Age-related donor return patterns among first-time blood donors in the United States.

BACKGROUND: Committed repeat donors are vital to the continued success of blood collections, yet the effect of age of first-time (FT) donation on return behavior is poorly described. Sixteen-year-old donors are increasingly allowed to donate and have the highest rates of adverse events, which negatively impacts return behavior. STUDY DESIGN AND METHODS: Annual cohorts of allogeneic FT donors from 2005 and 2006 were selected within the American Red Cross system and followed for 25 and 13 months, respectively. Return and total yield rates among different age groups were compared. RESULTS: A total of 2.3 million FT donors from 2005 and 2006 gave 4.2 million donations during the study. Sixteen- to 19-year old FT donors made up 41% of the FT donor base in 2005 and 16-, 17-, 18-, and 19-year-olds, respectively, had initial return rates of 62, 52, 35, and 28% and yield rates of 2.0, 1.76, 1.51, and 1.41 over 13 months. Multivariate analysis of FT yield rates shows that younger (16 and 17 years) and older (50+ years) donors, males, blood group O donors, and those without any initial adverse reaction are most likely to return. Increasing severity of donor adverse reactions correlated with a reduction in yield and return rates. CONCLUSION: FT 16-year-old donors had the highest return and yield rates despite the negative impact of increased adverse event rates. Donation at young age is critical to building a cadre of committed repeat donors but donor reactions must be addressed to ensure the donors' well-being and to sustain return behavior.

Current incidence and residual risk of hepatitis B infection among blood donors in the United States.

BACKGROUND: This study used two approaches to estimate the current incidence of hepatitis B virus (HBV) in a US donor population. METHODS: HBV incidence was estimated through the hepatitis B surface antigen (HBsAg) yield approach and the seroconversion method. Residual risk was estimated by the incidence­window period model. HBsAg yield refers to an HBsAg confirmed-positive, antibody against hepatitis B core antigen (anti-HBc)­nonreactive donation, adjusted for false-positive neutralization results. The number of HBsAg-seroconverting repeat donors divided by total number of person-years of evaluation or the HBsAg yield rate divided by HBsAg yield window gave rise to incidence estimates. RESULTS: The seroconversion and the yield approach, respectively, gave an incidence estimate of 3.41 or 3.43 per 105 person-years. Using a revised infectious window period of 38 or 30 days for current HBsAg assays, the current residual risk for HBV was respectively estimated for 2006 to 2008 at 1 in 282,000 or 1 in 357,000 donations from the seroconversion approach and 1 in 280,000 or 1 in 355,000 donations from the yield approach. With the same database and methods, this is a decrease from 1 in 86,000 to 1 in 110,000 observed in 1997 to 1999. CONCLUSIONS: Current HBV incidence and residual risk are lower than earlier estimates, especially in the youngest donors, but remain higher in the absence of HBV nucleic acid test than those for human immunodeficiency virus or hepatitis C virus (HCV). In addition to the exclusion of HBsAg false-positive donors, the reduction could reflect shortened window periods and decreased incidence rates due to vaccination or other reasons.

Current value of serologic test for syphilis as a surrogate marker for blood-borne viral infections among blood donors in the United States.

BACKGROUND: Serologic screening for syphilis has been justified in part as a surrogate marker for infections caused by other pathogens such as human immunodeficiency virus (HIV). This study assessed the current surrogate value of the test. STUDY DESIGN AND METHODS: Testing results for blood donors with the American Red Cross Blood Services between January 1, 2006, and December 31, 2007, were analyzed. All donations were tested according to standard procedures for markers of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), syphilis, and other infections. The frequency of window-period (w-p) infections interdicted by syphilis testing was estimated. RESULTS: There were significantly higher frequencies of HIV, HCV, hepatitis B surface antigen (HBsAg), and HTLV confirmed-positive donations among those with positive syphilis test results, although the sensitivity of syphilis test positivity in these groups was low. Among more than 3 million repeat donors with complete testing through reactive donation confirmation for both syphilis and HIV (anti-HIV and HIV RNA), 225 seroconverted for syphilis but not for anti-HIV or HIV RNA and 83 converted for HIV (anti-HIV or HIV RNA) but not for syphilis, with only 1 who converted for both syphilis and HIV, resulting in an incidence ratio of 150 (95% confidence interval, 21-1080) and a sensitivity of 1.2 percent. No syphilis seroconverters converted for HCV, HBsAg, or anti-HTLV. CONCLUSION: Syphilis testing presents no surrogate value for incident HCV, HBV, and HTLV infections and could only remove approximately 1 HIV w-p unit of every 148 million donations.

Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in a US surveillance study.

BACKGROUND: Since 2004, several reported transfusion transmissions of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom have reawakened concerns about the possible risk of similar transmissions of nonvariant or classic forms of CJD. STUDY DESIGN AND METHODS: Patients with a CJD diagnosis and a history of donating blood were reported to the study coordinator. Through review of blood distribution and hospital records, the recipients of blood components from these donors were identified. We then determined each recipient's vital status and, if deceased, the cause(s) of death identified by matching the recipient's personal identifiers with the Centers for Disease Control and Prevention's National Death Index database. We conducted such searches after recipients were enrolled in this study and annually thereafter for those who remained alive. RESULTS: The study included a total of 36 blood donors who subsequently developed CJD and 436 recipients. Through 2006, 91 of these recipients were still alive, 329 were deceased, and 16 were lost to follow-up. After transfusion, these three groups had survived a total of 2096.0 person-years. A total of 144 recipients survived 5 years or longer after transfusion and 68 of them had received blood donated 60 or fewer months before the onset of CJD in the donor. We identified no recipient with CJD. CONCLUSIONS: The current results of this large, ongoing lookback study show no evidence of transfusion transmission of CJD. They reinforce the conclusion that the risk, if any, of transfusion transmission of prion disease by CJD donors is significantly lower than the comparable risk of such transmission by vCJD donors.

Genetic analysis of West Nile virus isolates from US blood donors during 2002-2005.

BACKGROUND: Since its introduction into North America in 1999, West Nile virus (WNV) has spread rapidly across United States (US). OBJECTIVE: To genetically analyze WNV isolates from US blood donors during 2002-2005. STUDY DESIGN: Full-length nucleotide (NT) sequences of WNV isolates from 23 US volunteer blood donors of different geographic areas from 2002 to 2005 were determined and analyzed. RESULTS: Results indicated an overall lack of geographic pattern to WNV in US. Analyses of the viral genetic diversity demonstrated that the WNV evolved at approximately five NT substitutions and 0.8 amino acid (AA) mutations per genome per year. Comparison of the functional sequences of WNV genome showed a higher evolution rate in the coding region than in the non-coding region. Furthermore, a greater diversity was observed in the nonstructural proteins as compared to the structural proteins. Sequence alignment analysis revealed that the rapid spread of WNV in US was accompanied by the establishment of a dominant genetic variant with 11 conserved NT mutations. CONCLUSIONS: The establishment of a dominant genotype across US and the displacement and possible extinction of earlier progenitor genotypes appears to have resulted from the accumulation and fixation of 11 nucleotide mutations throughout the coding region of WNV genome.

Donor deferral and resulting donor loss at the American Red Cross Blood Services, 2001 through 2006.

BACKGROUND: A large number of blood donors are deferred each year and many of the temporarily deferred donors do not return to donate blood. This study analyzed actual deferral and return donation data from the American Red Cross to further assess the impact of donor deferral on donor availability. STUDY DESIGN AND METHODS: Voluntary blood donors who presented between 2001 and 2006 were included in this study. Deferred donors were classified into three groups according to their history of presentation during the prior 2 years: Group 1 with no prior donation or deferral, Group 2 with prior donation but no deferral, and Group 3 with prior deferral. Temporarily deferred donors in Groups 1 and 2 who did not return during the next 3 years were considered lost donors. All indefinitely deferred donors were lost donors. RESULTS: A mean of 12.8 percent of a total of 47,814,370 donor presentations between 2001 and 2006 resulted in a deferral. While majority of the deferrals were related to donor safety reasons, deferrals for recipient safety reasons accounted for 22.6 percent of deferrals or 2.9 percent of total presentations. Temporary and indefinite deferrals for recipient safety-related reasons collectively caused an estimated loss of 647,828 donors during the 6 years. An additional 1,042,743 donors were lost due to deferrals for donor safety-related reasons during the same period. CONCLUSIONS: The results on donor loss after deferral call attention to the impact of donor deferrals on donor availability and the need to monitor and assess the necessity and effectiveness of such deferrals.

