Increased incidence of infectious diseases during prospective follow-up of human T-lymphotropic virus type II- and I-infected blood donors. Retrovirus Epidemiology Donor Study.

BACKGROUND: To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities. METHODS: Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use. RESULTS: Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years). CONCLUSIONS: These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.

Delayed hypersensitivity skin testing to mumps and Candida albicans antigens is normal in middle-aged HTLV-I- and-II-infected U.S. cohorts.

It has been reported that human T cell lymphotropic virus (HTLV)-I-infected persons in Japan have decreased delayed hypersensitivity skin test reactivity to tuberculin purified protein derivative (PPD), but HTLV-I- or -II-infected persons do not generally develop opportunistic infections. We administered standardized intradermal testing with PPD, mumps, and Candida albicans antigens to 31 HTLV-I, 48 HTLV-II, and 143 seronegative subjects in the United States. Reactivity at 48 hr was compared among the three groups. Response rates to PPD were very low in all subjects. Fifty-five percent of seronegative subjects did not react to mumps antigen, compared with 55% of HTLV-I [adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.27-2.33] and 38% of HTLV-II (OR = 0.73, 95% CI 0.33-1.64). Fifty-one percent of seronegatives did not react to Candida albicans antigen, compared with 34% of HTLV-I (OR = 0.37, 95% CI 0.15-0.93) and 46% of HTLV-II (OR = 0.71, 95% CI 0.34-1.52). Anergy was present in 33% of seronegatives, 28% of HTLV-I (OR = 0.60, 95% CI 0.20-1.78), and 19% of HTLV-II (OR = 0.56, 95% CI 0.22-1.44). HTLV-I- and -II-infected persons appear to have intact delayed hypersensitivity skin test responses to mumps and Candida albicans antigens.

Lymphocyte transformation in presumed ocular histoplasmosis.

Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.

Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection.

OBJECTIVE: To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN: Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING: Four major medical centres in the United States. PATIENTS: 12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES: In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS: Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS: Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.

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.

Effect of visible light on canine distemper virus.

Nemo, George J. (The Catholic University of America, Washington, D.C.), and Ernest C. Cutchins. Effect of visible light on canine distemper virus. J. Bacteriol. 91:798-802. 1966.-Canine distemper virus (CDV) was inactivated by visible light. The virus was light-sensitive in fluid suspension (in vitro) as well as during intracellular replication (in vivo). The addition of calf serum or glutathione reduced the extent of inactivation. CDV was less sensitive when suspended in distilled water or in the amino acid or Earle's salts components of the minimal essential medium of Eagle than when suspended in the vitamin component of the minimal essential medium of Eagle or in riboflavine (0.1 mg per liter). These findings indicate that, whereas some ingredient of the medium may enhance light sensitivity, its presence is not necessary for light inactivation of CDV. It is proposed that some substance derived from the host cell and intimately associated with the virus particle serves to render CDV light-sensitive.

Antigenic relationship of human foamy virus to the simian foamy viruses.

A foamy virus isolated by Achong et al. from a human nasopharyngeal carcinoma was studied to determine its antigenic relationship to the eight known simiam foamy viruses (SFV). Using reciprocal cross-immunofluorescent and cross-neutralization techniques, we found the human isolate to be closely related to SFV type 6. In a seroepidemiological survey, neutralizing antibody to the human foamy virus was not detected in the sera of animal caretakers or laboratory personnel who routinely handled a wide variety of nonhuman primates. We conclude that the human isolate most probably represents a variant strain of SFV type 6.

Antibody levels to parainfluenza, rubella, measles, and influenza A virus in children with polymyositis.

The CF and HI antibody titers to rubella and measles viruses, the CF titers to influenxa A, and the HI titers to parainfluenza 1, 2, and 3 were carried out on the sera of 20 patients with childhood polymyositis and their matched controls. The titers for measles, parainfluenxa 1, and influenza A were slightly higher for patients than for controls. The control group had antibody titers to rubella and parainfluenza 2 and 3 higher than or similar to those of patients. Strong patterns or significant differences for a given virus or virus group were not encountered.

Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients.

BACKGROUND: Testing for antibody to hepatitis B core antigen (anti-HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion-transmitted hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In a study conducted in the 1970s, 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow-up visits were available for present-day assays for HBsAg, HBV DNA, anti-HBc, and antibody to HBsAg (anti-HBs). RESULTS: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti-HBc was detected in six HBsAg-negative donors. Two other donors were negative in all assays at donation, but positive for anti-HBc and anti-HBs 2 to 4 months later. The remaining donors were negative for all HBV markers, which left five recipient cases unexplained. No HBV transmission was observed when anti-HBs sample-to-negative control values were > or = 10. CONCLUSION: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg-negative donors are prevented by anti-HBc screening. Anti-HBc-positive donors unequivocally positive for anti-HBs should be considered noninfectious for HBV and should be allowed to donate. Anti-HBc screening of paid plasmapheresis donors, supplemented by anti-HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti-HBs in plasma pools.

Estimates of infectious disease risk factors in US blood donors. Retrovirus Epidemiology Donor Study.

OBJECTIVE: Individuals who do not respond accurately to questions about infectious disease risk factors at the time of blood donation represent a potential threat to the safety of the blood supply. This study was designed to estimate the prevalence of undetected behavioral and other risks in current blood donors. DESIGN: Anonymous mail surveys to collect demographic, medical, and behavioral information were administered to individuals who had donated blood within the previous 2 months. Sampling weights were used in the analysis to adjust for differential sampling and response rates among demographic groups to provide prevalence estimates for the donor population. SETTING: Five geographically and demographically diverse US blood centers. PARTICIPANTS: A stratified probability sample of 50,162 allogeneic blood donors. MAIN OUTCOME MEASURES: Estimated prevalence rates for risk behaviors that would have been a basis for deferral if reported at the time of the donor screening interview (deferrable risk). RESULTS: Completed questionnaires were received for 34,726 donors (69.2% of the sample). A total of 186 per 10,000 respondents (1.9%) reported a deferrable risk that was present at the time of their past donation, while 39 per 10,000 (0.4%) reported this behavior within the 3 months prior to donation. Rates (with 95% confidence intervals [CIs]) of deferrable risk behaviors were 1.4 (95% CI, 1.2-1.6) times higher for men than women, 1.6 (95% CI, 1.3-2.0) times higher for first-time vs repeat donors, 2.7 (95% CI, 2.0-3.6) times higher for donors with reactive screening tests, and 7.6 (95% CI, 3.6-15.8) times higher for donors who used the confidential unit exclusion option. CONCLUSIONS: Despite the high degree of transfusion safety in the United States today, a measurable percentage of active blood donors when assessed by anonymous survey report risks for human immunodeficiency virus and other infections not reported at the time of screening, suggesting the need for further refinements in the blood donor qualification process.

Prevalence of antibodies to human immunodeficiency virus type 1 among blood donors prior to screening. The Transfusion Safety Study/NHLBI Donor Repository.

The Transfusion Safety Study (TSS) and the National Heart, Lung, and Blood Institute (NHLBI) established a repository of approximately 200,000 sera from blood donors in late 1984 and early 1985. Collections were made in the four metropolitan areas with the highest prevalence of AIDS. Retrospective testing showed an overall anti-HIV-1 prevalence of 16 cases per 10,000 donations. In this study, the predictive value of a negative initial enzyme-linked immunoassay was estimated from both quality control specimens and the rescreening of 13,461 sera to be greater than 99.99 percent with respect to technical error. Among anti-HIV-1-positive persons, there was a 1.3- to 1.5-fold excess of first-time donors. The anti-HIV-1 prevalence among donors showed that infection was more common among young men than suggested by national reporting of AIDS cases. Anti-HIV-1 prevalence varied among the four metropolitan areas less than did reported AIDS cases, but, by 1987, the differences in the latter had decreased. Anti-HIV-1 prevalence in collection areas outside of the four major cities differed much more widely than that among the cities themselves. The TSS/NHLBI Donor Repository will remain available for the indefinite future for further evaluation of screening procedures for HIV-1 and other viruses for which transfusion is found to be an important route of transmission.

Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non-B, non-C outcomes.

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.

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.

Increased prevalence of infectious diseases and other adverse outcomes in human T lymphotropic virus types I- and II-infected blood donors. Retrovirus Epidemiology Donor Study (REDS) Study Group.

Disease associations of human T lymphotropic virus types I and II (HTLV-I and -II) infection were studied in 154 HTLV-I-infected, 387 HTLV-II-infected, and 799 uninfected blood donors. Adjusted odds ratios (ORs) and 99% confidence intervals (CIs) were derived from logistic regression models controlling for demographics and relevant confounders. All subjects were human immunodeficiency virus type 1-seronegative. HTLV-II was significantly associated with a history of pneumonia (OR, 2.6; 99% CI, 1.2-5.3), minor fungal infection (OR, 2.9; 99% CI, 1.2-7.1), and bladder or kidney infection (OR, 1.6; 99% CI, 1.0-2.5) within the past 5 years and with a lifetime history of tuberculosis (OR, 3.9; 99% CI, 1.3-11.6) and arthritis (OR, 1.8; 99% CI, 1.2-2.9). Lymphadenopathy (> or =1 cm) was associated with both HTLV-I (OR, 6.6; 99% CI, 2.2-19.2) and HTLV-II (OR, 2.8; 99% CI, 1.1-7.1) infection, although no case of adult T cell leukemia/lymphoma was diagnosed. Urinary urgency and gait disturbance were associated with both viruses. This new finding of increased prevalence of a variety of infections in HTLV-II-positive donors suggests immunologic impairment.

Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team.

BACKGROUND: Maternal, obstetrical, and infant-related factors associated with the risk of perinatal transmission of human immunodeficiency virus type 1 (HIV-1) were identified before the widespread use of zidovudine therapy in pregnant women. The risk factors for transmission when women and infants receive zidovudine are not well characterized. METHODS: We examined the effects of maternal, obstetrical, and infant-related characteristics and maternal virologic and immunologic variables on the risk of perinatal transmission of HIV-1 among 480 women and their infants, all of whom received zidovudine. The women and infants were participating in a phase 3 trial of passive immunoprophylaxis for the prevention of perinatal transmission. RESULTS: In univariate analyses, the risk of perinatal transmission was associated with each of the following: decreased maternal CD4+ lymphocyte counts at base line; decreased maternal HIV p24 antibody levels at base line and delivery; increased maternal HIV-1 titer at base line and delivery; increased maternal HIV-1 RNA levels at base line and delivery; and the presence of chorioamnionitis at delivery. In multivariate analyses, the only independent risk factor was the maternal HIV-1 RNA level at base line (odds ratio for transmission, 2.4 per log increase in the number of copies; 95 percent confidence interval, 1.2 to 4.7; P=0.02) and at delivery (odds ratio, 3.4; 95 percent confidence interval, 1.7 to 6.8; P=0.001). There was no perinatal transmission of HIV-1 among the 84 women who had HIV-1 levels below the limit of detection (500 copies per milliliter) at base line or the 107 women who had undetectable levels at delivery. CONCLUSIONS: Among pregnant women and their infants, all treated with zidovudine, the maternal plasma HIV-1 RNA level was the best predictor of the risk of perinatal transmission of HIV-1. Antiretroviral therapy that reduces the HIV-1 RNA level to below 500 copies per milliliter appears to minimize the risk of perinatal transmission as well as improve the health of the women.

Demographic determinants of hepatitis C virus seroprevalence among blood donors.

