening results. Retrovirus Epidemiology Donor Study

BACKGROUND: Blood donors who test repeatably reactive on enzyme immunoassay (EIA) and are not confirmed as positive are a continuing problem for blood banks. Units are discarded and donors are deferred, in spite of multiple studies indicating that such donors are very rarely infected with the transmissible agents. Few data are available, however, with which to evaluate whether the discarded units are more likely to come from particular demographic subgroups. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study database of over 2 million allogeneic whole‐blood donations collected in the years 1991 through 1993 was utilized. The prevalence of false‐positive and indeterminate test results within demographic subgroups was computed for antibodies to human immunodeficiency virus, hepatitis C virus, and human T‐lymphotropic virus (anti‐HIV, anti‐HCV, anti‐HTLV, respectively) and hepatitis B surface antigen (false‐positive only) as the proportion of donations that were repeatably reactive on EIA but negative or indeterminate on the confirmatory or supplemental test. RESULTS: Several demographic groups with increased prevalence of false‐ positive and indeterminate anti‐HIV results were the same females, younger age groups, blacks, and first‐time donors. Likewise, many of the demographic subgroups with increased prevalence of false‐positive and indeterminate anti‐HCV results were similar: older age groups, non‐ whites, lower education levels, first‐time donors, donors making directed donations, and donors who had received transfusions. For anti‐ HTLV, by contrast, the oldest group had the highest prevalence of false‐ positive results but the lowest prevalence of indeterminate results: blacks had the lowest prevalence of false positive results but the highest prevalence of indeterminate results. CONCLUSION: If units that test repeatably reactive on EIA but that are not confirmed as positive are almost always from individuals not infected with the virus in question, then these results indicate that there may be sex‐, race‐, and/or age‐linked proteins cross‐reacting with the test kit materials. Elucidation of these antigenic determinates and their subsequent removal should be a priority.

Quantitative estimate of the risks and benefits of possible alternative blood donor deferral strategies for men who have had sex with men

BACKGROUND: Implementation of sensitive screening methods for human immunodeficiency virus (HIV) and hepatitis viruses prompts the question of what quantitative risks may result from altered deferral strategies for donation of blood by men who have had sex with men (MSM).

Measures to prevent transfusion-related acute lung injury (TRALI)

H. W. Reesink, J. Lee, A. Keller, P. Dennington, J. Pink, R. Holdsworth, H. Schennach, M. Goldman, T. Petraszko, J. Sun, Y. Meng, K. Qian, V. Rehacek, P. Turek, T. Krusius, E. Juvonen, P. Tiberghien, D. Legrand, G. Semana, J. Y. Muller, J. Bux, A. Reil, C. K. Lin, H. Daly, E. McSweeney, L. Porretti, N. Greppi, P. Rebulla, H. Okazaki, S. A. Sanchez-Guerrero, H. A. Baptista-Gonzalez, C. Martinez-Murillo, A. Guerra-Marquez, H. Rodriguez-Moyado, R. A. Middelburg, J. C. Wiersum-Osselton, A. Brand, C. van Tilburg, D. Dinesh, J. Dagger, P. Dunn, E. Brojer, M. Letowska, K. Maslanka, E. Lachert, M. Uhrynowska, E. Zhiburt, M. Palfi, G. Berlin, B. M. Frey, L. Puig Rovira, E. Muniz-Diaz, E. Castro, C. Chapman, A. Green, E. Massey, N. Win, L. Williamson, C. C. Silliman, D. J. Chaffin, D. R. Ambruso, N. Blumberg, P. Tomasulo, K. J. Land, P. J. Norris, O. C. Illoh, R. J. Davey, R. J. Benjamin, A. F. Eder, L. McLaughlin, S. Kleinman & S. Panzer

A multidisciplinary "think tank": the top 10 clinical trial opportunities in transfusion medicine from the National Heart, Lung, and Blood Institute-sponsored 2009 state-of-the-science symposium.

BACKGROUND: In September 2009, the National Heart, Lung, and Blood Institute convened the State‐of‐the‐Science Symposium in Transfusion Medicine to identify Phase II and/or III clinical trials that would provide important information to advance transfusion medicine.

Frequency of human immunodeficiency virus (HIV) infection among contemporary anti-HIV-1 and anti-HIV-1/2 supplemental test-indeterminate blood donors. The Retrovirus Epidemiology Donor Study.

Background: Follow‐up studies from the mid‐1980s showed that 1 to 5 percent of blood donors testing reactive in anti‐human immunodeficiency virus type 1 (HIV‐1) enzyme immunoassay (EIA) and testing indeterminate in Western blot were infected with HIV‐1 and were in the process of seroconverting. The present study was conducted to establish the rate of HIV infection among contemporary anti‐HIV‐1/HIV type 2 (HIV‐2) EIA‐ reactive, Western blot‐indeterminate donors.

The frequency and specificity of human neutrophil antigen antibodies in a blood donor population.

BACKGROUND: Transfusion‐related acute lung injury (TRALI) has been associated with both human leukocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies. HNA antibody frequency, specificity, and demographic associations have not been well defined in the blood donor population.

Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation

Red blood cell (RBC) transfusion risks could be reduced if a robust technology for pathogen inactivation of RBC (PI‐RBCs) were to be approved.