Update: Serologic Testing for Human T-Lymphotropic Virus Type I -- United States, 1989 and 1990

Human T-lymphotropic virus type I (HTLV-I) * is a retrovirus that has been identified as a cause of human T-cell leukemia / lymphoma and tropical spastic paraparesis; HTLV-II is closely related to HTLV-I but has not been linked to human illness. Both viruses can be transmitted through blood transfusion and injecting- drug use; therefore, accurate and reliable HTLV-I-antibody test results are essential to diagnose HTLV-I infection, conduct public health surveillance and prevention programs, and improve the safety of blood and blood products collected for transfusion (1). During 1989, CDC expanded its Model Performance Evaluation Program (MPEP) to assess the performance of laboratories that conduct HTLV-I- antibody testing and to identify potential problems in the testing process (2). This report summarizes findings of CDC's laboratory performance evaluation surveys.

The approximately 300 laboratories enrolled in the MPEP that perform HTLV-I-antibody testing participated in CDC's HTLV-I-antibody testing surveys conducted during October 1989 and April and July 1990. Participating laboratories reported results to CDC after testing coded panels of eight undiluted HTLV-I/II-antibody-negative and HTLV-I/II-antibody-positive samples. The antibody-positive samples were obtained from five persons infected with HTLV-I and 11 infected with HTLV-II. CDC previously had determined the HTLV-I/II-antibody reactivity of these samples through composite testing by using enzyme immunoassay (EIA) kits licensed by the Food and Drug Administration (FDA) and by Western blot (WB) and radioimmunoprecipitation assay (RIPA) antibody tests using the interpretive criteria of the Public Health Service Working Group (1). Approximately 98% of the laboratories that participated in each of the three surveys reported EIA results; approximately 10% reported WB test results, and less than 2% reported indirect immunofluorescence or RIPA results (Table 1).

Laboratories that performed HTLV-I-antibody testing were classified into five types: blood bank, hospital, independent, health department, and other (i.e., test-kit manufacturer, sexually transmitted disease clinic, and research, drug-toxicology, and military laboratories). Of the laboratories that returned test results, approximately 80% were from blood banks and hospitals (Table 2).

Laboratory performance was described in terms of analytic sensitivity (i.e., of positive specimens, the proportion that were reactive), analytic specificity (i.e., of negative specimens, the proportion that were nonreactive), and overall analytic performance (i.e., for all specimens tested, the proportion for which test results were correct).

Enzyme immunoassay. In each survey, greater than 80% of the EIA results were reported by blood bank and hospital laboratories. The FDA-licensed Abbott ** HTLV-I EIA kit was used by approximately 75% of the laboratories reporting EIA results. From the October 1989 survey to the July 1990 survey, overall EIA analytic sensitivity declined from 99.4% to 96.7% (Table 3). Although the analytic sensitivity for HTLV-I-antibody-positive samples ranged from 99.8% to 100% during all three survey periods, the analytic sensitivity for HTLV-II-antibody-positive samples declined from 99.2% in October 1989 to 95.1% in July 1990. The EIA analytic specificity was more than 98% during all three survey periods. The decline in overall analytic performance from greater than 99% in October 1989 to 97.3% in July 1990 reflected changes in the EIA analytic sensitivity.

Western blot. Approximately 70% of the WB test results were reported by hospital, independent, and other laboratories. The WB tests manufactured either by Biotech or prepared by participating laboratories were used by approximately 70% of the laboratories reporting WB results. In all three surveys, the WB analytic specificity was greater than 97%, while the overall WB analytic sensitivity was less than 65%. The analytic sensitivity for HTLV-I-antibody-positive samples declined from 100% in October 1989 to 94.8% in July 1990. However, because the analytic sensitivity for HTLV-II-antibody-positive samples was less than or equal to 50% in the three surveys, the overall WB analytic performance was less than 76%.

Reported by: Model Performance Evaluation Program, Laboratory Performance Evaluation Section, Laboratory Practice Assessment Br, Div of Laboratory Systems, Public Health Practice Program Office, CDC.

