Long‐term serological follow‐up of blood donors with an HTLV‐Indeterminate Western Blot: Antibody Profile of Seroconverters and Individuals With False Reactions

Abstract

The high proportion of indeterminate results of the screening test for human T-lymphotropic virus (HTLV) infection has been a challenge worldwide. In this study, 60 persons with seroindeterminate results for HTLV were followed until their serological status was defined. At least two independent serological tests (EIA and WB) from sequential samples were performed at an average interval of 4.4 years, totaling 141 serum samples tested. Seroconversion occurred in 12 individuals (reactive by EIA, positive by WB and PCR), and 48 were classified as false reactions (non-reactive EIA and negative PCR, but indeterminate WB). The seroconverter group had epidemiological features similar to those seen in HTLV-1 carriers, and the average time of follow-up for seroconversion was 4 years. In the group with false reactions, the most frequent indeterminate WB pattern in the samples was the presence of p24 alone. This pattern was absent in the seroconverter group, suggesting that p24 alone is an indicator of false reactivity. In contrast, the presence of p19 and p24 seems to be an indicator of true reactivity, since this pattern was frequent (66.7%) among the seroconverters and much less common (10.4% of the first samples) among the individuals with false reactions (P = 0.0001). Thus, HTLV infection may be suspected when reactivity to p19 and p24 is observed. Individuals with an indeterminate WB pattern should be followed-up and retested. The improvement of the HTLV algorithm screening of blood donors has been necessary to reduce inconclusive results and to avoid unnecessary follow-up to define the status of infection.

A New and Frequent Human T-Cell Leukemia Virus Indeterminate Western Blot Pattern: Epidemiological Determinants and PCR Results in Central African Inhabitants

“…Thus, there is no evidence that it could be linked to an HTLV-1 seroconversion. This is also strengthened by the fact that during seroconversion following HTLV-1 primary infection, the occurrence of reactivity to p28 is always preceded by the occurrence of p19 and p24 reactivity (17,45,46). Lastly, it is also worth noting that analyses of large series of HTLV WB, performed more than 10/15 years ago in our laboratory, on a series of plasma samples mostly from Cameroon but also, to a lesser extent, from Central African Republic (RCA) and Zaire (now DRC), indicated at that time the presence of such a pattern in a significant percentage of the tested samples (A. Gessain, unpublished data).…”

“…HTLV indeterminate serologies observed using Western blotting comprise a large variety of patterns, ranging from unique and faint bands (mainly p19 or p24) to complex patterns exhibiting multiple clear bands (44,46,74). We have previously identified and characterized a frequent pattern that we named HGIP, for HTLV Gag indeterminate pattern (47).…”

“…The significance of these frequent indeterminate WB can be various but, in the majority of the cases, remains mostly unknown and a matter of discussion (24,28,57,69). Indeed, in rare cases, these patterns have been associated with (i) HTLV-1 but mostly HTLV-2 infection exhibiting an atypical HTLV serology (6,34,44,52,68,73,74), (ii) HTLV-1 seroconversion (17,45,46), and (iii) infection by a different HTLV, such as HTLV-3 or HTLV-4 (12,13,42,62,72). Furthermore, some have been considered the results of cross-reactivity against other microbial agents, especially Plasmodium falciparum in Central Africa and Indonesia (31,41,54).…”

Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results

“…The frequent occurrence of the indeterminate pattern in WB makes it difficult to diagnose the infection correctly. Causes of these indeterminate results have been reported to be cross-reactivity with Plasmodium falciparum infection (13)(14)(15), infection with HTLV-3 and HTLV-4 (16,17), and delayed seroconversion with low antibody titers (18)(19)(20)(21)(22). In those with WBindeterminate samples, the indeterminate result is sometimes sustained for a long time (18,19,23).…”

“…Causes of these indeterminate results have been reported to be cross-reactivity with Plasmodium falciparum infection (13)(14)(15), infection with HTLV-3 and HTLV-4 (16,17), and delayed seroconversion with low antibody titers (18)(19)(20)(21)(22). In those with WBindeterminate samples, the indeterminate result is sometimes sustained for a long time (18,19,23). Nevertheless, it has been reported that a significant portion of HTLV-1 WB-indeterminate samples are positive for provirus by DNA testing, i.e., 12.5% of WB-indeterminate blood donors in Iran, 9.2% in Brazil, 14.7% (5 of 34) in Argentina, and 42% of patients with neurologic symptoms and 44% of blood donors in the United States (19,(24)(25)(26)(27).…”