A method for estimating incidence rate of infectious diseases among first-time blood donors.

BACKGROUND: In certain circumstances, there is no method for estimating incidence based on testing results on a single blood sample from first-time blood donors, severely limiting the ability to assess the residual risk of blood-borne infections among this donor subpopulation. STUDY DESIGN AND METHODS: Incidence rates were estimated for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) among first-time donors using the formula (P(2) - P(1))/D, where P(1) is the prevalence among blood donations from first-time donors of the minimum eligible ages for donation, P(2) is the prevalence among donations from first-time donors of an older age group, and D is the age difference (in years) between the older and younger donor groups. RESULTS: Estimating incidence among first-time donors using the proposed method based on a single test for anti-HCV produced similar results to those based on HCV nucleic acid test (NAT) yield cases, by sex and in different periods. Comparison of the proposed method with HIV NAT yield also showed similar results although the small number of HIV NAT yield cases limits interpretation. CONCLUSIONS: The proposed method provides an alternative way for estimating incidence of certain blood-borne infections among first-time donors, provided that our assumptions are met. It helps residual risk assessment in donor populations where first-time donors account for most of the donations and only one test result is available for each donor.

Transfusion transmission of human prion diseases.

No transmission through transfusion has been reported for classic Creutzfeldt-Jakob disease (CJD). Moreover, a series of epidemiological surveillance, case-control, and look-back studies have provided no evidence of such transmission of CJD. Hence, the risk of such transfusion transmission of classic CJD remains theoretical. In contrast, based on data from the United Kingdom, the likelihood of transmission of the agent of the variant form of CJD (vCJD) through blood transfusion by donors who develop the disease within several years of donation is about 14% for recipients who survive longer than 5 years posttransfusion. Leukodepletion may reduce the likelihood of vCJD transmissions, although this procedure by itself removes less than half of the prion infectivity of blood. The potentially longer incubation periods of vCJD with infections in donors who are not methionine/methionine homozygous at codon 129 of the prion protein gene, the unknown number of such donors, and the unknown infectivity of their blood during the incubation period suggests caution in assuming that only known cases of vCJD represent a risk for the transfusion transmission of vCJD. Results from ongoing look-back investigations and other studies will enable continued monitoring and more precise estimations of the risks of the transfusion transmission of CJD and vCJD.

Human immunodeficiency virus-1 infection correlates strongly with herpes simplex virus-2 (genital herpes) seropositivity in South African and United States blood donations.

BACKGROUND: In South Africa, human immunodeficiency virus-1 (HIV-1) infection correlates with herpes simplex virus-2 (HSV-2; genital herpes) seropositivity in genitourinary disease clinic attendees. HSV-2 infection may be a marker for risk behavior and/or directly facilitate HIV-1 transmission. The rate of HSV-2 infection in HIV-infected South African and US blood donations was assessed, and whether the infections were correlated in donors screened and found negative for high-risk behavior by predonation interview was questioned. STUDY DESIGN AND METHODS: A total of 625 South African and 393 US HIV-1-infected repository samples previously characterized for longstanding or recent HIV-1 infection were tested with two commercially available HSV-2-specific assays. The prevalence of HSV-2 antibodies in South Africa was further assessed in 106 HIV-1-infected and 106 HIV-1-negative donors matched for sex, race, and donation history, as well as 200 random HIV-1-negative donors. RESULTS: A total of 52.2 percent of US and 69.3 percent of South African HIV-1-infected donations were HSV-2-seropositive. Age, race, and sex were independent risk factors for HSV-2 antibody prevalence in HIV-1-infected South African donors, who were more likely to be HSV-2 antibody-reactive than random HIV-1-negative donors (72.6% vs. 8.5%: odds ratio [OR], 28.6; 95% confidence interval [CI], 14.5-55) or matched donors (71.6% vs. 19.6%: OR, 10.3; 95% CI, 5.4-19.8). HIV-1 infection and HSV-2 seropositivity correlated in white and black populations when analyzed by age group. CONCLUSIONS: HIV-1 infection correlates strongly with HSV-2 seropositivity in US and South African blood donors. Our data describe the characteristics of HSV-2 antibody testing as a surrogate marker for HIV-1 infection and support a facilitating role for HSV-2 infection in HIV-1 transmission.

