Risk of transfusion-associated transmission of human herpesvirus 8.

Human herpesvirus 8 (HHV8), also known as Kaposi’s sarcoma herpesvirus, causes Kaposi’s sarcoma (1) and is associated with body cavity-based lymphomas and multicentric Castleman’s disease (2,3). HHV8 is spread sexually (4,5), but other routes of transmission probably exist because, in some cases, infection has been shown to be acquired in childhood in HHV8-endemic areas, such as Mediterranean Europe and subSaharan Africa (6–8). An unresolved question with public health implications is whether blood transfusions can transmit HHV8. HHV8 can be identified in circulating lymphocytes from healthy blood donors (9,10), although the proportion of infected donors with viremia is unknown. Cytomegalovirus, another cell-associated herpesvirus, is readily transmitted via blood transfusion (11), and both HHV8 and cytomegalovirus are transmitted through solid organ transplantation (12,13). However, no study to date has documented HHV8 transmission through transfusion; the only study to examine this question directly found no transmission of HHV8 from 14 HHV8seropositive donors (14). Furthermore, HHV8 infection is relatively rare in frequently transfused groups, such as hemophiliacs (14) and thalassemia or sickle cell anemia patients (15). Determining whether transfusions may transmit HHV8 has been difficult because HHV8 infection is fairly uncommon among many donor populations [e.g., 0%–5% seroprevalence in the United States (16–18), in the U.K. (17), and in the Caribbean (19)]. To determine whether blood transfusions can transmit HHV8, we evaluated individuals in the Jamaica Transfusion Study (20). Between May 1987 and September 1988, blood donors and recipients of units from these donors were enrolled in a study of human T-cell lymphotropic virus-I (HTLV-I) transfusion-associated transmission in Kingston, Jamaica (20). Donors were screened for HTLV-I antibodies by use of several investigational assays, but some units from HTLV-Iseropositive donors were transfused before infection was identified. Through standard blood bank screening, all donors had tested negative for infection with human immunodeficiency virus-1 (HIV), hepatitis B, and syphilis. In addition, donors denied previously using intravenous drug use or engaging in high-risk sexual behavior. This study was approved by institutional review committees at the National Cancer Institute and the University of the West Indies, and participating individuals provided their written informed consent. For the present examination of HHV8 transmission risk, we tested plasma or serum samples (stored at −70 °C) from this prior study. We measured HHV8 serostatus with an enzyme immunoassay (EIA) that uses a lysate of sucrose-purified whole virus obtained from HHV8-infected KS-1 cells (Advanced Biotechnologies, Inc., Columbia, MD) (21). This assay detects antibodies to most structural and nonstructural antigens present in HHV8 virions and has 75%–100% sensitivity (for detecting seroreactivity in persons with Kaposi’s sarcoma) and 90%–100% specificity (21,22). Twenty-seven (2.7%) of 1010 donors were HHV8 seropositive. Seroprevalence was similar for men and for women and increased with age (Table 1). HHV8 seroprevalence did not differ between HTLV-I-seropositive and HTLV-I-seronegative donors (Table 1). Nineteen recipients of units from these HHV8-seropositive donors had stored post-transfusion samples available and could thus be evaluated (Table 2). Fourteen recipients received one seropositive unit, four received two, and one received four. Transfused units included seven packed red blood cell units, four platelet units, five wholeblood units, seven fresh-frozen plasma units, and three cryoprecipitate units. For each evaluable recipient, we tested two post-transfusion specimens, obtained a median of 355 days after the last HHV8-seropositive transfusion (range, 29–1367 days), for HHV8 antibody. Only one recipient had antibodies to HHV8. However, before transfusion, this subject (No. 3013) was already HHV8 seropositive and had HHV8 DNA detected in peripheral blood by polymerase chain reaction, indicating that infection antedated transfusion (data not shown). None of the other 18 recipients were seropositive following transfusion (0%; exact 95% confidence interval [CI] 4 0%–15%). The transmission risk per HHV8-seropositive unit was 0% (exact 95% CI 4 0%–11%). One donor whose serology indicated co-infection with HHV8 and HTLV-I provided packed red blood cells to a recipient who was seronegative to both viruses before transfusion (subject No. 800). The recipient acquired HTLV-I from this transfusion (20) but remained HHV8 seronegative. Our findings of a lack of transmission of HHV8 through transfusion confirm observations from the Transfusion Safety Study, in which none of 14 recipients of HHV8-seropositive blood transfusions developed infection (14). These two studies, which together comprised 32 seronegative transfusion recipients, suggest that transfusionassociated transmission occurs infrequently (exact 95% CI for transmission risk 4 0%–9% per individual transfused). Single transfusions that transmitted HTLV-I (present study) or HIV [Transfusion Safety Study (14)] but not HHV8 provide further evidence that HHV8 is not efficiently spread via transfusion. One reason for the lack of transfusion-associated transmission may be that, in healthy blood donors, cellmediated immune responses reduce circulating virus levels. Among healthy blood donors and HIV-infected per-