Editorial Note

Editorial Note: Although HTLV-II has not been clearly linked with any disease (3), a high prevalence of HTLV-II infection has been reported among HTLV-seropositive U.S. injecting-drug users (91%-93%) (4,5) and HTLV seropositive U.S. blood donors (50%) (6). Because HTLV-I and HTLV-II are closely related, the genome of HTLV-II encodes viral proteins similar to those of HTLV-I causing extensive serologic cross-reactivity. FDA-licensed viral-lysate-based EIAs for HTLV-I do not distinguish HTLV-I from HLTV-II infection; therefore, many repeat-reactive HTLV-I EIA specimens submitted for WB supplemental testing are positive for HTLV-II antibody. Additionally, available but unlicensed HTLV-I WB test kits and reagents cannot distinguish HTLV-I from HTLV-II infection, and HTLV-II-antibody-positive samples frequently are interpreted as WB indeterminate. Depending on the sensitivity of the particular WB kit for envelope reactivity, HTLV-I-antibody-positive samples also may be interpreted as WB indeterminate.

The findings in this report for HTLV-I-antibody-positive samples by WB indicated high antibody reactivity to p19, p24, gp46, and/or gp61/68 and were consistently interpreted as seropositive. Because WB kits/reagents available for use during 1989-1990 often did not detect antibody to HTLV-II viral antigens, particularly envelope glycoprotein antigens, indeterminate interpretations were frequently reported for the HTLV-II-antibody-positive samples.

Although most laboratories performed well in testing the performance evaluation samples by EIA, the basis for decline in analytic sensitivity during the three survey periods is unknown; CDC is further analyzing the reported data to identify factors that may have contributed to the decline. In addition, the findings in this report indicate that the unlicensed WB assays used by the laboratories lack sensitivity and specificity in detecting HTLV-II antibody and in discriminating between HTLV-I and HTLV-II infections. However, recent reports indicate that new but unlicensed WB kits containing recombinant envelope antigens demonstrated 100% sensitivity for detecting envelope antibody (7). Also, both type-specific synthetic peptides and recombinant proteins recently became available for differentiating HTLV-I from HTLV-II infection (8,9); these test kits are not licensed by the FDA.

Because of the clinical importance of HTLV-I, the high prevalence of HTLV-II in high-risk behavior groups (1), and the need for precise medical diagnosis of HTLV-infection status for patient counseling, laboratories need licensed WB assays that are more sensitive and specific to detect HTLV-II antibody and to discriminate between HTLV-I and HTLV-II infections.

References

1. CDC. Licensure of screening tests for antibody to human T-lymphotropic virus type I. MMWR 1988;37:736-40,745-7.

2. CDC. Performance evaluation program: testing for human immunodeficiency virus infection. MMWR 1987;36:614.

3. Rosenblatt JD, Golde DW, Wachsman W, et al. A second isolate of HTLV-II associated with atypical hairy-cell leukemia. N Engl J Med 1986;315:372-7.

4. Lee H, Swanson P, Shorty VS, Zack JA, Rosenblatt JD, Chen ISY. High rate of HTLV-II infection in seropositive IV drug abusers in New Orleans. Science 1989;244:471-5.

5. Kwok S, Gallo D, Hanson C, McKinney N, Poiesz B, Sninsky JJ. High prevalence of HTLV-II among intravenous drug abusers: PCR confirmation and typing. AIDS Res Hum Retroviruses 1990;6:561-5.

6. CDC. Human T-lymphotropic virus type I screening in volunteer blood donors--United States, 1989. MMWR 1990;39:915,921-4.

7. Lillehoj EP, Alexander SS, Dubrule CJ, et al. Development and evaluation of a human T-cell leukemia virus type I serologic confirmatory assay incorporating a recombinant envelope polypeptide. J Clin Microbiol 1990;28:2653-8.

8. Lal RB, Heneine W, Rudolph DL, et al. Synthetic peptide-based immunoassays for distinguishing between human T-cell lymphotropic virus type I and type II infections in seropositive individuals. J Clin Microbiol 1991;29:2253-8.

9. Lipka JJ, Santiago P, Chan L, et al. Modified Western blot assay for confirmation and differentiation of human T-cell lymphotropic virus types I and II. J Infect Dis 1991;164:400-3.

• HTLV-I is not closely related to human immunodeficiency virus type 1, does not cause depletion of CD4+ cells, is not associated with immunosuppression, and does not cause acquired immunodeficiency syndrome (1). ** Use of trade names and commercial sources is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.

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