Changing age distribution of the blood donor population in the United States.

BACKGROUND: The American Red Cross has been maintaining a research database of all blood donors. Such a database provides a unique opportunity for monitoring changes over time in donor and donation patterns. STUDY DESIGN AND METHODS: Changes in age distribution among blood donors were analyzed through comparison of the volunteer donor population in 1996, 1999, 2002, and 2005, before and after adjustment for demographic changes of the general population in the United States. RESULTS: Donations by repeat donors 50 years or older as a proportion of total donations increased from 22.1 percent in 1996 to 34.5 percent in 2005, or 1.4 percent per year, whereas donations from repeat donors of 25 to 49 years decreased from 49.1 percent in 1996 to 37.1 percent in 2005, or 1.3 percent per year. After adjusting for general population trends, the effective number of donors decreased by more than 10 percent in female and male repeat donors of age 20 to 49 years and male first-time donors of age 25 to 49 years from 1996 to 2005; female and male repeat donors of age 25 to 39 years decreased by greater than 40 percent. Prevalence rates of major infectious disease markers decreased by 3.3 percent or more per year for first-time donations and by 6.4 percent or more per year for repeat donations. CONCLUSION: The aging patterns of blood donors suggest the need for improved recruitment and retention in the young adult and middle-aged groups. A severe shortage of blood and blood components may be forecast in the foreseeable future unless offset by significant increased supply or reduced usage of blood and blood components.

Implementation of the Uniform Donor History Questionnaire across the American Red Cross Blood Services: increased deferral among repeat presenters but no measurable impact on blood safety.

BACKGROUND: The Uniform Donor History Questionnaire (UDHQ) was implemented across the American Red Cross Blood Services in 2005. This study assessed the potential impact of changes inherent in UDHQ implementation on deferral and on prevalence of infectious disease markers among donated units. STUDY DESIGN AND METHODS: Deferral and donation records were extracted and analyzed for the period of April 1, 2005, to September 30, 2005, after the implementation of the UDHQ and for the same period in the previous year. For comparison, most of the questions in the UDHQ were aligned with corresponding questions in the previous questionnaire, although such alignment could not be exact because of changes in the wording and organization of the questions. RESULTS: From 2004 (1 year previously) to 2005 (UDHQ), significant changes in deferral rate were observed for different groups of deferral questions, with the largest being +99.2 percent for "man who had sex with another man" and +92.0 percent for "receipt of blood, tissue, organ, or clotting factor concentrates or a bleeding condition or a blood disease" among repeat presenters. Changes to the educational material and the wording of questions, elimination of compound questions, and other concurrent changes could have contributed to the changed deferral rates. There was no significant change in prevalence rates of major infectious disease markers. CONCLUSIONS: Implementation of the UDHQ impacted on donor deferral, including increased deferral among repeat presenters. No significant impact was observed for infectious disease marker rates. Further monitoring for longer-term trends is recommended.

Bacterial screening of apheresis platelets and the residual risk of septic transfusion reactions: the American Red Cross experience (2004-2006).

