Infectious Window Period Research Articles

Value and cost-effectiveness of screening blood donors for antibody to hepatitis B core antigen as a way of detecting window-phase human immunodeficiency virus type 1 infections. The HIV Blood Donor Study Group.

The value of screening donors for antibody to hepatitis B core antigen (anti-HBc) for the prevention of posttransfusion hepatitis has declined markedly. However, anti-HBc screening may still be useful as a surrogate marker for the window period (WP) of human immunodeficiency virus type 1 (HIV-1) infection. First, the relationship between anti-HBc reactivity and HIV-1 WP infections was examined among 225 donors who had seroconverted to anti-HIV-1 positivity between 1987 and 1990. In addition, data from 1654 HIV-1 seropositive donors were analyzed to characterize the relationship among anti-HBc reactivity, donor demographics, and HIV-1-related risk factors. The yield and cost-effectiveness of anti-HBc for HIV-1 prevention were then projected on the basis of a published decision analysis model. Forty (18%) of 225 HIV-1-seroconverting donors tested anti-HBc-reactive on the donation preceding anti-HIV-1 seroconversion; in contrast, 341 (34%) of 1014 HIV-1-seropositive donors interviewed tested anti-HBc-reactive (chi-square test; p < 0.001). Anti-HBc reactivity was more common among HIV-1-seropositive donors reporting male-to-male sexual contact (169/360, 47%) and injection drug use (44/83, 53%) than among those with heterosexual contacts known to be HIV-1-positive (31/190, 16%) or transfusion exposure (3/21, 14%) or among females with no identified risk factors (21/124, 17%). The estimates of 18 to 34 percent sensitivity for anti-HBc in detecting HIV-1 WP donations and a current rate of 1 in 676,000 HIV-1 WP donations (after p24 antigen screening) suggest that continued use of anti-HBc screening could result in the transfusion of 5 to 12 fewer HIV-1-infected units per year in the United States, which would add 19 to 48 quality-adjusted years of life for the 3.5 million annual transfusion recipients at a cost of $992,020 to $2,345,000 per quality-adjusted life-year saved. The low yield and very poor cost-effectiveness of anti-HBc screening indicate that this test is not an effective screening test for HIV-1 WP donations.

The Risk of Transfusion-Transmitted Viral Infections

Accurate estimates of the risk of transfusion-transmitted infectious disease are essential for monitoring the safety of the blood supply and evaluating the potential effect of new screening tests. We estimated the risk of transmitting the human Immuno-deficiency virus (HIV), the human T-cell lymphotropic virus (HTLV), the hepatitis C virus (HCV), and the hepatitis B virus (HBV) from screened blood units donated during the window period following a recent, undetected infection. Using data on 586,507 persons who each donated blood more than once between 1991 and 1993 at five blood centers (for a total of 2,318,356 allogeneic blood donations), we calculated the incidence rates of seroconversion among those whose donations passed all the screening tests used. We adjusted these rates for the estimated duration of the infectious window period for each virus. We then estimated the further reductions in risk that would result from the use of new and more sensitive viral-antigen or nucleic acid screening tests. Among donors whose units passed all screening tests, the risks of giving blood during an infectious window period were estimated as follows: for HIV, 1 in 493,000 (95 percent confidence interval, 202,000 to 2,778,000); for HTLV, 1 in 641,000 (256,000 to 2,000,000); for HCV, 1 in 103,000 (28,000 to 288,000); and for HBV, 1 in 63,000 (31,000 to 147,000). HBV and HCV accounted for 88 percent of the aggregate risk of 1 in 34,000. New screening tests that shorten the window periods for the four viruses should reduce the risks by 27 to 72 percent. The risk of transmitting HIV, HTLV, HCV, or HBV infection by the transfusion of screened blood is very small, and new screening tests will reduce the risk even further.

Donor‐to‐Donor and Donor‐to‐Patient Transmission of Hepatitis C Virus

A patient was reported with suspected acute post-transfusion hepatitis C virus (HCV) infection, 5 months after the transfusion of 2 units of red cells. The archived serum samples of the two implicated donations were retested by the original 3rd-generation assay together with another 3rd-generation assay and RI-BA III, and were tested for HCV RNA using the PCR. Both donations were anti-HCV negative but one was found to be PCR positive. This donor was a regular donor and was identified as the husband of a donor identified 18 months earlier as being HCV positive. This case is an example of transmission of HCV in the window period of infection, and a probable example of the transmission of HCV from wife to husband through intimate contact.

Donor-to-Donor and Donor-to-Patient Transmission of Hepatitis C Virus

A patient was reported with suspected acute post-transfusion hepatitis C virus (HCV) infection, 5 months after the transfusion of 2 units of red cells. The archived serum samples of the two implicated donations were retested by the original 3rd-generation assay together with another 3rd-generation assay and RIBA III, and were tested for HCV RNA using the PCR. Both donations were anti- HCV negative but one was found to be PCR positive. This donor was a regular donor and was identified as the husband of a donor identified 18 months earlier as being HCV positive. This case is an example of transmission of HCV in the window period of infection, and a probable example of the transmission of HCV from wife to husband through intimate contact.

Blood Borne Viral Infections in Transplantation: Hepatitis Viruses and Retroviruses

Hepatitis viruses B (HBV), C (HCV) and D (HDV) and the retroviruses human immunodeficiency virus (HIV‐1) and human T celllymphotropic virus type I (HTLV‐1) and type ll (HTLV‐11) have been transmitted from infected organ and tissue donors to allograft recipients. Ascertainment of personal risk factors by health questionnaire may exclude volunteer blood donors recently exposed to transmissible diseases who could be in the ′window period′ of the infection, when routine serological screening tests are negative. Difficulty in obtaining historical evidence of possible recent exposure from a critically ill prospective organ donor may make the residual risk of infection slightly higher than the risk estimated per unit of transfused products from serologically screened volunteer blood donors. Current estimates of residual risk from transfusion based on United States data are: one in 200,000 units for HBV; one in 2000 to one in 6000 units for HCV; one in 40.000 lo one in 60,000 units for HIV‐1; and one in 69,272 units for HTLV‐1/11. Despite recent improvements in anti‐HCV testing, current screening assays underestimate the incidence of transmission and prevalence of HCV infection among immunosuppressed organ recipients: evidence of ongoing HCV infection depends on detection of HCV RNA by polymerase chain reaction. Determination of I‐IIV‐1 p24 antigen may facilitate identification of prospective organ donors in ll1e window period of early infection and may enhance serological follow‐up of allograft recipients al risk of transplantation‐associated HIV‐1 infection. Highly sensitive assays that can be completed very rapidly are needed to ensure greater safely for the recipient of an emergency organ transplant, where time to screen a prospective donor for infectious diseases may be extremely limited.