OBJECTIVE: To measure demographic determinants of hepatitis C virus (HCV) seroprevalence among blood donors in the United States. DESIGN: Cross-sectional epidemiological study. SETTING: Five blood centers in different regions of the United States. SUBJECTS: A total of 862,398 consecutive volunteer blood donors with one or more nonautologous donations from March 1992 through December 1993. METHODS: Demographic data collection, serological screening with second-generation anti-HCV enzyme immunoassay, and confirmation with anti-HCV recombinant immunoblot. RESULTS: There were 3126 donors with at least one blood donation confirmed HCV-seropositive, for a crude prevalence of 3.6 per 1000. Age-specific HCV seroprevalence rose from 0.5 per 1000 donors younger than 20 years to a maximum of 6.9 per 1000 in donors aged 30 to 39 years and declined in older age groups. There was interaction between age and educational attainment, with 30- to 49-year-olds with less than a high school diploma at highest risk of HCV infection (odds ratio [OR], 33.0; 95% confidence interval [CI], 23.0 to 47.2 compared with those younger than 30 years with a bachelor's degree or higher degree). Other independent risk factors for HCV seropositivity included male sex (OR, 1.9; 95% CI, 1.8 to 2.1), black race (OR, 1.7; 95% CI, 1.6 to 1.9), Hispanic ethnicity (OR, 1.3; 95% CI, 1.1 to 1.5), previous blood transfusion (OR, 2.8; 95% CI, 2.5 to 3.1), and first/only time donor status (OR, 4.2; 95% CI, 3.9 to 4.5 compared with repeat donors). Seropositivity for human T-lymphotropic virus types I and II, human immunodeficiency virus, or hepatitis B core antigen was highly associated with HCV seropositivity (OR, 10.4; 95% CI, 9.6 to 11.4 for one vs no marker). CONCLUSIONS: Despite a low overall HCV prevalence in blood donors in the United States, there is a marked variation in HCV seroprevalence by demographic subgroup, even after controlling for prior blood transfusion, a recognized risk factor for HCV. Further study of the prevalence of other parenteral risk factors such as past injection drug use among blood donors is needed.

Relationship between antibody to hepatitis B core antigen and retroviral infections in blood from volunteer donors.

BACKGROUND: The value of the test for antibody to hepatitis B core antigen (anti-HBc) as a surrogate screening assay in the time before sensitive, virus-specific screening tests were available has been well established. There is significant debate, however about the residual value of anti-HBc screening after the implementation of human immunodeficiency virus (HIV)-, human T-lymphotrophic virus (HTLV)-, and hepatitis C virus (HCV)-specific assays and, in particular, about its utility as a lifestyle marker to identify persons at risk for retrovirus infections. STUDY DESIGN AND METHODS: Screening tests for antibodies to HIV, HTLV, and HBc, as well as confirmatory or supplemental test results for anti-HIV and anti-HTLV, were obtained from approximately 2.8 million donations collected from 1991 through 1993 by five blood centers within the United States. The sensitivity, positive predictive value, and relative prevalence of anti-HBc for each retrovirus were calculated and compared among demographic subgroups. RESULTS: The overall relationship between anti-HBc and anti-HIV was similar to that between anti-HBc and anti-HTLV. When calculated from the measured endpoint of the prevalence of anti-HIV-positive and anti-HTLV-positive donations, the sensitivities were 31.1 and 26.2 percent, the positive predictive values were 0.18 and 0.21 percent, and the relative prevalences were 30.1 and 23.8, respectively. Among 27 anti-HIV-seroconverting donors and 9 anti-HTLV-seroconverting donors, the sensitivities were 7.4 percent (95% CI: 0.9-24.3%) and 0 percent (95% CI: 0.0-28.3%), respectively. It was estimated that for each HIV-infected window-period donation detected by anti-HBc, from 19,000 to 81,000 HIV-noninfected donations are discarded. Similarly, more than 33,000 HTLV-noninfected donations are likely to be discarded for each HTLV-infected donation detected by anti-HBc. CONCLUSION: Although anti-HBc-reactive donations are more likely to be seropositive for a retrovirus than are anti-HBc-nonreactive donations, the low positive predictive value limits the test's effectiveness. If the anti-HBc test is retained in the blood donor setting, efforts should be focused on reducing the number of false-positive results.

Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays.

BACKGROUND: The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. METHODS: We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. RESULTS: Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. CONCLUSIONS: Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).