Serological, epidemiological, and molecular differences between human T-cell lymphotropic virus Type 1 (HTLV-1)-seropositive healthy carriers and persons with HTLV-I Gag indeterminate Western blot patterns from the Caribbean

Abstract

To investigate the significance of serological human T-cell lymphotropic virus type 1 (HLTV-1) Gag indeterminate Western blot (WB) patterns in the Caribbean, a 6-year (1993 to 1998) cross-sectional study was conducted with 37,724 blood donors from Guadeloupe (French West Indies), whose sera were routinely screened by enzyme immunoassay (EIA) for the presence of HTLV-1 and -2 antibodies. By using stringent WB criteria, 77 donors (0.20%) were confirmed HTLV-1 seropositive, whereas 150 (0.40%; P < 0.001) were considered HTLV seroindeterminate. Among them, 41.3% (62) exhibited a typical HTLV-1 Gag indeterminate profile (HGIP). Furthermore 76 (50.7%) out of the 150 HTLV-seroindeterminate subjects were sequentially retested, with a mean duration of follow-up of 18.3 months (range, 1 to 70 months). Of these, 55 (72.4%) were still EIA positive and maintained the same WB profile whereas the others became EIA negative. This follow-up survey included 33 persons with an HGIP. Twenty-three of them (69.7%) had profiles that did not evolve over time. Moreover, no case of HTLV-1 seroconversion could be documented over time by studying such sequential samples. HTLV-1 seroprevalence was characterized by an age-dependent curve, a uniform excess in females, a significant relation with hepatitis B core (HBc) antibodies, and a microcluster distribution along the Atlantic coast of Guadeloupe. In contrast, the persons with an HGIP were significantly younger, had a 1:1 sex ratio, did not present any association with HBc antibodies, and were not clustered along the Atlantic façade. These divergent epidemiological features, together with discordant serological screening test results for subjects with HGIP and with the lack of HTLV-1 proviral sequences detected by PCR in their peripheral blood mononuclear cell DNA, strongly suggest that an HGIP does not reflect true HTLV-1 infection. In regard to these data, healthy blood donors with HGIP should be reassured that they are unlikely to be infected with HTLV-1 or HTLV-2.

FIG. 1

Temporal trends of HTLV-1-positive, -indeterminate, and -negative results obtained from WB2.4 among Guadeloupean blood donors from 1993 to 1998.

FIG. 2

WB analysis using WB2.4 from Genelabs Diagnostic Biotechnology. Lane 1, HTLV-1-positive control; lane 2, HTLV-2-positive control; lane 3, serum from one Guadeloupean blood donor with an isolated p24 band; lanes 4 and 5, sera from two Guadeloupean blood donors with an HGIP; lane 6, serum from one Guadeloupean blood donor exhibiting gd21 (weak), p19, p26, p28, p32, p36, and pr53 bands but without reactivities to both p24 and env-encoded glycoprotein MTA-1; lanes 7 and 8, sera from three Guadeloupean blood donors exhibiting gd21, p19, p26, p28, p32, p36, and pr53 bands but without reactivities to both p24 and MTA-1; lane 9, serum from one Guadeloupean blood donor exhibiting reactivities to gd21, p24, and p28, but without reactivities to both p19 and MTA-1; lane 10, serum from one Guadeloupean blood donor with a nearly complete WB profile but lacking p24 reactivity. This subject was positive in PCR.

FIG. 3

(A) Seroprevalences of HTLV-1 and HGIP according to age among Guadeloupean blood donors (P = 0.03 between HTLV-1-positive and HGIP donors by WB2.4 [1993 to 1998]). (B) Seroprevalences of HTLV-1 and HGIP according to gender among Guadeloupean blood donors (P = 0.003 between HTLV-1-positive and HGIP donors by WB2.4 [1993 to 1998]). (C) Seroprevalences of HTLV-1 and HGIP according to HBc antibody positivity among Guadeloupean blood donors (P = 0.03 between HTLV-1-positive and HGIP donors by WB2.4 [1993 to 1998]). (D) Seroprevalences of HTLV-1 and HGIP according to HBc antibody positivity among Guadeloupean blood donors (P = 0.01 between HTLV-1-positive and HGIP donors by WB2.4 [1993 to 1998]).