BACKGROUND: The American Red Cross initiated systemwide bacterial testing of all apheresis platelet (PLT) collections in March 2004, yet continues to receive reports of septic reactions after transfusion of screened components. STUDY DESIGN AND METHODS: The rates of confirmed bacterial contamination of apheresis PLT collections detected by prospective quality control (QC) testing, and by surveillance of reported septic reactions to screened-negative apheresis PLTs, were analyzed according to the technology utilized for collection. RESULTS: Between March 1, 2004, and May 31, 2006, bacterial culture testing was performed on 1,004,206 donations; of these, 186 (1:5,399) had confirmed-positive culture results. Transfusion of all but 1 of the associated 293 components was prevented. A significantly higher rate of confirmed-positive bacterial cultures was seen with products collected utilizing two-arm collection procedures compared to one-arm procedures (22.7 vs. 11.9 per 10(5) donations; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.4-2.7). During this period, 20 septic transfusion reactions were reported, including 3 fatalities (1:498,711 fatalities per distributed component), which implicated screened-negative apheresis PLT products. The frequency of septic reactions was 4.7-fold higher for collections utilizing two-arm procedures (1:41,173; 95% CI, 1:25,000-1:66,667) compared to collections from one-arm procedures (1:193,305; 95% CI, 1:52,632-1:500,000; OR, 4.7; 95% CI, 1.2-18.4); most septic reactions (16 of 20) were due to Staphylococcus spp. and occurred on Day 5 (13 of 20) after collection. CONCLUSION: PLT contamination with bacteria that evade detection by QC culture remains a significant residual transfusion risk, in particular for older PLTs and skin-commensal bacteria in components collected by two-arm apheresis procedures during the study period.

Highly sensitive TaqMan RT-PCR assay for detection and quantification of both lineages of West Nile virus RNA.

BACKGROUND: Starting in 1999, the West Nile virus (WNV) epidemic represents the largest outbreak of arboviral encephalitis ever recorded in the U.S. The effective means to determine an infection are detection of viral nucleic acid and/or viral specific immunoglobulin, IgM and/or IgG. OBJECTIVE: To develop a highly sensitive and specific TaqMan RT-PCR assay for the detection and quantification of WNV RNA of lineage 1 and lineage 2. STUDY DESIGN: A TaqMan RT-PCR primer-probe was designed to perfectly match target sequences of all sequenced WNV strains and isolates, which added a layer of protection against false-negative results due to strain variability. In addition, the inclusion of a low level RNA internal control (IC) in the assay increased the precision and accuracy of the assay. RESULTS: By optimizing the RNA preparation procedure for increased WNV RNA recovery, together with optimizing the primer-probe and TaqMan conditions for improved amplification efficiency, we developed a highly sensitive assay with the detection limit of 10 copies/mL. To evaluate the assay, we tested plasma samples from 12 transfusion-transmitted implicated cases in 2002 and from 68 positive blood donors in 2003. All tested specimens were WNV positive. The viral load of 68 positive blood donor samples collected in 2003 ranged from 10 copies/mL to 67,000 copies/mL with a mean of 8100 copies/mL. Furthermore, high sensitivity of the assay was achieved without compromising specificity. All 100 routine donor samples tested negative. CONCLUSIONS: The assay results demonstrate that our in-house TaqMan RT-PCR procedure can detect and quantify WNV RNA of lineage1 and lineage 2 in human plasma with high sensitivity and specificity.

Detection of bacterial contamination in apheresis platelet products: American Red Cross experience, 2004.

