Sensitivity and specificity of human T‐lymphotropic virus (HTLV) types I and II polymerase chain reaction and several serologic assays in screening a population with a high prevalence of HTLV‐II

Liu, H.; Shah, Maqsood; Stramer, Susan L.; Chen, W.; Weiblen, Barbara J.; Murphy, Edward L.

doi:10.1046/j.1537-2995.1999.39111185.x

Cited by 26 publications

(21 citation statements)

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“…where infection is not endemic, such as metropolitan France (0.0033 per thousand) (8) and the United States (0.035%) (22,24,32), but much lower than the rates reached in Cameroon (11% among a rural population) (28) and in Congo (3% among pregnant women) (42). This high frequency of indeterminate results clearly emphasizes the difficulty in assessing the real HTLV-1 seroprevalence, especially in tropical areas where indeterminate WB patterns peak and lead to misclassification.…”

Section: Discussionmentioning

confidence: 99%

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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

Raffi

Meertens

Courouble³

et al. 2001

J Clin Microbiol

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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.

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Section: Discussionmentioning

confidence: 99%

“…There are several diagnostic methods for the detection of HTLV-1 and -2 antibodies, including enzyme immunoassays (EIAs), the particle agglutination assay (PAA), immunofluorescence assays, Western blotting (WB), and the radioimmunoprecipitation assay (3,4,7,10,21,24,37,45; Stramer et al, Abstr. 52nd Annu.…”

mentioning

confidence: 99%

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

Raffi

Meertens

Courouble³

et al. 2001

J Clin Microbiol

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“…The results indicated that WB failed to detect infection by HTLV type 2, and this was also observed in two other cases that were not included in this study. Previous studies have shown that the confirmatory sensitivity of WB for HTLV-2 is worse than for HTLV-1 and presents a greater frequency of indeterminate or false negative results [28][29][30][31] . Two (5%) out of the 40 WB-positive samples from blood donors did not present reactivity in the WB test for either of the recombinant proteins (rgp46-I or rgp46-II).…”

Section: Discussion Ethics Committee Approval This Study Was Approvedmentioning

confidence: 97%

“…The development of new EIA kits for HTLV that use recombinant proteins and synthetic peptides has increased the sensitivity and specificity of such kits, in comparison with kits that use viral lysate [25][26][27] . In contrast, the WB test for HTLV-1/2 has shown little development over recent years, and is unsuitable for blood banks because of its high costs and high proportion of indeterminate results [28][29][30][31][32] . This situation suggests that there is a need to confirm virus infection by means of molecular tests.…”

Section: Discussion Ethics Committee Approval This Study Was Approvedmentioning

confidence: 99%

Evaluation of the use of real-time PCR for human T cell lymphotropic virus 1 and 2 as a confirmatory test in screening for blood donors

Andrade¹,

Ribeiro²,

Namen-Lopes³

et al. 2010

Rev. Soc. Bras. Med. Trop.

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Introduction: HTLV-1/2 screening among blood donors commonly utilizes an enzymelinked immunosorbent assay (EIA), followed by a confirmatory method such as Western blot (WB) if the EIA is positive. However, this algorithm yields a high rate of inconclusive results, and is expensive. Methods: Two qualitative real-time PCR assays were developed to detect HTLV-1 and 2, and a total of 318 samples were tested (152 blood donors, 108 asymptomatic carriers, 26 HAM/TSP patients and 30 seronegative individuals). Results: The sensitivity and specificity of PCR in comparison with WB results were 99.4% and 98.5%, respectively. PCR tests were more efficient for identifying the virus type, detecting HTLV-2 infection and defining inconclusive cases. Conclusions: Because real-time PCR is sensitive and practical and costs much less than WB, this technique can be used as a confirmatory test for HTLV in blood banks, as a replacement for WB.

