Blackbourn and colleagues in San Francisco failed to find evidence by PCR analysis of HHV-8 (HSHV) in peripheral blood mono-nuclear cells or separated cells expressing CD19 (present on all B lymphocytes) in blood obtained from 72 normal blood donors. They then proceeded to examine CD19+ cells from an additional 12 blood donors by a culture technique. Peripheral blood CD19+ cells were activated by culture with IL-2, IL-6, and PMA for three days; the filtered supernatant was then used to inoculate target normal CD19+ cells or CD8-depleted normal umbilical cord blood mononuclear cells. The target cells were examined for HHV-8 genome by PCR after three days of cultivation.
One of the 11 blood donors was found to be infected with HHV-8 when tested on five of seven occasions over an 18-month period. He was a 38-year-old heterosexual man who had never had a blood transfusion and who was HIV-negative by multiple methods, including PCR. He did, however, have a history of shingles, and his CD4/CD8 ratio was reduced (0.91 and 0.88 on two occasions); the authors do not report the absolute numbers. He had serum antibody to HHV-8, as did his father.
Zucker-Franklin and Gorman at NYU collected blood from 100 randomly selected volunteer white blood donors. All were negative for antibodies to HTLV-I/II by standard serological tests. PCR (specific for the HTLV-I Tax sequence) analysis of mononuclear cell extracts of 11 of the donors nonetheless revealed the presence of HTLV-I provirus. Eight of these 11 had antibodies to the Tax protein; all with Tax antibody by Western Blot had Tax sequence detected in their mononuclear cells. None of the 92 donors who were Tax antibody-negative had detectable Tax sequences.
COMMENT BY STAN DERESINSKI, MD, FACP
The blood supply in the United States is remarkably safe. This is the result of multiple levels of screening and other protective measures. All donation is restricted to volunteers who undergo education and history-based screening followed by extensive laboratory testing. Confidential unit exclusion and callback procedures play additional roles in the maintenance of a safe blood supply.
Risk screening is not, however, foolproof. A recent study reported that 1.9% of respondents anonymously surveyed after blood donation admitted to risk for at least one blood-transmissible disease that should have prevented them from donation (Williams AE, et al. JAMA 1997;277:967-972). Thus, serological testing for transmissible infections remains of great importance.
One concern has been that serological screening may fail to detect individuals who are in the "window period" for serological conversion for a transfusion-transmissible viral infection. It has been estimated, however, that this risk is very small, even with currently used serological tests (Schreiber GB, et al. N Engl J Med 1996;334:1685-1690; Infect Dis Alert 1996;16:13-14). The estimated risk of an individual who had passed all screening tests donating blood during the infectious window period for HIV is one in 49,300, while for HTLV-III it is one in 64,100, for HBV it is one in 63,000, and for HCV it is one in 103,000. The aggregate risk is one in 34,000 donors, with 88% of this aggregate risk due to the hepatitis viruses. Planned improvements in testing methodologies will lower this risk even further.
The NYU study reviewed here, however, suggests that the risk of transmission of HTLV-1 may be significantly greater in a screened population than the estimate above, which is based upon the window period for a serological test that may miss a significant number of HTLV-I infected subjects, if Zucker-Franklin and Gorman are correct. Fortunately, HTLV-I is only transmitted via infected mononuclear cells. Complete leukocyte-depletion of red blood cell infusions should virtually eliminate the risk. Nonetheless, consideration should be given to improvement in serological tests. The NYU study indicates that detection of antibody to the Tax protein will detect individuals such as the ones described.
No serological screening is currently performed to detect HHV-8 (KSHV) infection of donors. While the results of seroprevalence studies vary widely depending upon the methodology used, one study indicates that "about 25% of adults (including volunteer blood donors) have detectable antibodies to HHV-8" (Lennette ET, et al. Lancet 1996;348:858-861). Other studies, however, have found much lower seroprevalence results. Whatever the true seroprevalence, the finding of cultivable virus in circulating mononuclear cells in this seronegative cohort (with standard tests) is worrisome. We await confirmation of these results and, if appropriate, alteration of screening methods.
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