BACKGROUND: Routine quality control (QC) testing for bacterial contamination in apheresis platelet (PLT) products was implemented in all 36 regional blood centers of the American Red Cross in March 2004. STUDY DESIGN AND METHODS: PLT samples were cultured under aerobic conditions until the end of the product shelf life or when a positive reaction was indicated. To confirm the initial positive reaction, a new sample was taken from the unit for reculturing. All positive culture bottles were referred for bacterial isolation and identification. Bacterial testing data along with apheresis PLT collection information were collected for analysis. Reports and investigations of potential septic reactions to apheresis PLTs were reviewed. RESULTS: In the first 10 months of bacterial testing, 226 of 350,658 collections tested initially positive. Sixty-eight were confirmed on resampling to be bacterially contaminated for an overall confirmed-positive rate of 0.019 percent or 1 in 5157. Staphylococcus spp. (47.1%) and Streptococcus spp. (26.5%) were the most frequently isolated bacteria; Gram-negative bacteria accounted for 17.6 percent of the confirmed-positive products. Of the 354 apheresis PLT products derived from all 226 initial test-positive cases, 38 (10.7%) were transfused by the time the initial positive reaction was indicated. None of these transfused products, however, had a confirmed-positive bacterial screen and no patient who had been transfused with an unconfirmed-positive product had evidence of a septic transfusion reaction. Three high-probability septic transfusion reactions to screened, negative components were identified. In all three cases, a coagulase-negative Staphylococcus was implicated. CONCLUSION: Our experience demonstrates that bacterial testing of apheresis PLT products as a QC measure was efficiently implemented throughout the American Red Cross system and that this new procedure has been effective in identifying and preventing the transfusion of many, although not all, bacterially contaminated PLT units.

West Nile virus among blood donors in the United States, 2003 and 2004.

BACKGROUND: West Nile virus first appeared in the United States in 1999 and has since spread throughout the contiguous states, resulting in thousands of cases of disease. By 2002, it was clear that the virus could be transmitted by blood transfusion, and by the middle of 2003, essentially all blood donations were being tested for West Nile virus RNA with the use of investigational nucleic acid amplification tests; testing was performed on individual samples or on "minipools" of up to 16 donations. METHODS: We analyzed data from the West Nile virus testing program of the American Red Cross for 2003 and 2004 to identify geographic and temporal trends. In areas with a high incidence of infection, individual donations were tested to increase the sensitivity of testing. Donors with reactive results participated in follow-up studies to confirm the original reactivity and to assess the natural history of infection. RESULTS: Routine testing in 2003 and 2004 identified 540 donations that were positive for West Nile virus RNA, of which 362 (67 percent) were IgM-antibody-negative and most likely infectious. Of the 540 positive donations, 148 (27 percent) were detectable only by testing of individual donations, but only 15 of the 148 (10 percent) were negative for IgM antibody. The overall frequencies of RNA-positive donations during the epidemic periods were 1.49 per 10,000 donations in 2003 and 0.44 per 10,000 in 2004. In 2004, 52 percent of the positive donations were from donors in four counties in southern California. CONCLUSIONS: Rapid implementation of a nucleic acid amplification test led to the prospective identification of 519 donors who were positive for West Nile virus RNA and the removal of more than 1000 potentially infectious related components from the blood supply of the Red Cross. No cases of transfusion-transmitted infection were confirmed among recipients of the tested blood.

Fluctuation of HCV viral load before seroconversion in a healthy volunteer blood donor.

BACKGROUND: Newly implemented NAT has been shown to be able to effectively identify HCV-positive blood donated during the preseroconversion period. STUDY DESIGN AND METHODS: EDTA-plasma pools of 24 donations were tested using an HIV-1/HCV multiplex NAT under an FDA-approved IND application. Samples in a positive pool were retested individually. Positive samples were further tested by two discriminatory assays to determine specific viral reactivity. Upon obtaining informed consent, seronegative donors with positive NAT results were enrolled into a follow-up study for risk factor analysis and laboratory testing. RESULTS: A donation by a 29 year old female was identified as HCV NAT-positive with negative serology and an elevated ALT. Her two previous donations, 5 and 12 months earlier, were both seronegative and with normal ALT. Her husband tested positive for HCV RNA. The donor remained seronegative for at least 36 days. The index donation had a viral RNA concentration of >500,000 copies per mL while the first seropositive sample was NAT-negative. Laboratory data on serial follow-up samples showed 100- to 1,000-fold fluctuations in viral load during a period of 48 days prior to seroconversion. CONCLUSIONS: This case suggests that, at least in some newly infected individuals, the HCV viral load can fluctuate dramatically prior to seroconversion, and that NAT, even on individual samples, will not totally prevent HCV transmission.