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“…The serologic and PCR results in this animal were consistent with reports of rare HTLV-1-infected individuals who are serologically negative while PCR positive for the virus in their PBMCs. [40][41][42] Another rabbit of interest in the ACH.195 group was R20, which mounted an antibody response not only to HTLV-1 Gag and Env proteins, but also to the HTLV-2 SU protein. In this rabbit, the antibody response to HTLV-2 SU was stronger than that mounted against HTLV-1 SU.…”

mentioning

confidence: 99%

In vivo analysis of replication and immunogenicity of proviral clones of human T-lymphotropic virus type 1 with selective envelope surface-unit mutations

Silverman

Phipps

Montgomery

et al. 2005

Blood

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell lymphoma/leukemia (ATL). The HTLV-1 envelope gene exhibits limited variability when examined from infected individuals, but has not been tested using infectious clones of the virus in animal models. In vitro assays indicate that HTLV-1 envelope (Env) Ser75Ile, Asn95Asp, and Asn195Asp surface unit (SU) mutants are able to replicate in and immortalize lymphocytes. Herein, we examined the effects of these Env mutants in rabbits inoculated with HTLV-1 immortalized ACH.75, ACH.95, or ACH.195 cell lines (expressing full-length molecular clones with the SU mutations) or the ACH.1 cell line (expressing wild-type SU). All rabbits became infected, and the fidelity of the mutations was maintained throughout the 8-week study. However , SU point mutations resulted in decreased antibody responses to viral group-associated antigen (Gag) and Env antigens. ACH.195 rabbits had a selective decreased antibody response to SU, and one ACH.195 rabbit had an antibody response to both HTLV-1 and HTLV-2 SUs. Some mutant inoculation groups had altered proviral loads. However, peripheral-blood mononuclear cell (PBMC) proviral loads did not correlate with antibody responses. Our data are the first to demonstrate that mutations in critical determinants of HTLV-1 Env SU altered antibody responses and proviral loads, but do not prevent viral replication in vivo. (Blood. 2005;106:3602-3608) Introduction Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus etiologically linked with adult T-cell leukemia/lym-phoma (ATL), HTLV-1-associated myelopathy/tropical spastic paresis (HAM/TSP), and a variety of other immune-mediated disorders. 1 ATL is an aggressive T-cell leukemia that typically manifests in middle-aged to elderly patients who were originally infected with the virus neonatally during breastfeeding. 2 There are 4 clinically overlapping subsets of ATL. In order of decreasing prognostic survival time, these include smoldering, chronic, lym-phoma, and acute. 3 The most severe form is the acute form, which manifests as an aggressive T-cell leukemia with concomitant hypercalcemia, bone marrow involvement, generalized lymphad-enopathy, skin lesions, and spleen and liver involvement. 4 Circulating leukemic cells in patients with ATL have a characteristic lobulated nuclear morphology and are most often CD2 , CD3 , CD4 , and CD8 T cells. 1 HTLV-1 envelope protein (Env) is unique among retroviral envelope proteins in that when isolates from ATL or HAM/TSP patients are compared, there is a high degree of sequence conservation in the env region, with variability ranging from 1% to at most 8%. 5-10 HTLV-1 Env is a 488-amino-acid protein. It is synthesized as a polyprotein precursor (gp62), which is subsequently glycosy-lated and cleaved into 2 proteins, surface unit gp46 (SU) and transmembrane gp21 (TM). 11,12 SU is required for entry into the target cell by mediating specific attachment to a cellular receptor, which was recently reported to be the glucose...

show abstract

Sensitivity and specificity of human T‐lymphotropic virus (HTLV) types I and II polymerase chain reaction and several serologic assays in screening a population with a high prevalence of HTLV‐II

Cited by 26 publications

References 21 publications

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

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

Evaluation of the use of real-time PCR for human T cell lymphotropic virus 1 and 2 as a confirmatory test in screening for blood donors

In vivo analysis of replication and immunogenicity of proviral clones of human T-lymphotropic virus type 1 with selective envelope surface-unit mutations

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